Prevalence and Persistence of Misconceptions in Tree Thinking.

PubMed

Kummer, Tyler A; Whipple, Clinton J; Jensen, Jamie L

2016-12-01

Darwin described evolution as "descent with modification." Descent, however, is not an explicit focus of most evolution instruction and often leaves deeply held misconceptions to dominate student understanding of common ancestry and species relatedness. Evolutionary trees are ways of visually depicting descent by illustrating the relationships between species and groups of species. The ability to properly interpret and use evolutionary trees has become known as "tree thinking." We used a 20-question assessment to measure misconceptions in tree thinking and compare the proportion of students who hold these misconceptions in an introductory biology course with students in two higher-level courses including a senior level biology course. We found that misconceptions related to reading the graphic ( reading the tips and node counting ) were variably influenced across time with reading the tips decreasing and node counting increasing in prevalence. On the other hand, misconceptions related to the fundamental underpinnings of evolutionary theory ( ladder thinking and similarity equals relatedness ) proved resistant to change during a typical undergraduate study of biology. A possible new misconception relating to the length of the branches in an evolutionary tree is described. Understanding the prevalence and persistence of misconceptions informs educators as to which misconceptions should be targeted in their courses.

Long-term evolution of the Luteoviridae: time scale and mode of virus speciation.

PubMed

Pagán, Israel; Holmes, Edward C

2010-06-01

Despite their importance as agents of emerging disease, the time scale and evolutionary processes that shape the appearance of new viral species are largely unknown. To address these issues, we analyzed intra- and interspecific evolutionary processes in the Luteoviridae family of plant RNA viruses. Using the coat protein gene of 12 members of the family, we determined their phylogenetic relationships, rates of nucleotide substitution, times to common ancestry, and patterns of speciation. An associated multigene analysis enabled us to infer the nature of selection pressures and the genomic distribution of recombination events. Although rates of evolutionary change and selection pressures varied among genes and species and were lower in some overlapping gene regions, all fell within the range of those seen in animal RNA viruses. Recombination breakpoints were commonly observed at gene boundaries but less so within genes. Our molecular clock analysis suggested that the origin of the currently circulating Luteoviridae species occurred within the last 4 millennia, with intraspecific genetic diversity arising within the last few hundred years. Speciation within the Luteoviridae may therefore be associated with the expansion of agricultural systems. Finally, our phylogenetic analysis suggested that viral speciation events tended to occur within the same plant host species and country of origin, as expected if speciation is largely sympatric, rather than allopatric, in nature.

Complex Ancestries of Isoprenoid Synthesis in Dinoflagellates.

PubMed

Bentlage, Bastian; Rogers, Travis S; Bachvaroff, Tsvetan R; Delwiche, Charles F

2016-01-01

Isoprenoid metabolism occupies a central position in the anabolic metabolism of all living cells. In plastid-bearing organisms, two pathways may be present for de novo isoprenoid synthesis, the cytosolic mevalonate pathway (MVA) and nuclear-encoded, plastid-targeted nonmevalonate pathway (DOXP). Using transcriptomic data we find that dinoflagellates apparently make exclusive use of the DOXP pathway. Using phylogenetic analyses of all DOXP genes we inferred the evolutionary origins of DOXP genes in dinoflagellates. Plastid replacements led to a DOXP pathway of multiple evolutionary origins. Dinoflagellates commonly referred to as dinotoms due to their relatively recent acquisition of a diatom plastid, express two completely redundant DOXP pathways. Dinoflagellates with a tertiary plastid of haptophyte origin, by contrast, express a hybrid pathway of dual evolutionary origin. Here, changes in the targeting motif of signal/transit peptide likely allow for targeting the new plastid by the proteins of core isoprenoid metabolism proteins. Parasitic dinoflagellates of the Amoebophyra species complex appear to have lost the DOXP pathway, suggesting that they may rely on their host for sterol synthesis. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

Ancestry of a human endogenous retrovirus family.

PubMed Central

Mariani-Costantini, R; Horn, T M; Callahan, R

1989-01-01

The human endogenous retrovirus type II (HERVII) family of HERV genomes has been found by Southern blot analysis to be characteristic of humans, apes, and Old World monkeys. New World monkeys and prosimians lack HERVII proviral genomes. Cellular DNAs of humans, common chimpanzees, gorillas, and orangutans, but not lesser ape lar gibbons, appear to contain the HERVII-related HLM-2 proviral genome integrated at the same site (HLM-2 maps to human chromosome 1). This suggests that the ancestral HERVII retrovirus(es) entered the genomes of Old World anthropoids by infection after the divergence of New World monkeys (platyrrhines) but before the evolutionary radiation of large hominoids. Images PMID:2507793

Identifying genetic variants that affect viability in large cohorts

PubMed Central

Berisa, Tomaz; Day, Felix R.; Perry, John R. B.

2017-01-01

A number of open questions in human evolutionary genetics would become tractable if we were able to directly measure evolutionary fitness. As a step towards this goal, we developed a method to examine whether individual genetic variants, or sets of genetic variants, currently influence viability. The approach consists in testing whether the frequency of an allele varies across ages, accounting for variation in ancestry. We applied it to the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort and to the parents of participants in the UK Biobank. Across the genome, we found only a few common variants with large effects on age-specific mortality: tagging the APOE ε4 allele and near CHRNA3. These results suggest that when large, even late-onset effects are kept at low frequency by purifying selection. Testing viability effects of sets of genetic variants that jointly influence 1 of 42 traits, we detected a number of strong signals. In participants of the UK Biobank of British ancestry, we found that variants that delay puberty timing are associated with a longer parental life span (P~6.2 × 10−6 for fathers and P~2.0 × 10−3 for mothers), consistent with epidemiological studies. Similarly, variants associated with later age at first birth are associated with a longer maternal life span (P~1.4 × 10−3). Signals are also observed for variants influencing cholesterol levels, risk of coronary artery disease (CAD), body mass index, as well as risk of asthma. These signals exhibit consistent effects in the GERA cohort and among participants of the UK Biobank of non-British ancestry. We also found marked differences between males and females, most notably at the CHRNA3 locus, and variants associated with risk of CAD and cholesterol levels. Beyond our findings, the analysis serves as a proof of principle for how upcoming biomedical data sets can be used to learn about selection effects in contemporary humans. PMID:28873088

Is xenodontine snake reproduction shaped by ancestry, more than by ecology?

PubMed

Bellini, Gisela P; Arzamendia, Vanesa; Giraudo, Alejandro R

2017-01-01

One of the current challenges of evolutionary ecology is to understand the effects of phylogenetic history (PH) and/or ecological factors (EF) on the life-history traits of the species. Here, the effects of environment and phylogeny are tested for the first time on the reproductive biology of South American xenodontine snakes. We studied 60% of the tribes of this endemic and most representative clade in a temperate region of South America. A comparative method (canonical phylogenetic ordination-CPO) was used to find the relative contributions of EF and PH upon life-history aspects of snakes, comparing the reproductive mode, mean fecundity, reproductive potential, and frequency of nearly 1,000 specimens. CPO analysis showed that PH or ancestry explained most of the variation in reproduction, whereas EF explained little of this variation. The reproductive traits under study are suggested to have a strong phylogenetic signal in this clade, the ancestry playing a big role in reproduction. The EF also influenced the reproduction of South American xenodontines, although to a lesser extent. Our finding provides new evidence of how the evolutionary history is embodied in the traits of living species.

Tracing Behçet's disease origins along the Silk Road: an anthropological evolutionary genetics perspective.

PubMed

Sazzini, Marco; Garagnani, Paolo; Sarno, Stefania; De Fanti, Sara; Lazzano, Teresa; Yang Yao, Daniele; Boattini, Alessio; Pazzola, Giulia; Maramotti, Sally; Boiardi, Luigi; Franceschi, Claudio; Salvarani, Carlo; Luiselli, Donata

2015-01-01

Behçet's disease is a multifactorial vasculitis that shows its highest prevalence in geographical areas historically involved in the Silk Road, suggesting that it might have originated somewhere along these ancient trade routes. This study aims to provide a first clue towards genetic evidence for this hypothesis by testing it via an anthropological evolutionary genetics approach. Behçet's disease variation at ancestry informative mitochondrial DNA control region and haplogroup diagnostic sites was characterised in 185 disease subjects of Italian descent and set into the Eurasian mitochondrial landscape by comparison with nearly 9,000 sequences representative of diversity observable in Italy and along the main Silk Road routes. Dissection of the actual genetic ancestry of disease individuals by means of population structure, spatial autocorrelation and haplogroup analyses revealed their closer relationships with some Middle Eastern and Central Asian groups settled along the Silk Road than with healthy Italians. These findings support the hypothesis that the Behçet's disease genetic risk has migrated to western Eurasia in parallel with ancestry components typical of Silk Road-related groups. This provided new insights that are useful to improve the understanding of disease origins and diffusion, as well as to inform future association studies aimed at properly accounting for the actual genetic ancestry of the examined Behçet's disease samples in order to minimise the detection of spurious associations and to improve the identification of genetic variants with actual clinical relevance.

Integrating Horizontal Gene Transfer and Common Descent to Depict Evolution and Contrast It with “Common Design”1

PubMed Central

GUILLERMO PAZ-Y-MIÑO-C; ESPINOSA, AVELINA

2016-01-01

Horizontal gene transfer (HGT) and common descent interact in space and time. Because events of HGT co-occur with phylogenetic evolution, it is difficult to depict evolutionary patterns graphically. Tree-like representations of life’s diversification are useful, but they ignore the significance of HGT in evolutionary history, particularly of unicellular organisms, ancestors of multicellular life. Here we integrate the reticulated-tree model, ring of life, symbiogenesis whole-organism model, and eliminative pattern pluralism to represent evolution. Using Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a bifunctional enzyme in the glycolytic pathway of amoeba, we illustrate how EhADH2 could be the product of both horizontally acquired features from ancestral prokaryotes (i.e. aldehyde dehydrogenase [ALDH] and alcohol dehydrogenase [ADH]), and subsequent functional integration of these enzymes into EhADH2, which is now inherited by amoeba via common descent. Natural selection has driven the evolution of EhADH2 active sites, which require specific amino acids (cysteine 252 in the ALDH domain; histidine 754 in the ADH domain), iron- and NAD+ as cofactors, and the substrates acetyl-CoA for ALDH and acetaldehyde for ADH. Alternative views invoking “common design” (i.e. the non-naturalistic emergence of major taxa independent from ancestry) to explain the interaction between horizontal and vertical evolution are unfounded. PMID:20021546

Molluscan engrailed expression, serial organization, and shell evolution

NASA Technical Reports Server (NTRS)

Jacobs, D. K.; Wray, C. G.; Wedeen, C. J.; Kostriken, R.; DeSalle, R.; Staton, J. L.; Gates, R. D.; Lindberg, D. R.

2000-01-01

Whether the serial features found in some molluscs are ancestral or derived is considered controversial. Here, in situ hybridization and antibody studies show iterated engrailed-gene expression in transverse rows of ectodermal cells bounding plate field development and spicule formation in the chiton, Lepidochitona cavema, as well as in cells surrounding the valves and in the early development of the shell hinge in the clam, Transennella tantilla. Ectodermal expression of engrailed is associated with skeletogenesis across a range of bilaterian phyla, suggesting a single evolutionary origin of invertebrate skeletons. The shared ancestry of bilaterian-invertebrate skeletons may help explain the sudden appearance of shelly fossils in the Cambrian. Our interpretation departs from the consideration of canonical metameres or segments as units of evolutionary analysis. In this interpretation, the shared ancestry of engrailed-gene function in the terminal/posterior addition of serially repeated elements during development explains the iterative expression of engrailed genes in a range of metazoan body plans.

A Hidden Markov Model Approach for Simultaneously Estimating Local Ancestry and Admixture Time Using Next Generation Sequence Data in Samples of Arbitrary Ploidy

PubMed Central

Nielsen, Rasmus

2017-01-01

Admixture—the mixing of genomes from divergent populations—is increasingly appreciated as a central process in evolution. To characterize and quantify patterns of admixture across the genome, a number of methods have been developed for local ancestry inference. However, existing approaches have a number of shortcomings. First, all local ancestry inference methods require some prior assumption about the expected ancestry tract lengths. Second, existing methods generally require genotypes, which is not feasible to obtain for many next-generation sequencing projects. Third, many methods assume samples are diploid, however a wide variety of sequencing applications will fail to meet this assumption. To address these issues, we introduce a novel hidden Markov model for estimating local ancestry that models the read pileup data, rather than genotypes, is generalized to arbitrary ploidy, and can estimate the time since admixture during local ancestry inference. We demonstrate that our method can simultaneously estimate the time since admixture and local ancestry with good accuracy, and that it performs well on samples of high ploidy—i.e. 100 or more chromosomes. As this method is very general, we expect it will be useful for local ancestry inference in a wider variety of populations than what previously has been possible. We then applied our method to pooled sequencing data derived from populations of Drosophila melanogaster on an ancestry cline on the east coast of North America. We find that regions of local recombination rates are negatively correlated with the proportion of African ancestry, suggesting that selection against foreign ancestry is the least efficient in low recombination regions. Finally we show that clinal outlier loci are enriched for genes associated with gene regulatory functions, consistent with a role of regulatory evolution in ecological adaptation of admixed D. melanogaster populations. Our results illustrate the potential of local ancestry inference for elucidating fundamental evolutionary processes. PMID:28045893

Prevalence and Persistence of Misconceptions in Tree Thinking†

PubMed Central

Kummer, Tyler A.; Whipple, Clinton J.; Jensen, Jamie L.

2016-01-01

Darwin described evolution as “descent with modification.” Descent, however, is not an explicit focus of most evolution instruction and often leaves deeply held misconceptions to dominate student understanding of common ancestry and species relatedness. Evolutionary trees are ways of visually depicting descent by illustrating the relationships between species and groups of species. The ability to properly interpret and use evolutionary trees has become known as “tree thinking.” We used a 20-question assessment to measure misconceptions in tree thinking and compare the proportion of students who hold these misconceptions in an introductory biology course with students in two higher-level courses including a senior level biology course. We found that misconceptions related to reading the graphic (reading the tips and node counting) were variably influenced across time with reading the tips decreasing and node counting increasing in prevalence. On the other hand, misconceptions related to the fundamental underpinnings of evolutionary theory (ladder thinking and similarity equals relatedness) proved resistant to change during a typical undergraduate study of biology. A possible new misconception relating to the length of the branches in an evolutionary tree is described. Understanding the prevalence and persistence of misconceptions informs educators as to which misconceptions should be targeted in their courses. PMID:28101265

Long-Term Evolution of the Luteoviridae: Time Scale and Mode of Virus Speciation▿ †

PubMed Central

Pagán, Israel; Holmes, Edward C.

2010-01-01

Despite their importance as agents of emerging disease, the time scale and evolutionary processes that shape the appearance of new viral species are largely unknown. To address these issues, we analyzed intra- and interspecific evolutionary processes in the Luteoviridae family of plant RNA viruses. Using the coat protein gene of 12 members of the family, we determined their phylogenetic relationships, rates of nucleotide substitution, times to common ancestry, and patterns of speciation. An associated multigene analysis enabled us to infer the nature of selection pressures and the genomic distribution of recombination events. Although rates of evolutionary change and selection pressures varied among genes and species and were lower in some overlapping gene regions, all fell within the range of those seen in animal RNA viruses. Recombination breakpoints were commonly observed at gene boundaries but less so within genes. Our molecular clock analysis suggested that the origin of the currently circulating Luteoviridae species occurred within the last 4 millennia, with intraspecific genetic diversity arising within the last few hundred years. Speciation within the Luteoviridae may therefore be associated with the expansion of agricultural systems. Finally, our phylogenetic analysis suggested that viral speciation events tended to occur within the same plant host species and country of origin, as expected if speciation is largely sympatric, rather than allopatric, in nature. PMID:20375155

Copy number variation signature to predict human ancestry

PubMed Central

2012-01-01

Background Copy number variations (CNVs) are genomic structural variants that are found in healthy populations and have been observed to be associated with disease susceptibility. Existing methods for CNV detection are often performed on a sample-by-sample basis, which is not ideal for large datasets where common CNVs must be estimated by comparing the frequency of CNVs in the individual samples. Here we describe a simple and novel approach to locate genome-wide CNVs common to a specific population, using human ancestry as the phenotype. Results We utilized our previously published Genome Alteration Detection Analysis (GADA) algorithm to identify common ancestry CNVs (caCNVs) and built a caCNV model to predict population structure. We identified a 73 caCNV signature using a training set of 225 healthy individuals from European, Asian, and African ancestry. The signature was validated on an independent test set of 300 individuals with similar ancestral background. The error rate in predicting ancestry in this test set was 2% using the 73 caCNV signature. Among the caCNVs identified, several were previously confirmed experimentally to vary by ancestry. Our signature also contains a caCNV region with a single microRNA (MIR270), which represents the first reported variation of microRNA by ancestry. Conclusions We developed a new methodology to identify common CNVs and demonstrated its performance by building a caCNV signature to predict human ancestry with high accuracy. The utility of our approach could be extended to large case–control studies to identify CNV signatures for other phenotypes such as disease susceptibility and drug response. PMID:23270563

Evolutionary relatedness does not predict competition and co-occurrence in natural or experimental communities of green algae

PubMed Central

Alexandrou, Markos A.; Cardinale, Bradley J.; Hall, John D.; Delwiche, Charles F.; Fritschie, Keith; Narwani, Anita; Venail, Patrick A.; Bentlage, Bastian; Pankey, M. Sabrina; Oakley, Todd H.

2015-01-01

The competition-relatedness hypothesis (CRH) predicts that the strength of competition is the strongest among closely related species and decreases as species become less related. This hypothesis is based on the assumption that common ancestry causes close relatives to share biological traits that lead to greater ecological similarity. Although intuitively appealing, the extent to which phylogeny can predict competition and co-occurrence among species has only recently been rigorously tested, with mixed results. When studies have failed to support the CRH, critics have pointed out at least three limitations: (i) the use of data poor phylogenies that provide inaccurate estimates of species relatedness, (ii) the use of inappropriate statistical models that fail to detect relationships between relatedness and species interactions amidst nonlinearities and heteroskedastic variances, and (iii) overly simplified laboratory conditions that fail to allow eco-evolutionary relationships to emerge. Here, we address these limitations and find they do not explain why evolutionary relatedness fails to predict the strength of species interactions or probabilities of coexistence among freshwater green algae. First, we construct a new data-rich, transcriptome-based phylogeny of common freshwater green algae that are commonly cultured and used for laboratory experiments. Using this new phylogeny, we re-analyse ecological data from three previously published laboratory experiments. After accounting for the possibility of nonlinearities and heterogeneity of variances across levels of relatedness, we find no relationship between phylogenetic distance and ecological traits. In addition, we show that communities of North American green algae are randomly composed with respect to their evolutionary relationships in 99% of 1077 lakes spanning the continental United States. Together, these analyses result in one of the most comprehensive case studies of how evolutionary history influences species interactions and community assembly in both natural and experimental systems. Our results challenge the generality of the CRH and suggest it may be time to re-evaluate the validity and assumptions of this hypothesis. PMID:25473009

Walking and talking the tree of life: Why and how to teach about biodiversity.

PubMed

Ballen, Cissy J; Greene, Harry W

2017-03-01

Taxonomic details of diversity are an essential scaffolding for biology education, yet outdated methods for teaching the tree of life (TOL), as implied by textbook content and usage, are still commonly employed. Here, we show that the traditional approach only vaguely represents evolutionary relationships, fails to denote major events in the history of life, and relies heavily on memorizing near-meaningless taxonomic ranks. Conversely, a clade-based strategy-focused on common ancestry, monophyletic groups, and derived functional traits-is explicitly based on Darwin's "descent with modification," provides students with a rational system for organizing the details of biodiversity, and readily lends itself to active learning techniques. We advocate for a phylogenetic classification that mirrors the TOL, a pedagogical format of increasingly complex but always hierarchical presentations, and the adoption of active learning technologies and tactics.

Genome-wide ancestry and divergence patterns from low-coverage sequencing data reveal a complex history of admixture in wild baboons

PubMed Central

Wall, Jeffrey D; Schlebusch, Stephen A; Alberts, Susan C; Cox, Laura A; Snyder-Mackler, Noah; Nevonen, Kimberly; Carbone, Lucia; Tung, Jenny

2017-01-01

Naturally occurring admixture has now been documented in every major primate lineage, suggesting its key role in primate evolutionary history. Active primate hybrid zones can provide valuable insight into this process. Here, we investigate the history of admixture in one of the best-studied natural primate hybrid zones, between yellow baboons (Papio cynocephalus) and anubis baboons (Papio anubis) in the Amboseli ecosystem of Kenya. We generated a new genome assembly for yellow baboon and low coverage genome-wide resequencing data from yellow baboons, anubis baboons, and known hybrids (n=44). Using a novel composite likelihood method for estimating local ancestry from low coverage data, we found high levels of genetic diversity and genetic differentiation between the parent taxa, and excellent agreement between genome-scale ancestry estimates and a priori pedigree, life history, and morphology-based estimates (r2=0.899). However, even putatively unadmixed Amboseli yellow individuals carried a substantial proportion of anubis ancestry, presumably due to historical admixture. Further, the distribution of shared versus fixed differences between a putatively unadmixed Amboseli yellow baboon and an unadmixed anubis baboon, both sequenced at high coverage, are inconsistent with simple isolation-migration or equilibrium migration models. Our findings suggest a complex process of intermittent contact that has occurred multiple times in baboon evolutionary history, despite no obvious fitness costs to hybrids or major geographic or behavioral barriers. In combination with the extensive phenotypic data available for baboon hybrids, our results provide valuable context for understanding the history of admixture in primates, including in our own lineage. PMID:27145036

Conservatism of lizard thermal tolerances and body temperatures across evolutionary history and geography.

PubMed

Grigg, Joseph W; Buckley, Lauren B

2013-04-23

Species may exhibit similar thermal tolerances via either common ancestry or environmental filtering and local adaptation, if the species inhabit similar environments. We ask whether upper and lower thermal limits (critical thermal maxima and minima) and body temperatures are more strongly conserved across evolutionary history or geography for lizard populations distributed globally. We find that critical thermal maxima are highly conserved with location accounting for a higher proportion of the variation than phylogeny. Notably, thermal tolerance breadth is conserved across the phylogeny despite critical thermal minima showing little niche conservatism. Body temperatures observed during activity in the field show the greatest degree of conservatism, with phylogeny accounting for most of the variation. This suggests that propensities for thermoregulatory behaviour, which can buffer body temperatures from environmental variation, are similar within lineages. Phylogeny and geography constrain thermal tolerances similarly within continents, but variably within clades. Conservatism of thermal tolerances across lineages suggests that the potential for local adaptation to alleviate the impacts of climate change on lizards may be limited.

The phylogenetic structure of plant-pollinator networks increases with habitat size and isolation.

PubMed

Aizen, Marcelo A; Gleiser, Gabriela; Sabatino, Malena; Gilarranz, Luis J; Bascompte, Jordi; Verdú, Miguel

2016-01-01

Similarity among species in traits related to ecological interactions is frequently associated with common ancestry. Thus, closely related species usually interact with ecologically similar partners, which can be reinforced by diverse co-evolutionary processes. The effect of habitat fragmentation on the phylogenetic signal in interspecific interactions and correspondence between plant and animal phylogenies is, however, unknown. Here, we address to what extent phylogenetic signal and co-phylogenetic congruence of plant-animal interactions depend on habitat size and isolation by analysing the phylogenetic structure of 12 pollination webs from isolated Pampean hills. Phylogenetic signal in interspecific interactions differed among webs, being stronger for flower-visiting insects than plants. Phylogenetic signal and overall co-phylogenetic congruence increased independently with hill size and isolation. We propose that habitat fragmentation would erode the phylogenetic structure of interaction webs. A decrease in phylogenetic signal and co-phylogenetic correspondence in plant-pollinator interactions could be associated with less reliable mutualism and erratic co-evolutionary change. © 2015 John Wiley & Sons Ltd/CNRS.

Parallel diversifications of Cremastosperma and Mosannona (Annonaceae), tropical rainforest trees tracking Neogene upheaval of South America

PubMed Central

Maas, Paul J. M.; Melchers-Sharrott, Heleen

2018-01-01

Much of the immense present day biological diversity of Neotropical rainforests originated from the Miocene onwards, a period of geological and ecological upheaval in South America. We assess the impact of the Andean orogeny, drainage of Lake Pebas and closure of the Panama isthmus on two clades of tropical trees (Cremastosperma, ca 31 spp.; and Mosannona, ca 14 spp.; both Annonaceae). Phylogenetic inference revealed similar patterns of geographically restricted clades and molecular dating showed diversifications in the different areas occurred in parallel, with timing consistent with Andean vicariance and Central American geodispersal. Ecological niche modelling approaches show phylogenetically conserved niche differentiation, particularly within Cremastosperma. Niche similarity and recent common ancestry of Amazon and Guianan Mosannona species contrast with dissimilar niches and more distant ancestry of Amazon, Venezuelan and Guianan species of Cremastosperma, suggesting that this element of the similar patterns of disjunct distributions in the two genera is instead a biogeographic parallelism, with differing origins. The results provide further independent evidence for the importance of the Andean orogeny, the drainage of Lake Pebas, and the formation of links between South and Central America in the evolutionary history of Neotropical lowland rainforest trees. PMID:29410860

Parallel diversifications of Cremastosperma and Mosannona (Annonaceae), tropical rainforest trees tracking Neogene upheaval of South America.

PubMed

Pirie, Michael D; Maas, Paul J M; Wilschut, Rutger A; Melchers-Sharrott, Heleen; Chatrou, Lars W

2018-01-01

Much of the immense present day biological diversity of Neotropical rainforests originated from the Miocene onwards, a period of geological and ecological upheaval in South America. We assess the impact of the Andean orogeny, drainage of Lake Pebas and closure of the Panama isthmus on two clades of tropical trees ( Cremastosperma , ca 31 spp.; and Mosannona , ca 14 spp.; both Annonaceae). Phylogenetic inference revealed similar patterns of geographically restricted clades and molecular dating showed diversifications in the different areas occurred in parallel, with timing consistent with Andean vicariance and Central American geodispersal. Ecological niche modelling approaches show phylogenetically conserved niche differentiation, particularly within Cremastosperma . Niche similarity and recent common ancestry of Amazon and Guianan Mosannona species contrast with dissimilar niches and more distant ancestry of Amazon, Venezuelan and Guianan species of Cremastosperma , suggesting that this element of the similar patterns of disjunct distributions in the two genera is instead a biogeographic parallelism, with differing origins. The results provide further independent evidence for the importance of the Andean orogeny, the drainage of Lake Pebas, and the formation of links between South and Central America in the evolutionary history of Neotropical lowland rainforest trees.

Genetic ancestry is associated with subclinical cardiovascular disease in African Americans and Hispanics from the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Wassel, Christina L.; Pankow, James S.; Peralta, Carmen A.; Choudhry, Shweta; Seldin, Michael F.; Arnett, Donna K.

2009-01-01

Background Differences in cardiovascular disease (CVD) burden exist among racial/ethnic groups in the United States, with African Americans having the highest prevalence. Subclinical CVD measures have also been shown to differ by race/ethnicity. In the United States, there has been significant intermixing among racial/ethnic groups creating admixed populations. Very little research exists on the relationship of genetic ancestry and subclinical CVD measures. Methods and Results These associations were investigated in 712 African-American and 705 Hispanic participants from the MESA candidate gene sub-study. Individual ancestry was estimated from 199 genetic markers using STRUCTURE. Associations of ancestry and coronary artery calcium (CAC) and common and internal carotid intima media thickness (cIMT) were evaluated using log-binomial and linear regression models. Splines indicated linear associations of ancestry with subclinical CVD measures in African-Americans, but presence of threshold effects in Hispanics. Among African Americans, each standard deviation (SD) increase in European ancestry was associated with an 8% (95% CI (1.02, 1.15), p=0.01) greater CAC prevalence. Each SD increase in European ancestry was also associated with a 2% (95% CI (−3.4%, −0.5%), p=0.008) lower common cIMT in African Americans. Among Hispanics, the highest tertile of European ancestry was associated with a 34% greater CAC prevalence, p=0.02 as compared to lowest tertile. Conclusions The linear association of ancestry and subclinical CVD suggests that genetic effects may be important in determining CAC and cIMT among African-Americans. Our results also suggest that CAC and common cIMT may be important phenotypes for further study with admixture mapping. PMID:20031644

Walking and talking the tree of life: Why and how to teach about biodiversity

PubMed Central

Ballen, Cissy J.; Greene, Harry W.

2017-01-01

Taxonomic details of diversity are an essential scaffolding for biology education, yet outdated methods for teaching the tree of life (TOL), as implied by textbook content and usage, are still commonly employed. Here, we show that the traditional approach only vaguely represents evolutionary relationships, fails to denote major events in the history of life, and relies heavily on memorizing near-meaningless taxonomic ranks. Conversely, a clade-based strategy—focused on common ancestry, monophyletic groups, and derived functional traits—is explicitly based on Darwin’s “descent with modification,” provides students with a rational system for organizing the details of biodiversity, and readily lends itself to active learning techniques. We advocate for a phylogenetic classification that mirrors the TOL, a pedagogical format of increasingly complex but always hierarchical presentations, and the adoption of active learning technologies and tactics. PMID:28319149

Tracking modern human population history from linguistic and cranial phenotype

PubMed Central

Reyes-Centeno, Hugo; Harvati, Katerina; Jäger, Gerhard

2016-01-01

Languages and genes arguably follow parallel evolutionary trajectories, descending from a common source and subsequently differentiating. However, although common ancestry is established within language families, it remains controversial whether language preserves a deep historical signal. To address this question, we evaluate the association between linguistic and geographic distances across 265 language families, as well as between linguistic, geographic, and cranial distances among eleven populations from Africa, Asia, and Australia. We take advantage of differential population history signals reflected by human cranial anatomy, where temporal bone shape reliably tracks deep population history and neutral genetic changes, while facial shape is more strongly associated with recent environmental effects. We show that linguistic distances are strongly geographically patterned, even within widely dispersed groups. However, they are correlated predominantly with facial, rather than temporal bone, morphology, suggesting that variation in vocabulary likely tracks relatively recent events and possibly population contact. PMID:27833101

Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution

PubMed Central

Smith, Jeramiah J; Kuraku, Shigehiro; Holt, Carson; Sauka-Spengler, Tatjana; Jiang, Ning; Campbell, Michael S; Yandell, Mark D; Manousaki, Tereza; Meyer, Axel; Bloom, Ona E; Morgan, Jennifer R; Buxbaum, Joseph D; Sachidanandam, Ravi; Sims, Carrie; Garruss, Alexander S; Cook, Malcolm; Krumlauf, Robb; Wiedemann, Leanne M; Sower, Stacia A; Decatur, Wayne A; Hall, Jeffrey A; Amemiya, Chris T; Saha, Nil R; Buckley, Katherine M; Rast, Jonathan P; Das, Sabyasachi; Hirano, Masayuki; McCurley, Nathanael; Guo, Peng; Rohner, Nicolas; Tabin, Clifford J; Piccinelli, Paul; Elgar, Greg; Ruffier, Magali; Aken, Bronwen L; Searle, Stephen MJ; Muffato, Matthieu; Pignatelli, Miguel; Herrero, Javier; Jones, Matthew; Brown, C Titus; Chung-Davidson, Yu-Wen; Nanlohy, Kaben G; Libants, Scot V; Yeh, Chu-Yin; McCauley, David W; Langeland, James A; Pancer, Zeev; Fritzsch, Bernd; de Jong, Pieter J; Zhu, Baoli; Fulton, Lucinda L; Theising, Brenda; Flicek, Paul; Bronner, Marianne E; Warren, Wesley C; Clifton, Sandra W; Wilson, Richard K; Li, Weiming

2013-01-01

Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ~500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms. PMID:23435085

Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry.

PubMed

Pittis, Alexandros A; Gabaldón, Toni

2016-03-03

The origin of eukaryotes stands as a major conundrum in biology. Current evidence indicates that the last eukaryotic common ancestor already possessed many eukaryotic hallmarks, including a complex subcellular organization. In addition, the lack of evolutionary intermediates challenges the elucidation of the relative order of emergence of eukaryotic traits. Mitochondria are ubiquitous organelles derived from an alphaproteobacterial endosymbiont. Different hypotheses disagree on whether mitochondria were acquired early or late during eukaryogenesis. Similarly, the nature and complexity of the receiving host are debated, with models ranging from a simple prokaryotic host to an already complex proto-eukaryote. Most competing scenarios can be roughly grouped into either mito-early, which consider the driving force of eukaryogenesis to be mitochondrial endosymbiosis into a simple host, or mito-late, which postulate that a significant complexity predated mitochondrial endosymbiosis. Here we provide evidence for late mitochondrial endosymbiosis. We use phylogenomics to directly test whether proto-mitochondrial proteins were acquired earlier or later than other proteins of the last eukaryotic common ancestor. We find that last eukaryotic common ancestor protein families of alphaproteobacterial ancestry and of mitochondrial localization show the shortest phylogenetic distances to their closest prokaryotic relatives, compared with proteins of different prokaryotic origin or cellular localization. Altogether, our results shed new light on a long-standing question and provide compelling support for the late acquisition of mitochondria into a host that already had a proteome of chimaeric phylogenetic origin. We argue that mitochondrial endosymbiosis was one of the ultimate steps in eukaryogenesis and that it provided the definitive selective advantage to mitochondria-bearing eukaryotes over less complex forms.

The Genetic Structure and History of Africans and African Americans

PubMed Central

Tishkoff, Sarah A.; Reed, Floyd A.; Friedlaender, Françoise R.; Ehret, Christopher; Ranciaro, Alessia; Froment, Alain; Hirbo, Jibril B.; Awomoyi, Agnes A.; Bodo, Jean-Marie; Doumbo, Ogobara; Ibrahim, Muntaser; Juma, Abdalla T.; Kotze, Maritha J.; Lema, Godfrey; Moore, Jason H.; Mortensen, Holly; Nyambo, Thomas B.; Omar, Sabah A.; Powell, Kweli; Pretorius, Gideon S.; Smith, Michael W.; Thera, Mahamadou A.; Wambebe, Charles; Weber, James L.; Williams, Scott M.

2010-01-01

Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (~71%), European (~13%), and other African (~8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies. PMID:19407144

Detection of Ancestry Informative HLA Alleles Confirms the Admixed Origins of Japanese Population

PubMed Central

Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

2013-01-01

The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago. PMID:23577161

Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population.

PubMed

Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

2013-01-01

The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago.

Evolutionary Origin of the Scombridae (Tunas and Mackerels): Members of a Paleogene Adaptive Radiation with 14 Other Pelagic Fish Families

PubMed Central

Miya, Masaki; Friedman, Matt; Satoh, Takashi P.; Takeshima, Hirohiko; Sado, Tetsuya; Iwasaki, Wataru; Yamanoue, Yusuke; Nakatani, Masanori; Mabuchi, Kohji; Inoue, Jun G.; Poulsen, Jan Yde; Fukunaga, Tsukasa; Sato, Yukuto; Nishida, Mutsumi

2013-01-01

Uncertainties surrounding the evolutionary origin of the epipelagic fish family Scombridae (tunas and mackerels) are symptomatic of the difficulties in resolving suprafamilial relationships within Percomorpha, a hyperdiverse teleost radiation that contains approximately 17,000 species placed in 13 ill-defined orders and 269 families. Here we find that scombrids share a common ancestry with 14 families based on (i) bioinformatic analyses using partial mitochondrial and nuclear gene sequences from all percomorphs deposited in GenBank (10,733 sequences) and (ii) subsequent mitogenomic analysis based on 57 species from those targeted 15 families and 67 outgroup taxa. Morphological heterogeneity among these 15 families is so extraordinary that they have been placed in six different perciform suborders. However, members of the 15 families are either coastal or oceanic pelagic in their ecology with diverse modes of life, suggesting that they represent a previously undetected adaptive radiation in the pelagic realm. Time-calibrated phylogenies imply that scombrids originated from a deep-ocean ancestor and began to radiate after the end-Cretaceous when large predatory epipelagic fishes were selective victims of the Cretaceous-Paleogene mass extinction. We name this clade of open-ocean fishes containing Scombridae “Pelagia” in reference to the common habitat preference that links the 15 families. PMID:24023883

A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.

PubMed

Haiman, Christopher A; Chen, Gary K; Vachon, Celine M; Canzian, Federico; Dunning, Alison; Millikan, Robert C; Wang, Xianshu; Ademuyiwa, Foluso; Ahmed, Shahana; Ambrosone, Christine B; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Blot, William J; Brauch, Hiltrud; Buring, Julie E; Carey, Lisa A; Carpenter, Jane E; Chang-Claude, Jenny; Chanock, Stephen J; Chasman, Daniel I; Clarke, Christine L; Cox, Angela; Cross, Simon S; Deming, Sandra L; Diasio, Robert B; Dimopoulos, Athanasios M; Driver, W Ryan; Dünnebier, Thomas; Durcan, Lorraine; Eccles, Diana; Edlund, Christopher K; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather S; Flesch-Janys, Dieter; Fostira, Florentia; Försti, Asta; Fountzilas, George; Gerty, Susan M; Giles, Graham G; Godwin, Andrew K; Goodfellow, Paul; Graham, Nikki; Greco, Dario; Hamann, Ute; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Holbrook, Andrea; Hoover, Robert N; Hu, Jennifer J; Hunter, David J; Ingles, Sue A; Irwanto, Astrid; Ivanovich, Jennifer; John, Esther M; Johnson, Nicola; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Ko, Yon-Dschun; Kolonel, Laurence N; Konstantopoulou, Irene; Kosma, Veli-Matti; Kulkarni, Swati; Lambrechts, Diether; Lee, Adam M; Marchand, Loïc Le; Lesnick, Timothy; Liu, Jianjun; Lindstrom, Sara; Mannermaa, Arto; Margolin, Sara; Martin, Nicholas G; Miron, Penelope; Montgomery, Grant W; Nevanlinna, Heli; Nickels, Stephan; Nyante, Sarah; Olswold, Curtis; Palmer, Julie; Pathak, Harsh; Pectasides, Dimitrios; Perou, Charles M; Peto, Julian; Pharoah, Paul D P; Pooler, Loreall C; Press, Michael F; Pylkäs, Katri; Rebbeck, Timothy R; Rodriguez-Gil, Jorge L; Rosenberg, Lynn; Ross, Eric; Rüdiger, Thomas; Silva, Isabel dos Santos; Sawyer, Elinor; Schmidt, Marjanka K; Schulz-Wendtland, Rüdiger; Schumacher, Fredrick; Severi, Gianluca; Sheng, Xin; Signorello, Lisa B; Sinn, Hans-Peter; Stevens, Kristen N; Southey, Melissa C; Tapper, William J; Tomlinson, Ian; Hogervorst, Frans B L; Wauters, Els; Weaver, JoEllen; Wildiers, Hans; Winqvist, Robert; Van Den Berg, David; Wan, Peggy; Xia, Lucy Y; Yannoukakos, Drakoulis; Zheng, Wei; Ziegler, Regina G; Siddiq, Afshan; Slager, Susan L; Stram, Daniel O; Easton, Douglas; Kraft, Peter; Henderson, Brian E; Couch, Fergus J

2011-10-30

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.

Impact of ancestry and common genetic variants on QT interval in African Americans.

PubMed

Smith, J Gustav; Avery, Christy L; Evans, Daniel S; Nalls, Michael A; Meng, Yan A; Smith, Erin N; Palmer, Cameron; Tanaka, Toshiko; Mehra, Reena; Butler, Anne M; Young, Taylor; Buxbaum, Sarah G; Kerr, Kathleen F; Berenson, Gerald S; Schnabel, Renate B; Li, Guo; Ellinor, Patrick T; Magnani, Jared W; Chen, Wei; Bis, Joshua C; Curb, J David; Hsueh, Wen-Chi; Rotter, Jerome I; Liu, Yongmei; Newman, Anne B; Limacher, Marian C; North, Kari E; Reiner, Alexander P; Quibrera, P Miguel; Schork, Nicholas J; Singleton, Andrew B; Psaty, Bruce M; Soliman, Elsayed Z; Solomon, Allen J; Srinivasan, Sathanur R; Alonso, Alvaro; Wallace, Robert; Redline, Susan; Zhang, Zhu-Ming; Post, Wendy S; Zonderman, Alan B; Taylor, Herman A; Murray, Sarah S; Ferrucci, Luigi; Arking, Dan E; Evans, Michele K; Fox, Ervin R; Sotoodehnia, Nona; Heckbert, Susan R; Whitsel, Eric A; Newton-Cheh, Christopher

2012-12-01

Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 × 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 × 10(-15)) and ATP1B1 (rs1320976, P=2 × 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN. We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.

Chromosome Connections: Compelling Clues to Common Ancestry

ERIC Educational Resources Information Center

Flammer, Larry

2013-01-01

Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

Developmental biology, the stem cell of biological disciplines.

PubMed

Gilbert, Scott F

2017-12-01

Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, developmental biology remains vigorous, pluripotent, and relatively undifferentiated. In many disciplines, especially in evolutionary biology and oncology, the developmental perspective is being reasserted as an important research program.

Human evolutionary genomics: ethical and interpretive issues.

PubMed

Vitti, Joseph J; Cho, Mildred K; Tishkoff, Sarah A; Sabeti, Pardis C

2012-03-01

Genome-wide computational studies can now identify targets of natural selection. The unique information about humans these studies reveal, and the media attention they attract, indicate the need for caution and precision in communicating results. This need is exacerbated by ways in which evolutionary and genetic considerations have been misapplied to support discriminatory policies, by persistent misconceptions of these fields and by the social sensitivity surrounding discussions of racial ancestry. We discuss the foundations, accomplishments and future directions of human evolutionary genomics, attending to ways in which the interpretation of good science can go awry, and offer suggestions for researchers to prevent misapplication of their work. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ancestry Estimation in Forensic Anthropology: Geometric Morphometric versus Standard and Nonstandard Interlandmark Distances.

PubMed

Katherine Spradley, M; Jantz, Richard L

2016-07-01

Standard cranial measurements are commonly used for ancestry estimation; however, 3D digitizers have made cranial landmark data collection and geometric morphometric (GM) analyses more popular within forensic anthropology. Yet there has been little focus on which data type works best. The goal of the present research is to test the discrimination ability of standard and nonstandard craniometric measurements and data derived from GM analysis. A total of 31 cranial landmarks were used to generate 465 interlandmark distances, including a subset of 20 commonly used measurements, and to generate principal component scores from procrustes coordinates. All were subjected to discriminant function analysis to ascertain which type of data performed best for ancestry estimation of American Black and White and Hispanic males and females. The nonstandard interlandmark distances generated the highest classification rates for females (90.5%) and males (88.2%). Using nonstandard interlandmark distances over more commonly used measurements leads to better ancestry estimates for our current population structure. © 2016 American Academy of Forensic Sciences.

Building Phylogenetic Trees from DNA Sequence Data: Investigating Polar Bear and Giant Panda Ancestry.

ERIC Educational Resources Information Center

Maier, Caroline Alexandra

2001-01-01

Presents an activity in which students seek answers to questions about evolutionary relationships by using genetic databases and bioinformatics software. Students build genetic distance matrices and phylogenetic trees based on molecular sequence data using web-based resources. Provides a flowchart of steps involved in accessing, retrieving, and…

The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes

PubMed Central

Di-Poï, Nicolas; Milinkovitch, Michel C.

2016-01-01

Most mammals, birds, and reptiles are readily recognized by their hairs, feathers, and scales, respectively. However, the lack of fossil intermediate forms between scales and hairs and substantial differences in their morphogenesis and protein composition have fueled the controversy pertaining to their potential common ancestry for decades. Central to this debate is the apparent lack of an “anatomical placode” (that is, a local epidermal thickening characteristic of feathers’ and hairs’ early morphogenesis) in reptile scale development. Hence, scenarios have been proposed for the independent development of the anatomical placode in birds and mammals and parallel co-option of similar signaling pathways for their morphogenesis. Using histological and molecular techniques on developmental series of crocodiles and snakes, as well as of unique wild-type and EDA (ectodysplasin A)–deficient scaleless mutant lizards, we show for the first time that reptiles, including crocodiles and squamates, develop all the characteristics of an anatomical placode: columnar cells with reduced proliferation rate, as well as canonical spatial expression of placode and underlying dermal molecular markers. These results reveal a new evolutionary scenario where hairs, feathers, and scales of extant species are homologous structures inherited, with modification, from their shared reptilian ancestor’s skin appendages already characterized by an anatomical placode and associated signaling molecules. PMID:28439533

The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes.

PubMed

Di-Poï, Nicolas; Milinkovitch, Michel C

2016-06-01

Most mammals, birds, and reptiles are readily recognized by their hairs, feathers, and scales, respectively. However, the lack of fossil intermediate forms between scales and hairs and substantial differences in their morphogenesis and protein composition have fueled the controversy pertaining to their potential common ancestry for decades. Central to this debate is the apparent lack of an "anatomical placode" (that is, a local epidermal thickening characteristic of feathers' and hairs' early morphogenesis) in reptile scale development. Hence, scenarios have been proposed for the independent development of the anatomical placode in birds and mammals and parallel co-option of similar signaling pathways for their morphogenesis. Using histological and molecular techniques on developmental series of crocodiles and snakes, as well as of unique wild-type and EDA (ectodysplasin A)-deficient scaleless mutant lizards, we show for the first time that reptiles, including crocodiles and squamates, develop all the characteristics of an anatomical placode: columnar cells with reduced proliferation rate, as well as canonical spatial expression of placode and underlying dermal molecular markers. These results reveal a new evolutionary scenario where hairs, feathers, and scales of extant species are homologous structures inherited, with modification, from their shared reptilian ancestor's skin appendages already characterized by an anatomical placode and associated signaling molecules.

Accuracy Rates of Ancestry Estimation by Forensic Anthropologists Using Identified Forensic Cases.

PubMed

Thomas, Richard M; Parks, Connie L; Richard, Adam H

2017-07-01

A common task in forensic anthropology involves the estimation of the ancestry of a decedent by comparing their skeletal morphology and measurements to skeletons of individuals from known geographic groups. However, the accuracy rates of ancestry estimation methods in actual forensic casework have rarely been studied. This article uses 99 forensic cases with identified skeletal remains to develop accuracy rates for ancestry estimations conducted by forensic anthropologists. The overall rate of correct ancestry estimation from these cases is 90.9%, which is comparable to most research-derived rates and those reported by individual practitioners. Statistical tests showed no significant difference in accuracy rates depending on examiner education level or on the estimated or identified ancestry. More recent cases showed a significantly higher accuracy rate. The incorporation of metric analyses into the ancestry estimate in these cases led to a higher accuracy rate. © 2017 American Academy of Forensic Sciences.

Fossil-based comparative analyses reveal ancient marine ancestry erased by extinction in ray-finned fishes.

PubMed

Betancur-R, Ricardo; Ortí, Guillermo; Pyron, Robert Alexander

2015-05-01

The marine-freshwater boundary is a major biodiversity gradient and few groups have colonised both systems successfully. Fishes have transitioned between habitats repeatedly, diversifying in rivers, lakes and oceans over evolutionary time. However, their history of habitat colonisation and diversification is unclear based on available fossil and phylogenetic data. We estimate ancestral habitats and diversification and transition rates using a large-scale phylogeny of extant fish taxa and one containing a massive number of extinct species. Extant-only phylogenetic analyses indicate freshwater ancestry, but inclusion of fossils reveal strong evidence of marine ancestry in lineages now restricted to freshwaters. Diversification and colonisation dynamics vary asymmetrically between habitats, as marine lineages colonise and flourish in rivers more frequently than the reverse. Our study highlights the importance of including fossils in comparative analyses, showing that freshwaters have played a role as refuges for ancient fish lineages, a signal erased by extinction in extant-only phylogenies. © 2015 John Wiley & Sons Ltd/CNRS.

The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans

PubMed Central

Smith, J. Gustav; Avery, Christy L.; Evans, Daniel S.; Nalls, Michael A.; Meng, Yan A.; Smith, Erin N.; Palmer, Cameron; Tanaka, Toshiko; Mehra, Reena; Butler, Anne M.; Young, Taylor; Buxbaum, Sarah G.; Kerr, Kathleen F.; Berenson, Gerald S.; Schnabel, Renate B.; Li, Guo; Ellinor, Patrick T.; Magnani, Jared W.; Chen, Wei; Bis, Joshua C.; Curb, J. David; Hsueh, Wen-Chi; Rotter, Jerome I.; Liu, Yongmei; Newman, Anne B.; Limacher, Marian C.; North, Kari E.; Reiner, Alexander P.; Quibrera, P. Miguel; Schork, Nicholas J.; Singleton, Andrew B.; Psaty, Bruce M.; Soliman, Elsayed Z.; Solomon, Allen J.; Srinivasan, Sathanur R.; Alonso, Alvaro; Wallace, Robert; Redline, Susan; Zhang, Zhu-Ming; Post, Wendy S.; Zonderman, Alan B.; Taylor, Herman A.; Murray, Sarah S.; Ferrucci, Luigi; Arking, Dan E.; Evans, Michele K.; Fox, Ervin R.; Sotoodehnia, Nona; Heckbert, Susan R.; Whitsel, Eric A.; Newton-Cheh, Christopher

2013-01-01

Background Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. Methods and Results First, individual estimates of African and European ancestry were inferred from genome-wide single nucleotide polymorphism (SNP) data in seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5×10−8) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2×10−15) and ATP1B1 (rs1320976, p=2×10−10). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low p-values (p<10−5) were observed for SNPs at several other loci previously identified in GWA studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF and PLN. Conclusions We observed no difference in duration of cardiac repolarization with global genetic indices of African ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans. PMID:23166209

A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer

PubMed Central

Haiman, Christopher A; Chen, Gary K; Vachon, Celine M; Canzian, Federico; Dunning, Alison; Millikan, Robert C; Wang, Xianshu; Ademuyiwa, Foluso; Ahmed, Shahana; Ambrosone, Christine B; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Blot, William J; Brauch, Hiltrud; Buring, Julie E; Carey, Lisa A; Carpenter, Jane E; Chang-Claude, Jenny; Chanock, Stephen J; Chasman, Daniel I; Clarke, Christine L; Cox, Angela; Cross, Simon S; Deming, Sandra L; Diasio, Robert B; Dimopoulos, Athanasios M; Driver, W Ryan; Dünnebier, Thomas; Durcan, Lorraine; Eccles, Diana; Edlund, Christopher K; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather S; Flesch-Janys, Dieter; Fostira, Florentia; Försti, Asta; Fountzilas, George; Gerty, Susan M; Giles, Graham G; Godwin, Andrew K; Goodfellow, Paul; Graham, Nikki; Greco, Dario; Hamann, Ute; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Holbrook, Andrea; Hoover, Robert N; Hu, Jennifer J; Hunter, David J; Ingles, Sue A; Irwanto, Astrid; Ivanovich, Jennifer; John, Esther M; Johnson, Nicola; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Ko, Yon-Dschun; Kolonel, Laurence N; Konstantopoulou, Irene; Kosma, Veli-Matti; Kulkarni, Swati; Lambrechts, Diether; Lee, Adam M; Le Marchand, Loïc; Lesnick, Timothy; Liu, Jianjun; Lindstrom, Sara; Mannermaa, Arto; Margolin, Sara; Martin, Nicholas G; Miron, Penelope; Montgomery, Grant W; Nevanlinna, Heli; Nickels, Stephan; Nyante, Sarah; Olswold, Curtis; Palmer, Julie; Pathak, Harsh; Pectasides, Dimitrios; Perou, Charles M; Peto, Julian; Pharoah, Paul D P; Pooler, Loreall C; Press, Michael F; Pylkäs, Katri; Rebbeck, Timothy R; Rodriguez-Gil, Jorge L; Rosenberg, Lynn; Ross, Eric; Rüdiger, Thomas; Silva, Isabel dos Santos; Sawyer, Elinor; Schmidt, Marjanka K; Schulz-Wendtland, Rüdiger; Schumacher, Fredrick; Severi, Gianluca; Sheng, Xin; Signorello, Lisa B; Sinn, Hans-Peter; Stevens, Kristen N; Southey, Melissa C; Tapper, William J; Tomlinson, Ian; Hogervorst, Frans B L; Wauters, Els; Weaver, JoEllen; Wildiers, Hans; Winqvist, Robert; Van Den Berg, David; Wan, Peggy; Xia, Lucy Y; Yannoukakos, Drakoulis; Zheng, Wei; Ziegler, Regina G; Siddiq, Afshan; Slager, Susan L; Stram, Daniel O; Easton, Douglas; Kraft, Peter; Henderson, Brian E; Couch, Fergus J

2012-01-01

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10−10). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10−9), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10−9). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. PMID:22037553

Genomic ancestry estimation quantifies use of wild species in grape breeding.

PubMed

Migicovsky, Zoë; Sawler, Jason; Money, Daniel; Eibach, Rudolph; Miller, Allison J; Luby, James J; Jamieson, Andrew R; Velasco, Dianne; von Kintzel, Sven; Warner, John; Wührer, Walter; Brown, Patrick J; Myles, Sean

2016-06-30

Grapes are one of the world's most valuable crops and most are made into wine. Grapes belong to the genus Vitis, which includes over 60 inter-fertile species. The most common grape cultivars derive their entire ancestry from the species Vitis vinifera, but wild relatives have also been exploited to create hybrid cultivars, often with increased disease resistance. We evaluate the genetic ancestry of some of the most widely grown commercial hybrids from North America and Europe. Using genotyping-by-sequencing (GBS), we generated 2482 SNPs and 56 indels from 7 wild Vitis, 7 V. vinifera, and 64 hybrid cultivars. We used a principal component analysis (PCA) based ancestry estimation procedure and verified its accuracy with both empirical and simulated data. V. vinifera ancestry ranged from 11 % to 76 % across hybrids studied. Approximately one third (22/64) of the hybrids have ancestry estimates consistent with F1 hybridization: they derive half of their ancestry from wild Vitis and half from V. vinifera. Our results suggest that hybrid grape breeding is in its infancy. The distribution of V. vinifera ancestry across hybrids also suggests that backcrosses to wild Vitis species have been more frequent than backcrosses to V. vinifera during hybrid grape breeding. This pattern is unusual in crop breeding, as it is most common to repeatedly backcross to elite, or domesticated, germplasm. We anticipate our method can be extended to facilitate marker-assisted selection in order to introgress beneficial wild Vitis traits, while allowing for offspring with the highest V. vinifera content to be selected at the seedling stage.

Snakes and Eels and Dogs! Oh, My! Evaluating High School Students' Tree-Thinking Skills: An Entry Point to Understanding Evolution

NASA Astrophysics Data System (ADS)

Catley, Kefyn M.; Phillips, Brenda C.; Novick, Laura R.

2013-12-01

The biological community is currently undertaking one its greatest scientific endeavours, that of constructing the Tree of Life, a phylogeny intended to be an evidenced-based, predictive road map of evolutionary relationships among Earth's biota. Unfortunately, we know very little about how such diagrams are understood, interpreted, or used as inferential tools by students—collectively referred to as tree thinking. The present study provides the first in-depth look at US high school students' competence at tree thinking and reports how they engage cognitively with tree representations as a precursor to developing curricula that will provide an entry point into macroevolution. Sixty tenth graders completed a 12-question instrument that assessed five basic tree-thinking skills. We present data that show patterns of misunderstandings are largely congruent between tenth graders and undergraduates and identify competences that are pivotal to address during instruction. Two general principles that emerge from this study are: (a) Students need to be taught that cladograms are an authoritative source of evidence that should be weighted more than other superficial or ecological similarities; (b) students need to understand the vital importance and critical difference between most recent common ancestry and common ancestry. Further, we show how the objectives of this study are closely aligned with US and International Standards and argue that scientifically-literate citizens need at least a basic understanding of the science behind the Tree of Life to understand and engage in twenty-first century societal issues such as human health, agriculture, and biotechnology.

Banteng and Bali cattle in Indonesia: status and forecasts.

PubMed

Purwantara, B; Noor, R R; Andersson, G; Rodriguez-Martinez, H

2012-01-01

Bali cattle still represents 27% of the total cattle population in Indonesia, and it is considered the pillar breed for small farmers. Moreover, it is a breed of evolutionary importance regarding its direct ancestry from Banteng. However, there is a need for the establishment of a rational system for the evaluation of breeding soundness for indigenous Bali bulls to be used as sires for artificial insemination breeding programmes. Moreover, there is a need for cryobanking of well-identified genetic resources pertaining their use in evolutionary research and application as essential germplasm in breeding programmes. © 2012 Blackwell Verlag GmbH.

Origins of Genes: "Big Bang" or Continuous Creation?

NASA Astrophysics Data System (ADS)

Kesse, Paul K.; Gibbs, Adrian

1992-10-01

Many protein families are common to all cellular organisms, indicating that many genes have ancient origins. Genetic variation is mostly attributed to processes such as mutation, duplication, and rearrangement of ancient modules. Thus it is widely assumed that much of present-day genetic diversity can be traced by common ancestry to a molecular "big bang." A rarely considered alternative is that proteins may arise continuously de novo. One mechanism of generating different coding sequences is by "overprinting," in which an existing nucleotide sequence is translated de novo in a different reading frame or from noncoding open reading frames. The clearest evidence for overprinting is provided when the original gene function is retained, as in overlapping genes. Analysis of their phylogenies indicates which are the original genes and which are their informationally novel partners. We report here the phylogenetic relationships of overlapping coding sequences from steroid-related receptor genes and from tymovirus, luteovirus, and lentivirus genomes. For each pair of overlapping coding sequences, one is confined to a single lineage, whereas the other is more widespread. This suggests that the phylogenetically restricted coding sequence arose only in the progenitor of that lineage by translating an out-of-frame sequence to yield the new polypeptide. The production of novel exons by alternative splicing in thyroid receptor and lentivirus genes suggests that introns can be a valuable evolutionary source for overprinting. New genes and their products may drive major evolutionary changes.

Genomic Evidence of Widespread Admixture from Polar Bears into Brown Bears during the Last Ice Age.

PubMed

Cahill, James A; Heintzman, Peter D; Harris, Kelley; Teasdale, Matthew D; Kapp, Joshua; Soares, Andre E R; Stirling, Ian; Bradley, Daniel; Edwards, Ceiridwen J; Graim, Kiley; Kisleika, Aliaksandr A; Malev, Alexander V; Monaghan, Nigel; Green, Richard E; Shapiro, Beth

2018-05-01

Recent genomic analyses have provided substantial evidence for past periods of gene flow from polar bears (Ursus maritimus) into Alaskan brown bears (Ursus arctos), with some analyses suggesting a link between climate change and genomic introgression. However, because it has mainly been possible to sample bears from the present day, the timing, frequency, and evolutionary significance of this admixture remains unknown. Here, we analyze genomic DNA from three additional and geographically distinct brown bear populations, including two that lived temporally close to the peak of the last ice age. We find evidence of admixture in all three populations, suggesting that admixture between these species has been common in their recent evolutionary history. In addition, analyses of ten fossil bears from the now-extinct Irish population indicate that admixture peaked during the last ice age, whereas brown bear and polar bear ranges overlapped. Following this peak, the proportion of polar bear ancestry in Irish brown bears declined rapidly until their extinction. Our results support a model in which ice age climate change created geographically widespread conditions conducive to admixture between polar bears and brown bears, as is again occurring today. We postulate that this model will be informative for many admixing species pairs impacted by climate change. Our results highlight the power of paleogenomics to reveal patterns of evolutionary change that are otherwise masked in contemporary data.

Evo-devo and accounting for Darwin's endless forms

PubMed Central

Brakefield, Paul M.

2011-01-01

Evo-devo has led to dramatic advances in our understanding of how the processes of development can contribute to explaining patterns of evolutionary diversification that underlie the endless forms of animal life on the Earth. This is increasingly the case not only for the origins of evolutionary novelties that permit new functions and open up new adaptive zones, but also for the processes of evolutionary tinkering that occur within the subsequent radiations of related species. Evo-devo has time and again yielded spectacular examples of Darwin's notions of common ancestry and of descent with modification. It has also shown that the evolution of endless forms is more about the evolution of the regulatory machinery of ancient genes than the origin and elaboration of new genes. Evolvability, especially with respect to the capacity of a developmental system to evolve and to generate the variation in form for natural selection to screen, has become a pivotal focus of evo-devo. As a consequence, a balancing of the concept of endless forms in morphospace with a greater awareness of the potential for developmental constraints and bias is becoming more general. The prospect of parallel horizons opening up for the evolution of behaviour is exciting; in particular, does Sean Carroll's phrase referring to old genes learning new tricks in the evolution of endless forms apply equally as well to patterns of diversity and disparity in behavioural trait-space? PMID:21690125

Evo-devo and accounting for Darwin's endless forms.

PubMed

Brakefield, Paul M

2011-07-27

Evo-devo has led to dramatic advances in our understanding of how the processes of development can contribute to explaining patterns of evolutionary diversification that underlie the endless forms of animal life on the Earth. This is increasingly the case not only for the origins of evolutionary novelties that permit new functions and open up new adaptive zones, but also for the processes of evolutionary tinkering that occur within the subsequent radiations of related species. Evo-devo has time and again yielded spectacular examples of Darwin's notions of common ancestry and of descent with modification. It has also shown that the evolution of endless forms is more about the evolution of the regulatory machinery of ancient genes than the origin and elaboration of new genes. Evolvability, especially with respect to the capacity of a developmental system to evolve and to generate the variation in form for natural selection to screen, has become a pivotal focus of evo-devo. As a consequence, a balancing of the concept of endless forms in morphospace with a greater awareness of the potential for developmental constraints and bias is becoming more general. The prospect of parallel horizons opening up for the evolution of behaviour is exciting; in particular, does Sean Carroll's phrase referring to old genes learning new tricks in the evolution of endless forms apply equally as well to patterns of diversity and disparity in behavioural trait-space?

Locus-specific ancestry to detect recent response to selection in admixed Swiss Fleckvieh cattle.

PubMed

Khayatzadeh, N; Mészáros, G; Utsunomiya, Y T; Garcia, J F; Schnyder, U; Gredler, B; Curik, I; Sölkner, J

2016-12-01

Identification of selection signatures is one of the current endeavors of evolutionary genetics. Admixed populations may be used to infer post-admixture selection. We calculated local ancestry for Swiss Fleckvieh, a composite of Simmental (SI) and Red Holstein Friesian (RHF), to infer such signals. Illumina Bovine SNP50 BeadChip data for 300 admixed, 88 SI and 97 RHF bulls were used. The average RHF ancestry across the whole genome was 0.70. To identify regions with high deviation from average, we considered two significance thresholds, based on a permutation test and extreme deviation from normal distribution. Regions on chromosomes 13 (46.3-47.3 Mb) and 18 (18.7-25.9 Mb) passed both thresholds in the direction of increased SI. Extended haplotype homozygosity within (iHS) and between (Rsb) populations was calculated to explore additional patterns of pre- and post-admixture selection signals. The Rsb score of admixed and SI was significant in a wide region of chromosome 18 (6.6-24.6 Mb) overlapped with one area of strong local ancestry deviation. FTO, with pleiotropic effect on milk and fertility, NOD2 on dairy and NKD1 and SALL1 on fertility traits are located there. Genetic differentiation of RHF and SI (F st ), an alternative indicator of pre-admixture selection in pure populations, was calculated. No considerable overlap of peaks of local ancestry deviations and F st was observed. We found two regions with significant signatures of post-admixture selection in this very young composite, applying comparatively stringent significance thresholds. The signals cover relatively large genomic areas and did not allow pinpointing of the gene(s) responsible for the apparent shift in ancestry proportions. © 2016 Stichting International Foundation for Animal Genetics.

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

PubMed

Brutsaert, Tom D; Parra, Esteban J; Shriver, Mark D; Gamboa, Alfredo; Rivera-Ch, Maria; León-Velarde, Fabiola

2005-07-01

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

Targeted Metabolomics Demonstrates Distinct and Overlapping Maternal Metabolites Associated With BMI, Glucose, and Insulin Sensitivity During Pregnancy Across Four Ancestry Groups.

PubMed

Jacob, Saya; Nodzenski, Michael; Reisetter, Anna C; Bain, James R; Muehlbauer, Michael J; Stevens, Robert D; Ilkayeva, Olga R; Lowe, Lynn P; Metzger, Boyd E; Newgard, Christopher B; Scholtens, Denise M; Lowe, William L

2017-07-01

We used targeted metabolomics in pregnant mothers to compare maternal metabolite associations with maternal BMI, glycemia, and insulin sensitivity. Targeted metabolomic assays of clinical metabolites, amino acids, and acylcarnitines were performed on fasting and 1-h postglucose serum samples from European ancestry, Afro-Caribbean, Thai, and Mexican American mothers (400 from each ancestry group) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and underwent an oral glucose tolerance test at ∼28 weeks gestation. K-means clustering, which identified patterns of metabolite levels across ancestry groups, demonstrated that, at both fasting and 1-h, levels of the majority of metabolites were similar across ancestry groups. Meta-analyses demonstrated association of a broad array of fasting and 1-h metabolites, including lipids and amino acids and their metabolites, with maternal BMI, glucose levels, and insulin sensitivity before and after adjustment for the different phenotypes. At fasting and 1 h, a mix of metabolites was identified that were common across phenotypes or associated with only one or two phenotypes. Partial correlation estimates, which allowed comparison of the strength of association of different metabolites with maternal phenotypes, demonstrated that metabolites most strongly associated with different phenotypes included some that were common across as well as unique to each phenotype. Maternal BMI and glycemia have metabolic signatures that are both shared and unique to each phenotype. These signatures largely remain consistent across different ancestry groups and may contribute to the common and independent effects of these two phenotypes on adverse pregnancy outcomes. © 2017 by the American Diabetes Association.

Development of a novel forensic STR multiplex for ancestry analysis and extended identity testing.

PubMed

Phillips, Chris; Fernandez-Formoso, Luis; Gelabert-Besada, Miguel; Garcia-Magariños, Manuel; Santos, Carla; Fondevila, Manuel; Carracedo, Angel; Lareu, Maria Victoria

2013-04-01

There is growing interest in developing additional DNA typing techniques to provide better investigative leads in forensic analysis. These include inference of genetic ancestry and prediction of common physical characteristics of DNA donors. To date, forensic ancestry analysis has centered on population-divergent SNPs but these binary loci cannot reliably detect DNA mixtures, common in forensic samples. Furthermore, STR genotypes, forming the principal DNA profiling system, are not routinely combined with forensic SNPs to strengthen frequency data available for ancestry inference. We report development of a 12-STR multiplex composed of ancestry informative marker STRs (AIM-STRs) selected from 434 tetranucleotide repeat loci. We adapted our online Bayesian classifier for AIM-SNPs: Snipper, to handle multiallele STR data using frequency-based training sets. We assessed the ability of the 12-plex AIM-STRs to differentiate CEPH Human Genome Diversity Panel populations, plus their informativeness combined with established forensic STRs and AIM-SNPs. We found combining STRs and SNPs improves the success rate of ancestry assignments while providing a reliable mixture detection system lacking from SNP analysis alone. As the 12 STRs generally show a broad range of alleles in all populations, they provide highly informative supplementary STRs for extended relationship testing and identification of missing persons with incomplete reference pedigrees. Lastly, mixed marker approaches (combining STRs with binary loci) for simple ancestry inference tests beyond forensic analysis bring advantages and we discuss the genotyping options available. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Replaying evolutionary transitions from the dental fossil record

PubMed Central

Harjunmaa, Enni; Seidel, Kerstin; Häkkinen, Teemu; Renvoisé, Elodie; Corfe, Ian J.; Kallonen, Aki; Zhang, Zhao-Qun; Evans, Alistair R.; Mikkola, Marja L.; Salazar-Ciudad, Isaac; Klein, Ophir D.; Jernvall, Jukka

2014-01-01

The evolutionary relationships of extinct species are ascertained primarily through the analysis of morphological characters. Character inter-dependencies can have a substantial effect on evolutionary interpretations, but the developmental underpinnings of character inter-dependence remain obscure because experiments frequently do not provide detailed resolution of morphological characters. Here we show experimentally and computationally how gradual modification of development differentially affects characters in the mouse dentition. We found that intermediate phenotypes could be produced by gradually adding ectodysplasin A (EDA) protein in culture to tooth explants carrying a null mutation in the tooth-patterning gene Eda. By identifying development-based character interdependencies, we show how to predict morphological patterns of teeth among mammalian species. Finally, in vivo inhibition of sonic hedgehog signalling in Eda null teeth enabled us to reproduce characters deep in the rodent ancestry. Taken together, evolutionarily informative transitions can be experimentally reproduced, thereby providing development-based expectations for character state transitions used in evolutionary studies. PMID:25079326

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-10-22

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners.

Population Genomics and the Statistical Values of Race: An Interdisciplinary Perspective on the Biological Classification of Human Populations and Implications for Clinical Genetic Epidemiological Research

PubMed Central

Maglo, Koffi N.; Mersha, Tesfaye B.; Martin, Lisa J.

2016-01-01

The biological status and biomedical significance of the concept of race as applied to humans continue to be contentious issues despite the use of advanced statistical and clustering methods to determine continental ancestry. It is thus imperative for researchers to understand the limitations as well as potential uses of the concept of race in biology and biomedicine. This paper deals with the theoretical assumptions behind cluster analysis in human population genomics. Adopting an interdisciplinary approach, it demonstrates that the hypothesis that attributes the clustering of human populations to “frictional” effects of landform barriers at continental boundaries is empirically incoherent. It then contrasts the scientific status of the “cluster” and “cline” constructs in human population genomics, and shows how cluster may be instrumentally produced. It also shows how statistical values of race vindicate Darwin's argument that race is evolutionarily meaningless. Finally, the paper explains why, due to spatiotemporal parameters, evolutionary forces, and socio-cultural factors influencing population structure, continental ancestry may be pragmatically relevant to global and public health genomics. Overall, this work demonstrates that, from a biological systematic and evolutionary taxonomical perspective, human races/continental groups or clusters have no natural meaning or objective biological reality. In fact, the utility of racial categorizations in research and in clinics can be explained by spatiotemporal parameters, socio-cultural factors, and evolutionary forces affecting disease causation and treatment response. PMID:26925096

CoAIMs: A Cost-Effective Panel of Ancestry Informative Markers for Determining Continental Origins

PubMed Central

Londin, Eric R.; Keller, Margaret A.; Maista, Cathleen; Smith, Gretchen; Mamounas, Laura A.; Zhang, Ran; Madore, Steven J.; Gwinn, Katrina; Corriveau, Roderick A.

2010-01-01

Background Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification. Methodology/Principal Findings Here we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (Fst), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race. Conclusion/Significance CoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic association studies, as it can control for the confounding effects of population stratification. The MSAT-based approach used here has potential for broad applicability as a cost effective tool toward determining admixture proportions. PMID:20976178

Exploring Population Admixture Dynamics via Empirical and Simulated Genome-wide Distribution of Ancestral Chromosomal Segments

PubMed Central

Jin, Wenfei; Wang, Sijia; Wang, Haifeng; Jin, Li; Xu, Shuhua

2012-01-01

The processes of genetic admixture determine the haplotype structure and linkage disequilibrium patterns of the admixed population, which is important for medical and evolutionary studies. However, most previous studies do not consider the inherent complexity of admixture processes. Here we proposed two approaches to explore population admixture dynamics, and we demonstrated, by analyzing genome-wide empirical and simulated data, that the approach based on the distribution of chromosomal segments of distinct ancestry (CSDAs) was more powerful than that based on the distribution of individual ancestry proportions. Analysis of 1,890 African Americans showed that a continuous gene flow model, in which the African American population continuously received gene flow from European populations over about 14 generations, best explained the admixture dynamics of African Americans among several putative models. Interestingly, we observed that some African Americans had much more European ancestry than the simulated samples, indicating substructures of local ancestries in African Americans that could have been caused by individuals from some particular lineages having repeatedly admixed with people of European ancestry. In contrast, the admixture dynamics of Mexicans could be explained by a gradual admixture model in which the Mexican population continuously received gene flow from both European and Amerindian populations over about 24 generations. Our results also indicated that recent gene flows from Sub-Saharan Africans have contributed to the gene pool of Middle Eastern populations such as Mozabite, Bedouin, and Palestinian. In summary, this study not only provides approaches to explore population admixture dynamics, but also advances our understanding on population history of African Americans, Mexicans, and Middle Eastern populations. PMID:23103229

Synaptic, transcriptional and chromatin genes disrupted in autism.

PubMed

De Rubeis, Silvia; He, Xin; Goldberg, Arthur P; Poultney, Christopher S; Samocha, Kaitlin; Cicek, A Erucment; Kou, Yan; Liu, Li; Fromer, Menachem; Walker, Susan; Singh, Tarinder; Klei, Lambertus; Kosmicki, Jack; Shih-Chen, Fu; Aleksic, Branko; Biscaldi, Monica; Bolton, Patrick F; Brownfeld, Jessica M; Cai, Jinlu; Campbell, Nicholas G; Carracedo, Angel; Chahrour, Maria H; Chiocchetti, Andreas G; Coon, Hilary; Crawford, Emily L; Curran, Sarah R; Dawson, Geraldine; Duketis, Eftichia; Fernandez, Bridget A; Gallagher, Louise; Geller, Evan; Guter, Stephen J; Hill, R Sean; Ionita-Laza, Juliana; Jimenz Gonzalez, Patricia; Kilpinen, Helena; Klauck, Sabine M; Kolevzon, Alexander; Lee, Irene; Lei, Irene; Lei, Jing; Lehtimäki, Terho; Lin, Chiao-Feng; Ma'ayan, Avi; Marshall, Christian R; McInnes, Alison L; Neale, Benjamin; Owen, Michael J; Ozaki, Noriio; Parellada, Mara; Parr, Jeremy R; Purcell, Shaun; Puura, Kaija; Rajagopalan, Deepthi; Rehnström, Karola; Reichenberg, Abraham; Sabo, Aniko; Sachse, Michael; Sanders, Stephan J; Schafer, Chad; Schulte-Rüther, Martin; Skuse, David; Stevens, Christine; Szatmari, Peter; Tammimies, Kristiina; Valladares, Otto; Voran, Annette; Li-San, Wang; Weiss, Lauren A; Willsey, A Jeremy; Yu, Timothy W; Yuen, Ryan K C; Cook, Edwin H; Freitag, Christine M; Gill, Michael; Hultman, Christina M; Lehner, Thomas; Palotie, Aaarno; Schellenberg, Gerard D; Sklar, Pamela; State, Matthew W; Sutcliffe, James S; Walsh, Christiopher A; Scherer, Stephen W; Zwick, Michael E; Barett, Jeffrey C; Cutler, David J; Roeder, Kathryn; Devlin, Bernie; Daly, Mark J; Buxbaum, Joseph D

2014-11-13

The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.

Insight into the Peopling of Mainland Southeast Asia from Thai Population Genetic Structure

PubMed Central

Chaichoompu, Kridsadakorn; Ngamphiw, Chumpol; Assawamakin, Anunchai; Nuinoon, Manit; Sripichai, Orapan; Svasti, Saovaros; Fucharoen, Suthat; Praphanphoj, Verayuth; Tongsima, Sissades

2013-01-01

There is considerable ethno-linguistic and genetic variation among human populations in Asia, although tracing the origins of this diversity is complicated by migration events. Thailand is at the center of Mainland Southeast Asia (MSEA), a region within Asia that has not been extensively studied. Genetic substructure may exist in the Thai population, since waves of migration from southern China throughout its recent history may have contributed to substantial gene flow. Autosomal SNP data were collated for 438,503 markers from 992 Thai individuals. Using the available self-reported regional origin, four Thai subpopulations genetically distinct from each other and from other Asian populations were resolved by Neighbor-Joining analysis using a 41,569 marker subset. Using an independent Principal Components-based unsupervised clustering approach, four major MSEA subpopulations were resolved in which regional bias was apparent. A major ancestry component was common to these MSEA subpopulations and distinguishes them from other Asian subpopulations. On the other hand, these MSEA subpopulations were admixed with other ancestries, in particular one shared with Chinese. Subpopulation clustering using only Thai individuals and the complete marker set resolved four subpopulations, which are distributed differently across Thailand. A Sino-Thai subpopulation was concentrated in the Central region of Thailand, although this constituted a minority in an otherwise diverse region. Among the most highly differentiated markers which distinguish the Thai subpopulations, several map to regions known to affect phenotypic traits such as skin pigmentation and susceptibility to common diseases. The subpopulation patterns elucidated have important implications for evolutionary and medical genetics. The subpopulation structure within Thailand may reflect the contributions of different migrants throughout the history of MSEA. The information will also be important for genetic association studies to account for population-structure confounding effects. PMID:24223962

Nine-locus Y-STR profiles of Afrikaner Caucasian and mixed ancestry populations from Cape Town, South Africa.

PubMed

Ehrenreich, Liezle; Benjeddou, Mongi; Davison, Sean; D'Amato, Maria; Leat, Neil

2008-07-01

Samples were collected from 108 Afrikaner males and 114 males of mixed ancestry. The term mixed ancestry is being used to denote a complex community which was established with contributions from Asians, Caucasians and Indigenous populations and constitutes a significant proportion of the Cape Town metropolitan population. Allele and haplotype frequencies were determined for nine Y-STR loci (DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393 and the duplicated locus DYS385). Unique haplotypes were obtained for 64 Afrikaner males and 90 males of mixed ancestry. Both population groups shared the same most common haplotype.

Origins of genes: "big bang" or continuous creation?

PubMed Central

Keese, P K; Gibbs, A

1992-01-01

Many protein families are common to all cellular organisms, indicating that many genes have ancient origins. Genetic variation is mostly attributed to processes such as mutation, duplication, and rearrangement of ancient modules. Thus it is widely assumed that much of present-day genetic diversity can be traced by common ancestry to a molecular "big bang." A rarely considered alternative is that proteins may arise continuously de novo. One mechanism of generating different coding sequences is by "overprinting," in which an existing nucleotide sequence is translated de novo in a different reading frame or from noncoding open reading frames. The clearest evidence for overprinting is provided when the original gene function is retained, as in overlapping genes. Analysis of their phylogenies indicates which are the original genes and which are their informationally novel partners. We report here the phylogenetic relationships of overlapping coding sequences from steroid-related receptor genes and from tymovirus, luteovirus, and lentivirus genomes. For each pair of overlapping coding sequences, one is confined to a single lineage, whereas the other is more widespread. This suggests that the phylogenetically restricted coding sequence arose only in the progenitor of that lineage by translating an out-of-frame sequence to yield the new polypeptide. The production of novel exons by alternative splicing in thyroid receptor and lentivirus genes suggests that introns can be a valuable evolutionary source for overprinting. New genes and their products may drive major evolutionary changes. PMID:1329098

Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

PubMed Central

Calaza, Manuel; Witte, Torsten; Papasteriades, Chryssa; Marchini, Maurizio; Migliaresi, Sergio; Kovacs, Attila; Ordi-Ros, Josep; Bijl, Marc; Santos, Maria Jose; Ruzickova, Sarka; Pullmann, Rudolf; Carreira, Patricia; Skopouli, Fotini N.; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Suarez, Ana; Blanco, Francisco J.; Gomez-Reino, Juan J.; Gonzalez, Antonio

2011-01-01

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10−4), oral ulcers (P = 6.9×10−4) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested. PMID:22194982

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.

PubMed

Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I; Conti, David V; Schumacher, Fredrick; Han, Ying; Benlloch, Sara; Hazelett, Dennis J; Wang, Zhaoming; Saunders, Ed; Leongamornlert, Daniel; Lindstrom, Sara; Jugurnauth-Little, Sara; Dadaev, Tokhir; Tymrakiewicz, Malgorzata; Stram, Daniel O; Rand, Kristin; Wan, Peggy; Stram, Alex; Sheng, Xin; Pooler, Loreall C; Park, Karen; Xia, Lucy; Tyrer, Jonathan; Kolonel, Laurence N; Le Marchand, Loic; Hoover, Robert N; Machiela, Mitchell J; Yeager, Merideth; Burdette, Laurie; Chung, Charles C; Hutchinson, Amy; Yu, Kai; Goh, Chee; Ahmed, Mahbubl; Govindasami, Koveela; Guy, Michelle; Tammela, Teuvo L J; Auvinen, Anssi; Wahlfors, Tiina; Schleutker, Johanna; Visakorpi, Tapio; Leinonen, Katri A; Xu, Jianfeng; Aly, Markus; Donovan, Jenny; Travis, Ruth C; Key, Tim J; Siddiq, Afshan; Canzian, Federico; Khaw, Kay-Tee; Takahashi, Atsushi; Kubo, Michiaki; Pharoah, Paul; Pashayan, Nora; Weischer, Maren; Nordestgaard, Borge G; Nielsen, Sune F; Klarskov, Peter; Røder, Martin Andreas; Iversen, Peter; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Stanford, Janet L; Kolb, Suzanne; Holt, Sarah; Knudsen, Beatrice; Coll, Antonio Hurtado; Gapstur, Susan M; Diver, W Ryan; Stevens, Victoria L; Maier, Christiane; Luedeke, Manuel; Herkommer, Kathleen; Rinckleb, Antje E; Strom, Sara S; Pettaway, Curtis; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; Cannon-Albright, Lisa; Cybulski, Cezary; Wokołorczyk, Dominika; Kluźniak, Wojciech; Park, Jong; Sellers, Thomas; Lin, Hui-Yi; Isaacs, William B; Partin, Alan W; Brenner, Hermann; Dieffenbach, Aida Karina; Stegmaier, Christa; Chen, Constance; Giovannucci, Edward L; Ma, Jing; Stampfer, Meir; Penney, Kathryn L; Mucci, Lorelei; John, Esther M; Ingles, Sue A; Kittles, Rick A; Murphy, Adam B; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej M; Blot, William; Signorello, Lisa B; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, Cristina; Wu, Suh-Yuh; Hennis, Anselm; Kibel, Adam S; Rybicki, Benjamin A; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Zheng, S Lilly; Batra, Jyotsna; Clements, Judith; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Witte, John S; Casey, Graham; Gillanders, Elizabeth M; Seminara, Daniella; Riboli, Elio; Hamdy, Freddie C; Coetzee, Gerhard A; Li, Qiyuan; Freedman, Matthew L; Hunter, David J; Muir, Kenneth; Gronberg, Henrik; Neal, David E; Southey, Melissa; Giles, Graham G; Severi, Gianluca; Cook, Michael B; Nakagawa, Hidewaki; Wiklund, Fredrik; Kraft, Peter; Chanock, Stephen J; Henderson, Brian E; Easton, Douglas F; Eeles, Rosalind A; Haiman, Christopher A

2014-10-01

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?

PubMed

Seedat, Yackoob K; Brewster, Lizzy M

2014-02-01

This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and β-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to β-adrenergic blockers and ACEI are attenuated. Available data are very limited but self-defined ancestry seems to be the best predictor of individual responses to antihypertensive drugs. Knowledge of the factors like economic and social consideration affect the lower rate of detection, treatment and control of hypertension in the African ancestry population of the USA. For regions in which health care resources are particularly scarce, investment in population-based primary prevention strategies may yield the largest benefit.

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed Central

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-01-01

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners. PMID:12396487

African Ancestry Is Associated with Asthma Risk in African Americans

PubMed Central

Pino-Yanes, María; Wade, Michael S.; Pérez-Méndez, Lina; Kittles, Rick A.; Wang, Deli; Papaiahgari, Srinivas; Ford, Jean G.; Kumar, Rajesh; Garcia, Joe G. N.

2012-01-01

Background Asthma is a common complex condition with clear racial and ethnic differences in both prevalence and severity. Asthma consultation rates, mortality, and severe symptoms are greatly increased in African descent populations of developed countries. African ancestry has been associated with asthma, total serum IgE and lower pulmonary function in African-admixed populations. To replicate previous findings, here we aimed to examine whether African ancestry was associated with asthma susceptibility in African Americans. In addition, we examined for the first time whether African ancestry was associated with asthma exacerbations. Methodology/Principal Findings After filtering for self-reported ancestry and genotype data quality, samples from 1,117 self-reported African-American individuals from New York and Baltimore (394 cases, 481 controls), and Chicago (321 cases followed for asthma exacerbations) were analyzed. Genetic ancestry was estimated based on ancestry informative markers (AIMs) selected for being highly divergent among European and West African populations (95 AIMs for New York and Baltimore, and 66 independent AIMs for Chicago). Among case-control samples, the mean African ancestry was significantly higher in asthmatics than in non-asthmatics (82.0±14.0% vs. 77.8±18.1%, mean difference 4.2% [95% confidence interval (CI):2.0–6.4], p<0.0001). This association remained significant after adjusting for potential confounders (odds ratio: 4.55, 95% CI: 1.69–12.29, p = 0.003). African ancestry failed to show an association with asthma exacerbations (p = 0.965) using a model based on longitudinal data of the number of exacerbations followed over 1.5 years. Conclusions/Significance These data replicate previous findings indicating that African ancestry constitutes a risk factor for asthma and suggest that elevated asthma rates in African Americans can be partially attributed to African genetic ancestry. PMID:22235241

African ancestry protects against Alzheimer's disease-related neuropathology

PubMed Central

Schlesinger, D; Grinberg, L T; Alba, J G; Naslavsky, M S; Licinio, L; Farfel, J M; Suemoto, C K; de Lucena Ferretti, R E; Leite, R E P; de Andrade, M P; dos Santos, A C F; Brentani, H; Pasqualucci, C A; Nitrini, R; Jacob-Filho, W; Zatz, M

2013-01-01

Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of São Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry-informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55–0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21–0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil. PMID:22064377

Adaptive cultural transmission biases in children and nonhuman primates.

PubMed

Price, Elizabeth E; Wood, Lara A; Whiten, Andrew

2017-08-01

Comparative and evolutionary developmental analyses seek to discover the similarities and differences between humans and non-human species that might illuminate both the evolutionary foundations of our nature that we share with other animals, and the distinctive characteristics that make human development unique. As our closest animal relatives, with whom we last shared common ancestry, non-human primates have been particularly important in this endeavour. Such studies have focused on social learning, traditions, and culture, and have discovered much about the 'how' of social learning, concerned with key underlying processes such as imitation and emulation. One of the core discoveries is that the adaptive adjustment of social learning options to different contexts is not unique to human, therefore multiple new strands of research have begun to focus on more subtle questions about when, from whom, and why such learning occurs. Here we review illustrative studies on both human infants and young children and on non-human primates to identify the similarities shared more broadly across the primate order, and the apparent specialisms that distinguish human development. Adaptive biases in social learning discussed include those modulated by task comprehension, experience, conformity to majorities, and the age, skill, proficiency and familiarity of potential alternative cultural models. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Neoendemism in Madagascan scaly tree ferns results from recent, coincident diversification bursts.

PubMed

Janssen, Thomas; Bystriakova, Nadia; Rakotondrainibe, France; Coomes, David; Labat, Jean-Noël; Schneider, Harald

2008-08-01

More than 80% of Madagascar's 12,000 plant species are endemic with the degree of endemism reaching as much as 95% in the scaly tree ferns, an important species rich component of Madagascar's evergreen rainforests. Predominantly African or Asian ancestry and divergence times usually postdating the separation of Madagascar from the Gondwanan landmasses have been demonstrated for several Madagascan animal and angiosperm groups. However, evolutionary studies of rainforest-specific lineages are scarce and the ecological context of radiation events has rarely been investigated. Here, we examine the evolution of Madagascan tree ferns as a rainforest-specific model family, integrate results from bioclimatic niche analysis with a dated phylogenetic framework, and propose an evolutionary scenario casting new light on our knowledge of the evolution of large island endemic clades. We show that Madagascar's extant tree fern diversity springs from three distinct ancestors independently colonizing Madagascar in the Miocene and that these three monophyletic clades diversified in three coincident radiation bursts during the Pliocene, reaching exceptionally high diversification rates and most likely responding to a common climatic trigger. Recent diversification bursts may thus have played a major role in the evolution of the extant Madagascan rainforest biome, which hence contains a significant number of young, neoendemic taxa.

The evolution of traditional knowledge: environment shapes medicinal plant use in Nepal

PubMed Central

Saslis-Lagoudakis, C. Haris; Hawkins, Julie A.; Greenhill, Simon J.; Pendry, Colin A.; Watson, Mark F.; Tuladhar-Douglas, Will; Baral, Sushim R.; Savolainen, Vincent

2014-01-01

Traditional knowledge is influenced by ancestry, inter-cultural diffusion and interaction with the natural environment. It is problematic to assess the contributions of these influences independently because closely related ethnic groups may also be geographically close, exposed to similar environments and able to exchange knowledge readily. Medicinal plant use is one of the most important components of traditional knowledge, since plants provide healthcare for up to 80% of the world's population. Here, we assess the significance of ancestry, geographical proximity of cultures and the environment in determining medicinal plant use for 12 ethnic groups in Nepal. Incorporating phylogenetic information to account for plant evolutionary relatedness, we calculate pairwise distances that describe differences in the ethnic groups' medicinal floras and floristic environments. We also determine linguistic relatedness and geographical separation for all pairs of ethnic groups. We show that medicinal uses are most similar when cultures are found in similar floristic environments. The correlation between medicinal flora and floristic environment was positive and strongly significant, in contrast to the effects of shared ancestry and geographical proximity. These findings demonstrate the importance of adaptation to local environments, even at small spatial scale, in shaping traditional knowledge during human cultural evolution. PMID:24523269

The evolution of traditional knowledge: environment shapes medicinal plant use in Nepal.

PubMed

Saslis-Lagoudakis, C Haris; Hawkins, Julie A; Greenhill, Simon J; Pendry, Colin A; Watson, Mark F; Tuladhar-Douglas, Will; Baral, Sushim R; Savolainen, Vincent

2014-04-07

Traditional knowledge is influenced by ancestry, inter-cultural diffusion and interaction with the natural environment. It is problematic to assess the contributions of these influences independently because closely related ethnic groups may also be geographically close, exposed to similar environments and able to exchange knowledge readily. Medicinal plant use is one of the most important components of traditional knowledge, since plants provide healthcare for up to 80% of the world's population. Here, we assess the significance of ancestry, geographical proximity of cultures and the environment in determining medicinal plant use for 12 ethnic groups in Nepal. Incorporating phylogenetic information to account for plant evolutionary relatedness, we calculate pairwise distances that describe differences in the ethnic groups' medicinal floras and floristic environments. We also determine linguistic relatedness and geographical separation for all pairs of ethnic groups. We show that medicinal uses are most similar when cultures are found in similar floristic environments. The correlation between medicinal flora and floristic environment was positive and strongly significant, in contrast to the effects of shared ancestry and geographical proximity. These findings demonstrate the importance of adaptation to local environments, even at small spatial scale, in shaping traditional knowledge during human cultural evolution.

Assessment of coyote-wolf-dog admixture using ancestry-informative diagnostic SNPs

PubMed Central

Monzón, J.; Kays, R.; Dykhuizen, D. E.

2014-01-01

The evolutionary importance of hybridization as a source of new adaptive genetic variation is rapidly gaining recognition. Hybridization between coyotes and wolves may have introduced adaptive alleles into the coyote gene pool that facilitated an expansion in their geographic range and dietary niche. Furthermore, hybridization between coyotes and domestic dogs may facilitate adaptation to human-dominated environments. We genotyped 63 ancestry-informative single nucleotide polymorphisms in 427 canids in order to examine the prevalence, spatial distribution, and ecology of admixture in eastern coyotes. Using multivariate methods and Bayesian clustering analyses, we estimated the relative contributions of western coyotes, western and eastern wolves, and domestic dogs to the admixed ancestry of Ohio and eastern coyotes. We found that eastern coyotes form an extensive hybrid swarm, with all our samples having varying levels of admixture. Ohio coyotes, previously thought to be free of admixture, are also highly admixed with wolves and dogs. Coyotes in areas of high deer density are genetically more wolf-like, suggesting that natural selection for wolf-like traits may result in local adaptation at a fine geographic scale. Our results, in light of other previously published studies of admixture in Canis, reveal a pattern of sex-biased hybridization, presumably generated by male wolves and dogs mating with female coyotes. This study is the most comprehensive genetic survey of admixture in eastern coyotes and demonstrates that the frequency and scope of hybridization can be quantified with relatively few ancestry-informative markers. PMID:24148003

Assessment of coyote-wolf-dog admixture using ancestry-informative diagnostic SNPs.

PubMed

Monzón, J; Kays, R; Dykhuizen, D E

2014-01-01

The evolutionary importance of hybridization as a source of new adaptive genetic variation is rapidly gaining recognition. Hybridization between coyotes and wolves may have introduced adaptive alleles into the coyote gene pool that facilitated an expansion in their geographic range and dietary niche. Furthermore, hybridization between coyotes and domestic dogs may facilitate adaptation to human-dominated environments. We genotyped 63 ancestry-informative single-nucleotide polymorphisms in 427 canids to examine the prevalence, spatial distribution and the ecology of admixture in eastern coyotes. Using multivariate methods and Bayesian clustering analyses, we estimated the relative contributions of western coyotes, western and eastern wolves, and domestic dogs to the admixed ancestry of Ohio and eastern coyotes. We found that eastern coyotes form an extensive hybrid swarm, with all our samples having varying levels of admixture. Ohio coyotes, previously thought to be free of admixture, are also highly admixed with wolves and dogs. Coyotes in areas of high deer density are genetically more wolf-like, suggesting that natural selection for wolf-like traits may result in local adaptation at a fine geographic scale. Our results, in light of other previously published studies of admixture in Canis, revealed a pattern of sex-biased hybridization, presumably generated by male wolves and dogs mating with female coyotes. This study is the most comprehensive genetic survey of admixture in eastern coyotes and demonstrates that the frequency and scope of hybridization can be quantified with relatively few ancestry-informative markers. © 2013 John Wiley & Sons Ltd.

[Familial pulmonary fibrosis in 2 Mexican sisters with Hermansky-Pudlak syndrome].

PubMed

Zamora, Ana C; Alonso-Martínez, Delfino; Barrera, Lourdes; Mendoza, Felipe; Gaxiola, Miguel; Carrillo, Guillermo

2009-08-01

Hermansky-Pudlak syndrome is an autosomal recessive disorder commonly found in individuals of Puerto Rican ancestry. We present 2 cases of familial pulmonary fibrosis in 2 Mexican sisters with Hermansky-Pudlak syndrome. Pulmonary fibrosis was biopsy-proven in 1 of the patients. This report shows that Hermansky-Pudlak syndrome may occur in individuals of Mexican ancestry.

European Genetic Ancestry is Associated with a Decreased Risk of Lupus Nephritis

PubMed Central

Richman, Ilana B.; Taylor, Kimberly E.; Chung, Sharon A.; Trupin, Laura; Petri, Michelle; Yelin, Edward; Graham, Robert R.; Lee, Annette; Behrens, Timothy W.; Gregersen, Peter K.; Seldin, Michael F.; Criswell, Lindsey A.

2013-01-01

Objective African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than SLE patients of European descent. We investigated whether European genetic ancestry protects against the development of lupus nephritis and explored genetic and socioeconomic factors that might explain this effect. Methods This was a cross-sectional study of 1906 adults with SLE. Participants were genotyped for 126 single nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. We used logistic regression to test the association between European ancestry and renal disease. Analyses adjusted for continental ancestries, socioeconomic status, and candidate genes. Results Participants (n=1906) had on average 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among participants, 34% (n=656) had renal disease. A 10% increase in European ancestry was associated with a 15% reduction in the odds of having renal disease after adjustment for disease duration and sex (OR 0.85, 95% CI 0.82-0.87, p=1.9 × 10−30). Adjusting for other genetic ancestries, measures of socioeconomic status, or SNPs in genes most associated with renal disease (IRF5 (rs4728142), BLK (rs2736340), STAT4 (rs3024912), ITGAM (rs9937837) and HLA-DRB1*0301 and DRB1*1501, p<0.05) did not substantively alter this relationship. Conclusion European ancestry is protective against the development of renal disease in SLE, an effect independent of other genetic ancestries, common risk alleles, and socioeconomic status. PMID:23023776

Breast cancer disparities: high-risk breast cancer and African ancestry.

PubMed

Newman, Lisa A

2014-07-01

African American women have a lower lifetime incidence of breast cancer than white/Caucasian Americans yet have a higher risk of breast cancer mortality. African American women are also more likely to be diagnosed with breast cancer at young ages, and they have higher risk for the biologically more aggressive triple-negative breast cancers. These features are also more common among women from western, sub-Saharan Africa who share ancestry with African Americans, and this prompts questions regarding an association between African ancestry and inherited susceptibility for certain patterns of mammary carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

The dynamics of mergers and acquisitions: ancestry as the seminal determinant

PubMed Central

Viegas, Eduardo; Cockburn, Stuart P.; Jensen, Henrik J.; West, Geoffrey B.

2014-01-01

Understanding the fundamental mechanisms behind the complex landscape of corporate mergers and acquisitions is of crucial importance to economies across the world. Adapting ideas from the fields of complexity and evolutionary dynamics to analyse business ecosystems, we show here that ancestry, i.e. the cumulative sum of historical mergers across all ancestors, is the key characteristic to company mergers and acquisitions. We verify this by comparing an agent-based model to an extensive range of business data, covering the period from the 1830s to the present day and a range of industries and geographies. This seemingly universal mechanism leads to imbalanced business ecosystems, with the emergence of a few very large, but sluggish ‘too big to fail’ entities, and very small, niche entities, thereby creating a paradigm where a configuration akin to effective oligopoly or monopoly is a likely outcome for free market systems. PMID:25383025

The dynamics of mergers and acquisitions: ancestry as the seminal determinant.

PubMed

Viegas, Eduardo; Cockburn, Stuart P; Jensen, Henrik J; West, Geoffrey B

2014-11-08

Understanding the fundamental mechanisms behind the complex landscape of corporate mergers and acquisitions is of crucial importance to economies across the world. Adapting ideas from the fields of complexity and evolutionary dynamics to analyse business ecosystems, we show here that ancestry, i.e. the cumulative sum of historical mergers across all ancestors, is the key characteristic to company mergers and acquisitions. We verify this by comparing an agent-based model to an extensive range of business data, covering the period from the 1830s to the present day and a range of industries and geographies. This seemingly universal mechanism leads to imbalanced business ecosystems, with the emergence of a few very large, but sluggish 'too big to fail' entities, and very small, niche entities, thereby creating a paradigm where a configuration akin to effective oligopoly or monopoly is a likely outcome for free market systems.

Ancestry Informative Marker Sets for Determining Continental Origin and Admixture Proportions in Common Populations in America

PubMed Central

Kosoy, Roman; Nassir, Rami; Tian, Chao; White, Phoebe A; Butler, Lesley M.; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E.; Gregersen, Peter K.; Belmont, John W.; De La Vega, Francisco M.; Seldin, Michael F.

2011-01-01

To provide a resource for assessing continental ancestry in a wide variety of genetic studies we identified, validated and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan® assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations. PMID:18683858

A Genome-wide Admixture Scan for Ancestry-linked Genes Predisposing to Sarcoidosis in African Americans

PubMed Central

Rybicki, Benjamin A.; Levin, Albert M.; McKeigue, Paul; Datta, Indrani; Gray-McGuire, Courtney; Colombo, Marco; Reich, David; Burke, Robert R.; Iannuzzi, Michael C.

2010-01-01

Genome-wide linkage and association studies have uncovered variants associated with sarcoidosis, a multi-organ granulomatous inflammatory disease. African ancestry may influence disease pathogenesis since African Americans are more commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis genome-wide ancestry scan using a map of 1,384 highly ancestry informative single nucleotide polymorphisms genotyped on 1,357 sarcoidosis cases and 703 unaffected controls self-identified as African American. The most significant ancestry association was at marker rs11966463 on chromosome 6p22.3 (ancestry association risk ratio (aRR)= 1.90; p=0.0002). When we restricted the analysis to biopsy-confirmed cases, the aRR for this marker increased to 2.01; p=0.00007. Among the eight other markers that demonstrated suggestive ancestry associations with sarcoidosis were rs1462906 on chromosome 8p12 which had the most significant association with European ancestry (aRR=0.65; p=0.002), and markers on chromosomes 5p13 (aRR=1.46; p=0.005) and 5q31 (aRR=0.67; p=0.005), which correspond to regions we previously identified through sib pair linkage analyses. Overall, the most significant ancestry association for Scadding stage IV cases was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; p=2×10−5), a region not associated with disease susceptibility. In summary, through admixture mapping of sarcoidosis we have confirmed previous genetic linkages and identified several novel putative candidate loci for sarcoidosis. PMID:21179114

African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans

PubMed Central

Behar, Doron M.; Rosset, Saharon; Tzur, Shay; Selig, Sara; Yudkovsky, Guennady; Bercovici, Sivan; Kopp, Jeffrey B.; Winkler, Cheryl A.; Nelson, George W.; Wasser, Walter G.; Skorecki, Karl

2010-01-01

Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD. PMID:20144966

African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans.

PubMed

Behar, Doron M; Rosset, Saharon; Tzur, Shay; Selig, Sara; Yudkovsky, Guennady; Bercovici, Sivan; Kopp, Jeffrey B; Winkler, Cheryl A; Nelson, George W; Wasser, Walter G; Skorecki, Karl

2010-05-01

Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD.

Rare variation facilitates inferences of fine-scale population structure in humans.

PubMed

O'Connor, Timothy D; Fu, Wenqing; Mychaleckyj, Josyf C; Logsdon, Benjamin; Auer, Paul; Carlson, Christopher S; Leal, Suzanne M; Smith, Joshua D; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A; Akey, Joshua M

2015-03-01

Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European-American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Evaluating allopolyploid origins in strawberries (Fragaria) using haplotypes generated from target capture sequencing.

PubMed

Kamneva, Olga K; Syring, John; Liston, Aaron; Rosenberg, Noah A

2017-08-04

Hybridization is observed in many eukaryotic lineages and can lead to the formation of polyploid species. The study of hybridization and polyploidization faces challenges both in data generation and in accounting for population-level phenomena such as coalescence processes in phylogenetic analysis. Genus Fragaria is one example of a set of plant taxa in which a range of ploidy levels is observed across species, but phylogenetic origins are unknown. Here, using 20 diploid and polyploid Fragaria species, we combine approaches from NGS data analysis and phylogenetics to infer evolutionary origins of polyploid strawberries, taking into account coalescence processes. We generate haplotype sequences for 257 low-copy nuclear markers assembled from Illumina target capture sequence data. We then identify putative hybridization events by analyzing gene tree topologies, and further test predicted hybridizations in a coalescence framework. This approach confirms the allopolyploid ancestry of F. chiloensis and F. virginiana, and provides new allopolyploid ancestry hypotheses for F. iturupensis, F. moschata, and F. orientalis. Evidence of gene flow between diploids F. bucharica and F. vesca is also detected, suggesting that it might be appropriate to consider these groups as conspecifics. This study is one of the first in which target capture sequencing followed by computational deconvolution of individual haplotypes is used for tracing origins of polyploid taxa. The study also provides new perspectives on the evolutionary history of Fragaria.

The Origin and Evolutionary Biology of Pinnipeds: Seals, Sea Lions, and Walruses

NASA Astrophysics Data System (ADS)

Berta, Annalisa; Churchill, Morgan; Boessenecker, Robert W.

2018-05-01

The oldest definitive pinniped fossils date from approximately 30.6–23 million years ago (Ma) in the North Pacific. Pinniped monophyly is consistently supported; the group shares a common ancestry with arctoid carnivorans, either ursids or musteloids. Crown pinnipeds comprise the Otariidae (fur seals and sea lions), Odobenidae (walruses), and Phocidae (seals), with paraphyletic “enaliarctines” falling outside the crown group. The position of extinct Desmatophocidae is debated; they are considered to be closely related to both otariids and odobenids or, alternatively, to phocids. Both otariids and odobenids are known from the North Pacific, diverging approximately 19 Ma, with phocids originating in the North Atlantic or Paratethys region 19–14 Ma. Our understanding of pinniped paleobiology has been enriched by studies that incorporate anatomical and behavioral data into a phylogenetic framework. There is now evidence for sexual dimorphism in the earliest pinnipeds, heralding polygynous breeding systems, followed by increased body sizes, diving capabilities, and diverse feeding strategies in later-diverging phocid and otarioid lineages.

Actionable exomic incidental findings in 6503 participants: challenges of variant classification

PubMed Central

Amendola, Laura M.; Dorschner, Michael O.; Robertson, Peggy D.; Salama, Joseph S.; Hart, Ragan; Shirts, Brian H.; Murray, Mitzi L.; Tokita, Mari J.; Gallego, Carlos J.; Kim, Daniel Seung; Bennett, James T.; Crosslin, David R.; Ranchalis, Jane; Jones, Kelly L.; Rosenthal, Elisabeth A.; Jarvik, Ella R.; Itsara, Andy; Turner, Emily H.; Herman, Daniel S.; Schleit, Jennifer; Burt, Amber; Jamal, Seema M.; Abrudan, Jenica L.; Johnson, Andrew D.; Conlin, Laura K.; Dulik, Matthew C.; Santani, Avni; Metterville, Danielle R.; Kelly, Melissa; Foreman, Ann Katherine M.; Lee, Kristy; Taylor, Kent D.; Guo, Xiuqing; Crooks, Kristy; Kiedrowski, Lesli A.; Raffel, Leslie J.; Gordon, Ora; Machini, Kalotina; Desnick, Robert J.; Biesecker, Leslie G.; Lubitz, Steven A.; Mulchandani, Surabhi; Cooper, Greg M.; Joffe, Steven; Richards, C. Sue; Yang, Yaoping; Rotter, Jerome I.; Rich, Stephen S.; O’Donnell, Christopher J.; Berg, Jonathan S.; Spinner, Nancy B.; Evans, James P.; Fullerton, Stephanie M.; Leppig, Kathleen A.; Bennett, Robin L.; Bird, Thomas; Sybert, Virginia P.; Grady, William M.; Tabor, Holly K.; Kim, Jerry H.; Bamshad, Michael J.; Wilfond, Benjamin; Motulsky, Arno G.; Scott, C. Ronald; Pritchard, Colin C.; Walsh, Tom D.; Burke, Wylie; Raskind, Wendy H.; Byers, Peter; Hisama, Fuki M.; Rehm, Heidi; Nickerson, Debbie A.; Jarvik, Gail P.

2015-01-01

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base. PMID:25637381

Following the footprints of polymorphic inversions on SNP data: from detection to association tests

PubMed Central

Cáceres, Alejandro; González, Juan R.

2015-01-01

Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined: OR= 2.00, P = 0.001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease. PMID:25672393

Rare, low frequency, and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans

PubMed Central

Olfson, Emily; Saccone, Nancy L.; Johnson, Eric O.; Chen, Li-Shiun; Culverhouse, Robert; Doheny, Kimberly; Foltz, Steven M.; Fox, Louis; Gogarten, Stephanie M.; Hartz, Sarah; Hetrick, Kurt; Laurie, Cathy C.; Marosy, Beth; Amin, Najaf; Arnett, Donna; Barr, R. Graham; Bartz, Traci M.; Bertelsen, Sarah; Borecki, Ingrid B.; Brown, Michael R.; Chasman, Daniel I.; van Duijn, Cornelia M.; Feitosa, Mary F.; Fox, Ervin R.; Franceschini, Nora; Franco, Oscar H.; Grove, Megan L.; Guo, Xiuqing; Hofman, Albert; Kardia, Sharon L.R.; Morrison, Alanna C.; Musani, Solomon K.; Psaty, Bruce M.; Rao, D.C.; Reiner, Alex P.; Rice, Kenneth; Ridker, Paul M.; Rose, Lynda M.; Schick, Ursula M.; Schwander, Karen; Uitterlinden, Andre G.; Vojinovic, Dina; Wang, Jen-Chyong; Ware, Erin B.; Wilson, Gregory; Yao, Jie; Zhao, Wei; Breslau, Naomi; Hatsukami, Dorothy; Stitzel, Jerry A.; Rice, John; Goate, Alison; Bierut, Laura J.

2015-01-01

The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine dependent cases (Fagerström Test for Nicotine Dependence score≥4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (MAF≥0.05), aggregate low frequency variants (0.05>MAF≥0.005), and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180X coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: OR=1.3, p=3.5×10−11; African ancestry: OR=1.3, p=0.01) and demonstrated that 3 low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, p=0.005; African ancestry: OR=1.4, p=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, p=0.01) and in the same risk direction in African Americans (OR=1.5, p=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence risk for smoking-related diseases such as lung cancer. PMID:26239294

Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

PubMed

Olfson, E; Saccone, N L; Johnson, E O; Chen, L-S; Culverhouse, R; Doheny, K; Foltz, S M; Fox, L; Gogarten, S M; Hartz, S; Hetrick, K; Laurie, C C; Marosy, B; Amin, N; Arnett, D; Barr, R G; Bartz, T M; Bertelsen, S; Borecki, I B; Brown, M R; Chasman, D I; van Duijn, C M; Feitosa, M F; Fox, E R; Franceschini, N; Franco, O H; Grove, M L; Guo, X; Hofman, A; Kardia, S L R; Morrison, A C; Musani, S K; Psaty, B M; Rao, D C; Reiner, A P; Rice, K; Ridker, P M; Rose, L M; Schick, U M; Schwander, K; Uitterlinden, A G; Vojinovic, D; Wang, J-C; Ware, E B; Wilson, G; Yao, J; Zhao, W; Breslau, N; Hatsukami, D; Stitzel, J A; Rice, J; Goate, A; Bierut, L J

2016-05-01

The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer.

Socioeconomic and Nutritional Factors Account for the Association of Gastric Cancer with Amerindian Ancestry in a Latin American Admixed Population

PubMed Central

Pereira, Latife; Zamudio, Roxana; Soares-Souza, Giordano; Herrera, Phabiola; Cabrera, Lilia; Hooper, Catherine C.; Cok, Jaime; Combe, Juan M.; Vargas, Gloria; Prado, William A.; Schneider, Silvana; Kehdy, Fernanda; Rodrigues, Maira R.; Chanock, Stephen J.; Berg, Douglas E.; Gilman, Robert H.; Tarazona-Santos, Eduardo

2012-01-01

Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group. PMID:22870209

Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry.

PubMed

Gichohi-Wainaina, Wanjiku N; Tanaka, Toshiko; Towers, G Wayne; Verhoef, Hans; Veenemans, Jacobien; Talsma, Elise F; Harryvan, Jan; Boekschoten, Mark V; Feskens, Edith J; Melse-Boonstra, Alida

2016-01-01

Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations.

Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry

PubMed Central

Tanaka, Toshiko; Towers, G. Wayne; Verhoef, Hans; Veenemans, Jacobien; Talsma, Elise F.; Harryvan, Jan; Boekschoten, Mark V.; Feskens, Edith J.; Melse-Boonstra, Alida

2016-01-01

Background Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. Methods We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. Results In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. Conclusions In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations. PMID:27332551

Associations among ancestry, geography and breast cancer incidence, mortality, and survival in Trinidad and Tobago.

PubMed

Warner, Wayne A; Morrison, Robert L; Lee, Tammy Y; Williams, Tanisha M; Ramnarine, Shelina; Roach, Veronica; Slovacek, Simeon; Maharaj, Ravi; Bascombe, Nigel; Bondy, Melissa L; Ellis, Matthew J; Toriola, Adetunji T; Roach, Allana; Llanos, Adana A M

2015-11-01

Breast cancer (BC) is the most common newly diagnosed cancer among women in Trinidad and Tobago (TT) and BC mortality rates are among the highest in the world. Globally, racial/ethnic trends in BC incidence, mortality and survival have been reported. However, such investigations have not been conducted in TT, which has been noted for its rich diversity. In this study, we investigated associations among ancestry, geography and BC incidence, mortality and survival in TT. Data on 3767 incident BC cases, reported to the National Cancer Registry of TT, from 1995 to 2007, were analyzed in this study. Women of African ancestry had significantly higher BC incidence and mortality rates ( 66.96; 30.82 per 100,000) compared to women of East Indian ( 41.04, MORTALITY: 14.19 per 100,000) or mixed ancestry ( 36.72, MORTALITY: 13.80 per 100,000). Geographically, women residing in the North West Regional Health Authority (RHA) catchment area followed by the North Central RHA exhibited the highest incidence and mortality rates. Notable ancestral differences in survival were also observed. Women of East Indian and mixed ancestry experienced significantly longer survival than those of African ancestry. Differences in survival by geography were not observed. In TT, ancestry and geographical residence seem to be strong predictors of BC incidence and mortality rates. Additionally, disparities in survival by ancestry were found. These data should be considered in the design and implementation of strategies to reduce BC incidence and mortality rates in TT. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Genetic structure of Miscanthus sinensis and Miscanthus sacchariflorus in Japan indicates a gradient of bidirectional but asymmetric introgression

DOE PAGES

Clark, Lindsay V.; Stewart, J. Ryan; Nishiwaki, Aya; ...

2015-01-24

Unilateral introgression from diploids to tetraploids has been hypothesized to be an important evolutionary mechanism in plants. However, few examples have been definitively identified, perhaps because data of sufficient depth and breadth were difficult to obtain before the advent of affordable high-density genotyping. Throughout Japan, tetraploid Miscanthus sacchariflorus and diploid Miscanthus sinensis are common, and occasionally hybridize. In this study, 667 M. sinensis and 78 M. sacchariflorus genotypes from Japan were characterized using 20 704 SNPs and ten plastid microsatellites. Similarity of SNP genotypes between diploid and tetraploid M. sacchariflorus indicated that the tetraploids originated through autopolyploidy. Structure analysis indicatedmore » a gradient of introgression from diploid M. sinensis into tetraploid M. sacchariflorus throughout Japan; most tetraploids had some M. sinensis DNA. Among phenotypically M. sacchariflorus tetraploids, M. sinensis ancestry averaged 7% and ranged from 1-39%, with introgression greatest in southern Japan. Unexpectedly, rare (~1%) diploid M. sinensis individuals from northern Japan were found with 6-27% M. sacchariflorus ancestry. Population structure of M. sinensis in Japan included three groups, and was driven primarily by distance, and secondarily by geographic barriers such as mountains and straits. Miscanthus speciation is a complex and dynamic process. In contrast to limited introgression between diploid M. sacchariflorus and M. sinensis in northern China, selection for adaptation to a moderate maritime climate probably favoured cross-ploidy introgressants in southern Japan. Ultimately, these results will help guide the selection of Miscanthus accessions for the breeding of biomass cultivars.« less

Genetic structure of Miscanthus sinensis and Miscanthus sacchariflorus in Japan indicates a gradient of bidirectional but asymmetric introgression.

PubMed

Clark, Lindsay V; Stewart, J Ryan; Nishiwaki, Aya; Toma, Yo; Kjeldsen, Jens Bonderup; Jørgensen, Uffe; Zhao, Hua; Peng, Junhua; Yoo, Ji Hye; Heo, Kweon; Yu, Chang Yeon; Yamada, Toshihiko; Sacks, Erik J

2015-07-01

Unilateral introgression from diploids to tetraploids has been hypothesized to be an important evolutionary mechanism in plants. However, few examples have been definitively identified, perhaps because data of sufficient depth and breadth were difficult to obtain before the advent of affordable high-density genotyping. Throughout Japan, tetraploid Miscanthus sacchariflorus and diploid Miscanthus sinensis are common, and occasionally hybridize. In this study, 667 M. sinensis and 78 M. sacchariflorus genotypes from Japan were characterized using 20 704 SNPs and ten plastid microsatellites. Similarity of SNP genotypes between diploid and tetraploid M. sacchariflorus indicated that the tetraploids originated through autopolyploidy. Structure analysis indicated a gradient of introgression from diploid M. sinensis into tetraploid M. sacchariflorus throughout Japan; most tetraploids had some M. sinensis DNA. Among phenotypically M. sacchariflorus tetraploids, M. sinensis ancestry averaged 7% and ranged from 1-39%, with introgression greatest in southern Japan. Unexpectedly, rare (~1%) diploid M. sinensis individuals from northern Japan were found with 6-27% M. sacchariflorus ancestry. Population structure of M. sinensis in Japan included three groups, and was driven primarily by distance, and secondarily by geographic barriers such as mountains and straits. Miscanthus speciation is a complex and dynamic process. In contrast to limited introgression between diploid M. sacchariflorus and M. sinensis in northern China, selection for adaptation to a moderate maritime climate probably favoured cross-ploidy introgressants in southern Japan. These results will help guide the selection of Miscanthus accessions for the breeding of biomass cultivars. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Genetic structure of Miscanthus sinensis and Miscanthus sacchariflorus in Japan indicates a gradient of bidirectional but asymmetric introgression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, Lindsay V.; Stewart, J. Ryan; Nishiwaki, Aya

Unilateral introgression from diploids to tetraploids has been hypothesized to be an important evolutionary mechanism in plants. However, few examples have been definitively identified, perhaps because data of sufficient depth and breadth were difficult to obtain before the advent of affordable high-density genotyping. Throughout Japan, tetraploid Miscanthus sacchariflorus and diploid Miscanthus sinensis are common, and occasionally hybridize. In this study, 667 M. sinensis and 78 M. sacchariflorus genotypes from Japan were characterized using 20 704 SNPs and ten plastid microsatellites. Similarity of SNP genotypes between diploid and tetraploid M. sacchariflorus indicated that the tetraploids originated through autopolyploidy. Structure analysis indicatedmore » a gradient of introgression from diploid M. sinensis into tetraploid M. sacchariflorus throughout Japan; most tetraploids had some M. sinensis DNA. Among phenotypically M. sacchariflorus tetraploids, M. sinensis ancestry averaged 7% and ranged from 1-39%, with introgression greatest in southern Japan. Unexpectedly, rare (~1%) diploid M. sinensis individuals from northern Japan were found with 6-27% M. sacchariflorus ancestry. Population structure of M. sinensis in Japan included three groups, and was driven primarily by distance, and secondarily by geographic barriers such as mountains and straits. Miscanthus speciation is a complex and dynamic process. In contrast to limited introgression between diploid M. sacchariflorus and M. sinensis in northern China, selection for adaptation to a moderate maritime climate probably favoured cross-ploidy introgressants in southern Japan. Ultimately, these results will help guide the selection of Miscanthus accessions for the breeding of biomass cultivars.« less

Genetic structure of Miscanthus sinensis and Miscanthus sacchariflorus in Japan indicates a gradient of bidirectional but asymmetric introgression

PubMed Central

Clark, Lindsay V.; Stewart, J. Ryan; Nishiwaki, Aya; Toma, Yo; Kjeldsen, Jens Bonderup; Jørgensen, Uffe; Zhao, Hua; Peng, Junhua; Yoo, Ji Hye; Heo, Kweon; Yu, Chang Yeon; Yamada, Toshihiko

2015-01-01

Unilateral introgression from diploids to tetraploids has been hypothesized to be an important evolutionary mechanism in plants. However, few examples have been definitively identified, perhaps because data of sufficient depth and breadth were difficult to obtain before the advent of affordable high-density genotyping. Throughout Japan, tetraploid Miscanthus sacchariflorus and diploid Miscanthus sinensis are common, and occasionally hybridize. In this study, 667 M. sinensis and 78 M. sacchariflorus genotypes from Japan were characterized using 20 704 SNPs and ten plastid microsatellites. Similarity of SNP genotypes between diploid and tetraploid M. sacchariflorus indicated that the tetraploids originated through autopolyploidy. Structure analysis indicated a gradient of introgression from diploid M. sinensis into tetraploid M. sacchariflorus throughout Japan; most tetraploids had some M. sinensis DNA. Among phenotypically M. sacchariflorus tetraploids, M. sinensis ancestry averaged 7% and ranged from 1–39%, with introgression greatest in southern Japan. Unexpectedly, rare (~1%) diploid M. sinensis individuals from northern Japan were found with 6–27% M. sacchariflorus ancestry. Population structure of M. sinensis in Japan included three groups, and was driven primarily by distance, and secondarily by geographic barriers such as mountains and straits. Miscanthus speciation is a complex and dynamic process. In contrast to limited introgression between diploid M. sacchariflorus and M. sinensis in northern China, selection for adaptation to a moderate maritime climate probably favoured cross-ploidy introgressants in southern Japan. These results will help guide the selection of Miscanthus accessions for the breeding of biomass cultivars. PMID:25618143

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

PubMed

Mahajan, Anubha; Go, Min Jin; Zhang, Weihua; Below, Jennifer E; Gaulton, Kyle J; Ferreira, Teresa; Horikoshi, Momoko; Johnson, Andrew D; Ng, Maggie C Y; Prokopenko, Inga; Saleheen, Danish; Wang, Xu; Zeggini, Eleftheria; Abecasis, Goncalo R; Adair, Linda S; Almgren, Peter; Atalay, Mustafa; Aung, Tin; Baldassarre, Damiano; Balkau, Beverley; Bao, Yuqian; Barnett, Anthony H; Barroso, Ines; Basit, Abdul; Been, Latonya F; Beilby, John; Bell, Graeme I; Benediktsson, Rafn; Bergman, Richard N; Boehm, Bernhard O; Boerwinkle, Eric; Bonnycastle, Lori L; Burtt, Noël; Cai, Qiuyin; Campbell, Harry; Carey, Jason; Cauchi, Stephane; Caulfield, Mark; Chan, Juliana C N; Chang, Li-Ching; Chang, Tien-Jyun; Chang, Yi-Cheng; Charpentier, Guillaume; Chen, Chien-Hsiun; Chen, Han; Chen, Yuan-Tsong; Chia, Kee-Seng; Chidambaram, Manickam; Chines, Peter S; Cho, Nam H; Cho, Young Min; Chuang, Lee-Ming; Collins, Francis S; Cornelis, Marylin C; Couper, David J; Crenshaw, Andrew T; van Dam, Rob M; Danesh, John; Das, Debashish; de Faire, Ulf; Dedoussis, George; Deloukas, Panos; Dimas, Antigone S; Dina, Christian; Doney, Alex S; Donnelly, Peter J; Dorkhan, Mozhgan; van Duijn, Cornelia; Dupuis, Josée; Edkins, Sarah; Elliott, Paul; Emilsson, Valur; Erbel, Raimund; Eriksson, Johan G; Escobedo, Jorge; Esko, Tonu; Eury, Elodie; Florez, Jose C; Fontanillas, Pierre; Forouhi, Nita G; Forsen, Tom; Fox, Caroline; Fraser, Ross M; Frayling, Timothy M; Froguel, Philippe; Frossard, Philippe; Gao, Yutang; Gertow, Karl; Gieger, Christian; Gigante, Bruna; Grallert, Harald; Grant, George B; Grrop, Leif C; Groves, Chrisropher J; Grundberg, Elin; Guiducci, Candace; Hamsten, Anders; Han, Bok-Ghee; Hara, Kazuo; Hassanali, Neelam; Hattersley, Andrew T; Hayward, Caroline; Hedman, Asa K; Herder, Christian; Hofman, Albert; Holmen, Oddgeir L; Hovingh, Kees; Hreidarsson, Astradur B; Hu, Cheng; Hu, Frank B; Hui, Jennie; Humphries, Steve E; Hunt, Sarah E; Hunter, David J; Hveem, Kristian; Hydrie, Zafar I; Ikegami, Hiroshi; Illig, Thomas; Ingelsson, Erik; Islam, Muhammed; Isomaa, Bo; Jackson, Anne U; Jafar, Tazeen; James, Alan; Jia, Weiping; Jöckel, Karl-Heinz; Jonsson, Anna; Jowett, Jeremy B M; Kadowaki, Takashi; Kang, Hyun Min; Kanoni, Stavroula; Kao, Wen Hong L; Kathiresan, Sekar; Kato, Norihiro; Katulanda, Prasad; Keinanen-Kiukaanniemi, Kirkka M; Kelly, Ann M; Khan, Hassan; Khaw, Kay-Tee; Khor, Chiea-Chuen; Kim, Hyung-Lae; Kim, Sangsoo; Kim, Young Jin; Kinnunen, Leena; Klopp, Norman; Kong, Augustine; Korpi-Hyövälti, Eeva; Kowlessur, Sudhir; Kraft, Peter; Kravic, Jasmina; Kristensen, Malene M; Krithika, S; Kumar, Ashish; Kumate, Jesus; Kuusisto, Johanna; Kwak, Soo Heon; Laakso, Markku; Lagou, Vasiliki; Lakka, Timo A; Langenberg, Claudia; Langford, Cordelia; Lawrence, Robert; Leander, Karin; Lee, Jen-Mai; Lee, Nanette R; Li, Man; Li, Xinzhong; Li, Yun; Liang, Junbin; Liju, Samuel; Lim, Wei-Yen; Lind, Lars; Lindgren, Cecilia M; Lindholm, Eero; Liu, Ching-Ti; Liu, Jian Jun; Lobbens, Stéphane; Long, Jirong; Loos, Ruth J F; Lu, Wei; Luan, Jian'an; Lyssenko, Valeriya; Ma, Ronald C W; Maeda, Shiro; Mägi, Reedik; Männisto, Satu; Matthews, David R; Meigs, James B; Melander, Olle; Metspalu, Andres; Meyer, Julia; Mirza, Ghazala; Mihailov, Evelin; Moebus, Susanne; Mohan, Viswanathan; Mohlke, Karen L; Morris, Andrew D; Mühleisen, Thomas W; Müller-Nurasyid, Martina; Musk, Bill; Nakamura, Jiro; Nakashima, Eitaro; Navarro, Pau; Ng, Peng-Keat; Nica, Alexandra C; Nilsson, Peter M; Njølstad, Inger; Nöthen, Markus M; Ohnaka, Keizo; Ong, Twee Hee; Owen, Katharine R; Palmer, Colin N A; Pankow, James S; Park, Kyong Soo; Parkin, Melissa; Pechlivanis, Sonali; Pedersen, Nancy L; Peltonen, Leena; Perry, John R B; Peters, Annette; Pinidiyapathirage, Janini M; Platou, Carl G; Potter, Simon; Price, Jackie F; Qi, Lu; Radha, Venkatesan; Rallidis, Loukianos; Rasheed, Asif; Rathman, Wolfgang; Rauramaa, Rainer; Raychaudhuri, Soumya; Rayner, N William; Rees, Simon D; Rehnberg, Emil; Ripatti, Samuli; Robertson, Neil; Roden, Michael; Rossin, Elizabeth J; Rudan, Igor; Rybin, Denis; Saaristo, Timo E; Salomaa, Veikko; Saltevo, Juha; Samuel, Maria; Sanghera, Dharambir K; Saramies, Jouko; Scott, James; Scott, Laura J; Scott, Robert A; Segrè, Ayellet V; Sehmi, Joban; Sennblad, Bengt; Shah, Nabi; Shah, Sonia; Shera, A Samad; Shu, Xiao Ou; Shuldiner, Alan R; Sigurđsson, Gunnar; Sijbrands, Eric; Silveira, Angela; Sim, Xueling; Sivapalaratnam, Suthesh; Small, Kerrin S; So, Wing Yee; Stančáková, Alena; Stefansson, Kari; Steinbach, Gerald; Steinthorsdottir, Valgerdur; Stirrups, Kathleen; Strawbridge, Rona J; Stringham, Heather M; Sun, Qi; Suo, Chen; Syvänen, Ann-Christine; Takayanagi, Ryoichi; Takeuchi, Fumihiko; Tay, Wan Ting; Teslovich, Tanya M; Thorand, Barbara; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Trakalo, Joseph; Tremoli, Elena; Trip, Mieke D; Tsai, Fuu Jen; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Uitterlinden, Andre G; Valladares-Salgado, Adan; Vedantam, Sailaja; Veglia, Fabrizio; Voight, Benjamin F; Wang, Congrong; Wareham, Nicholas J; Wennauer, Roman; Wickremasinghe, Ananda R; Wilsgaard, Tom; Wilson, James F; Wiltshire, Steven; Winckler, Wendy; Wong, Tien Yin; Wood, Andrew R; Wu, Jer-Yuarn; Wu, Ying; Yamamoto, Ken; Yamauchi, Toshimasa; Yang, Mingyu; Yengo, Loic; Yokota, Mitsuhiro; Young, Robin; Zabaneh, Delilah; Zhang, Fan; Zhang, Rong; Zheng, Wei; Zimmet, Paul Z; Altshuler, David; Bowden, Donald W; Cho, Yoon Shin; Cox, Nancy J; Cruz, Miguel; Hanis, Craig L; Kooner, Jaspal; Lee, Jong-Young; Seielstad, Mark; Teo, Yik Ying; Boehnke, Michael; Parra, Esteban J; Chambers, Jonh C; Tai, E Shyong; McCarthy, Mark I; Morris, Andrew P

2014-03-01

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America.

PubMed

Kosoy, Roman; Nassir, Rami; Tian, Chao; White, Phoebe A; Butler, Lesley M; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E; Gregersen, Peter K; Belmont, John W; De La Vega, Francisco M; Seldin, Michael F

2009-01-01

To provide a resource for assessing continental ancestry in a wide variety of genetic studies, we identified, validated, and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations. Copyright 2008 Wiley-Liss, Inc.

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

PubMed Central

2014-01-01

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS) including 26,488 cases and 83,964 controls of European, East Asian, South Asian, and Mexican and Mexican American ancestry. We observed significant excess in directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven novel T2D susceptibility loci. Furthermore, we observed considerable improvements in fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterisation of complex trait loci, and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. PMID:24509480

Culture extends the scope of evolutionary biology in the great apes.

PubMed

Whiten, Andrew

2017-07-24

Discoveries about the cultures and cultural capacities of the great apes have played a leading role in the recognition emerging in recent decades that cultural inheritance can be a significant factor in the lives not only of humans but also of nonhuman animals. This prominence derives in part from these primates being those with whom we share the most recent common ancestry, thus offering clues to the origins of our own thoroughgoing reliance on cumulative cultural achievements. In addition, the intense research focus on these species has spawned an unprecedented diversity of complementary methodological approaches, the results of which suggest that cultural phenomena pervade the lives of these apes, with potentially major implications for their broader evolutionary biology. Here I review what this extremely broad array of observational and experimental methodologies has taught us about the cultural lives of chimpanzees, gorillas, and orangutans and consider the ways in which this knowledge extends our wider understanding of primate biology and the processes of adaptation and evolution that shape it. I address these issues first by evaluating the extent to which the results of cultural inheritance echo a suite of core principles that underlie organic Darwinian evolution but also extend them in new ways and then by assessing the principal causal interactions between the primary, genetically based organic processes of evolution and the secondary system of cultural inheritance that is based on social learning from others.

Culture extends the scope of evolutionary biology in the great apes

PubMed Central

2017-01-01

Discoveries about the cultures and cultural capacities of the great apes have played a leading role in the recognition emerging in recent decades that cultural inheritance can be a significant factor in the lives not only of humans but also of nonhuman animals. This prominence derives in part from these primates being those with whom we share the most recent common ancestry, thus offering clues to the origins of our own thoroughgoing reliance on cumulative cultural achievements. In addition, the intense research focus on these species has spawned an unprecedented diversity of complementary methodological approaches, the results of which suggest that cultural phenomena pervade the lives of these apes, with potentially major implications for their broader evolutionary biology. Here I review what this extremely broad array of observational and experimental methodologies has taught us about the cultural lives of chimpanzees, gorillas, and orangutans and consider the ways in which this knowledge extends our wider understanding of primate biology and the processes of adaptation and evolution that shape it. I address these issues first by evaluating the extent to which the results of cultural inheritance echo a suite of core principles that underlie organic Darwinian evolution but also extend them in new ways and then by assessing the principal causal interactions between the primary, genetically based organic processes of evolution and the secondary system of cultural inheritance that is based on social learning from others. PMID:28739927

Dissecting Complex Diseases in Complex Populations

PubMed Central

Choudhry, Shweta; Seibold, Max A.; Borrell, Luisa N.; Tang, Hua; Serebrisky, Denise; Chapela, Rocio; Rodriguez-Santana, José R.; Avila, Pedro C.; Ziv, Elad; Rodriguez-Cintron, William; Risch, Neil J.; Burchard, Esteban González

2007-01-01

Asthma is a common but complex respiratory ailment; current data indicate that interaction of genetic and environmental factors lead to its clinical expression. In the United States, asthma prevalence, morbidity, and mortality vary widely among different Latino ethnic groups. The prevalence of asthma is highest in Puerto Ricans, intermediate in Dominicans and Cubans, and lowest in Mexicans and Central Americans. Independently, known socioeconomic, environmental, and genetic differences do not fully account for this observation. One potential explanation is that there may be unique and ethnic-specific gene–environment interactions that can differentially modify risk for asthma in Latino ethnic groups. These gene–environment interactions can be tested using genetic ancestry as a surrogate for genetic risk factors. Latinos are admixed and share varying proportions of African, Native American, and European ancestry. Most Latinos are unaware of their precise ancestry and report their ancestry based on the national origin of their family and their physical appearance. The unavailability of precise ancestry and the genetic complexity among Latinos may complicate asthma research studies in this population. On the other hand, precisely because of this rich mixture of ancestry, Latinos present a unique opportunity to disentangle the clinical, social, environmental, and genetic underpinnings of population differences in asthma prevalence, severity, and bronchodilator drug responsiveness. PMID:17607004

Resolving the Etiology of Atopic Disorders by Genetic Analysis of Racial Ancestry

PubMed Central

Gupta, Jayanta; Johansson, Elisabet; Bernstein, Jonathan A.; Chakraborty, Ranajit; Khurana Hershey, Gurjit K.; Rothenberg, Marc E.; Mersha, Tesfaye B.

2016-01-01

Atopic dermatitis (AD), food allergy (FA), allergic rhinitis (AR) and asthma are common atopic disorders of complex etiology. The frequently observed “atopic march” from early AD to asthma and/or AR later in life as well as the extensive comorbidity of atopic disorders, suggests common causal mechanisms in addition to distinct ones. Indeed, both disease-specific and shared genomic regions exist for atopic disorders. Their prevalence also varies among races; for example, AD and asthma have a higher prevalence in African-Americans when compared to European-Americans. Whether this disparity stems from true genetic or race-specific environmental risk factors or both is unknown. Thus far, the majority of the genetic studies on atopic diseases have utilized populations of European ancestry, limiting their generalizability. Large cohort initiatives and new analytic methods such as admixture mapping are currently being employed to address this knowledge gap. Here we discuss the unique and shared genetic risk factors for atopic disorders in the context of ancestry variations, and the promise of high-throughput “-omics” based systems biology approach in providing greater insight to deconstruct into their genetic and non-genetic etiologies. Future research will also focus on deep phenotyping and genotyping of diverse racial ancestry, gene-environment, and gene-gene interactions. PMID:27297995

Genetic analysis of ancestry, admixture and selection in Bolivian and Totonac populations of the New World.

PubMed

Watkins, W Scott; Xing, Jinchuan; Huff, Chad; Witherspoon, David J; Zhang, Yuhua; Perego, Ugo A; Woodward, Scott R; Jorde, Lynn B

2012-05-20

Populations of the Americas were founded by early migrants from Asia, and some have experienced recent genetic admixture. To better characterize the native and non-native ancestry components in populations from the Americas, we analyzed 815,377 autosomal SNPs, mitochondrial hypervariable segments I and II, and 36 Y-chromosome STRs from 24 Mesoamerican Totonacs and 23 South American Bolivians. We analyzed common genomic regions from native Bolivian and Totonac populations to identify 324 highly predictive Native American ancestry informative markers (AIMs). As few as 40-50 of these AIMs perform nearly as well as large panels of random genome-wide SNPs for predicting and estimating Native American ancestry and admixture levels. These AIMs have greater New World vs. Old World specificity than previous AIMs sets. We identify highly-divergent New World SNPs that coincide with high-frequency haplotypes found at similar frequencies in all populations examined, including the HGDP Pima, Maya, Colombian, Karitiana, and Surui American populations. Some of these regions are potential candidates for positive selection. European admixture in the Bolivian sample is approximately 12%, though individual estimates range from 0-48%. We estimate that the admixture occurred ~360-384 years ago. Little evidence of European or African admixture was found in Totonac individuals. Bolivians with pre-Columbian mtDNA and Y-chromosome haplogroups had 5-30% autosomal European ancestry, demonstrating the limitations of Y-chromosome and mtDNA haplogroups and the need for autosomal ancestry informative markers for assessing ancestry in admixed populations.

Imputation-Based Genomic Coverage Assessments of Current Human Genotyping Arrays

PubMed Central

Nelson, Sarah C.; Doheny, Kimberly F.; Pugh, Elizabeth W.; Romm, Jane M.; Ling, Hua; Laurie, Cecelia A.; Browning, Sharon R.; Weir, Bruce S.; Laurie, Cathy C.

2013-01-01

Microarray single-nucleotide polymorphism genotyping, combined with imputation of untyped variants, has been widely adopted as an efficient means to interrogate variation across the human genome. “Genomic coverage” is the total proportion of genomic variation captured by an array, either by direct observation or through an indirect means such as linkage disequilibrium or imputation. We have performed imputation-based genomic coverage assessments of eight current genotyping arrays that assay from ~0.3 to ~5 million variants. Coverage was determined separately in each of the four continental ancestry groups in the 1000 Genomes Project phase 1 release. We used the subset of 1000 Genomes variants present on each array to impute the remaining variants and assessed coverage based on correlation between imputed and observed allelic dosages. More than 75% of common variants (minor allele frequency > 0.05) are covered by all arrays in all groups except for African ancestry, and up to ~90% in all ancestries for the highest density arrays. In contrast, less than 40% of less common variants (0.01 < minor allele frequency < 0.05) are covered by low density arrays in all ancestries and 50–80% in high density arrays, depending on ancestry. We also calculated genome-wide power to detect variant-trait association in a case-control design, across varying sample sizes, effect sizes, and minor allele frequency ranges, and compare these array-based power estimates with a hypothetical array that would type all variants in 1000 Genomes. These imputation-based genomic coverage and power analyses are intended as a practical guide to researchers planning genetic studies. PMID:23979933

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile

PubMed Central

González Silos, Rosa; Marcelain, Katherine; Baez Benavides, Pablo; Barahona Ponce, Carol; Fischer, Christine; Peil, Barbara; Sinsheimer, Janet; Barajas, Olga; Gonzalez-Jose, Rolando; Cátira Bortolini, Maria; Canizales-Quinteros, Samuel; Gallo, Carla; Ruiz Linares, Andres; Rothhammer, Francisco

2017-01-01

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data. PMID:28542165

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile.

PubMed

Lorenzo Bermejo, Justo; Boekstegers, Felix; González Silos, Rosa; Marcelain, Katherine; Baez Benavides, Pablo; Barahona Ponce, Carol; Müller, Bettina; Ferreccio, Catterina; Koshiol, Jill; Fischer, Christine; Peil, Barbara; Sinsheimer, Janet; Fuentes Guajardo, Macarena; Barajas, Olga; Gonzalez-Jose, Rolando; Bedoya, Gabriel; Cátira Bortolini, Maria; Canizales-Quinteros, Samuel; Gallo, Carla; Ruiz Linares, Andres; Rothhammer, Francisco

2017-05-01

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.

The Geography of Recent Genetic Ancestry across Europe

PubMed Central

Ralph, Peter; Coop, Graham

2013-01-01

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (in the Population Reference Sample [POPRES] dataset) to conduct one of the first surveys of recent genealogical ancestry over the past 3,000 years at a continental scale. We detected 1.9 million shared long genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 2–12 genetic common ancestors from the last 1,500 years, and upwards of 100 genetic ancestors from the previous 1,000 years. These numbers drop off exponentially with geographic distance, but since these genetic ancestors are a tiny fraction of common genealogical ancestors, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1,000 years. There is also substantial regional variation in the number of shared genetic ancestors. For example, there are especially high numbers of common ancestors shared between many eastern populations that date roughly to the migration period (which includes the Slavic and Hunnic expansions into that region). Some of the lowest levels of common ancestry are seen in the Italian and Iberian peninsulas, which may indicate different effects of historical population expansions in these areas and/or more stably structured populations. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world. PMID:23667324

Repetitive transpositions of mitochondrial DNA sequences to the nucleus during the radiation of horseshoe bats (Rhinolophus, Chiroptera).

PubMed

Shi, Huizhen; Dong, Ji; Irwin, David M; Zhang, Shuyi; Mao, Xiuguang

2016-05-01

Transposition of mitochondrial DNA into the nucleus, which gives rise to nuclear mitochondrial DNAs (NUMTs), has been well documented in eukaryotes. However, very few studies have assessed the frequency of these transpositions during the evolutionary history of a specific taxonomic group. Here we used the horseshoe bats (Rhinolophus) as a case study to determine the frequency and relative timing of nuclear transfers of mitochondrial control region sequences. For this, phylogenetic and coalescent analyzes were performed on NUMTs and authentic mtDNA sequences generated from eight horseshoe bat species. Our results suggest at least three independent transpositions, including two ancient and one more recent, during the evolutionary history of Rhinolophus. The two ancient transpositions are represented by the NUMT-1 and -2 clades, with each clade consisting of NUMTs from almost all studied species but originating from different portions of the mtDNA genome. Furthermore, estimates of the most recent common ancestor for each clade corresponded to the time of the initial diversification of this genus. The recent transposition is represented by NUMT-3, which was discovered only in a specific subgroup of Rhinolophus and exhibited a close relationship to its mitochondrial counterpart. Our similarity searches of mtDNA in the R. ferrumequinum genome confirmed the presence of NUMT-1 and NUMT-2 clade sequences and, for the first time, assessed the extent of NUMTs in a bat genome. To our knowledge, this is the first study to report on the frequency of transpositions of mtDNA occurring before the common ancestry of a genus. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolutionary trends of European bat lyssavirus type 2 including genetic characterization of Finnish strains of human and bat origin 24 years apart.

PubMed

Jakava-Viljanen, Miia; Miia, Jakava-Viljanen; Nokireki, Tiina; Tiina, Nokireki; Sironen, Tarja; Tarja, Sironen; Vapalahti, Olli; Olli, Vapalahti; Sihvonen, Liisa; Liisa, Sihvonen; Huovilainen, Anita; Anita, Huovilainen

2015-06-01

Among other Lyssaviruses, Daubenton's and pond-bat-related European bat lyssavirus type 2 (EBLV-2) can cause human rabies. To investigate the diversity and evolutionary trends of EBLV-2, complete genome sequences of two Finnish isolates were analysed. One originated from a human case in 1985, and the other originated from a bat in 2009. The overall nucleotide and deduced amino acid sequence identity of the two Finnish isolates were high, as well as the similarity to fully sequenced EBLV-2 strains originating from the UK and the Netherlands. In phylogenetic analysis, the EBLV-2 strains formed a monophyletic group that was separate from other bat-type lyssaviruses, with significant support. EBLV-2 shared the most recent common ancestry with Bokeloh bat lyssavirus (BBLV) and Khujan virus (KHUV). EBLV-2 showed limited diversity compared to RABV and appears to be well adapted to its host bat species. The slow tempo of viral evolution was evident in the estimations of divergence times for EBLV-2: the current diversity was estimated to have built up during the last 2000 years, and EBLV-2 diverged from KHUV about 8000 years ago. In a phylogenetic tree of partial N gene sequences, the Finnish EBLV-2 strains clustered with strains from Central Europe, supporting the hypothesis that EBLV-2 circulating in Finland might have a Central European origin. The Finnish EBLV-2 strains and a Swiss strain were estimated to have diverged from other EBLV-2 strains during the last 1000 years, and the two Finnish strains appear to have evolved from a common ancestor during the last 200 years.

[Reasons for banishing the concept of race from Brazilian medicine].

PubMed

Pena, Sérgio D J

2005-01-01

As part of medicine's canonical framework, the concept of race has been associated with the idea that color and/or biological ancestry are relevant indicators of a predisposition to a certain disease or reaction to drugs. This stance derives from a typological view of human races. The low level of genetic variability and of structuring of the human species is incompatible with the existence of races as biological entities and tells us that color and/or geographical ancestry have little or nothing useful to contribute to medical practice, particularly when it comes to caring for an individual patient. We show that even so-called racial diseases like sickle cell anemia are really the product of evolutionary strategies used by populations exposed to specific infectious agents, whose territories have no unequivocal relation with either color or continental origin. Furthermore, in the words of sociologist Paul Gilroy, the social concept of race is "toxic," contaminating society as a whole, and it has been used to oppress and to foster injustice, even within a medical context.

Teaching the process of molecular phylogeny and systematics: a multi-part inquiry-based exercise.

PubMed

Lents, Nathan H; Cifuentes, Oscar E; Carpi, Anthony

2010-01-01

Three approaches to molecular phylogenetics are demonstrated to biology students as they explore molecular data from Homo sapiens and four related primates. By analyzing DNA sequences, protein sequences, and chromosomal maps, students are repeatedly challenged to develop hypotheses regarding the ancestry of the five species. Although these exercises were designed to supplement and enhance classroom instruction on phylogeny, cladistics, and systematics in the context of a postsecondary majors-level introductory biology course, the activities themselves require very little prior student exposure to these topics. Thus, they are well suited for students in a wide range of educational levels, including a biology class at the secondary level. In implementing this exercise, we have observed measurable gains, both in student comprehension of molecular phylogeny and in their acceptance of modern evolutionary theory. By engaging students in modern phylogenetic activities, these students better understood how biologists are currently using molecular data to develop a more complete picture of the shared ancestry of all living things.

Distinct Transcript Isoforms of the Atypical Chemokine Receptor 1 (ACKR1) / Duffy Antigen Receptor for Chemokines (DARC) Gene Are Expressed in Lymphoblasts and Altered Isoform Levels Are Associated with Genetic Ancestry and the Duffy-Null Allele

PubMed Central

Davis, Melissa B.; Walens, Andrea; Hire, Rupali; Mumin, Kauthar; Brown, Andrea M.; Ford, DeJuana; Howerth, Elizabeth W.; Monteil, Michele

2015-01-01

The Atypical ChemoKine Receptor 1 (ACKR1) gene, better known as Duffy Antigen Receptor for Chemokines (DARC or Duffy), is responsible for the Duffy Blood Group and plays a major role in regulating the circulating homeostatic levels of pro-inflammatory chemokines. Previous studies have shown that one common variant, the Duffy Null (Fy-) allele that is specific to African Ancestry groups, completely removes expression of the gene on erythrocytes; however, these individuals retain endothelial expression. Additional alleles are associated with a myriad of clinical outcomes related to immune responses and inflammation. In addition to allele variants, there are two distinct transcript isoforms of DARC which are expressed from separate promoters, and very little is known about the distinct transcriptional regulation or the distinct functionality of these protein isoforms. Our objective was to determine if the African specific Fy- allele alters the expression pattern of DARC isoforms and therefore could potentially result in a unique signature of the gene products, commonly referred to as antigens. Our work is the first to establish that there is expression of DARC on lymphoblasts. Our data indicates that people of African ancestry have distinct relative levels of DARC isoforms expressed in these cells. We conclude that the expression of both isoforms in combination with alternate alleles yields multiple Duffy antigens in ancestry groups, depending upon the haplotypes across the gene. Importantly, we hypothesize that DARC isoform expression patterns will translate into ancestry-specific inflammatory responses that are correlated with the axis of pro-inflammatory chemokine levels and distinct isoform-specific interactions with these chemokines. Ultimately, this work will increase knowledge of biological mechanisms underlying disparate clinical outcomes of inflammatory-related diseases among ethnic and geographic ancestry groups. PMID:26473357

Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

PubMed

Amendola, Laura M; Dorschner, Michael O; Robertson, Peggy D; Salama, Joseph S; Hart, Ragan; Shirts, Brian H; Murray, Mitzi L; Tokita, Mari J; Gallego, Carlos J; Kim, Daniel Seung; Bennett, James T; Crosslin, David R; Ranchalis, Jane; Jones, Kelly L; Rosenthal, Elisabeth A; Jarvik, Ella R; Itsara, Andy; Turner, Emily H; Herman, Daniel S; Schleit, Jennifer; Burt, Amber; Jamal, Seema M; Abrudan, Jenica L; Johnson, Andrew D; Conlin, Laura K; Dulik, Matthew C; Santani, Avni; Metterville, Danielle R; Kelly, Melissa; Foreman, Ann Katherine M; Lee, Kristy; Taylor, Kent D; Guo, Xiuqing; Crooks, Kristy; Kiedrowski, Lesli A; Raffel, Leslie J; Gordon, Ora; Machini, Kalotina; Desnick, Robert J; Biesecker, Leslie G; Lubitz, Steven A; Mulchandani, Surabhi; Cooper, Greg M; Joffe, Steven; Richards, C Sue; Yang, Yaoping; Rotter, Jerome I; Rich, Stephen S; O'Donnell, Christopher J; Berg, Jonathan S; Spinner, Nancy B; Evans, James P; Fullerton, Stephanie M; Leppig, Kathleen A; Bennett, Robin L; Bird, Thomas; Sybert, Virginia P; Grady, William M; Tabor, Holly K; Kim, Jerry H; Bamshad, Michael J; Wilfond, Benjamin; Motulsky, Arno G; Scott, C Ronald; Pritchard, Colin C; Walsh, Tom D; Burke, Wylie; Raskind, Wendy H; Byers, Peter; Hisama, Fuki M; Rehm, Heidi; Nickerson, Debbie A; Jarvik, Gail P

2015-03-01

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base. © 2015 Amendola et al.; Published by Cold Spring Harbor Laboratory Press.

Persistence of vigilance and flight response behaviour in wild reindeer with varying domestic ancestry.

PubMed

Reimers, E; Røed, K H; Colman, J E

2012-08-01

Knowledge about changes in behavioural traits related to wildness and tameness is for most mammals lacking, despite the increased trend of using domestic stock to re-establish wild populations into historical ranges. To test for persistence of behavioural traits of wild reindeer (Rangifer tarandus L.) exposed to hunting, we sampled DNA, vigilance and flight responses in wild reindeer herds with varying domestic ancestry. Analyses of 14 DNA microsatellite loci revealed a dichotomous main genetic structure reflecting their native origin, with the Rondane reindeer genetically different from the others and with least differentiation towards the Hardangervidda reindeer. The genetic clustering of the reindeer in Norefjell-Reinsjøfjell, Ottadalen and Forollhogna, together with domestic reindeer, supports a predominant domestic origin of these herds. Despite extensive hunting in all herds, the behavioural measures indicate increasing vigilance, alert and flight responses with increasing genetic dissimilarity with domestic herds. Vigilance frequency and time spent vigilant were higher in Rondane compared to Hardangervidda, which again were higher than herds with a domestic origin. We conclude that previous domestication has preserved a hard wired behavioural trait in some reindeer herds exhibiting less fright responses towards humans that extensive hunting has, but only slightly, altered. This brings novel and relevant knowledge to discussions about genetic diversity of wildlife in general and wild reindeer herds in Norway in specific. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Evolutionary History of the Enzymes Involved in the Calvin-Benson Cycle in Euglenids.

PubMed

Markunas, Chelsea M; Triemer, Richard E

2016-05-01

Euglenids are an ancient lineage that may have existed as early as 2 billion years ago. A mere 65 years ago, Melvin Calvin and Andrew A. Benson performed experiments on Euglena gracilis and elucidated the series of reactions by which carbon was fixed and reduced during photosynthesis. However, the evolutionary history of this pathway (Calvin-Benson cycle) in euglenids was more complex than Calvin and Benson could have imagined. The chloroplast present today in euglenophytes arose from a secondary endosymbiosis between a phagotrophic euglenid and a prasinophyte green alga. A long period of evolutionary time existed before this secondary endosymbiotic event took place, which allowed for other endosymbiotic events or gene transfers to occur prior to the establishment of the green chloroplast. This research revealed the evolutionary history of the major enzymes of the Calvin-Benson cycle throughout the euglenid lineage and showed that the majority of genes for Calvin-Benson cycle enzymes shared an ancestry with red algae and/or chromophytes suggesting they may have been transferred to the nucleus prior to the acquisition of the green chloroplast. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

Femoral subtrochanteric shape variation in Albania: implications for use in forensic applications.

PubMed

McIlvaine, B K; Schepartz, L A

2015-02-01

This paper investigates temporal trends in femoral subtrochanteric shape in Albanian skeletal material to evaluate levels of platymeria in a set of populations with European ancestry. Although flattening of the diaphysis in the subtrochanteric region has been associated with individuals of Native American and Asian ancestry, high levels of platymeria may not be unique to those groups. The forensic utility of Gilbert and Gill's (Skeletal Attribution of Race: Methods for Forensic Anthropology, University of New Mexico, Albuquerque, 1990) method for identifying ancestry from femoral subtrochanteric shape is examined using non-American skeletons of European ancestry. Femoral subtrochanteric anteroposterior and mediolateral diameters for Albanian skeletons from Apollonia (n=117) and Lofkënd (n=50) are assessed for temporal trends and then compared with published data using one-way ANOVA and post-hoc Tukey tests. High degrees of subtrochanteric flattening are identified in the Albanian samples and statistically significant temporal trends of decreasing platymeria are documented. Although recent publications suggest that subtrochanteric shape is less effective in identifying ancestry then was initially proposed, forensic anthropologists still commonly use femoral subtrochanteric shape to determine ancestry among skeletonized remains. This paper's findings support the assertion that proximal femoral morphology is functionally related, and more likely to be influenced by biomechanical adaptation and body proportions than genetic constraints. Copyright © 2014 Elsevier GmbH. All rights reserved.

Genomic and evolutionary comparisons of diazotrophic and pathogenic bacteria of the order Rhizobiales.

PubMed

Carvalho, Fabíola M; Souza, Rangel C; Barcellos, Fernando G; Hungria, Mariangela; Vasconcelos, Ana Tereza R

2010-02-08

Species belonging to the Rhizobiales are intriguing and extensively researched for including both bacteria with the ability to fix nitrogen when in symbiosis with leguminous plants and pathogenic bacteria to animals and plants. Similarities between the strategies adopted by pathogenic and symbiotic Rhizobiales have been described, as well as high variability related to events of horizontal gene transfer. Although it is well known that chromosomal rearrangements, mutations and horizontal gene transfer influence the dynamics of bacterial genomes, in Rhizobiales, the scenario that determine pathogenic or symbiotic lifestyle are not clear and there are very few studies of comparative genomic between these classes of prokaryotic microorganisms trying to delineate the evolutionary characterization of symbiosis and pathogenesis. Non-symbiotic nitrogen-fixing bacteria and bacteria involved in bioremediation closer to symbionts and pathogens in study may assist in the origin and ancestry genes and the gene flow occurring in Rhizobiales. The genomic comparisons of 19 species of Rhizobiales, including nitrogen-fixing, bioremediators and pathogens resulted in 33 common clusters to biological nitrogen fixation and pathogenesis, 15 clusters exclusive to all nitrogen-fixing bacteria and bacteria involved in bioremediation, 13 clusters found in only some nitrogen-fixing and bioremediation bacteria, 01 cluster exclusive to some symbionts, and 01 cluster found only in some pathogens analyzed. In BBH performed to all strains studied, 77 common genes were obtained, 17 of which were related to biological nitrogen fixation and pathogenesis. Phylogenetic reconstructions for Fix, Nif, Nod, Vir, and Trb showed possible horizontal gene transfer events, grouping species of different phenotypes. The presence of symbiotic and virulence genes in both pathogens and symbionts does not seem to be the only determinant factor for lifestyle evolution in these microorganisms, although they may act in common stages of host infection. The phylogenetic analysis for many distinct operons involved in these processes emphasizes the relevance of horizontal gene transfer events in the symbiotic and pathogenic similarity.

Race, genetics, and human reproductive strategies.

PubMed

Rushton, J P

1996-02-01

The international literature on racial differences is reviewed, novel data are reported, and a distinct pattern is found. People of east Asian ancestry and people of African ancestry average at opposite ends of a continuum, with people of European ancestry averaging intermediately, albeit with much variability within each major race. The racial matrix emerges from measures taken of reproductive behavior, sex hormones, twinning rate, speed of physical maturation, personality, family stability, brain size, intelligence, law abidingness, and social organization. An evolutionary theory of human reproduction is proposed, familiar to biologists as the r-K scale of reproductive strategies. At one end of this scale are r-strategies, which emphasize high reproductive rates; at the other end are K-strategies, which emphasize high levels of parental investment. This scale is generally used to compare the life histories of widely disparate species, but here it is used to describe the immensely smaller variations among human races. It is hypothesized that, again on average, Mongoloid people are more K-selected than Caucasoids, who are more K-selected than Negroids. The r-K scale of reproductive strategies is also mapped on to human evolution. Genetic distances indicate that Africans emerged from the ancestral hominid line about 200,000 years ago, with an African/non-African split about 110,000 years ago, and a Caucasoid/Mongoloid split about 41,000 years ago. Such an ordering fits with and explains how and why the variables cluster.

Genetic analysis of ancestry, admixture and selection in Bolivian and Totonac populations of the New World

PubMed Central

2012-01-01

Background Populations of the Americas were founded by early migrants from Asia, and some have experienced recent genetic admixture. To better characterize the native and non-native ancestry components in populations from the Americas, we analyzed 815,377 autosomal SNPs, mitochondrial hypervariable segments I and II, and 36 Y-chromosome STRs from 24 Mesoamerican Totonacs and 23 South American Bolivians. Results and Conclusions We analyzed common genomic regions from native Bolivian and Totonac populations to identify 324 highly predictive Native American ancestry informative markers (AIMs). As few as 40–50 of these AIMs perform nearly as well as large panels of random genome-wide SNPs for predicting and estimating Native American ancestry and admixture levels. These AIMs have greater New World vs. Old World specificity than previous AIMs sets. We identify highly-divergent New World SNPs that coincide with high-frequency haplotypes found at similar frequencies in all populations examined, including the HGDP Pima, Maya, Colombian, Karitiana, and Surui American populations. Some of these regions are potential candidates for positive selection. European admixture in the Bolivian sample is approximately 12%, though individual estimates range from 0–48%. We estimate that the admixture occurred ~360–384 years ago. Little evidence of European or African admixture was found in Totonac individuals. Bolivians with pre-Columbian mtDNA and Y-chromosome haplogroups had 5–30% autosomal European ancestry, demonstrating the limitations of Y-chromosome and mtDNA haplogroups and the need for autosomal ancestry informative markers for assessing ancestry in admixed populations. PMID:22606979

Straightforward Inference of Ancestry and Admixture Proportions through Ancestry-Informative Insertion Deletion Multiplexing

PubMed Central

Pereira, Rui; Phillips, Christopher; Pinto, Nádia; Santos, Carla; dos Santos, Sidney Emanuel Batista; Amorim, António; Carracedo, Ángel; Gusmão, Leonor

2012-01-01

Ancestry-informative markers (AIMs) show high allele frequency divergence between different ancestral or geographically distant populations. These genetic markers are especially useful in inferring the likely ancestral origin of an individual or estimating the apportionment of ancestry components in admixed individuals or populations. The study of AIMs is of great interest in clinical genetics research, particularly to detect and correct for population substructure effects in case-control association studies, but also in population and forensic genetics studies. This work presents a set of 46 ancestry-informative insertion deletion polymorphisms selected to efficiently measure population admixture proportions of four different origins (African, European, East Asian and Native American). All markers are analyzed in short fragments (under 230 basepairs) through a single PCR followed by capillary electrophoresis (CE) allowing a very simple one tube PCR-to-CE approach. HGDP-CEPH diversity panel samples from the four groups, together with Oceanians, were genotyped to evaluate the efficiency of the assay in clustering populations from different continental origins and to establish reference databases. In addition, other populations from diverse geographic origins were tested using the HGDP-CEPH samples as reference data. The results revealed that the AIM-INDEL set developed is highly efficient at inferring the ancestry of individuals and provides good estimates of ancestry proportions at the population level. In conclusion, we have optimized the multiplexed genotyping of 46 AIM-INDELs in a simple and informative assay, enabling a more straightforward alternative to the commonly available AIM-SNP typing methods dependent on complex, multi-step protocols or implementation of large-scale genotyping technologies. PMID:22272242

Genomic analyses of dominant U.S. clonal lineages of Phytophthora infestans reveals a shared common ancestry for clonal lineages US11 and US18 and a lack of recently shared ancestry among all other U.S. lineages

USDA-ARS?s Scientific Manuscript database

The populations of the potato and tomato late blight pathogen, Phytophthora infestans, in the US are well known for emerging repeatedly as novel clonal lineages. These successions of dominant clones have historically been named US1-US24, in order of appearance, since their first characterization usi...

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots

PubMed Central

Fernández-Domínguez, Eva; Bertoncini, Stefania; Chimonas, Marios; Christofi, Vasilis; King, Jonathan; Budowle, Bruce; Manoli, Panayiotis

2017-01-01

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7–8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry. PMID:28622394

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots.

PubMed

Heraclides, Alexandros; Bashiardes, Evy; Fernández-Domínguez, Eva; Bertoncini, Stefania; Chimonas, Marios; Christofi, Vasilis; King, Jonathan; Budowle, Bruce; Manoli, Panayiotis; Cariolou, Marios A

2017-01-01

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7-8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

PubMed

Ng, Maggie C Y; Graff, Mariaelisa; Lu, Yingchang; Justice, Anne E; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Yanek, Lisa R; Feitosa, Mary F; Wojczynski, Mary K; Rand, Kristin; Brody, Jennifer A; Cade, Brian E; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A; Nalls, Michael A; Okut, Hayrettin; Tajuddin, Salman M; Tayo, Bamidele O; Vedantam, Sailaja; Bradfield, Jonathan P; Chen, Guanjie; Chen, Wei-Min; Chesi, Alessandra; Irvin, Marguerite R; Padhukasahasram, Badri; Smith, Jennifer A; Zheng, Wei; Allison, Matthew A; Ambrosone, Christine B; Bandera, Elisa V; Bartz, Traci M; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bottinger, Erwin P; Carpten, John; Chanock, Stephen J; Chen, Yii-Der Ida; Conti, David V; Cooper, Richard S; Fornage, Myriam; Freedman, Barry I; Garcia, Melissa; Goodman, Phyllis J; Hsu, Yu-Han H; Hu, Jennifer; Huff, Chad D; Ingles, Sue A; John, Esther M; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Ogunniyi, Adesola; Olshan, Andrew; Press, Michael F; Rohde, Rebecca; Rybicki, Benjamin A; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S; Stanford, Janet L; Stevens, Victoria L; Stram, Alex; Strom, Sara S; Vaidya, Dhananjay; Witte, John S; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G; Zonderman, Alan B; Adeyemo, Adebowale; Ambs, Stefan; Cushman, Mary; Faul, Jessica D; Hakonarson, Hakon; Levin, Albert M; Nathanson, Katherine L; Ware, Erin B; Weir, David R; Zhao, Wei; Zhi, Degui; Arnett, Donna K; Grant, Struan F A; Kardia, Sharon L R; Oloapde, Olufunmilayo I; Rao, D C; Rotimi, Charles N; Sale, Michele M; Williams, L Keoki; Zemel, Babette S; Becker, Diane M; Borecki, Ingrid B; Evans, Michele K; Harris, Tamara B; Hirschhorn, Joel N; Li, Yun; Patel, Sanjay R; Psaty, Bruce M; Rotter, Jerome I; Wilson, James G; Bowden, Donald W; Cupples, L Adrienne; Haiman, Christopher A; Loos, Ruth J F; North, Kari E

2017-04-01

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

Late acquisition of mitochondria by a host with chimeric prokaryotic ancestry

PubMed Central

Pittis, Alexandros A.; Gabaldón, Toni

2016-01-01

The origin of eukaryotes stands as a major conundrum in biology1. Current evidence indicates that the Last Eukaryotic Common Ancestor (LECA) already possessed many eukaryotic hallmarks, including a complex subcellular organization1–3. In addition, the lack of evolutionary intermediates challenges the elucidation of the relative order of emergence of eukaryotic traits. Mitochondria are ubiquitous organelles derived from an alpha-proteobacterial endosymbiont4. Different hypotheses disagree on whether mitochondria were acquired early or late during eukaryogenesis5. Similarly, the nature and complexity of the receiving host are debated, with models ranging from a simple prokaryotic host to an already complex proto-eukaryote1,3,6,7. Most competing scenarios can be roughly grouped into either mito-early, which consider the driving force of eukaryogenesis to be mitochondrial endosymbiosis into a simple host, or mito-late, which postulate that a significant complexity predated mitochondrial endosymbiosis3. Here we provide evidence for late mitochondrial endosymbiosis. We used phylogenomics to directly test whether proto-mitochondrial proteins were acquired earlier or later than other LECA proteins. We found that LECA protein families of alpha-proteobacterial ancestry and of mitochondrial localization show the shortest phylogenetic distances to their closest prokaryotic relatives, when compared to proteins of different prokaryotic origin or cellular localization. Altogether, our results shed new light on a long-standing question and provide compelling support for the late acquisition of mitochondria into a host that already had a proteome of chimeric phylogenetic origin. We argue that mitochondrial endosymbiosis was one of the ultimate steps in eukaryogenesis and that it provided the definitive selective advantage to mitochondria-bearing eukaryotes over less complex forms. PMID:26840490

Right hand, left brain: genetic and evolutionary bases of cerebral asymmetries for language and manual action.

PubMed

Corballis, Michael C; Badzakova-Trajkov, Gjurgjica; Häberling, Isabelle S

2012-01-01

Most people are right-handed and left-cerebrally dominant for language. This pattern of asymmetry, as well as departures from it, have been reasonably accommodated in terms of a postulated gene with two alleles, one disposing to this common pattern and the other leaving the direction of handedness and language asymmetry to chance. There are some leads as to the location of the gene or genes concerned, but no clear resolution; one possibility is that the chance factor is achieved by epigenetic cancelling of the lateralizing gene rather than through a chance allele. Neurological evidence suggests that the neural basis of manual praxis, including pantomime and tool use, is more closely associated with cerebral asymmetry for language than with handedness, and is homologous with the so-called "mirror system" in the primate brain, which is specialized for manual grasping. The evidence reviewed supports the theory that language itself evolved within the praxic system, and became lateralized in humans, and perhaps to a lesser extent in our common ancestry with the great apes. WIREs Cogn Sci 2012, 3:1-17. doi: 10.1002/wcs.158 For further resources related to this article, please visit the WIREs website. Copyright © 2011 John Wiley & Sons, Ltd.

Evolutionary Relationships among Actinophages and a Putative Adaptation for Growth in Streptomyces spp.

PubMed Central

Hendrix, Roger W.; Dedrick, Rebekah; Mitchell, Kaitlin; Ko, Ching-Chung; Russell, Daniel; Bell, Emma; Gregory, Matthew; Bibb, Maureen J.; Pethick, Florence; Jacobs-Sera, Deborah; Herron, Paul; Buttner, Mark J.; Hatfull, Graham F.

2013-01-01

The genome sequences of eight Streptomyces phages are presented, four of which were isolated for this study. Phages R4, TG1, ϕHau3, and SV1 were isolated previously and have been exploited as tools for understanding and genetically manipulating Streptomyces spp. We also extracted five apparently intact prophages from recent Streptomyces spp. genome projects and, together with six phage genomes in the database, we analyzed all 19 Streptomyces phage genomes with a view to understanding their relationships to each other and to other actinophages, particularly the mycobacteriophages. Fifteen of the Streptomyces phages group into four clusters of related genomes. Although the R4-like phages do not share nucleotide sequence similarity with other phages, they clearly have common ancestry with cluster A mycobacteriophages, sharing many protein homologues, common gene syntenies, and similar repressor-stoperator regulatory systems. The R4-like phage ϕHau3 and the prophage StrepC.1 (from Streptomyces sp. strain C) appear to have hijacked a unique adaptation of the streptomycetes, i.e., use of the rare UUA codon, to control translation of the essential phage protein, the terminase. The Streptomyces venezuelae generalized transducing phage SV1 was used to predict the presence of other generalized transducing phages for different Streptomyces species. PMID:23995638

Race, common genetic variation, and therapeutic response disparities in heart failure.

PubMed

Taylor, Mathew R; Sun, Albert Y; Davis, Gordon; Fiuzat, Mona; Liggett, Stephen B; Bristow, Michael R

2014-12-01

Because of its comparatively recent evolution, Homo sapiens exhibit relatively little within-species genomic diversity. However, because of genome size, a proportionately small amount of variation creates ample opportunities for both rare mutations that may cause disease as well as more common genetic variations that may be important in disease modification or pharmacogenetics. Primarily because of the East African origin of modern humans, individuals of African ancestry (AA) exhibit greater degrees of genetic diversity than more recently established populations, such as those of European ancestry (EA) or Asian ancestry. Those population effects extend to differences in frequency of common gene variants that may be important in heart failure natural history or therapy. For cell-signaling mechanisms important in heart failure, we review and present new data for genetic variation between AA and EA populations. Data indicate that: 1) neurohormonal signaling mechanisms frequently (16 of the 19 investigated polymorphisms) exhibit racial differences in the allele frequencies of variants comprising key constituents; 2) some of these differences in allele frequency may differentially affect the natural history of heart failure in AA compared with EA individuals; and 3) in many cases, these differences likely play a role in observed racial differences in drug or device response. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

BLAST and FASTA similarity searching for multiple sequence alignment.

PubMed

Pearson, William R

2014-01-01

BLAST, FASTA, and other similarity searching programs seek to identify homologous proteins and DNA sequences based on excess sequence similarity. If two sequences share much more similarity than expected by chance, the simplest explanation for the excess similarity is common ancestry-homology. The most effective similarity searches compare protein sequences, rather than DNA sequences, for sequences that encode proteins, and use expectation values, rather than percent identity, to infer homology. The BLAST and FASTA packages of sequence comparison programs provide programs for comparing protein and DNA sequences to protein databases (the most sensitive searches). Protein and translated-DNA comparisons to protein databases routinely allow evolutionary look back times from 1 to 2 billion years; DNA:DNA searches are 5-10-fold less sensitive. BLAST and FASTA can be run on popular web sites, but can also be downloaded and installed on local computers. With local installation, target databases can be customized for the sequence data being characterized. With today's very large protein databases, search sensitivity can also be improved by searching smaller comprehensive databases, for example, a complete protein set from an evolutionarily neighboring model organism. By default, BLAST and FASTA use scoring strategies target for distant evolutionary relationships; for comparisons involving short domains or queries, or searches that seek relatively close homologs (e.g. mouse-human), shallower scoring matrices will be more effective. Both BLAST and FASTA provide very accurate statistical estimates, which can be used to reliably identify protein sequences that diverged more than 2 billion years ago.

Molecular phylogeny of a genetically divergent hantavirus harbored by the Geoffroy's rousette (Rousettus amplexicaudatus), a frugivorous bat species in the Philippines.

PubMed

Arai, Satoru; Taniguchi, Satoshi; Aoki, Keita; Yoshikawa, Yasuhiro; Kyuwa, Shigeru; Tanaka-Taya, Keiko; Masangkay, Joseph S; Omatsu, Tsutomu; Puentespina, Roberto; Watanabe, Shumpei; Alviola, Phillip; Alvarez, James; Eres, Eduardo; Cosico, Edison; Quibod, Ma Niña Regina M; Morikawa, Shigeru; Yanagihara, Richard; Oishi, Kazunori

2016-11-01

The recent discovery of genetically distinct hantaviruses in multiple species of shrews and moles (order Eulipotyphla, families Soricidae and Talpidae) prompted a further exploration of their host diversification and geographic distribution by analyzing lung tissues from 376 fruit bats representing six genera (order Chiroptera, suborder Yinpterochiroptera, family Pteropodidae), collected in the Republic of the Philippines during 2008 to 2013. Hantavirus RNA was detected by RT-PCR in one of 15 Geoffroy's rousettes (Rousettus amplexicaudatus), captured in Quezon Memorial National Park on Luzon Island in 2009. Phylogenetic analyses of the S, M and L segments, using maximum-likelihood and Bayesian methods, showed that the newfound hantavirus, designated Quezon virus (QZNV), shared a common ancestry with hantaviruses hosted by insectivorous bats, in keeping with their evolutionary relationships and suggests that ancestral bats may have served as the early or original mammalian hosts of primordial hantaviruses. As the first hantavirus detected in a megabat or flying fox species, QZNV extends our knowledge about the reservoir host range. Copyright © 2016 Elsevier B.V. All rights reserved.

Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for nociception

PubMed Central

Arenas, Oscar M.; Zaharieva, Emanuela E.; Para, Alessia; Vásquez-Doorman, Constanza; Petersen, Christian P.; Gallio, Marco

2017-01-01

All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here, we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea, and that the conserved ion channel TRPA1 is required for these responses. TRPA1 mutant flies (Drosophila) are also defective in noxious heat responses. Unexpectedly, we find that either planarian or human TRPA1 can restore noxious heat avoidance to TRPA1 mutant Drosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/Reactive Oxygen Species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago. PMID:29184198

Shared Ancestry between a Newfound Mole-Borne Hantavirus and Hantaviruses Harbored by Cricetid Rodents ▿†

PubMed Central

Kang, Hae Ji; Bennett, Shannon N.; Hope, Andrew G.; Cook, Joseph A.; Yanagihara, Richard

2011-01-01

Discovery of genetically distinct hantaviruses in multiple species of shrews (order Soricomorpha, family Soricidae) and moles (family Talpidae) contests the conventional view that rodents (order Rodentia, families Muridae and Cricetidae) are the principal reservoir hosts and suggests that the evolutionary history of hantaviruses is far more complex than previously hypothesized. We now report on Rockport virus (RKPV), a hantavirus identified in archival tissues of the eastern mole (Scalopus aquaticus) collected in Rockport, TX, in 1986. Pairwise comparison of the full-length S, M, and L genomic segments indicated moderately low sequence similarity between RKPV and other soricomorph-borne hantaviruses. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that RKPV shared a most recent common ancestor with cricetid-rodent-borne hantaviruses. Distributed widely across the eastern United States, the fossorial eastern mole is sympatric and syntopic with cricetid rodents known to harbor hantaviruses, raising the possibility of host-switching events in the distant past. Our findings warrant more-detailed investigations on the dynamics of spillover and cross-species transmission of present-day hantaviruses within communities of rodents and moles. PMID:21632770

Hepatitis B virus infection in Latin America: A genomic medicine approach

PubMed Central

Roman, Sonia; Jose-Abrego, Alexis; Fierro, Nora Alma; Escobedo-Melendez, Griselda; Ojeda-Granados, Claudia; Martinez-Lopez, Erika; Panduro, Arturo

2014-01-01

Hepatitis B virus (HBV) infection is the leading cause of severe chronic liver disease. This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America. Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection. Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America; these strains have historically circulated among the indigenous population. Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans. In contrast, genotypes F, A and D are common in acute and chronic infections among mestizos with Caucasian ancestry. Hepatocellular carcinoma is rare in Mexicans, but it has been associated with genotype F1b among Argentineans. This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America, which contrast with those reported in other regions of the world. PMID:24966588

Global divergence of the human follicle mite Demodex folliculorum: Persistent associations between host ancestry and mite lineages

PubMed Central

Palopoli, Michael F.; Fergus, Daniel J.; Minot, Samuel; Pei, Dorothy T.; Simison, W. Brian; Fernandez-Silva, Iria; Thoemmes, Megan S.; Dunn, Robert R.; Trautwein, Michelle

2015-01-01

Microscopic mites of the genus Demodex live within the hair follicles of mammals and are ubiquitous symbionts of humans, but little molecular work has been done to understand their genetic diversity or transmission. Here we sampled mite DNA from 70 human hosts of diverse geographic ancestries and analyzed 241 sequences from the mitochondrial genome of the species Demodex folliculorum. Phylogenetic analyses recovered multiple deep lineages including a globally distributed lineage common among hosts of European ancestry and three lineages that primarily include hosts of Asian, African, and Latin American ancestry. To a great extent, the ancestral geography of hosts predicted the lineages of mites found on them; 27% of the total molecular variance segregated according to the regional ancestries of hosts. We found that D. folliculorum populations are stable on an individual over the course of years and that some Asian and African American hosts maintain specific mite lineages over the course of years or generations outside their geographic region of birth or ancestry. D. folliculorum haplotypes were much more likely to be shared within families and between spouses than between unrelated individuals, indicating that transmission requires close contact. Dating analyses indicated that D. folliculorum origins may predate modern humans. Overall, D. folliculorum evolution reflects ancient human population divergences, is consistent with an out-of-Africa dispersal hypothesis, and presents an excellent model system for further understanding the history of human movement. PMID:26668374

Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers

PubMed Central

Huo, Dezheng

2013-01-01

Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11–1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09–1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08–1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1–q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16–1.27; P = 9.7 × 10–16). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora. PMID:23475944

Population Stratification in the Context of Diverse Epidemiologic Surveys Sans Genome-Wide Data

PubMed Central

Oetjens, Matthew T.; Brown-Gentry, Kristin; Goodloe, Robert; Dilks, Holli H.; Crawford, Dana C.

2016-01-01

Population stratification or confounding by genetic ancestry is a potential cause of false associations in genetic association studies. Estimation of and adjustment for genetic ancestry has become common practice thanks in part to the availability of ancestry informative markers on genome-wide association study (GWAS) arrays. While array data is now widespread, these data are not ubiquitous as several large epidemiologic and clinic-based studies lack genome-wide data. One such large epidemiologic-based study lacking genome-wide data accessible to investigators is the National Health and Nutrition Examination Surveys (NHANES), population-based cross-sectional surveys of Americans linked to demographic, health, and lifestyle data conducted by the Centers for Disease Control and Prevention. DNA samples (n = 14,998) were extracted from biospecimens from consented NHANES participants between 1991–1994 (NHANES III, phase 2) and 1999–2002 and represent three major self-identified racial/ethnic groups: non-Hispanic whites (n = 6,634), non-Hispanic blacks (n = 3,458), and Mexican Americans (n = 3,950). We as the Epidemiologic Architecture for Genes Linked to Environment study genotyped candidate gene and GWAS-identified index variants in NHANES as part of the larger Population Architecture using Genomics and Epidemiology I study for collaborative genetic association studies. To enable basic quality control such as estimation of genetic ancestry to control for population stratification in NHANES san genome-wide data, we outline here strategies that use limited genetic data to identify the markers optimal for characterizing genetic ancestry. From among 411 and 295 autosomal SNPs available in NHANES III and NHANES 1999–2002, we demonstrate that markers with ancestry information can be identified to estimate global ancestry. Despite limited resolution, global genetic ancestry is highly correlated with self-identified race for the majority of participants, although less so for ethnicity. Overall, the strategies outlined here for a large epidemiologic study can be applied to other datasets accessible for genotype–phenotype studies but are sans genome-wide data. PMID:27200085

Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Brazilian population with high African ancestry.

PubMed

do Rego Borges, Andrea; Sá, Jamile; Hoshi, Ryuichi; Viena, Camila Sane; Mariano, Lorena C; de Castro Veiga, Patricia; Medrado, Alena Peixoto; Machado, Renato Assis; de Aquino, Sibele Nascimento; Messetti, Ana Camila; Spritz, Richard A; Coletta, Ricardo D; Reis, Silvia R A

2015-10-01

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is the most common orofacial birth defect, exhibiting variable prevalence around the world, often attributed to ethnic and environmental differences. Linkage analyses and genome-wide association studies have identified several genomic susceptibility regions for NSCL ± P, mostly in European-derived or Asian populations. Genetic predisposition to NSCL ± P is ethnicity-dependent, and the genetic basis of susceptibility to NSCL ± P likely varies among populations. The population of Brazil is highly admixed, with highly variable ancestry; thus, the genetic determinants of NSCL ± P susceptibility may be quite different. This study tested association of 8 single-nucleotide polymorphisms (SNPs), previously identified by genome-wide studies in other populations, with NSCL ± P in a Brazilian population with high African ancestry. SNPs rs560426, rs642961, rs1530300, rs987525, rs3758249, rs7078160, rs17085106, and rs13041247 were genotyped in 293 Brazilian patients with NSCL ± P and 352 unaffected Brazilian controls. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphic markers to characterize genetic ancestry. The average African ancestry background was 31.1% for the NSCL ± P group and 36.7% for the control group. After adjustment for ancestry and multiple testing, the minor alleles of rs3758249 (OR: 1.58, 95% CI: 1.25-2.01, P = 0.0001) and rs7078160 (OR: 1.59, 95% CI: 1.21-2.07, P = 0.0002) were significantly associated with risk of NSCL ± P. Polymorphisms located in IRF6 (rs642961) and 8q24 (rs1530300 and rs987525) showed marginal associations in this Brazilian population with high African ancestry. These results indicate that rs3758249 at 9q22 and rs7078160 at 10q25.3 represent risk loci for NSCL ± P in the Brazilian population with high African ancestry. © 2015 Wiley Periodicals, Inc.

Race, Ancestry, and Development of Food-Allergen Sensitization in Early Childhood

PubMed Central

Tsai, Hui-Ju; Hong, Xiumei; Liu, Xin; Wang, Guoying; Pearson, Colleen; Ortiz, Katherin; Fu, Melanie; Pongracic, Jacqueline A.; Bauchner, Howard; Wang, Xiaobin

2011-01-01

OBJECTIVE: We examined whether the risk of food-allergen sensitization varied according to self-identified race or genetic ancestry. METHODS: We studied 1104 children (mean age: 2.7 years) from an urban multiethnic birth cohort. Food sensitization was defined as specific immunoglobulin E (sIgE) levels of ≥0.35 kilo–units of allergen (kUA)/L for any of 8 common food allergens. Multivariate logistic regression analyses were used to evaluate the associations of self-identified race and genetic ancestry with food sensitization. Analyses also examined associations with numbers of food sensitizations (0, 1 or 2, and ≥3 foods) and with logarithmically transformed allergen sIgE levels. RESULTS: In this predominantly minority cohort (60.9% black and 22.5% Hispanic), 35.5% of subjects exhibited food sensitizations. In multivariate models, both self-reported black race (odds ratio [OR]: 2.34 [95% confidence interval [CI]: 1.24–4.44]) and African ancestry (in 10% increments; OR: 1.07 [95% CI: 1.02–1.14]) were associated with food sensitization. Self-reported black race (OR: 3.76 [95% CI: 1.09–12.97]) and African ancestry (OR: 1.19 [95% CI: 1.07–1.32]) were associated with a high number (≥3) of food sensitizations. African ancestry was associated with increased odds of peanut sIgE levels of ≥5 kUA/L (OR: 1.25 [95% CI: 1.01–1.52]). Similar ancestry associations were seen for egg sIgE levels of ≥2 kUA/L (OR: 1.13 [95% CI: 1.01–1.27]) and milk sIgE levels of ≥5 kUA/L (OR: 1.24 [95% CI: 0.94–1.63]), although findings were not significant for milk. CONCLUSIONS: Black children were more likely to be sensitized to food allergens and were sensitized to more foods. African ancestry was associated with peanut sensitization. PMID:21890831

Heterogeneity in Genetic Admixture across Different Regions of Argentina

PubMed Central

Avena, Sergio; Via, Marc; Ziv, Elad; Pérez-Stable, Eliseo J.; Gignoux, Christopher R.; Dejean, Cristina; Huntsman, Scott; Torres-Mejía, Gabriela; Dutil, Julie; Matta, Jaime L.; Beckman, Kenneth; Burchard, Esteban González; Parolin, María Laura; Goicoechea, Alicia; Acreche, Noemí; Boquet, Mariel; Ríos Part, María Del Carmen; Fernández, Vanesa; Rey, Jorge; Stern, Mariana C.; Carnese, Raúl F.; Fejerman, Laura

2012-01-01

The population of Argentina is the result of the intermixing between several groups, including Indigenous American, European and African populations. Despite the commonly held idea that the population of Argentina is of mostly European origin, multiple studies have shown that this process of admixture had an impact in the entire Argentine population. In the present study we characterized the distribution of Indigenous American, European and African ancestry among individuals from different regions of Argentina and evaluated the level of discrepancy between self-reported grandparental origin and genetic ancestry estimates. A set of 99 autosomal ancestry informative markers (AIMs) was genotyped in a sample of 441 Argentine individuals to estimate genetic ancestry. We used non-parametric tests to evaluate statistical significance. The average ancestry for the Argentine sample overall was 65% European (95%CI: 63–68%), 31% Indigenous American (28–33%) and 4% African (3–4%). We observed statistically significant differences in European ancestry across Argentine regions [Buenos Aires province (BA) 76%, 95%CI: 73–79%; Northeast (NEA) 54%, 95%CI: 49–58%; Northwest (NWA) 33%, 95%CI: 21–41%; South 54%, 95%CI: 49–59%; p<0.0001] as well as between the capital and immediate suburbs of Buenos Aires city compared to more distant suburbs [80% (95%CI: 75–86%) versus 68% (95%CI: 58–77%), p = 0.01]. European ancestry among individuals that declared all grandparents born in Europe was 91% (95%CI: 88–94%) compared to 54% (95%CI: 51–57%) among those with no European grandparents (p<0.001). Our results demonstrate the range of variation in genetic ancestry among Argentine individuals from different regions in the country, highlighting the importance of taking this variation into account in genetic association and admixture mapping studies in this population. PMID:22506044

Unravelling the distinct strains of Tharu ancestry.

PubMed

Chaubey, Gyaneshwer; Singh, Manvendra; Crivellaro, Federica; Tamang, Rakesh; Nandan, Amrita; Singh, Kamayani; Sharma, Varun Kumar; Pathak, Ajai Kumar; Shah, Anish M; Sharma, Vishwas; Singh, Vipin Kumar; Selvi Rani, Deepa; Rai, Niraj; Kushniarevich, Alena; Ilumäe, Anne-Mai; Karmin, Monika; Phillip, Anand; Verma, Abhilasha; Prank, Erik; Singh, Vijay Kumar; Li, Blaise; Govindaraj, Periyasamy; Chaubey, Akhilesh Kumar; Dubey, Pavan Kumar; Reddy, Alla G; Premkumar, Kumpati; Vishnupriya, Satti; Pande, Veena; Parik, Jüri; Rootsi, Siiri; Endicott, Phillip; Metspalu, Mait; Lahr, Marta Mirazon; van Driem, George; Villems, Richard; Kivisild, Toomas; Singh, Lalji; Thangaraj, Kumarasamy

2014-12-01

The northern region of the Indian subcontinent is a vast landscape interlaced by diverse ecologies, for example, the Gangetic Plain and the Himalayas. A great number of ethnic groups are found there, displaying a multitude of languages and cultures. The Tharu is one of the largest and most linguistically diverse of such groups, scattered across the Tarai region of Nepal and bordering Indian states. Their origins are uncertain. Hypotheses have been advanced postulating shared ancestry with Austroasiatic, or Tibeto-Burman-speaking populations as well as aboriginal roots in the Tarai. Several Tharu groups speak a variety of Indo-Aryan languages, but have traditionally been described by ethnographers as representing East Asian phenotype. Their ancestry and intra-population diversity has previously been tested only for haploid (mitochondrial DNA and Y-chromosome) markers in a small portion of the population. This study presents the first systematic genetic survey of the Tharu from both Nepal and two Indian states of Uttarakhand and Uttar Pradesh, using genome-wide SNPs and haploid markers. We show that the Tharu have dual genetic ancestry as up to one-half of their gene pool is of East Asian origin. Within the South Asian proportion of the Tharu genetic ancestry, we see vestiges of their common origin in the north of the South Asian Subcontinent manifested by mitochondrial DNA haplogroup M43.

Genome-wide SNP data suggest complex ancestry of sympatric North Pacific killer whale ecotypes.

PubMed

Foote, A D; Morin, P A

2016-11-01

Three ecotypes of killer whale occur in partial sympatry in the North Pacific. Individuals assortatively mate within the same ecotype, resulting in correlated ecological and genetic differentiation. A key question is whether this pattern of evolutionary divergence is an example of incipient sympatric speciation from a single panmictic ancestral population, or whether sympatry could have resulted from multiple colonisations of the North Pacific and secondary contact between ecotypes. Here, we infer multilocus coalescent trees from >1000 nuclear single-nucleotide polymorphisms (SNPs) and find evidence of incomplete lineage sorting so that the genealogies of SNPs do not all conform to a single topology. To disentangle whether uncertainty in the phylogenetic inference of the relationships among ecotypes could also result from ancestral admixture events we reconstructed the relationship among the ecotypes as an admixture graph and estimated f 4 -statistics using TreeMix. The results were consistent with episodes of admixture between two of the North Pacific ecotypes and the two outgroups (populations from the Southern Ocean and the North Atlantic). Gene flow may have occurred via unsampled 'ghost' populations rather than directly between the populations sampled here. Our results indicate that because of ancestral admixture events and incomplete lineage sorting, a single bifurcating tree does not fully describe the relationship among these populations. The data are therefore most consistent with the genomic variation among North Pacific killer whale ecotypes resulting from multiple colonisation events, and secondary contact may have facilitated evolutionary divergence. Thus, the present-day populations of North Pacific killer whale ecotypes have a complex ancestry, confounding the tree-based inference of ancestral geography.

Lowering sample size in comparative analyses can indicate a correlation where there is none: example from Rensch's rule in primates.

PubMed

Lindenfors, P; Tullberg, B S

2006-07-01

The fact that characters may co-vary in organism groups because of shared ancestry and not always because of functional correlations was the initial rationale for developing phylogenetic comparative methods. Here we point out a case where similarity due to shared ancestry can produce an undesired effect when conducting an independent contrasts analysis. Under special circumstances, using a low sample size will produce results indicating an evolutionary correlation between characters where an analysis of the same pattern utilizing a larger sample size will show that this correlation does not exist. This is the opposite effect of increased sample size to that expected; normally an increased sample size increases the chance of finding a correlation. The situation where the problem occurs is when co-variation between the two continuous characters analysed is clumped in clades; e.g. when some phylogenetically conservative factors affect both characters simultaneously. In such a case, the correlation between the two characters becomes contingent on the number of clades sharing this conservative factor that are included in the analysis, in relation to the number of species contained within these clades. Removing species scattered evenly over the phylogeny will in this case remove the exact variation that diffuses the evolutionary correlation between the two characters - the variation contained within the clades sharing the conservative factor. We exemplify this problem by discussing a parallel in nature where the described problem may be of importance. This concerns the question of the presence or absence of Rensch's rule in primates.

Victorian spectacle: Julia Pastrana, the bearded and hairy female.

PubMed

Browne, Janet; Messenger, Sharon

2003-12-01

Julia Pastrana toured Europe in the late 1850s advertising herself as the 'Bearded and hairy Lady' or 'Nonedescript'. She suffered from a rare inherited disorder, not understood until the late 20th century, which manifested itself in facial distortion and considerable facial hair in the male pattern. Doctors, as well as sensation seekers, were very keen to examine her. Her story is unusual, not least because she was mummified after death by her husband-manager and continued to tour as a mounted exhibit for a number of decades. Indirectly, she participated in the evolutionary debate in Britain. In 1857, when she arrived in Britain from America, she was popularly known as the baboon-woman. When Darwin's Origin of Species was published, and evolutionary controversy about ape-ancestry was hot in the air, she was more often likened to the gorilla or orang-utan - as a possible specimen of a missing link.

Maximum-likelihood estimation of recent shared ancestry (ERSA).

PubMed

Huff, Chad D; Witherspoon, David J; Simonson, Tatum S; Xing, Jinchuan; Watkins, W Scott; Zhang, Yuhua; Tuohy, Therese M; Neklason, Deborah W; Burt, Randall W; Guthery, Stephen L; Woodward, Scott R; Jorde, Lynn B

2011-05-01

Accurate estimation of recent shared ancestry is important for genetics, evolution, medicine, conservation biology, and forensics. Established methods estimate kinship accurately for first-degree through third-degree relatives. We demonstrate that chromosomal segments shared by two individuals due to identity by descent (IBD) provide much additional information about shared ancestry. We developed a maximum-likelihood method for the estimation of recent shared ancestry (ERSA) from the number and lengths of IBD segments derived from high-density SNP or whole-genome sequence data. We used ERSA to estimate relationships from SNP genotypes in 169 individuals from three large, well-defined human pedigrees. ERSA is accurate to within one degree of relationship for 97% of first-degree through fifth-degree relatives and 80% of sixth-degree and seventh-degree relatives. We demonstrate that ERSA's statistical power approaches the maximum theoretical limit imposed by the fact that distant relatives frequently share no DNA through a common ancestor. ERSA greatly expands the range of relationships that can be estimated from genetic data and is implemented in a freely available software package.

Disparities in birth weight and gestational age by ethnic ancestry in South American countries.

PubMed

Wehby, George L; Gili, Juan A; Pawluk, Mariela; Castilla, Eduardo E; López-Camelo, Jorge S

2015-03-01

We examine disparities in birth weight and gestational age by ethnic ancestry in 2000-2011 in eight South American countries. The sample included 60,480 singleton live births. Regression models were estimated to evaluate differences in birth outcomes by ethnic ancestry controlling for time trends. Significant disparities were found in seven countries. In four countries-Brazil, Ecuador, Uruguay, and Venezuela-we found significant disparities in both low birth weight and preterm birth. Disparities in preterm birth alone were observed in Argentina, Bolivia, and Colombia. Several differences in continuous birth weight, gestational age, and fetal growth rate were also observed. There were no systematic patterns of disparities between the evaluated ethnic ancestry groups across the study countries, in that no racial/ethnic group consistently had the best or worst outcomes in all countries. Racial/ethnic disparities in infant health are common in several South American countries. Differences across countries suggest that racial/ethnic disparities are driven by social and economic mechanisms. Researchers and policymakers should acknowledge these disparities and develop research and policy programs to effectively target them.

Influence of environmental and genetic factors on CYP1A2 activity in individuals of South Asian and European ancestry.

PubMed

Perera, V; Gross, A S; McLachlan, A J

2012-10-01

The drug-metabolizing enzyme CYP1A2 contributes to the metabolism of a number of commonly used medicines and displays wide interindividual variability. The aim of this study was to investigate CYP1A2 activity in a population of South Asian ancestry and compare it with a population of European ancestry. CYP1A2 activity was determined using the 4 h paraxanthine/caffeine saliva concentration ratio following a 100-mg oral dose of caffeine in healthy individuals of South Asian (n = 166) and European (n = 166) ancestry. Participants were surveyed for extrinsic ethnic factors and genotyped for polymorphisms in CYP1A2 and related genes. Significantly lower CYP1A2 activity was observed in South Asian participants (median: 0.42; range: 0.10-1.06) as compared with European participants (0.54; 0.12-1.64) (P < 0.01). Multiple linear regression indicated that 41% of the variability in CYP1A2 activity could be explained by the diet, lifestyle, and genetic factors studied.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium

PubMed Central

Lu, Yingchang; Justice, Anne E.; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Feitosa, Mary F.; Rand, Kristin; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A.; Nalls, Michael A.; Okut, Hayrettin; Tayo, Bamidele O.; Vedantam, Sailaja; Bradfield, Jonathan P.; Chen, Guanjie; Chesi, Alessandra; Irvin, Marguerite R.; Padhukasahasram, Badri; Zheng, Wei; Allison, Matthew A.; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Blot, William J.; Bottinger, Erwin P.; Carpten, John; Chanock, Stephen J.; Chen, Yii-Der Ida; Conti, David V.; Cooper, Richard S.; Fornage, Myriam; Freedman, Barry I.; Garcia, Melissa; Goodman, Phyllis J.; Hsu, Yu-Han H.; Hu, Jennifer; Huff, Chad D.; Ingles, Sue A.; John, Esther M.; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Olshan, Andrew; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S.; Stanford, Janet L.; Strom, Sara S.; Witte, John S.; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G.; Zonderman, Alan B.; Ambs, Stefan; Cushman, Mary; Faul, Jessica D.; Hakonarson, Hakon; Levin, Albert M.; Nathanson, Katherine L.; Weir, David R.; Zhi, Degui; Arnett, Donna K.; Kardia, Sharon L. R.; Oloapde, Olufunmilayo I.; Rao, D. C.; Williams, L. Keoki; Becker, Diane M.; Borecki, Ingrid B.; Evans, Michele K.; Harris, Tamara B.; Hirschhorn, Joel N.; Psaty, Bruce M.; Wilson, James G.; Bowden, Donald W.; Cupples, L. Adrienne; Haiman, Christopher A.; Loos, Ruth J. F.; North, Kari E.

2017-01-01

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations. PMID:28430825

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

PubMed

Paternoster, Lavinia; Standl, Marie; Waage, Johannes; Baurecht, Hansjörg; Hotze, Melanie; Strachan, David P; Curtin, John A; Bønnelykke, Klaus; Tian, Chao; Takahashi, Atsushi; Esparza-Gordillo, Jorge; Alves, Alexessander Couto; Thyssen, Jacob P; den Dekker, Herman T; Ferreira, Manuel A; Altmaier, Elisabeth; Sleiman, Patrick Ma; Xiao, Feng Li; Gonzalez, Juan R; Marenholz, Ingo; Kalb, Birgit; Yanes, Maria Pino; Xu, Cheng-Jian; Carstensen, Lisbeth; Groen-Blokhuis, Maria M; Venturini, Cristina; Pennell, Craig E; Barton, Sheila J; Levin, Albert M; Curjuric, Ivan; Bustamante, Mariona; Kreiner-Møller, Eskil; Lockett, Gabrielle A; Bacelis, Jonas; Bunyavanich, Supinda; Myers, Rachel A; Matanovic, Anja; Kumar, Ashish; Tung, Joyce Y; Hirota, Tomomitsu; Kubo, Michiaki; McArdle, Wendy L; Henderson, A J; Kemp, John P; Zheng, Jie; Smith, George Davey; Rüschendorf, Franz; Bauerfeind, Anja; Lee-Kirsch, Min Ae; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Mangold, Elisabeth; Cichon, Sven; Keil, Thomas; Rodríguez, Elke; Peters, Annette; Franke, Andre; Lieb, Wolfgang; Novak, Natalija; Fölster-Holst, Regina; Horikoshi, Momoko; Pekkanen, Juha; Sebert, Sylvain; Husemoen, Lise L; Grarup, Niels; de Jongste, Johan C; Rivadeneira, Fernando; Hofman, Albert; Jaddoe, Vincent Wv; Pasmans, Suzanne Gma; Elbert, Niels J; Uitterlinden, André G; Marks, Guy B; Thompson, Philip J; Matheson, Melanie C; Robertson, Colin F; Ried, Janina S; Li, Jin; Zuo, Xian Bo; Zheng, Xiao Dong; Yin, Xian Yong; Sun, Liang Dan; McAleer, Maeve A; O'Regan, Grainne M; Fahy, Caoimhe Mr; Campbell, Linda E; Macek, Milan; Kurek, Michael; Hu, Donglei; Eng, Celeste; Postma, Dirkje S; Feenstra, Bjarke; Geller, Frank; Hottenga, Jouke Jan; Middeldorp, Christel M; Hysi, Pirro; Bataille, Veronique; Spector, Tim; Tiesler, Carla Mt; Thiering, Elisabeth; Pahukasahasram, Badri; Yang, James J; Imboden, Medea; Huntsman, Scott; Vilor-Tejedor, Natàlia; Relton, Caroline L; Myhre, Ronny; Nystad, Wenche; Custovic, Adnan; Weiss, Scott T; Meyers, Deborah A; Söderhäll, Cilla; Melén, Erik; Ober, Carole; Raby, Benjamin A; Simpson, Angela; Jacobsson, Bo; Holloway, John W; Bisgaard, Hans; Sunyer, Jordi; Hensch, Nicole M Probst; Williams, L Keoki; Godfrey, Keith M; Wang, Carol A; Boomsma, Dorret I; Melbye, Mads; Koppelman, Gerard H; Jarvis, Deborah; McLean, Wh Irwin; Irvine, Alan D; Zhang, Xue Jun; Hakonarson, Hakon; Gieger, Christian; Burchard, Esteban G; Martin, Nicholas G; Duijts, Liesbeth; Linneberg, Allan; Jarvelin, Marjo-Riitta; Noethen, Markus M; Lau, Susanne; Hübner, Norbert; Lee, Young-Ae; Tamari, Mayumi; Hinds, David A; Glass, Daniel; Brown, Sara J; Heinrich, Joachim; Evans, David M; Weidinger, Stephan

2015-12-01

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry.

PubMed

Feng, Ye; Rhie, Suhn Kyong; Huo, Dezheng; Ruiz-Narvaez, Edward A; Haddad, Stephen A; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Zheng, Yonglan; Yao, Song; Han, Yoo-Jeong; Ogundiran, Temidayo O; Rebbeck, Timothy R; Adebamowo, Clement; Ojengbede, Oladosu; Falusi, Adeyinka G; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Blot, William; Cai, Qiuyin; Signorello, Lisa; Nathanson, Katherine L; Lunetta, Kathryn L; Sucheston-Campbell, Lara E; Bensen, Jeannette T; Chanock, Stephen J; Marchand, Loic Le; Olshan, Andrew F; Kolonel, Laurence N; Conti, David V; Coetzee, Gerhard A; Stram, Daniel O; Olopade, Olufunmilayo I; Palmer, Julie R; Haiman, Christopher A

2017-07-01

Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT). Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant ( P < 0.05). Through fine-mapping, in six regions ( 3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13 ), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions ( 11q13, 16q12/TOX3 ), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality. Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry. Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016-26. ©2017 AACR . ©2017 American Association for Cancer Research.

Statistical evidence for common ancestry: Application to primates.

PubMed

Baum, David A; Ané, Cécile; Larget, Bret; Solís-Lemus, Claudia; Ho, Lam Si Tung; Boone, Peggy; Drummond, Chloe P; Bontrager, Martin; Hunter, Steven J; Saucier, William

2016-06-01

Since Darwin, biologists have come to recognize that the theory of descent from common ancestry (CA) is very well supported by diverse lines of evidence. However, while the qualitative evidence is overwhelming, we also need formal methods for quantifying the evidential support for CA over the alternative hypothesis of separate ancestry (SA). In this article, we explore a diversity of statistical methods using data from the primates. We focus on two alternatives to CA, species SA (the separate origin of each named species) and family SA (the separate origin of each family). We implemented statistical tests based on morphological, molecular, and biogeographic data and developed two new methods: one that tests for phylogenetic autocorrelation while correcting for variation due to confounding ecological traits and a method for examining whether fossil taxa have fewer derived differences than living taxa. We overwhelmingly rejected both species and family SA with infinitesimal P values. We compare these results with those from two companion papers, which also found tremendously strong support for the CA of all primates, and discuss future directions and general philosophical issues that pertain to statistical testing of historical hypotheses such as CA. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Ultrastructure of book gill development in embryos and first instars of the horseshoe crab Limulus polyphemus L. (Chelicerata, Xiphosura)

PubMed Central

2012-01-01

Background The transmission electron microscope (TEM) is used for the first time to study the development of book gills in the horseshoe crab. Near the end of the nineteenth century the hypothesis was presented for homology and a common ancestry for horseshoe crab book gills and arachnid book lungs. The present developmental study and the author's recent ones of book gills (SEM) and scorpion book lungs (TEM) are intended to clarify early histological work and provide new ultrastructural details for further research and for hypotheses about evolutionary history and relationships. Results The observations herein are in agreement with earlier reports that the book gill lamellae are formed by proliferation and evagination of epithelial cells posterior to opisthosomal branchial appendages. A cartilage-like endoskeleton is produced in the base of the opisthosomal appendages. The lamellar precursor cells in the appendage base proliferate, migrate outward and secrete the lamellar cuticle from their apical surface. A series of external, posteriorly-directed lamellae is formed, with each lamella having a central channel for hemolymph and pillar-type space holders formed from cells of the opposed walls. This repeated, page-like pattern results also in water channels (without space holders) between the sac-like hemolymph lamellae. Conclusions The developmental observations herein and in an earlier study (TEM) of scorpion book lungs show that the lamellae in book gills and book lungs result from some similar activities and features of the precursor epithelial cells: proliferation, migration, alignment and apical/basal polarity with secretion of cuticle from the apical surface and the basal surface in contact with hemolymph. These cellular similarities and the resulting book-like structure suggest a common ancestry, but there are also substantial developmental differences in producing these organs for gas exchange in the different environments, aqueous and terrestrial. For scorpion book lungs, the invaginated precursor cells align in rows and secrete rows of cell fragments that are the basis for the internal, anterior-directed air sacs. The hemolymph sacs of book gills are formed by epithelial evagination or outfolding from the posterior surface of the branchial appendages. PMID:22433580

Generalization and dilution of association results from European GWAS in populations of non-European ancestry: the PAGE study.

PubMed

Carlson, Christopher S; Matise, Tara C; North, Kari E; Haiman, Christopher A; Fesinmeyer, Megan D; Buyske, Steven; Schumacher, Fredrick R; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D; Duggan, David J; Spencer, Kylee L; Dumitrescu, Logan; Eaton, Charles B; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C; Hindorff, Lucia A; Kooperberg, Charles L

2013-09-01

The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification of functional variants remains challenging.

Generalization and Dilution of Association Results from European GWAS in Populations of Non-European Ancestry: The PAGE Study

PubMed Central

Carlson, Christopher S.; Matise, Tara C.; North, Kari E.; Haiman, Christopher A.; Fesinmeyer, Megan D.; Buyske, Steven; Schumacher, Fredrick R.; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D.; Duggan, David J.; Spencer, Kylee L.; Dumitrescu, Logan; Eaton, Charles B.; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C.; Hindorff, Lucia A.; Kooperberg, Charles L.

2013-01-01

The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification of functional variants remains challenging. PMID:24068893

Unravelling the distinct strains of Tharu ancestry

PubMed Central

Chaubey, Gyaneshwer; Singh, Manvendra; Crivellaro, Federica; Tamang, Rakesh; Nandan, Amrita; Singh, Kamayani; Sharma, Varun Kumar; Pathak, Ajai Kumar; Shah, Anish M; Sharma, Vishwas; Singh, Vipin Kumar; Selvi Rani, Deepa; Rai, Niraj; Kushniarevich, Alena; Ilumäe, Anne-Mai; Karmin, Monika; Phillip, Anand; Verma, Abhilasha; Prank, Erik; Singh, Vijay Kumar; Li, Blaise; Govindaraj, Periyasamy; Chaubey, Akhilesh Kumar; Dubey, Pavan Kumar; Reddy, Alla G; Premkumar, Kumpati; Vishnupriya, Satti; Pande, Veena; Parik, Jüri; Rootsi, Siiri; Endicott, Phillip; Metspalu, Mait; Lahr, Marta Mirazon; van Driem, George; Villems, Richard; Kivisild, Toomas; Singh, Lalji; Thangaraj, Kumarasamy

2014-01-01

The northern region of the Indian subcontinent is a vast landscape interlaced by diverse ecologies, for example, the Gangetic Plain and the Himalayas. A great number of ethnic groups are found there, displaying a multitude of languages and cultures. The Tharu is one of the largest and most linguistically diverse of such groups, scattered across the Tarai region of Nepal and bordering Indian states. Their origins are uncertain. Hypotheses have been advanced postulating shared ancestry with Austroasiatic, or Tibeto-Burman-speaking populations as well as aboriginal roots in the Tarai. Several Tharu groups speak a variety of Indo-Aryan languages, but have traditionally been described by ethnographers as representing East Asian phenotype. Their ancestry and intra-population diversity has previously been tested only for haploid (mitochondrial DNA and Y-chromosome) markers in a small portion of the population. This study presents the first systematic genetic survey of the Tharu from both Nepal and two Indian states of Uttarakhand and Uttar Pradesh, using genome-wide SNPs and haploid markers. We show that the Tharu have dual genetic ancestry as up to one-half of their gene pool is of East Asian origin. Within the South Asian proportion of the Tharu genetic ancestry, we see vestiges of their common origin in the north of the South Asian Subcontinent manifested by mitochondrial DNA haplogroup M43. PMID:24667789

Recent Admixture in an Indian Population of African Ancestry

PubMed Central

Narang, Ankita; Jha, Pankaj; Rawat, Vimal; Mukhopadhayay, Arijit; Dash, Debasis; Basu, Analabha; Mukerji, Mitali

2011-01-01

Identification and study of genetic variation in recently admixed populations not only provides insight into historical population events but also is a powerful approach for mapping disease loci. We studied a population (OG-W-IP) that is of African-Indian origin and has resided in the western part of India for 500 years; members of this population are believed to be descendants of the Bantu-speaking population of Africa. We have carried out this study by using a set of 18,534 autosomal markers common between Indian, CEPH-HGDP, and HapMap populations. Principal-components analysis clearly revealed that the African-Indian population derives its ancestry from Bantu-speaking west-African as well as Indo-European-speaking north and northwest Indian population(s). STRUCTURE and ADMIXTURE analyses show that, overall, the OG-W-IPs derive 58.7% of their genomic ancestry from their African past and have very little inter-individual ancestry variation (8.4%). The extent of linkage disequilibrium also reveals that the admixture event has been recent. Functional annotation of genes encompassing the ancestry-informative markers that are closer in allele frequency to the Indian ancestral population revealed significant enrichment of biological processes, such as ion-channel activity, and cadherins. We briefly examine the implications of determining the genetic diversity of this population, which could provide opportunities for studies involving admixture mapping. PMID:21737057

European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil

PubMed Central

Santos, Antônio Carlos; Lana-Peixoto, Marco Aurélio; Rocha, Cristiane Franklin; Brito, Maria Lucia; de Oliveira, Enedina Maria Lobato; Bichuetti, Denis Bernardi; Gabbai, Alberto Alan; Diniz, Denise Sisterolli; Kaimen-Maciel, Damacio Ramon; Comini-Frota, Elizabeth Regina; Vieira Wiezel, Claudia E.; Muniz, Yara Costa Netto; da Silva Costa, Roberta Martins; Mendes-Junior, Celso Teixeira; Donadi, Eduardo Antônio; Barreira, Amilton Antunes; Simões, Aguinaldo Luiz

2013-01-01

Background Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil. PMID:23527051

The evolutionary history of protein fold families and proteomes confirms that the archaeal ancestor is more ancient than the ancestors of other superkingdoms

PubMed Central

2012-01-01

Background The entire evolutionary history of life can be studied using myriad sequences generated by genomic research. This includes the appearance of the first cells and of superkingdoms Archaea, Bacteria, and Eukarya. However, the use of molecular sequence information for deep phylogenetic analyses is limited by mutational saturation, differential evolutionary rates, lack of sequence site independence, and other biological and technical constraints. In contrast, protein structures are evolutionary modules that are highly conserved and diverse enough to enable deep historical exploration. Results Here we build phylogenies that describe the evolution of proteins and proteomes. These phylogenetic trees are derived from a genomic census of protein domains defined at the fold family (FF) level of structural classification. Phylogenomic trees of FF structures were reconstructed from genomic abundance levels of 2,397 FFs in 420 proteomes of free-living organisms. These trees defined timelines of domain appearance, with time spanning from the origin of proteins to the present. Timelines are divided into five different evolutionary phases according to patterns of sharing of FFs among superkingdoms: (1) a primordial protein world, (2) reductive evolution and the rise of Archaea, (3) the rise of Bacteria from the common ancestor of Bacteria and Eukarya and early development of the three superkingdoms, (4) the rise of Eukarya and widespread organismal diversification, and (5) eukaryal diversification. The relative ancestry of the FFs shows that reductive evolution by domain loss is dominant in the first three phases and is responsible for both the diversification of life from a universal cellular ancestor and the appearance of superkingdoms. On the other hand, domain gains are predominant in the last two phases and are responsible for organismal diversification, especially in Bacteria and Eukarya. Conclusions The evolution of functions that are associated with corresponding FFs along the timeline reveals that primordial metabolic domains evolved earlier than informational domains involved in translation and transcription, supporting the metabolism-first hypothesis rather than the RNA world scenario. In addition, phylogenomic trees of proteomes reconstructed from FFs appearing in each of the five phases of the protein world show that trees reconstructed from ancient domain structures were consistently rooted in archaeal lineages, supporting the proposal that the archaeal ancestor is more ancient than the ancestors of other superkingdoms. PMID:22284070

Genetic effects influencing risk for major depressive disorder in China and Europe.

PubMed

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-03-28

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log 10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Genetic effects influencing risk for major depressive disorder in China and Europe

PubMed Central

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-01-01

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies. PMID:28350396

Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.

PubMed

Wen, Wanqing; Shu, Xiao-Ou; Guo, Xingyi; Cai, Qiuyin; Long, Jirong; Bolla, Manjeet K; Michailidou, Kyriaki; Dennis, Joe; Wang, Qin; Gao, Yu-Tang; Zheng, Ying; Dunning, Alison M; García-Closas, Montserrat; Brennan, Paul; Chen, Shou-Tung; Choi, Ji-Yeob; Hartman, Mikael; Ito, Hidemi; Lophatananon, Artitaya; Matsuo, Keitaro; Miao, Hui; Muir, Kenneth; Sangrajrang, Suleeporn; Shen, Chen-Yang; Teo, Soo H; Tseng, Chiu-Chen; Wu, Anna H; Yip, Cheng Har; Simard, Jacques; Pharoah, Paul D P; Hall, Per; Kang, Daehee; Xiang, Yongbing; Easton, Douglas F; Zheng, Wei

2016-12-08

Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P < 0.05. Compared with women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15-3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively. Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.

A substantial prehistoric European ancestry amongst Ashkenazi maternal lineages.

PubMed

Costa, Marta D; Pereira, Joana B; Pala, Maria; Fernandes, Verónica; Olivieri, Anna; Achilli, Alessandro; Perego, Ugo A; Rychkov, Sergei; Naumova, Oksana; Hatina, Jiři; Woodward, Scott R; Eng, Ken Khong; Macaulay, Vincent; Carr, Martin; Soares, Pedro; Pereira, Luísa; Richards, Martin B

2013-01-01

The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders. However, due to their rarity in the general population, these founders have been difficult to trace to a source. Here we show that all four major founders, ~40% of Ashkenazi mtDNA variation, have ancestry in prehistoric Europe, rather than the Near East or Caucasus. Furthermore, most of the remaining minor founders share a similar deep European ancestry. Thus the great majority of Ashkenazi maternal lineages were not brought from the Levant, as commonly supposed, nor recruited in the Caucasus, as sometimes suggested, but assimilated within Europe. These results point to a significant role for the conversion of women in the formation of Ashkenazi communities, and provide the foundation for a detailed reconstruction of Ashkenazi genealogical history.

A substantial prehistoric European ancestry amongst Ashkenazi maternal lineages

PubMed Central

Costa, Marta D.; Pereira, Joana B.; Pala, Maria; Fernandes, Verónica; Olivieri, Anna; Achilli, Alessandro; Perego, Ugo A.; Rychkov, Sergei; Naumova, Oksana; Hatina, Jiři; Woodward, Scott R.; Eng, Ken Khong; Macaulay, Vincent; Carr, Martin; Soares, Pedro; Pereira, Luísa; Richards, Martin B.

2013-01-01

The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders. However, due to their rarity in the general population, these founders have been difficult to trace to a source. Here we show that all four major founders, ~40% of Ashkenazi mtDNA variation, have ancestry in prehistoric Europe, rather than the Near East or Caucasus. Furthermore, most of the remaining minor founders share a similar deep European ancestry. Thus the great majority of Ashkenazi maternal lineages were not brought from the Levant, as commonly supposed, nor recruited in the Caucasus, as sometimes suggested, but assimilated within Europe. These results point to a significant role for the conversion of women in the formation of Ashkenazi communities, and provide the foundation for a detailed reconstruction of Ashkenazi genealogical history. PMID:24104924

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

PubMed

Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

2016-12-01

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

An evaluation of non-metric cranial traits used to estimate ancestry in a South African sample.

PubMed

L'Abbé, E N; Van Rooyen, C; Nawrocki, S P; Becker, P J

2011-06-15

Establishing ancestry from a skeleton for forensic purposes has been shown to be difficult. The purpose of this paper is to address the application of thirteen non-metric traits to estimate ancestry in three South African groups, namely White, Black and "Coloured". In doing so, the frequency distribution of thirteen non-metric traits among South Africans are presented; the relationship of these non-metric traits with ancestry, sex, age at death are evaluated; and Kappa statistics are utilized to assess the inter and intra-rater reliability. Crania of 520 known individuals were obtained from four skeletal samples in South Africa: the Pretoria Bone Collection, the Raymond A. Dart Collection, the Kirsten Collection and the Student Bone Collection from the University of the Free State. Average age at death was 51, with an age range between 18 and 90. Thirteen commonly used non-metric traits from the face and jaw were scored; definition and illustrations were taken from Hefner, Bass and Hauser and De Stephano. Frequency distributions, ordinal regression and Cohen's Kappa statistics were performed as a means to assess population variation and repeatability. Frequency distributions were highly variable among South Africans. Twelve of the 13 variables had a statistically significant relationship with ancestry. Sex significantly affected only one variable, inter-orbital breadth, and age at death affected two (anterior nasal spine and alveolar prognathism). The interaction of ancestry and sex independently affected three variables (nasal bone contour, nasal breadth, and interorbital breadth). Seven traits had moderate to excellent repeatability, while poor scoring consistency was noted for six variables. Difficulties in repeating several of the trait scores may require either a need for refinement of the definitions, or these character states may not adequately describe the observable morphology in the population. The application of the traditional experience-based approach for estimating ancestry in forensic case work is problematic. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Genetic African Ancestry and Markers of Mineral Metabolism in CKD

PubMed Central

Parsa, Afshin; Isakova, Tamara; Scialla, Julia J.; Chen, Jing; Flack, John M.; Nessel, Lisa C.; Gupta, Jayanta; Bellovich, Keith A.; Steigerwalt, Susan; Sondheimer, James H.; Wright, Jackson T.; Feldman, Harold I.; Kusek, John W.; Lash, James P.; Wolf, Myles

2016-01-01

Background and objectives Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. Design, setting, participants, & measurements In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). Results Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). Conclusions A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional excretion of phosphorus among African Americans with CKD. These findings suggest that genetic variability might contribute to racial differences in urinary phosphorus excretion in CKD. PMID:26912553

Genetic African Ancestry and Markers of Mineral Metabolism in CKD.

PubMed

Gutiérrez, Orlando M; Parsa, Afshin; Isakova, Tamara; Scialla, Julia J; Chen, Jing; Flack, John M; Nessel, Lisa C; Gupta, Jayanta; Bellovich, Keith A; Steigerwalt, Susan; Sondheimer, James H; Wright, Jackson T; Feldman, Harold I; Kusek, John W; Lash, James P; Wolf, Myles

2016-04-07

Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional excretion of phosphorus among African Americans with CKD. These findings suggest that genetic variability might contribute to racial differences in urinary phosphorus excretion in CKD. Copyright © 2016 by the American Society of Nephrology.

Phenylketonuria (PKU)

MedlinePlus

... less common among people of African, Hispanic, or Asian ancestry. 3 NICHD. (2000, updated 2006). Report of the NIH consensus development conference on phenylketonuria (PKU): Screening and management . Retrieved May 15, 2012, from http://www.nichd. ...

Molecular and morphological data reveal non-monophyly and speciation in imperiled freshwater mussels (Anodontoides and Strophitus)

USGS Publications Warehouse

Smith, Chase; Johnson, Nathan A.; Pfeiffer, John M.; Gangloff, Michael M.

2018-01-01

Accurate taxonomic placement is vital to conservation efforts considering many intrinsic biological characteristics of understudied species are inferred from closely related taxa. The rayed creekshell, Anodontoides radiatus (Conrad, 1834), exists in the Gulf of Mexico drainages from western Florida to Louisiana and has been petitioned for listing under the Endangered Species Act. We set out to resolve the evolutionary history of A. radiatus, primarily generic placement and species boundaries, using phylogenetic, morphometric, and geographic information. Our molecular matrix contained 3 loci: cytochrome c oxidase subunit I, NADH dehydrogenase subunit I, and the nuclear-encoded ribosomal internal transcribed spacer I. We employed maximum likelihood and Bayesian inference to estimate a phylogeny and test the monophyly of Anodontoides and Strophitus. We implemented two coalescent-based species delimitation models to test seven species models and evaluate species boundaries within A. radiatus. Concomitant to molecular data, we also employed linear morphometrics and geographic information to further evaluate species boundaries. Molecular and morphological evidence supports the inclusion of A. radiatus in the genus Strophitus, and we resurrect the binomial Strophitus radiatus to reflect their shared common ancestry. We also found strong support for polyphyly in Strophitus and advocate the resurrection of the genus Pseudodontoideus to represent ‘Strophitus’ connasaugaensis and ‘Strophitus’ subvexus. Strophitus radiatus exists in six well-supported clades that were distinguished as evolutionary independent lineages using Bayesian inference, maximum likelihood, and coalescent-based species delimitation models. Our integrative approach found evidence for as many as 4 evolutionary divergent clades within S. radiatus. Therefore, we formally describe two new species from the S. radiatus species complex (Strophitus williamsi and Strophitus pascagoulaensis) and recognize the potential for a third putative species (Strophitus sp. cf. pascagoulaensis). Our findings aid stakeholders in establishing conservation and management strategies for the members of Anodontoides, Strophitus, and Pseudodontoideus.

A phylogenetic perspective on species diversity, β-diversity and biogeography for the microbial world.

PubMed

Barberán, Albert; Casamayor, Emilio O

2014-12-01

There is an increasing interest to combine phylogenetic data with distributional and ecological records to assess how natural communities arrange under an evolutionary perspective. In the microbial world, there is also a need to go beyond the problematic species definition to deeply explore ecological patterns using genetic data. We explored links between evolution/phylogeny and community ecology using bacterial 16S rRNA gene information from a high-altitude lakes district data set. We described phylogenetic community composition, spatial distribution, and β-diversity and biogeographical patterns applying evolutionary relatedness without relying on any particular operational taxonomic unit definition. High-altitude lakes districts usually contain a large mosaic of highly diverse small water bodies and conform a fine biogeographical model of spatially close but environmentally heterogeneous ecosystems. We sampled 18 lakes in the Pyrenees with a selection criteria focused on capturing the maximum environmental variation within the smallest geographical area. The results showed highly diverse communities nonrandomly distributed with phylogenetic β-diversity patterns mainly shaped by the environment and not by the spatial distance. Community similarity based on both bacterial taxonomic composition and phylogenetic β-diversity shared similar patterns and was primarily structured by similar environmental drivers. We observed a positive relationship between lake area and phylogenetic diversity with a slope consistent with highly dispersive planktonic organisms. The phylogenetic approach incorporated patterns of common ancestry into bacterial community analysis and emerged as a very convenient analytical tool for direct inter- and intrabiome biodiversity comparisons and sorting out microbial habitats with potential application in conservation studies. © 2014 John Wiley & Sons Ltd.

Genome Wide Identification, Evolutionary, and Expression Analysis of VQ Genes from Two Pyrus Species.

PubMed

Cao, Yunpeng; Meng, Dandan; Abdullah, Muhammad; Jin, Qing; Lin, Yi; Cai, Yongping

2018-04-23

The VQ motif-containing gene, a member of the plant-specific genes, is involved in the plant developmental process and various stress responses. The VQ motif-containing gene family has been studied in several plants, such as rice ( Oryza sativa ), maize ( Zea mays ), and Arabidopsis ( Arabidopsis thaliana ). However, no systematic study has been performed in Pyrus species, which have important economic value. In our study, we identified 41 and 28 VQ motif-containing genes in Pyrus bretschneideri and Pyrus communis , respectively. Phylogenetic trees were calculated using A. thaliana and O. sativa VQ motif-containing genes as a template, allowing us to categorize these genes into nine subfamilies. Thirty-two and eight paralogous of VQ motif-containing genes were found in P. bretschneideri and P. communis , respectively, showing that the VQ motif-containing genes had a more remarkable expansion in P. bretschneideri than in P. communis . A total of 31 orthologous pairs were identified from the P. bretschneideri and P. communis VQ motif-containing genes. Additionally, among the paralogs, we found that these duplication gene pairs probably derived from segmental duplication/whole-genome duplication (WGD) events in the genomes of P. bretschneideri and P. communis , respectively. The gene expression profiles in both P. bretschneideri and P. communis fruits suggested functional redundancy for some orthologous gene pairs derived from a common ancestry, and sub-functionalization or neo-functionalization for some of them. Our study provided the first systematic evolutionary analysis of the VQ motif-containing genes in Pyrus , and highlighted the diversification and duplication of VQ motif-containing genes in both P. bretschneideri and P. communis .

Tandem duplications of a degenerated GTP-binding domain at the origin of GTPase receptors Toc159 and thylakoidal SRP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernandez Torres, Jorge; Maldonado, Monica Alexandra Arias; Chomilier, Jacques

2007-12-14

The evolutionary origin of some nuclear encoded proteins that translocate proteins across the chloroplast envelope remains unknown. Therefore, sequences of GTPase proteins constituting the Arabidopsis thaliana translocon at the outer membrane of chloroplast (atToc) complexes were analyzed by means of HCA. In particular, atToc159 and related proteins (atToc132, atToc120, and atToc90) do not have proven homologues of prokaryotic or eukaryotic ancestry. We established that the three domains commonly referred to as A, G, and M originate from the GTPase G domain, tandemly repeated, and probably evolving toward an unstructured conformation in the case of the A domain. It resulted frommore » this study a putative common ancestor for these proteins and a new domain definition, in particular the splitting of A into three domains (A1, A2, and A3), has been proposed. The family of Toc159, previously containing A. thaliana and Pisum sativum, has been extended to Medicago truncatula and Populus trichocarpa and it has been revised for Oryza sativa. They have also been compared to GTPase subunits involved in the cpSRP system. A distant homology has been revealed among Toc and cpSRP GTP-hydrolyzing proteins of A. thaliana, and repetitions of a GTPase domain were also found in cpSRP protein receptors, by means of HCA analysis.« less

The History of African Gene Flow into Southern Europeans, Levantines, and Jews

PubMed Central

Moorjani, Priya; Patterson, Nick; Hirschhorn, Joel N.; Keinan, Alon; Hao, Li; Atzmon, Gil; Burns, Edward; Ostrer, Harry; Price, Alkes L.; Reich, David

2011-01-01

Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%–3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%–15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%–5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas. PMID:21533020

Abundant mtDNA diversity and ancestral admixture in Colombian criollo cattle (Bos taurus).

PubMed

Carvajal-Carmona, Luis G; Bermudez, Nelson; Olivera-Angel, Martha; Estrada, Luzardo; Ossa, Jorge; Bedoya, Gabriel; Ruiz-Linares, Andrés

2003-11-01

Various cattle populations in the Americas (known as criollo breeds) have an origin in some of the first livestock introduced to the continent early in the colonial period (16th and 17th centuries). These cattle constitute a potentially important genetic reserve as they are well adapted to local environments and show considerable variation in phenotype. To examine the genetic ancestry and diversity of Colombian criollo we obtained mitochondrial DNA control region sequence information for 110 individuals from seven breeds. Old World haplogroup T3 is the most commonly observed CR lineage in criollo (0.65), in agreement with a mostly European ancestry for these cattle. However, criollo also shows considerable frequencies of haplogroups T2 (0.9) and T1 (0.26), with T1 lineages in criollo being more diverse than those reported for West Africa. The distribution and diversity of Old World lineages suggest some North African ancestry for criollo, probably as a result of the Arab occupation of Iberia prior to the European migration to the New World. The mtDNA diversity of criollo is higher than that reported for European and African cattle and is consistent with a differentiated ancestry for some criollo breeds.

The history of African gene flow into Southern Europeans, Levantines, and Jews.

PubMed

Moorjani, Priya; Patterson, Nick; Hirschhorn, Joel N; Keinan, Alon; Hao, Li; Atzmon, Gil; Burns, Edward; Ostrer, Harry; Price, Alkes L; Reich, David

2011-04-01

Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%-3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%-15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%-5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas.

A genome-wide association study of breast cancer in women of African ancestry

PubMed Central

Chen, Fang; Chen, Gary K.; Stram, Daniel O.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R.; Hu, Jennifer J.; Rebbeck, Tim R.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Ruiz-Narvaez, Edward A.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; DeMichele, Angela; Chanock, Stephen J.; Blot, William; Signorello, Lisa; Cai, Qiuyin; Li, Guoliang; Long, Jirong; Huo, Dezheng; Zheng, Yonglan; Cox, Nancy J.; Olopade, Olufunmilayo I.; Ogundiran, Temidayo O.; Adebamowo, Clement; Nathanson, Katherine L.; Domchek, Susan M.; Simon, Michael S.; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Ambs, Stefan; Hutter, Carolyn M.; Young, Alicia; Kooperberg, Charles; Peters, Ulrike; Rhie, Suhn K.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Le Marchand, Loic; Kolonel, Laurence N.; Henderson, Brian E.; Haiman, Christopher A.

2013-01-01

Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10−6 and 10−5 in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3×10−6; rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5×10−5). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample. PMID:22923054

Genome-wide SNP data suggest complex ancestry of sympatric North Pacific killer whale ecotypes

PubMed Central

Foote, A D; Morin, P A

2016-01-01

Three ecotypes of killer whale occur in partial sympatry in the North Pacific. Individuals assortatively mate within the same ecotype, resulting in correlated ecological and genetic differentiation. A key question is whether this pattern of evolutionary divergence is an example of incipient sympatric speciation from a single panmictic ancestral population, or whether sympatry could have resulted from multiple colonisations of the North Pacific and secondary contact between ecotypes. Here, we infer multilocus coalescent trees from >1000 nuclear single-nucleotide polymorphisms (SNPs) and find evidence of incomplete lineage sorting so that the genealogies of SNPs do not all conform to a single topology. To disentangle whether uncertainty in the phylogenetic inference of the relationships among ecotypes could also result from ancestral admixture events we reconstructed the relationship among the ecotypes as an admixture graph and estimated f4-statistics using TreeMix. The results were consistent with episodes of admixture between two of the North Pacific ecotypes and the two outgroups (populations from the Southern Ocean and the North Atlantic). Gene flow may have occurred via unsampled ‘ghost' populations rather than directly between the populations sampled here. Our results indicate that because of ancestral admixture events and incomplete lineage sorting, a single bifurcating tree does not fully describe the relationship among these populations. The data are therefore most consistent with the genomic variation among North Pacific killer whale ecotypes resulting from multiple colonisation events, and secondary contact may have facilitated evolutionary divergence. Thus, the present-day populations of North Pacific killer whale ecotypes have a complex ancestry, confounding the tree-based inference of ancestral geography. PMID:27485668

Social-group identity and population substructure in admixed populations in New Mexico and Latin America.

PubMed

Healy, Meghan E; Hill, Deirdre; Berwick, Marianne; Edgar, Heather; Gross, Jessica; Hunley, Keith

2017-01-01

We examined the relationship between continental-level genetic ancestry and racial and ethnic identity in an admixed population in New Mexico with the goal of increasing our understanding of how racial and ethnic identity influence genetic substructure in admixed populations. Our sample consists of 98 New Mexicans who self-identified as Hispanic or Latino (NM-HL) and who further categorized themselves by race and ethnic subgroup membership. The genetic data consist of 270 newly-published autosomal microsatellites from the NM-HL sample and previously published data from 57 globally distributed populations, including 13 admixed samples from Central and South America. For these data, we 1) summarized the major axes of genetic variation using principal component analyses, 2) performed tests of Hardy Weinberg equilibrium, 3) compared empirical genetic ancestry distributions to those predicted under a model of admixture that lacked substructure, 4) tested the hypotheses that individuals in each sample had 100%, 0%, and the sample-mean percentage of African, European, and Native American ancestry. We found that most NM-HL identify themselves and their parents as belonging to one of two groups, conforming to a region-specific narrative that distinguishes recent immigrants from Mexico from individuals whose families have resided in New Mexico for generations and who emphasize their Spanish heritage. The "Spanish" group had significantly lower Native American ancestry and higher European ancestry than the "Mexican" group. Positive FIS values, PCA plots, and heterogeneous ancestry distributions suggest that most Central and South America admixed samples also contain substructure, and that this substructure may be related to variation in social identity. Genetic substructure appears to be common in admixed populations in the Americas and may confound attempts to identify disease-causing genes and to understand the social causes of variation in health outcomes and social inequality.

Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren’s Syndrome According to Ancestry

PubMed Central

Taylor, Kimberly E.; Wong, Quenna; Levine, David M.; McHugh, Caitlin; Laurie, Cathy; Doheny, Kimberly; Lam, Mi Y.; Baer, Alan N.; Challacombe, Stephen; Lanfranchi, Hector; Schiødt, Morten; Srinivasan, M.; Umehara, Hisanori; Vivino, Frederick B.; Zhao, Yan; Shiboski, Stephen; Daniels, Troy E.; Greenspan, John S.; Shiboski, Caroline H.; Criswell, Lindsey A.

2017-01-01

Objective Sjögren's Syndrome (SS) is a systemic autoimmune disease affecting primarily the lacrimal and salivary glands. The Sjögren's International Collaborative Clinical Alliance (SICCA) is an international multisite observational study whose participants have been genotyped on the Omni 2.5M platform and undergone deep phenotyping using common protocol-directed methods, providing a unique opportunity to examine the genetic etiology of SS across ancestry and disease subsets. Methods We perform GWAS analyses utilizing dbGaP controls on all subjects (1405 cases, 1622 SICCA controls, 3125 external controls), European (similarly 585, 966, 2580), and Asian (similarly 460, 224, 901) with ancestry adjustments via principal component analyses. We also investigate whether subphenotype distributions differ by ethnicity and if this contributes to heterogeneity of genetic associations. Results We see significant associations in established regions of the MHC, IRF5, and STAT4 (p=3e-42, p=3e-14, p=9e-10, respectively), and several suggestive novel regions (2 or more associations with p<1e-5). Two regions have been previously implicated in autoimmune disease: KLRG1 (p=6e-7, Asian) and SH2D2A (p=2e-6, all). We observe striking differences between the European and Asian associations, with high heterogeneity especially in the MHC; representative SNPs from established and suggestive regions have highly significant differences in population allele frequencies. We show that SSA/SSB autoantibody production and labial salivary gland Focus Score criteria are associated with higher non-European ancestry (p=4e-15, 4e-5, respectively), but that subphenotype differences do not explain most of the ancestry differences in genetic associations. Conclusion Genetic associations with SS differ markedly by ancestry, however this is not explained by differences in subphenotypes. PMID:28076899

Intrahepatic Cholestasis of Pregnancy (ICP) in U.S. Latinas and Chileans: Clinical features, Ancestry Analysis, and Admixture Mapping.

PubMed

Bull, Laura N; Hu, Donglei; Shah, Sohela; Temple, Luisa; Silva, Karla; Huntsman, Scott; Melgar, Jennifer; Geiser, Mary T; Sanford, Ukina; Ortiz, Juan A; Lee, Richard H; Kusanovic, Juan P; Ziv, Elad; Vargas, Juan E

2015-01-01

In the Americas, women with Indigenous American ancestry are at increased risk of intrahepatic cholestasis of pregnancy (ICP), relative to women of other ethnicities. We hypothesized that ancestry-related genetic factors contribute to this increased risk. We collected clinical and laboratory data, and performed biochemical assays on samples from U.S. Latinas and Chilean women, with and without ICP. The study sample included 198 women with ICP (90 from California, U.S., and 108 from Chile) and 174 pregnant control women (69 from California, U.S., and 105 from Chile). SNP genotyping was performed using Affymetrix arrays. We compared overall genetic ancestry between cases and controls, and used a genome-wide admixture mapping approach to screen for ICP susceptibility loci. We identified commonalities and differences in features of ICP between the 2 countries and determined that cases had a greater proportion of Indigenous American ancestry than did controls (p = 0.034). We performed admixture mapping, taking country of origin into account, and identified one locus for which Native American ancestry was associated with increased risk of ICP at a genome-wide level of significance (P = 3.1 x 10(-5), Pcorrected = 0.035). This locus has an odds ratio of 4.48 (95% CI: 2.21-9.06) for 2 versus zero Indigenous American chromosomes. This locus lies on chromosome 2, with a 10 Mb 95% confidence interval which does not contain any previously identified hereditary 'cholestasis genes.' Our results indicate that genetic factors contribute to the risk of developing ICP in the Americas, and support the utility of clinical and genetic studies of ethnically mixed populations for increasing our understanding of ICP.

Evolutionary Analyses of Entire Genomes Do Not Support the Association of mtDNA Mutations with Ras/MAPK Pathway Syndromes

PubMed Central

Cerezo, María; Balboa, Emilia; Heredia, Claudia; Castro-Feijóo, Lidia; Rica, Itxaso; Barreiro, Jesús; Eirís, Jesús; Cabanas, Paloma; Martínez-Soto, Isabel; Fernández-Toral, Joaquín; Castro-Gago, Manuel; Pombo, Manuel; Carracedo, Ángel; Barros, Francisco

2011-01-01

Background There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). Methods/Principal Findings The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. Conclusions/Significance As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS. PMID:21526175

Evidence for common ancestry among viruses isolated from wild birds in Beringia and highly pathogenic intercontinental reassortant H5N1 and H5N2 influenza A viruses

USGS Publications Warehouse

Ramey, Andy M.; Reeves, Andrew; Teslaa, Joshua L.; Nashold, Sean W.; Donnelly, Tyrone F.; Bahl, Justin; Hall, Jeffrey S.

2016-01-01

Highly pathogenic clade 2.3.4.4 H5N8, H5N2, and H5N1 influenza A viruses were first detected in wild, captive, and domestic birds in North America in November–December 2014. In this study, we used wild waterbird samples collected in Alaska prior to the initial detection of clade 2.3.4.4 H5 influenza A viruses in North America to assess the evidence for: (1) dispersal of highly pathogenic influenza A viruses from East Asia to North America by migratory birds via Alaska and (2) ancestral origins of clade 2.3.4.4 H5 reassortant viruses in Beringia. Although we did not detect highly pathogenic influenza A viruses in our sample collection from western Alaska, we did identify viruses that contained gene segments sharing recent common ancestry with intercontinental reassortant H5N2 and H5N1 viruses. Results of phylogenetic analyses and estimates for times of most recent common ancestry support migratory birds sampled in Beringia as maintaining viral diversity closely related to novel highly pathogenic influenza A virus genotypes detected in North America. Although our results do not elucidate the route by which highly pathogenic influenza A viruses were introduced into North America, genetic evidence is consistent with the hypothesized trans-Beringian route of introduction via migratory birds.

Genome measures used for quality control are dependent on gene function and ancestry.

PubMed

Wang, Jing; Raskin, Leon; Samuels, David C; Shyr, Yu; Guo, Yan

2015-02-01

The transition/transversion (Ti/Tv) ratio and heterozygous/nonreference-homozygous (het/nonref-hom) ratio have been commonly computed in genetic studies as a quality control (QC) measurement. Additionally, these two ratios are helpful in our understanding of the patterns of DNA sequence evolution. To thoroughly understand these two genomic measures, we performed a study using 1000 Genomes Project (1000G) released genotype data (N=1092). An additional two datasets (N=581 and N=6) were used to validate our findings from the 1000G dataset. We compared the two ratios among continental ancestry, genome regions and gene functionality. We found that the Ti/Tv ratio can be used as a quality indicator for single nucleotide polymorphisms inferred from high-throughput sequencing data. The Ti/Tv ratio varies greatly by genome region and functionality, but not by ancestry. The het/nonref-hom ratio varies greatly by ancestry, but not by genome regions and functionality. Furthermore, extreme guanine + cytosine content (either high or low) is negatively associated with the Ti/Tv ratio magnitude. Thus, when performing QC assessment using these two measures, care must be taken to apply the correct thresholds based on ancestry and genome region. Failure to take these considerations into account at the QC stage will bias any following analysis. yan.guo@vanderbilt.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ultraconserved words point to deep language ancestry across Eurasia.

PubMed

Pagel, Mark; Atkinson, Quentin D; S Calude, Andreea; Meade, Andrew

2013-05-21

The search for ever deeper relationships among the World's languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some "ultraconserved" words exist that might be used to find evidence for deep linguistic relationships beyond that time barrier. Here we use a statistical model, which takes into account the frequency with which words are used in common everyday speech, to predict the existence of a set of such highly conserved words among seven language families of Eurasia postulated to form a linguistic superfamily that evolved from a common ancestor around 15,000 y ago. We derive a dated phylogenetic tree of this proposed superfamily with a time-depth of ~14,450 y, implying that some frequently used words have been retained in related forms since the end of the last ice age. Words used more than once per 1,000 in everyday speech were 7- to 10-times more likely to show deep ancestry on this tree. Our results suggest a remarkable fidelity in the transmission of some words and give theoretical justification to the search for features of language that might be preserved across wide spans of time and geography.

Ultraconserved words point to deep language ancestry across Eurasia

PubMed Central

Pagel, Mark; Atkinson, Quentin D.; S. Calude, Andreea; Meade, Andrew

2013-01-01

The search for ever deeper relationships among the World’s languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some “ultraconserved” words exist that might be used to find evidence for deep linguistic relationships beyond that time barrier. Here we use a statistical model, which takes into account the frequency with which words are used in common everyday speech, to predict the existence of a set of such highly conserved words among seven language families of Eurasia postulated to form a linguistic superfamily that evolved from a common ancestor around 15,000 y ago. We derive a dated phylogenetic tree of this proposed superfamily with a time-depth of ∼14,450 y, implying that some frequently used words have been retained in related forms since the end of the last ice age. Words used more than once per 1,000 in everyday speech were 7- to 10-times more likely to show deep ancestry on this tree. Our results suggest a remarkable fidelity in the transmission of some words and give theoretical justification to the search for features of language that might be preserved across wide spans of time and geography. PMID:23650390

Determining and dating recent rodent speciation events by using L1 (LINE-1) retrotransposons

PubMed Central

Verneau, Olivier; Catzeflis, François; Furano, Anthony V.

1998-01-01

Phylogenies based on the inheritance of shared derived characters will be ambiguous when the shared characters are not the result of common ancestry. Such characters are called homoplasies. Phylogenetic analysis also can be problematic if the characters have not changed sufficiently, as might be the case for rapid or recent speciations. The latter are of particular interest because evolutionary processes may be more accessible the more recent the speciation. The repeated DNA subfamilies generated by the mammalian L1 (LINE-1) retrotransposon are apparently homoplasy-free phylogenetic characters. L1 retrotransposons are transmitted only by inheritance and rapidly generate novel variants that produce distinct subfamilies of mostly defective copies, which then “age” as they diverge. Here we show that the L1 character can both resolve and date recent speciation events within the large group of very closely related rats known as Rattus sensu stricto. This lineage arose 5–6 million years ago (Mya) and subsequently underwent two episodes of speciation: an intense one, ≈2.7 Mya, produced at least five lineages in <0.3 My; a second began ≈1.2 Mya and may still be continuing. PMID:9736728

Determining and dating recent rodent speciation events by using L1 (LINE-1) retrotransposons.

PubMed

Verneau, O; Catzeflis, F; Furano, A V

1998-09-15

Phylogenies based on the inheritance of shared derived characters will be ambiguous when the shared characters are not the result of common ancestry. Such characters are called homoplasies. Phylogenetic analysis also can be problematic if the characters have not changed sufficiently, as might be the case for rapid or recent speciations. The latter are of particular interest because evolutionary processes may be more accessible the more recent the speciation. The repeated DNA subfamilies generated by the mammalian L1 (LINE-1) retrotransposon are apparently homoplasy-free phylogenetic characters. L1 retrotransposons are transmitted only by inheritance and rapidly generate novel variants that produce distinct subfamilies of mostly defective copies, which then "age" as they diverge. Here we show that the L1 character can both resolve and date recent speciation events within the large group of very closely related rats known as Rattus sensu stricto. This lineage arose 5-6 million years ago (Mya) and subsequently underwent two episodes of speciation: an intense one, approximately 2.7 Mya, produced at least five lineages in <0.3 My; a second began approximately 1.2 Mya and may still be continuing.

Ringiculid bubble snails recovered as the sister group to sea slugs (Nudipleura).

PubMed

Kano, Yasunori; Brenzinger, Bastian; Nützel, Alexander; Wilson, Nerida G; Schrödl, Michael

2016-08-08

Euthyneuran gastropods represent one of the most diverse lineages in Mollusca (with over 30,000 species), play significant ecological roles in aquatic and terrestrial environments and affect many aspects of human life. However, our understanding of their evolutionary relationships remains incomplete due to missing data for key phylogenetic lineages. The present study integrates such a neglected, ancient snail family Ringiculidae into a molecular systematics of Euthyneura for the first time, and is supplemented by the first microanatomical data. Surprisingly, both molecular and morphological features present compelling evidence for the common ancestry of ringiculid snails with the highly dissimilar Nudipleura-the most species-rich and well-known taxon of sea slugs (nudibranchs and pleurobranchoids). A new taxon name Ringipleura is proposed here for these long-lost sisters, as one of three major euthyneuran clades with late Palaeozoic origins, along with Acteonacea (Acteonoidea + Rissoelloidea) and Tectipleura (Euopisthobranchia + Panpulmonata). The early Euthyneura are suggested to be at least temporary burrowers with a characteristic 'bubble' shell, hypertrophied foot and headshield as exemplified by many extant subtaxa with an infaunal mode of life, while the expansion of the mantle might have triggered the explosive Mesozoic radiation of the clade into diverse ecological niches.

Chromera velia: The Missing Link in the Evolution of Parasitism.

PubMed

Weatherby, Kate; Carter, Dee

2013-01-01

Since the pivotal publication announcing the discovery of Chromera velia in 2008, there has been a flurry of interest and research into this novel alga. Found by chance while studying the symbionts of corals in Australian reefs, C. velia has turned out to be a very important organism. It holds a unique position as the evolutionary intermediate between photosynthetic dinoflagellate algae and parasitic apicomplexans. Biological characterization has revealed similarities to both dinoflagellates and apicomplexans. Of particular interest is the photosynthetic plastid that is closely related to the apicomplexan apicoplast. This plastid in C. velia has a highly effective photosynthetic system with photoprotective properties such as nonphotochemical quenching. The apicoplast is essential for cell health and is therefore a potential drug target for the apicomplexans that cause malaria and other diseases. The tetrapyrrole, sterol, and galactolipid pathways have been explored in C. velia to find parallels with apicomplexans that could lead to new insights to fight these parasites. Ecologically, C. velia is very similar to dinoflagellates, reflecting their common ancestry and revealing how the ancestors of apicomplexans may have lived before they evolved to become parasitic. © 2013 Elsevier Inc. All rights reserved.

BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures

PubMed Central

Medina-Gómez, Carolina; Chesi, Alessandra; Heppe, Denise H.M.; Zemel, Babette S.; Yin, Jia-Lian; Kalkwarf, Heidi J.; Hofman, Albert; Lappe, Joan M.; Kelly, Andrea; Kayser, Manfred; Oberfield, Sharon E.; Gilsanz, Vicente; Uitterlinden, André G.; Shepherd, John A.; Jaddoe, Vincent W.V.; Grant, Struan F.A.; Lao, Oscar; Rivadeneira, Fernando

2015-01-01

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait. PMID:26226985

Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL)

PubMed Central

Morrison, Jean; Laurie, Cathy C.; Marazita, Mary L.; Sanders, Anne E.; Offenbacher, Steven; Salazar, Christian R.; Conomos, Matthew P.; Thornton, Timothy; Jain, Deepti; Laurie, Cecelia A.; Kerr, Kathleen F.; Papanicolaou, George; Taylor, Kent; Kaste, Linda M.; Beck, James D.; Shaffer, John R.

2016-01-01

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18–74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20–53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10−10), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10−8) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata. PMID:26662797

Genetic Misdiagnoses and the Potential for Health Disparities.

PubMed

Manrai, Arjun K; Funke, Birgit H; Rehm, Heidi L; Olesen, Morten S; Maron, Bradley A; Szolovits, Peter; Margulies, David M; Loscalzo, Joseph; Kohane, Isaac S

2016-08-18

For more than a decade, risk stratification for hypertrophic cardiomyopathy has been enhanced by targeted genetic testing. Using sequencing results, clinicians routinely assess the risk of hypertrophic cardiomyopathy in a patient's relatives and diagnose the condition in patients who have ambiguous clinical presentations. However, the benefits of genetic testing come with the risk that variants may be misclassified. Using publicly accessible exome data, we identified variants that have previously been considered causal in hypertrophic cardiomyopathy and that are overrepresented in the general population. We studied these variants in diverse populations and reevaluated their initial ascertainments in the medical literature. We reviewed patient records at a leading genetic-testing laboratory for occurrences of these variants during the near-decade-long history of the laboratory. Multiple patients, all of whom were of African or unspecified ancestry, received positive reports, with variants misclassified as pathogenic on the basis of the understanding at the time of testing. Subsequently, all reported variants were recategorized as benign. The mutations that were most common in the general population were significantly more common among black Americans than among white Americans (P<0.001). Simulations showed that the inclusion of even small numbers of black Americans in control cohorts probably would have prevented these misclassifications. We identified methodologic shortcomings that contributed to these errors in the medical literature. The misclassification of benign variants as pathogenic that we found in our study shows the need for sequencing the genomes of diverse populations, both in asymptomatic controls and the tested patient population. These results expand on current guidelines, which recommend the use of ancestry-matched controls to interpret variants. As additional populations of different ancestry backgrounds are sequenced, we expect variant reclassifications to increase, particularly for ancestry groups that have historically been less well studied. (Funded by the National Institutes of Health.).

Genomic Variation of Inbreeding and Ancestry in the Remaining Two Isle Royale Wolves.

PubMed

Hedrick, Philip W; Kardos, Marty; Peterson, Rolf O; Vucetich, John A

2017-03-01

Inbreeding, relatedness, and ancestry have traditionally been estimated with pedigree information, however, molecular genomic data can provide more detailed examination of these properties. For example, pedigree information provides estimation of the expected value of these measures but molecular genomic data can estimate the realized values of these measures in individuals. Here, we generate the theoretical distribution of inbreeding, relatedness, and ancestry for the individuals in the pedigree of the Isle Royale wolves, the first examination of such variation in a wild population with a known pedigree. We use the 38 autosomes of the dog genome and their estimated map lengths in our genomic analysis. Although it is known that the remaining wolves are highly inbred, closely related, and descend from only 3 ancestors, our analyses suggest that there is significant variation in the realized inbreeding and relatedness around pedigree expectations. For example, the expected inbreeding in a hypothetical offspring from the 2 remaining wolves is 0.438 but the realized 95% genomic confidence interval is from 0.311 to 0.565. For individual chromosomes, a substantial proportion of the whole chromosomes are completely identical by descent. This examination provides a background to use when analyzing molecular genomic data for individual levels of inbreeding, relatedness, and ancestry. The level of variation in these measures is a function of the time to the common ancestor(s), the number of chromosomes, and the rate of recombination. In the Isle Royale wolf population, the few generations to a common ancestor results in the high variance in genomic inbreeding. © The American Genetic Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium

PubMed Central

Kabagambe, Edmond K.; Nettleton, Jennifer A.; King, Irena B.; Weng, Lu-Chen; Bhattacharya, Sayanti; Bandinelli, Stefania; Bis, Joshua C.; Rich, Stephen S.; Jacobs, David R.; Cherubini, Antonio; McKnight, Barbara; Liang, Shuang; Gu, Xiangjun; Rice, Kenneth; Laurie, Cathy C.; Lumley, Thomas; Browning, Brian L.; Psaty, Bruce M.; Chen, Yii-Der I.; Friedlander, Yechiel; Djousse, Luc; Wu, Jason H. Y.; Siscovick, David S.; Uitterlinden, André G.; Arnett, Donna K.; Ferrucci, Luigi; Fornage, Myriam; Tsai, Michael Y.; Mozaffarian, Dariush; Steffen, Lyn M.

2011-01-01

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries. PMID:21829377

JUNCTOPHILIN 3 (JPH3) EXPANSION MUTATIONS CAUSING HUNTINGTON DISEASE LIKE 2 (HDL2) ARE COMMON IN SOUTH AFRICAN PATIENTS WITH AFRICAN ANCESTRY AND A HUNTINGTON DISEASE PHENOTYPE

PubMed Central

Krause, A; Mitchell, CL; Essop, F; Tager, S; Temlett, J; Stevanin, G; Ross, CA; Rudnicki, DD; Margolis, RL

2015-01-01

Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. PMID:26079385

Genomic Evidence for Island Population Conversion Resolves Conflicting Theories of Polar Bear Evolution

PubMed Central

Cahill, James A.; Green, Richard E.; Fulton, Tara L.; Stiller, Mathias; Jay, Flora; Ovsyanikov, Nikita; Salamzade, Rauf; St. John, John; Stirling, Ian; Slatkin, Montgomery; Shapiro, Beth

2013-01-01

Despite extensive genetic analysis, the evolutionary relationship between polar bears (Ursus maritimus) and brown bears (U. arctos) remains unclear. The two most recent comprehensive reports indicate a recent divergence with little subsequent admixture or a much more ancient divergence followed by extensive admixture. At the center of this controversy are the Alaskan ABC Islands brown bears that show evidence of shared ancestry with polar bears. We present an analysis of genome-wide sequence data for seven polar bears, one ABC Islands brown bear, one mainland Alaskan brown bear, and a black bear (U. americanus), plus recently published datasets from other bears. Surprisingly, we find clear evidence for gene flow from polar bears into ABC Islands brown bears but no evidence of gene flow from brown bears into polar bears. Importantly, while polar bears contributed <1% of the autosomal genome of the ABC Islands brown bear, they contributed 6.5% of the X chromosome. The magnitude of sex-biased polar bear ancestry and the clear direction of gene flow suggest a model wherein the enigmatic ABC Island brown bears are the descendants of a polar bear population that was gradually converted into brown bears via male-dominated brown bear admixture. We present a model that reconciles heretofore conflicting genetic observations. We posit that the enigmatic ABC Islands brown bears derive from a population of polar bears likely stranded by the receding ice at the end of the last glacial period. Since then, male brown bear migration onto the island has gradually converted these bears into an admixed population whose phenotype and genotype are principally brown bear, except at mtDNA and X-linked loci. This process of genome erosion and conversion may be a common outcome when climate change or other forces cause a population to become isolated and then overrun by species with which it can hybridize. PMID:23516372

Genomic evidence for island population conversion resolves conflicting theories of polar bear evolution.

PubMed

Cahill, James A; Green, Richard E; Fulton, Tara L; Stiller, Mathias; Jay, Flora; Ovsyanikov, Nikita; Salamzade, Rauf; St John, John; Stirling, Ian; Slatkin, Montgomery; Shapiro, Beth

2013-01-01

Despite extensive genetic analysis, the evolutionary relationship between polar bears (Ursus maritimus) and brown bears (U. arctos) remains unclear. The two most recent comprehensive reports indicate a recent divergence with little subsequent admixture or a much more ancient divergence followed by extensive admixture. At the center of this controversy are the Alaskan ABC Islands brown bears that show evidence of shared ancestry with polar bears. We present an analysis of genome-wide sequence data for seven polar bears, one ABC Islands brown bear, one mainland Alaskan brown bear, and a black bear (U. americanus), plus recently published datasets from other bears. Surprisingly, we find clear evidence for gene flow from polar bears into ABC Islands brown bears but no evidence of gene flow from brown bears into polar bears. Importantly, while polar bears contributed <1% of the autosomal genome of the ABC Islands brown bear, they contributed 6.5% of the X chromosome. The magnitude of sex-biased polar bear ancestry and the clear direction of gene flow suggest a model wherein the enigmatic ABC Island brown bears are the descendants of a polar bear population that was gradually converted into brown bears via male-dominated brown bear admixture. We present a model that reconciles heretofore conflicting genetic observations. We posit that the enigmatic ABC Islands brown bears derive from a population of polar bears likely stranded by the receding ice at the end of the last glacial period. Since then, male brown bear migration onto the island has gradually converted these bears into an admixed population whose phenotype and genotype are principally brown bear, except at mtDNA and X-linked loci. This process of genome erosion and conversion may be a common outcome when climate change or other forces cause a population to become isolated and then overrun by species with which it can hybridize.

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

PubMed Central

Liang, Jingjing; Le, Thu H.; Edwards, Digna R. Velez; Tayo, Bamidele O.; Gaulton, Kyle J.; Lu, Yingchang; Jensen, Richard A.; Chen, Guanjie; Schwander, Karen; McKenzie, Colin A.; Fox, Ervin; Nalls, Michael A.; Young, J. Hunter; Lane, Jacqueline M.; Zhou, Jie; Tang, Hua; Fornage, Myriam; Musani, Solomon K.; Wang, Heming; Forrester, Terrence; Chu, Pei-Lun; Evans, Michele K.; Morrison, Alanna C.; Martin, Lisa W.; Wiggins, Kerri L.; Hui, Qin; Zhao, Wei; Jackson, Rebecca D.; Faul, Jessica D.; Reiner, Alex P.; Bray, Michael; Denny, Joshua C.; Mosley, Thomas H.; Palmas, Walter; Guo, Xiuqing; Polak, Joseph F.; Taylor, Ken D.; Boerwinkle, Eric; Bottinger, Erwin P.; Liu, Kiang; Risch, Neil; Hunt, Steven C.; Kooperberg, Charles; Zonderman, Alan B.; Becker, Diane M.; Cai, Jianwen; Loos, Ruth J. F.; Psaty, Bruce M.; Weir, David R.; Kardia, Sharon L. R.; Arnett, Donna K.; Won, Sungho; Edwards, Todd L.; Redline, Susan; Cooper, Richard S.; Rao, D. C.; Rotimi, Charles; Levy, Daniel; Chakravarti, Aravinda

2017-01-01

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension. PMID:28498854

Inferring Geographic Coordinates of Origin for Europeans Using Small Panels of Ancestry Informative Markers

PubMed Central

Paschou, Peristera

2010-01-01

Recent large-scale studies of European populations have demonstrated the existence of population genetic structure within Europe and the potential to accurately infer individual ancestry when information from hundreds of thousands of genetic markers is used. In fact, when genomewide genetic variation of European populations is projected down to a two-dimensional Principal Components Analysis plot, a surprising correlation with actual geographic coordinates of self-reported ancestry has been reported. This substructure can hamper the search of susceptibility genes for common complex disorders leading to spurious correlations. The identification of genetic markers that can correct for population stratification becomes therefore of paramount importance. Analyzing 1,200 individuals from 11 populations genotyped for more than 500,000 SNPs (Population Reference Sample), we present a systematic exploration of the extent to which geographic coordinates of origin within Europe can be predicted, with small panels of SNPs. Markers are selected to correlate with the top principal components of the dataset, as we have previously demonstrated. Performing thorough cross-validation experiments we show that it is indeed possible to predict individual ancestry within Europe down to a few hundred kilometers from actual individual origin, using information from carefully selected panels of 500 or 1,000 SNPs. Furthermore, we show that these panels can be used to correctly assign the HapMap Phase 3 European populations to their geographic origin. The SNPs that we propose can prove extremely useful in a variety of different settings, such as stratification correction or genetic ancestry testing, and the study of the history of European populations. PMID:20805874

Assessing the prevalence of hybridization between sympatric Canis species surrounding the red wolf (Canis rufus) recovery area in North Carolina.

PubMed

Bohling, Justin H; Waits, Lisette P

2011-05-01

Predicting spatial patterns of hybridization is important for evolutionary and conservation biology yet are hampered by poor understanding of how hybridizing species can interact. This is especially pertinent in contact zones where hybridizing populations are sympatric. In this study, we examined the extent of red wolf (Canis rufus) colonization and introgression where the species contacts a coyote (C. latrans) population in North Carolina, USA. We surveyed 22,000km(2) in the winter of 2008 for scat and identified individual canids through genetic analysis. Of 614 collected scats, 250 were assigned to canids by mitochondrial DNA (mtDNA) sequencing. Canid samples were genotyped at 6-17 microsatellite loci (nDNA) and assigned to species using three admixture criteria implemented in two Bayesian clustering programs. We genotyped 82 individuals but none were identified as red wolves. Two individuals had red wolf mtDNA but no significant red wolf nDNA ancestry. One individual possessed significant red wolf nDNA ancestry (approximately 30%) using all criteria, although seven other individuals showed evidence of red wolf ancestry (11-21%) using the relaxed criterion. Overall, seven individuals were classified as hybrids using the conservative criteria and 37 using the relaxed criterion. We found evidence of dog (C. familiaris) and gray wolf (C. lupus) introgression into the coyote population. We compared the performance of different methods and criteria by analyzing known red wolves and hybrids. These results suggest that red wolf colonization and introgression in North Carolina is minimal and provide insights into the utility of Bayesian clustering methods to detect hybridization. © 2011 Blackwell Publishing Ltd.

Surveillance for highly pathogenic influenza A viruses in California during 2014–2015 provides insights into viral evolutionary pathways and the spatiotemporal extent of viruses in the Pacific Americas Flyway

USGS Publications Warehouse

Ramey, Andy M.; Hill, Nichola J.; Cline, Troy; Plancarte, Magdalena; De La Cruz, Susan; Casazza, Michael L.; Ackerman, Joshua T.; Fleskes, Joseph; Vickers, T. Winston; Reeves, Andrew; Gulland, Frances; Fontaine, Christine; Prosser, Diann J.; Runstadler, Jonathan; Boyce, Walter M.

2017-01-01

We used surveillance data collected in California before, concurrent with, and subsequent to an outbreak of highly pathogenic (HP) clade 2.3.4.4 influenza A viruses (IAVs) in 2014–2015 to (i) evaluate IAV prevalence in waterfowl, (ii) assess the evidence for spill-over infections in marine mammals and (iii) genetically characterize low-pathogenic (LP) and HP IAVs to refine inference on the spatiotemporal extent of HP genome constellations and to evaluate possible evolutionary pathways. We screened samples from 1496 waterfowl and 1142 marine mammals collected from April 2014 to August 2015 and detected IAV RNA in 159 samples collected from birds (n=157) and pinnipeds (n=2). HP IAV RNA was identified in three samples originating from American wigeon (Anas americana). Genetic sequence data were generated for a clade 2.3.4.4 HP IAV-positive diagnostic sample and 57 LP IAV isolates. Phylogenetic analyses revealed that the HP IAV was a reassortant H5N8 virus with gene segments closely related to LP IAVs detected in mallards (Anas platyrhynchos) sampled in California and other IAVs detected in wild birds sampled within the Pacific Americas Flyway. In addition, our analysis provided support for common ancestry between LP IAVs recovered from waterfowl sampled in California and gene segments of reassortant HP H5N1 IAVs detected in British Columbia, Canada and Washington, USA. Our investigation provides evidence that waterfowl are likely to have played a role in the evolution of reassortant HP IAVs in the Pacific Americas Flyway during 2014–2015, whereas we did not find support for spill-over infections in potential pinniped hosts.

Genome Wide Identification, Evolutionary, and Expression Analysis of VQ Genes from Two Pyrus Species

PubMed Central

Meng, Dandan; Abdullah, Muhammad; Jin, Qing; Lin, Yi; Cai, Yongping

2018-01-01

The VQ motif-containing gene, a member of the plant-specific genes, is involved in the plant developmental process and various stress responses. The VQ motif-containing gene family has been studied in several plants, such as rice (Oryza sativa), maize (Zea mays), and Arabidopsis (Arabidopsis thaliana). However, no systematic study has been performed in Pyrus species, which have important economic value. In our study, we identified 41 and 28 VQ motif-containing genes in Pyrus bretschneideri and Pyrus communis, respectively. Phylogenetic trees were calculated using A. thaliana and O. sativa VQ motif-containing genes as a template, allowing us to categorize these genes into nine subfamilies. Thirty-two and eight paralogous of VQ motif-containing genes were found in P. bretschneideri and P. communis, respectively, showing that the VQ motif-containing genes had a more remarkable expansion in P. bretschneideri than in P. communis. A total of 31 orthologous pairs were identified from the P. bretschneideri and P. communis VQ motif-containing genes. Additionally, among the paralogs, we found that these duplication gene pairs probably derived from segmental duplication/whole-genome duplication (WGD) events in the genomes of P. bretschneideri and P. communis, respectively. The gene expression profiles in both P. bretschneideri and P. communis fruits suggested functional redundancy for some orthologous gene pairs derived from a common ancestry, and sub-functionalization or neo-functionalization for some of them. Our study provided the first systematic evolutionary analysis of the VQ motif-containing genes in Pyrus, and highlighted the diversification and duplication of VQ motif-containing genes in both P. bretschneideri and P. communis. PMID:29690608

Evolutionary processes in a continental island system: molecular phylogeography of the Aegean Nigella arvensis alliance (Ranunculaceae) inferred from chloroplast DNA.

PubMed

Bittkau, C; Comes, H P

2005-11-01

Continental shelf island systems, created by rising sea levels, provide a premier setting for studying the effects of past fragmentation, dispersal, and genetic drift on taxon diversification. We used phylogeographical (nested clade) and population genetic analyses to elucidate the relative roles of these processes in the evolutionary history of the Aegean Nigella arvensis alliance (= 'coenospecies'). We surveyed chloroplast DNA (cpDNA) variation in 455 individuals from 47 populations (nine taxa) of the alliance throughout its core range in the Aegean Archipelago and surrounding mainland areas of Greece and Turkey. The study revealed the presence of three major lineages, with largely nonoverlapping distributions in the Western, Central, and Eastern Aegean. There is evidence supporting the idea that these major lineages evolved in situ from a widespread (pan-Aegean) ancestral stock as a result of multiple fragmentation events, possibly due to the influence of post-Messinian sea flooding, Pleistocene eustatic changes and corresponding climate fluctuations. Over-sea dispersal and founder events appear to have played a rather insignificant role in the group's history. Rather, all analytical approaches identified the alliance as an organism group with poor seed dispersal capabilities and a susceptibility to genetic drift. In particular, we inferred that the observed level of cpDNA differentiation between Kikladian island populations of Nigella degenii largely reflects population history, (viz. Holocene island fragmentation) and genetic drift in the near absence of seed flow since their time of common ancestry. Overall, our cpDNA data for the N. arvensis alliance in general, and N. degenii in particular, indicate that historical events were important in determining the phylogeographical patterns seen, and that genetic drift has historically been relatively more influential on population structure than has cytoplasmic gene flow.

Surveillance for highly pathogenic influenza A viruses in California during 2014-2015 provides insights into viral evolutionary pathways and the spatiotemporal extent of viruses in the Pacific Americas Flyway.

PubMed

Ramey, Andrew M; Hill, Nichola J; Cline, Troy; Plancarte, Magdalena; De La Cruz, Susan; Casazza, Michael L; Ackerman, Joshua T; Fleskes, Joseph P; Vickers, T Winston; Reeves, Andrew B; Gulland, Frances; Fontaine, Christine; Prosser, Diann J; Runstadler, Jonathan A; Boyce, Walter M

2017-09-06

We used surveillance data collected in California before, concurrent with, and subsequent to an outbreak of highly pathogenic (HP) clade 2.3.4.4 influenza A viruses (IAVs) in 2014-2015 to (i) evaluate IAV prevalence in waterfowl, (ii) assess the evidence for spill-over infections in marine mammals and (iii) genetically characterize low-pathogenic (LP) and HP IAVs to refine inference on the spatiotemporal extent of HP genome constellations and to evaluate possible evolutionary pathways. We screened samples from 1496 waterfowl and 1142 marine mammals collected from April 2014 to August 2015 and detected IAV RNA in 159 samples collected from birds (n=157) and pinnipeds (n=2). HP IAV RNA was identified in three samples originating from American wigeon (Anas americana). Genetic sequence data were generated for a clade 2.3.4.4 HP IAV-positive diagnostic sample and 57 LP IAV isolates. Phylogenetic analyses revealed that the HP IAV was a reassortant H5N8 virus with gene segments closely related to LP IAVs detected in mallards (Anas platyrhynchos) sampled in California and other IAVs detected in wild birds sampled within the Pacific Americas Flyway. In addition, our analysis provided support for common ancestry between LP IAVs recovered from waterfowl sampled in California and gene segments of reassortant HP H5N1 IAVs detected in British Columbia, Canada and Washington, USA. Our investigation provides evidence that waterfowl are likely to have played a role in the evolution of reassortant HP IAVs in the Pacific Americas Flyway during 2014-2015, whereas we did not find support for spill-over infections in potential pinniped hosts.

Brain size evolution in pipefishes and seahorses: the role of feeding ecology, life history and sexual selection.

PubMed

Tsuboi, M; Lim, A C O; Ooi, B L; Yip, M Y; Chong, V C; Ahnesjö, I; Kolm, N

2017-01-01

Brain size varies greatly at all taxonomic levels. Feeding ecology, life history and sexual selection have been proposed as key components in generating contemporary diversity in brain size across vertebrates. Analyses of brain size evolution have, however, been limited to lineages where males predominantly compete for mating and females choose mates. Here, we present the first original data set of brain sizes in pipefishes and seahorses (Syngnathidae) a group in which intense female mating competition occurs in many species. After controlling for the effect of shared ancestry and overall body size, brain size was positively correlated with relative snout length. Moreover, we found that females, on average, had 4.3% heavier brains than males and that polyandrous species demonstrated more pronounced (11.7%) female-biased brain size dimorphism. Our results suggest that adaptations for feeding on mobile prey items and sexual selection in females are important factors in brain size evolution of pipefishes and seahorses. Most importantly, our study supports the idea that sexual selection plays a major role in brain size evolution, regardless of on which sex sexual selection acts stronger. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Social-group identity and population substructure in admixed populations in New Mexico and Latin America

PubMed Central

Healy, Meghan E.; Hill, Deirdre; Berwick, Marianne; Edgar, Heather; Gross, Jessica

2017-01-01

We examined the relationship between continental-level genetic ancestry and racial and ethnic identity in an admixed population in New Mexico with the goal of increasing our understanding of how racial and ethnic identity influence genetic substructure in admixed populations. Our sample consists of 98 New Mexicans who self-identified as Hispanic or Latino (NM-HL) and who further categorized themselves by race and ethnic subgroup membership. The genetic data consist of 270 newly-published autosomal microsatellites from the NM-HL sample and previously published data from 57 globally distributed populations, including 13 admixed samples from Central and South America. For these data, we 1) summarized the major axes of genetic variation using principal component analyses, 2) performed tests of Hardy Weinberg equilibrium, 3) compared empirical genetic ancestry distributions to those predicted under a model of admixture that lacked substructure, 4) tested the hypotheses that individuals in each sample had 100%, 0%, and the sample-mean percentage of African, European, and Native American ancestry. We found that most NM-HL identify themselves and their parents as belonging to one of two groups, conforming to a region-specific narrative that distinguishes recent immigrants from Mexico from individuals whose families have resided in New Mexico for generations and who emphasize their Spanish heritage. The “Spanish” group had significantly lower Native American ancestry and higher European ancestry than the “Mexican” group. Positive FIS values, PCA plots, and heterogeneous ancestry distributions suggest that most Central and South America admixed samples also contain substructure, and that this substructure may be related to variation in social identity. Genetic substructure appears to be common in admixed populations in the Americas and may confound attempts to identify disease-causing genes and to understand the social causes of variation in health outcomes and social inequality. PMID:28977000

A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13

PubMed Central

Leslie, Elizabeth J.; Carlson, Jenna C.; Shaffer, John R.; Feingold, Eleanor; Wehby, George; Laurie, Cecelia A.; Jain, Deepti; Laurie, Cathy C.; Doheny, Kimberly F.; McHenry, Toby; Resick, Judith; Sanchez, Carla; Jacobs, Jennifer; Emanuele, Beth; Vieira, Alexandre R.; Neiswanger, Katherine; Lidral, Andrew C.; Valencia-Ramirez, Luz Consuelo; Lopez-Palacio, Ana Maria; Valencia, Dora Rivera; Arcos-Burgos, Mauricio; Czeizel, Andrew E.; Field, L. Leigh; Padilla, Carmencita D.; Cutiongco-de la Paz, Eva Maria, C.; Deleyiannis, Frederic; Christensen, Kaare; Munger, Ronald G.; Lie, Rolv T.; Wilcox, Allen; Romitti, Paul A.; Castilla, Eduardo E.; Mereb, Juan C.; Poletta, Fernando A.; Orioli, Iêda M.; Carvalho, Flavia M.; Hecht, Jacqueline T.; Blanton, Susan H.; Buxó, Carmen J.; Butali, Azeez; Mossey, Peter A.; Adeyemo, Wasiu L.; James, Olutayo; Braimah, Ramat O.; Aregbesola, Babatunde S.; Eshete, Mekonen A.; Abate, Fikre; Koruyucu, Mine; Seymen, Figen; Ma, Lian; de Salamanca, Javier Enríquez; Weinberg, Seth M.; Moreno, Lina; Murray, Jeffrey C.; Marazita, Mary L.

2016-01-01

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case–parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10−8), and 19q13 near RHPN2, a gene involved in organizing the actin cytoskeleton (P = 4.17 × 10−8). Other regions reaching genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and 17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group revealed a novel association with a region on 17q23 (P = 2.92 × 10−8) among individuals with European ancestry. This region included several promising candidates including TANC2, an oncogene required for development, and DCAF7, a scaffolding protein required for craniofacial development. In the Central and South American ancestry group, significant associations with loci previously identified in Asian or European ancestry groups reflected their admixed ancestry. In summary, we have identified novel CL/P risk loci and suggest new genes involved in craniofacial development, confirming the highly heterogeneous etiology of OFCs. PMID:27033726

One-shot genitalia are not an evolutionary dead end - Regained male polygamy in a sperm limited spider species

PubMed Central

2011-01-01

Background Monogynous mating systems with extremely low male mating rates have several independent evolutionary origins and are associated with drastic adaptations involving self-sacrifice, one-shot genitalia, genital damage, and termination of spermatogenesis immediately after maturation. The combination of such extreme traits likely restricts evolutionary potential perhaps up to the point of making low male mating rates irreversible and hence may constitute an evolutionary dead end. Here, we explore the case of a reversion to multiple mating from monogynous ancestry in golden orb-web spiders, Nephila senegalensis. Results Male multiple mating is regained by the loss of genital damage and sexual cannibalism but spermatogenesis is terminated with maturation, restricting males to a single loading of their secondary mating organs and a fixed supply of sperm. However, males re-use their mating organs and by experimentally mating males to many females, we show that the sperm supply is divided between copulations without reloading the pedipalps. Conclusion By portioning their precious sperm supply, males achieve an average mating rate of four females which effectively doubles the maximal mating rate of their ancestors. A heritage of one-shot genitalia does not completely restrict the potential to increase mating rates in Nephila although an upper limit is defined by the available sperm load. Future studies should now investigate how males use this potential in the field and identify selection pressures responsible for a reversal from monogynous to polygynous mating strategies. PMID:21740561

Shifts in Selective Pressures on Snake Phototransduction Genes Associated with Photoreceptor Transmutation and Dim-Light Ancestry.

PubMed

Schott, Ryan K; Van Nynatten, Alexander; Card, Daren C; Castoe, Todd A; S W Chang, Belinda

2018-06-01

The visual systems of snakes are heavily modified relative to other squamates, a condition often thought to reflect their fossorial origins. Further modifications are seen in caenophidian snakes, where evolutionary transitions between rod and cone photoreceptors, termed photoreceptor transmutations, have occurred in many lineages. Little previous work, however, has focused on the molecular evolutionary underpinnings of these morphological changes. To address this, we sequenced seven snake eye transcriptomes and utilized new whole-genome and targeted capture sequencing data. We used these data to analyze gene loss and shifts in selection pressures in phototransduction genes that may be associated with snake evolutionary origins and photoreceptor transmutation. We identified the surprising loss of rhodopsin kinase (GRK1), despite a low degree of gene loss overall and a lack of relaxed selection early during snake evolution. These results provide some of the first evolutionary genomic corroboration for a dim-light ancestor that lacks strong fossorial adaptations. Our results also indicate that snakes with photoreceptor transmutation experienced significantly different selection pressures from other reptiles. Significant positive selection was found primarily in cone-specific genes, but not rod-specific genes, contrary to our expectations. These results reveal potential molecular adaptations associated with photoreceptor transmutation and also highlight unappreciated functional differences between rod- and cone-specific phototransduction proteins. This intriguing example of snake visual system evolution illustrates how the underlying molecular components of a complex system can be reshaped in response to changing selection pressures.

One-shot genitalia are not an evolutionary dead end - regained male polygamy in a sperm limited spider species.

PubMed

Schneider, Jutta M; Michalik, Peter

2011-07-08

Monogynous mating systems with extremely low male mating rates have several independent evolutionary origins and are associated with drastic adaptations involving self-sacrifice, one-shot genitalia, genital damage, and termination of spermatogenesis immediately after maturation. The combination of such extreme traits likely restricts evolutionary potential perhaps up to the point of making low male mating rates irreversible and hence may constitute an evolutionary dead end. Here, we explore the case of a reversion to multiple mating from monogynous ancestry in golden orb-web spiders, Nephila senegalensis. Male multiple mating is regained by the loss of genital damage and sexual cannibalism but spermatogenesis is terminated with maturation, restricting males to a single loading of their secondary mating organs and a fixed supply of sperm. However, males re-use their mating organs and by experimentally mating males to many females, we show that the sperm supply is divided between copulations without reloading the pedipalps. By portioning their precious sperm supply, males achieve an average mating rate of four females which effectively doubles the maximal mating rate of their ancestors. A heritage of one-shot genitalia does not completely restrict the potential to increase mating rates in Nephila although an upper limit is defined by the available sperm load. Future studies should now investigate how males use this potential in the field and identify selection pressures responsible for a reversal from monogynous to polygynous mating strategies.

What Is Genetic Ancestry Testing?

MedlinePlus

... Testing What is genetic ancestry testing? What is genetic ancestry testing? Genetic ancestry testing, or genetic genealogy, ... mixed with other groups. For more information about genetic ancestry testing: The University of Utah provides video ...

Functional anatomy and adaptation of male gorillas (Gorilla gorilla gorilla) with comparison to male orangutans (Pongo pygmaeus).

PubMed

Zihlman, Adrienne L; McFarland, Robin K; Underwood, Carol E

2011-11-01

Great apes diversified during the Miocene in Old World forests. Two lineages, gorillas in Africa and orangutans in Asia, have sexual dimorphisms of super-sized males, though they presumably diverged from a smaller common ancestor. We test the hypothesis that they increased in body mass independently and convergently, and that their many postcranial differences reflect locomotor differences. Whole body dissections of five adult male gorillas and four adult male orangutans allowed quantification of body mass distribution to limb segments, of body composition (muscle, bone, skin, and fat relative to total body mass), and of muscle distribution and proportions. Results demonstrate that gorilla forelimb anatomy accommodates shoulder joint mobility for vertical climbing and reaching while maintaining joint stability during quadrupedal locomotion. The heavily muscled hind limbs are equipped for propulsion and weight-bearing over relatively stable substrates on the forest floor. In contrast, orangutan forelimb length, muscle mass, and joint construction are modified for strength and mobility in climbing, bridging, and traveling over flexible supports through the forest canopy. Muscles of hip, knee, and ankle joints provide rotational and prehensile strength essential for moving on unstable and discontinuous branches. We conclude that anatomical similarities are due to common ancestry and that differences in postcranial anatomy reflect powerful selection for divergent locomotor adaptations. These data further support the evolutionary conclusion that gorillas fall with chimpanzees and humans as part of the African hominoid radiation; orangutans are a specialized outlier. Copyright © 2011 Wiley-Liss, Inc.

Evolution of external genitalia: insights from reptilian development.

PubMed

Gredler, Marissa L; Larkins, Christine E; Leal, Francisca; Lewis, A Kelsey; Herrera, Ana M; Perriton, Claire L; Sanger, Thomas J; Cohn, Martin J

2014-01-01

External genitalia are found in each of the major clades of amniotes. The phallus is an intromittent organ that functions to deliver sperm into the female reproductive tract for internal fertilization. The cellular and molecular genetic mechanisms of external genital development have begun to be elucidated from studies of the mouse genital tubercle, an embryonic appendage adjacent to the cloaca that is the precursor of the penis and clitoris. Progress in this area has improved our understanding of genitourinary malformations, which are among the most common birth defects in humans, and created new opportunities for comparative studies of other taxa. External genitalia evolve rapidly, which has led to a striking diversity of anatomical forms. Within the past year, studies of external genital development in non-mammalian amniotes, including birds, lizards, snakes, alligators, and turtles, have begun to shed light on the molecular and morphogenetic mechanisms underlying the diversification of phallus morphology. Here, we review recent progress in the comparative developmental biology of external genitalia and discuss the implications of this work for understanding external genital evolution. We address the question of the deep homology (shared common ancestry) of genital structures and of developmental mechanisms, and identify new areas of investigation that can be pursued by taking a comparative approach to studying development of the external genitalia. We propose an evolutionary interpretation of hypospadias, a congenital malformation of the urethra, and discuss how investigations of non-mammalian species can provide novel perspectives on human pathologies.

Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

PubMed Central

Hollenbach, Jill A.; Saperstein, Aliya; Albrecht, Mark; Vierra-Green, Cynthia; Parham, Peter; Norman, Paul J.; Maiers, Martin

2015-01-01

We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals. PMID:26287376

What are our AIMs? Interdisciplinary Perspectives on the Use of Ancestry Estimation in Disease Research

PubMed Central

Taylor, Janelle S.; Edwards, Karen L.; Fullerton, Stephanie M.

2014-01-01

Background Ancestry estimation serves as a tool to identify genetic contributions to disease but may contribute to racial discrimination and stigmatization. We sought to understand user perspectives on the benefits and harms of ancestry estimation to inform research practice and contribute to debates about the use of race and ancestry in genetics. Methods Key informant interviews with 22 scientists were conducted to examine scientists’ understandings of the benefits and harms of ancestry estimation. Results Three main perspectives were observed among key informant scientists who use ancestry estimation in genetic epidemiology research. Population geneticists self identified as educators who controlled the meaning and application of ancestry estimation in research. Clinician-researchers were optimistic about the application of ancestry estimation to individualized risk assessment and personalized medicine. Epidemiologists remained ambivalent toward ancestry estimation and suggested a continued role for race in their research. Conclusions We observed an imbalance of control over the meaning and application of ancestry estimation among disciplines that may result in unwarranted or premature translation of ancestry estimation into medicine and public health. Differences in disciplinary perspectives need to be addressed if translational benefits of genetic ancestry estimation are to be realized. PMID:25419472

A Comparative Analysis of Genetic Ancestry and Admixture in the Colombian Populations of Chocó and Medellín

PubMed Central

Conley, Andrew B.; Rishishwar, Lavanya; Norris, Emily T.; Valderrama-Aguirre, Augusto; Mariño-Ramírez, Leonardo; Medina-Rivas, Miguel A.; Jordan, I. King

2017-01-01

At least 20% of Colombians identify as having African ancestry, yielding the second largest population of Afro-descendants in Latin America. To date, there have been relatively few studies focused on the genetic ancestry of Afro-Latino populations. We report a comparative analysis of the genetic ancestry of Chocó, a state located on Colombia’s Pacific coast with a population that is >80% Afro-Colombian. We compared genome-wide patterns of genetic ancestry and admixture for Chocó to six other admixed American populations, with an emphasis on a Mestizo population from the nearby Colombian city of Medellín. One hundred sample donors from Chocó were genotyped across 610,545 genomic sites and compared with 94 publicly available whole genome sequences from Medellín. At the continental level, Chocó shows mostly African genetic ancestry (76%) with a nearly even split between European (13%) and Native American (11%) fractions, whereas Medellín has primarily European ancestry (75%), followed by Native American (18%) and African (7%). Sample donors from Chocó self-identify as having more African ancestry, and conversely less European and Native American ancestry, than can be genetically inferred, as opposed to what we previously found for Medellín, where individuals tend to overestimate levels of European ancestry. We developed a novel approach for subcontinental ancestry assignment, which allowed us to characterize subcontinental source populations for each of the three distinct continental ancestry fractions separately. Despite the clear differences between Chocó and Medellín at the level of continental ancestry, the two populations show overall patterns of subcontinental ancestry that are highly similar. Their African subcontinental ancestries are only slightly different, with Chocó showing more exclusive shared ancestry with the modern Yoruba (Nigerian) population, and Medellín having relatively more shared ancestry with West African populations in Sierra Leone and Gambia. Both populations show very similar Spanish ancestry within Europe and virtually identical patterns of Native American ancestry, with main contributions from the Embera and Waunana tribes. When the three subcontinental ancestry components are considered jointly, the populations of Chocó and Medellín are shown to be most closely related, to the exclusion of the other admixed American populations that we analyzed. We consider the implications of the existence of shared subcontinental ancestries for Colombian populations that appear, at first glance, to be clearly distinct with respect to competing notions of national identity that emphasize ethnic mixing (mestizaje) vs. group-specific identities (multiculturalism). PMID:28855283

Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children.

PubMed

Brehm, John M; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael; Boutaoui, Nadia; Forno, Erick; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Litonjua, Augusto A; Cabana, Michael; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2012-07-15

Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. A cross-sectional study was conducted of 560 children ages 6-14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P = 0.001) and atopy, and a lower FEV(1)/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P = 0.04) cases. Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.

Evaluation of Group Genetic Ancestry of Populations from Philadelphia and Dakar in the Context of Sex-Biased Admixture in the Americas

PubMed Central

Stefflova, Klara; Dulik, Matthew C.; Pai, Athma A.; Walker, Amy H.; Zeigler-Johnson, Charnita M.; Gueye, Serigne M.; Schurr, Theodore G.; Rebbeck, Timothy R.

2009-01-01

Background Population history can be reflected in group genetic ancestry, where genomic variation captured by the mitochondrial DNA (mtDNA) and non-recombining portion of the Y chromosome (NRY) can separate female- and male-specific admixture processes. Genetic ancestry may influence genetic association studies due to differences in individual admixture within recently admixed populations like African Americans. Principal Findings We evaluated the genetic ancestry of Senegalese as well as European Americans and African Americans from Philadelphia. Senegalese mtDNA consisted of ∼12% U haplotypes (U6 and U5b1b haplotypes, common in North Africa) while the NRY haplotypes belonged solely to haplogroup E. In Philadelphia, we observed varying degrees of admixture. While African Americans have 9–10% mtDNAs and ∼31% NRYs of European origin, these results are not mirrored in the mtDNA/NRY pools of European Americans: they have less than 7% mtDNAs and less than 2% NRYs from non-European sources. Additionally, there is <2% Native American contribution to Philadelphian African American ancestry and the admixture from combined mtDNA/NRY estimates is consistent with the admixture derived from autosomal genetic data. To further dissect these estimates, we have analyzed our samples in the context of different demographic groups in the Americas. Conclusions We found that sex-biased admixture in African-derived populations is present throughout the Americas, with continual influence of European males, while Native American females contribute mainly to populations of the Caribbean and South America. The high non-European female contribution to the pool of European-derived populations is consistently characteristic of Iberian colonization. These data suggest that genomic data correlate well with historical records of colonization in the Americas. PMID:19946364

Most Common SNPs Associated with Rheumatoid Arthritis in Subjects of European Ancestry Confer Risk of Rheumatoid Arthritis in African-Americans

PubMed Central

Hughes, Laura B.; Reynolds, Richard J.; Brown, Elizabeth E.; Kelley, James M.; Thomson, Brian; Conn, Doyt L.; Jonas, Beth L.; Westfall, Andrew O.; Padilla, Miguel A.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard D.; Edberg, Jeffrey C.; Kimberly, Robert P.; Moreland, Larry W.; Plenge, Robert M.; Bridges, S. Louis

2010-01-01

Objective Large-scale genetic association studies have identified over 20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African-Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA in an African-American population. Methods 27 candidate SNPs were genotyped in 556 autoantibody-positive African-Americans with RA and 791 healthy African-American controls. Odds ratios (OR) and 95% confidence intervals (CI) for each SNP were compared to previously published ORs of RA patients of European ancestry. We then calculated a composite Genetic Risk Score (GRS) for each individual based on the sum of all risk alleles. Results There was overlap in the OR and 95% CI between the European and African-American populations in 24 of the 27 candidate SNPs. Conversely, 3 of the 27 SNPs (CCR6 rs3093023, TAGAP rs394581, TNFAIP3 rs6920220) demonstrated an OR in the opposite direction from those reported in RA patients of European ancestry. The GRS analysis indicated a small but highly significant probability that African-American cases were enriched for the European RA risk alleles relative to controls (p=0.00005). Conclusion The majority of RA risk alleles previously validated among European ancestry RA patients showed similar ORs in our population of African-Americans with RA. Furthermore, the aggregate GRS supports the hypothesis that these SNPs are risk alleles for RA in the African-American population. Future large-scale genetic studies are needed to validate these risk alleles and identify novel risk alleles for RA in African-Americans. PMID:21120996

Most common single-nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans.

PubMed

Hughes, Laura B; Reynolds, Richard J; Brown, Elizabeth E; Kelley, James M; Thomson, Brian; Conn, Doyt L; Jonas, Beth L; Westfall, Andrew O; Padilla, Miguel A; Callahan, Leigh F; Smith, Edwin A; Brasington, Richard D; Edberg, Jeffrey C; Kimberly, Robert P; Moreland, Larry W; Plenge, Robert M; Bridges, S Louis

2010-12-01

Large-scale genetic association studies have identified >20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA risk in an African American population. Twenty-seven candidate single-nucleotide polymorphisms (SNPs) were genotyped in 556 autoantibody-positive African Americans with RA and 791 healthy African American control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were compared with previously published ORs for RA patients of European ancestry. We then calculated a composite genetic risk score (GRS) for each individual based on the sum of all risk alleles. Overlap of the ORs and 95% CIs between the European and African American populations was observed for 24 of the 27 candidate SNPs. Conversely, 3 of the 27 SNPs (CCR6 rs3093023, TAGAP rs394581, and TNFAIP3 rs6920220) demonstrated ORs in the opposite direction from those reported for RA patients of European ancestry. The GRS analysis indicated a small but highly significant probability that African American patients relative to control subjects were enriched for the risk alleles validated in European RA patients (P = 0.00005). The majority of RA risk alleles previously validated for RA patients of European ancestry showed similar ORs in our population of African Americans with RA. Furthermore, the aggregate GRS supports the hypothesis that these SNPs are risk alleles for RA in the African American population. Future large-scale genetic studies are needed to validate these risk alleles and identify novel RA risk alleles in African Americans. Copyright © 2010 by the American College of Rheumatology.

Analysis of Latino populations from GALA and MEC studies reveals genomic loci with biased local ancestry estimation

PubMed Central

Pasaniuc, Bogdan; Sankararaman, Sriram; Torgerson, Dara G.; Gignoux, Christopher; Zaitlen, Noah; Eng, Celeste; Rodriguez-Cintron, William; Chapela, Rocio; Ford, Jean G.; Avila, Pedro C.; Rodriguez-Santana, Jose; Chen, Gary K.; Le Marchand, Loic; Henderson, Brian; Reich, David; Haiman, Christopher A.; Gonzàlez Burchard, Esteban; Halperin, Eran

2013-01-01

Motivation: Local ancestry analysis of genotype data from recently admixed populations (e.g. Latinos, African Americans) provides key insights into population history and disease genetics. Although methods for local ancestry inference have been extensively validated in simulations (under many unrealistic assumptions), no empirical study of local ancestry accuracy in Latinos exists to date. Hence, interpreting findings that rely on local ancestry in Latinos is challenging. Results: Here, we use 489 nuclear families from the mainland USA, Puerto Rico and Mexico in conjunction with 3204 unrelated Latinos from the Multiethnic Cohort study to provide the first empirical characterization of local ancestry inference accuracy in Latinos. Our approach for identifying errors does not rely on simulations but on the observation that local ancestry in families follows Mendelian inheritance. We measure the rate of local ancestry assignments that lead to Mendelian inconsistencies in local ancestry in trios (MILANC), which provides a lower bound on errors in the local ancestry estimates. We show that MILANC rates observed in simulations underestimate the rate observed in real data, and that MILANC varies substantially across the genome. Second, across a wide range of methods, we observe that loci with large deviations in local ancestry also show enrichment in MILANC rates. Therefore, local ancestry estimates at such loci should be interpreted with caution. Finally, we reconstruct ancestral haplotype panels to be used as reference panels in local ancestry inference and show that ancestry inference is significantly improved by incoroprating these reference panels. Availability and implementation: We provide the reconstructed reference panels together with the maps of MILANC rates as a public resource for researchers analyzing local ancestry in Latinos at http://bogdanlab.pathology.ucla.edu. Contact: bpasaniuc@mednet.ucla.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23572411

The evolution of episodic memory

PubMed Central

Allen, Timothy A.; Fortin, Norbert J.

2013-01-01

One prominent view holds that episodic memory emerged recently in humans and lacks a “(neo)Darwinian evolution” [Tulving E (2002) Annu Rev Psychol 53:1–25]. Here, we review evidence supporting the alternative perspective that episodic memory has a long evolutionary history. We show that fundamental features of episodic memory capacity are present in mammals and birds and that the major brain regions responsible for episodic memory in humans have anatomical and functional homologs in other species. We propose that episodic memory capacity depends on a fundamental neural circuit that is similar across mammalian and avian species, suggesting that protoepisodic memory systems exist across amniotes and, possibly, all vertebrates. The implication is that episodic memory in diverse species may primarily be due to a shared underlying neural ancestry, rather than the result of evolutionary convergence. We also discuss potential advantages that episodic memory may offer, as well as species-specific divergences that have developed on top of the fundamental episodic memory architecture. We conclude by identifying possible time points for the emergence of episodic memory in evolution, to help guide further research in this area. PMID:23754432

Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

PubMed

Lemaitre, Rozenn N; Tanaka, Toshiko; Tang, Weihong; Manichaikul, Ani; Foy, Millennia; Kabagambe, Edmond K; Nettleton, Jennifer A; King, Irena B; Weng, Lu-Chen; Bhattacharya, Sayanti; Bandinelli, Stefania; Bis, Joshua C; Rich, Stephen S; Jacobs, David R; Cherubini, Antonio; McKnight, Barbara; Liang, Shuang; Gu, Xiangjun; Rice, Kenneth; Laurie, Cathy C; Lumley, Thomas; Browning, Brian L; Psaty, Bruce M; Chen, Yii-Der I; Friedlander, Yechiel; Djousse, Luc; Wu, Jason H Y; Siscovick, David S; Uitterlinden, André G; Arnett, Donna K; Ferrucci, Luigi; Fornage, Myriam; Tsai, Michael Y; Mozaffarian, Dariush; Steffen, Lyn M

2011-07-01

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL).

PubMed

Morrison, Jean; Laurie, Cathy C; Marazita, Mary L; Sanders, Anne E; Offenbacher, Steven; Salazar, Christian R; Conomos, Matthew P; Thornton, Timothy; Jain, Deepti; Laurie, Cecelia A; Kerr, Kathleen F; Papanicolaou, George; Taylor, Kent; Kaste, Linda M; Beck, James D; Shaffer, John R

2016-02-15

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18-74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20-53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10(-10)), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10(-8)) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

PubMed

Fan, Qiao; Verhoeven, Virginie J M; Wojciechowski, Robert; Barathi, Veluchamy A; Hysi, Pirro G; Guggenheim, Jeremy A; Höhn, René; Vitart, Veronique; Khawaja, Anthony P; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E; Williams, Katie M; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F; Joshi, Peter K; McMahon, George; St Pourcain, Beate; Evans, David M; Simpson, Claire L; Schwantes-An, Tae-Hwi; Igo, Robert P; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M; Amin, Najaf; Uitterlinden, André G; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E H; Lim, Wan'e; Beuerman, Roger W; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B; Teo, Yik-Ying; Mackey, David A; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N; Stambolian, Dwight; Wilson, Joan E Bailey; Cheng, Ching-Yu; Hammond, Christopher J; Klaver, Caroline C W; Saw, Seang-Mei; Rahi, Jugnoo S; Korobelnik, Jean-François; Kemp, John P; Timpson, Nicholas J; Smith, George Davey; Craig, Jamie E; Burdon, Kathryn P; Fogarty, Rhys D; Iyengar, Sudha K; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F; Fondran, Jeremy R; Lass, Jonathan H; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O; Jhanji, Vishal; Young, Alvin L; Döring, Angela; Raffel, Leslie J; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K H; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L; Tedja, Milly; Deangelis, Margaret M; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

2016-03-29

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

PubMed Central

Fan, Qiao; Verhoeven, Virginie J. M.; Wojciechowski, Robert; Barathi, Veluchamy A.; Hysi, Pirro G.; Guggenheim, Jeremy A.; Höhn, René; Vitart, Veronique; Khawaja, Anthony P.; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W.; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E.; Williams, Katie M.; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F.; Joshi, Peter K.; McMahon, George; St Pourcain, Beate; Evans, David M.; Simpson, Claire L.; Schwantes-An, Tae-Hwi; Igo, Robert P.; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S.; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M.; Amin, Najaf; Uitterlinden, André G.; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R.; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M. Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E. H.; Lim, Wan'e; Beuerman, Roger W.; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N.; Foster, Paul J.; Klein, Barbara E. K.; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L.; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M.; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B.; Teo, Yik-Ying; Mackey, David A.; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D.; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N.; Stambolian, Dwight; Wilson, Joan E. Bailey; Cheng, Ching-Yu; Hammond, Christopher J.; Klaver, Caroline C. W.; Saw, Seang-Mei; Rahi, Jugnoo S.; Korobelnik, Jean-François; Kemp, John P.; Timpson, Nicholas J.; Smith, George Davey; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G.; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F.; Fondran, Jeremy R.; Lass, Jonathan H.; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J.; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O.; Jhanji, Vishal; Young, Alvin L.; Döring, Angela; Raffel, Leslie J.; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K.H.; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L.; Tedja, Milly; Deangelis, Margaret M.; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

2016-01-01

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10−5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia. PMID:27020472

Inferring Genetic Ancestry: Opportunities, Challenges, and Implications

PubMed Central

Royal, Charmaine D.; Novembre, John; Fullerton, Stephanie M.; Goldstein, David B.; Long, Jeffrey C.; Bamshad, Michael J.; Clark, Andrew G.

2010-01-01

Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of “ancestry” is subject to misunderstanding in both the general and scientific communities. What do we mean by ancestry? How exactly is ancestry measured? How far back can such ancestry be defined and by which genetic tools? How do we validate inferences about ancestry in genetic research? What are the data that demonstrate our ability to do this correctly? What can we say and what can we not say from our research findings and the test results that we generate? This white paper from the American Society of Human Genetics (ASHG) Ancestry and Ancestry Testing Task Force builds upon the 2008 ASHG Ancestry Testing Summary Statement in providing a more in-depth analysis of key scientific and non-scientific aspects of genetic ancestry inference in academia and industry. It culminates with recommendations for advancing the current debate and facilitating the development of scientifically based, ethically sound, and socially attentive guidelines concerning the use of these continually evolving technologies. PMID:20466090

Genetic Heterogeneity of Self-Reported Ancestry Groups in an Admixed Brazilian Population

PubMed Central

Lins, Tulio C; Vieira, Rodrigo G; Abreu, Breno S; Gentil, Paulo; Moreno-Lima, Ricardo; Oliveira, Ricardo J; Pereira, Rinaldo W

2011-01-01

Background Population stratification is the main source of spurious results and poor reproducibility in genetic association findings. Population heterogeneity can be controlled for by grouping individuals in ethnic clusters; however, in admixed populations, there is evidence that such proxies do not provide efficient stratification control. The aim of this study was to evaluate the relation of self-reported with genetic ancestry and the statistical risk of grouping an admixed sample based on self-reported ancestry. Methods A questionnaire that included an item on self-reported ancestry was completed by 189 female volunteers from an admixed Brazilian population. Individual genetic ancestry was then determined by genotyping ancestry informative markers. Results Self-reported ancestry was classified as white, intermediate, and black. The mean difference among self-reported groups was significant for European and African, but not Amerindian, genetic ancestry. Pairwise fixation index analysis revealed a significant difference among groups. However, the increase in the chance of type 1 error was estimated to be 14%. Conclusions Self-reporting of ancestry was not an appropriate methodology to cluster groups in a Brazilian population, due to high variance at the individual level. Ancestry informative markers are more useful for quantitative measurement of biological ancestry. PMID:21498954

A Comparative Analysis of Genetic Ancestry and Admixture in the Colombian Populations of Chocó and Medellín.

PubMed

Conley, Andrew B; Rishishwar, Lavanya; Norris, Emily T; Valderrama-Aguirre, Augusto; Mariño-Ramírez, Leonardo; Medina-Rivas, Miguel A; Jordan, I King

2017-10-05

At least 20% of Colombians identify as having African ancestry, yielding the second largest population of Afro-descendants in Latin America. To date, there have been relatively few studies focused on the genetic ancestry of Afro-Latino populations. We report a comparative analysis of the genetic ancestry of Chocó, a state located on Colombia's Pacific coast with a population that is >80% Afro-Colombian. We compared genome-wide patterns of genetic ancestry and admixture for Chocó to six other admixed American populations, with an emphasis on a Mestizo population from the nearby Colombian city of Medellín. One hundred sample donors from Chocó were genotyped across 610,545 genomic sites and compared with 94 publicly available whole genome sequences from Medellín. At the continental level, Chocó shows mostly African genetic ancestry (76%) with a nearly even split between European (13%) and Native American (11%) fractions, whereas Medellín has primarily European ancestry (75%), followed by Native American (18%) and African (7%). Sample donors from Chocó self-identify as having more African ancestry, and conversely less European and Native American ancestry, than can be genetically inferred, as opposed to what we previously found for Medellín, where individuals tend to overestimate levels of European ancestry. We developed a novel approach for subcontinental ancestry assignment, which allowed us to characterize subcontinental source populations for each of the three distinct continental ancestry fractions separately. Despite the clear differences between Chocó and Medellín at the level of continental ancestry, the two populations show overall patterns of subcontinental ancestry that are highly similar. Their African subcontinental ancestries are only slightly different, with Chocó showing more exclusive shared ancestry with the modern Yoruba (Nigerian) population, and Medellín having relatively more shared ancestry with West African populations in Sierra Leone and Gambia. Both populations show very similar Spanish ancestry within Europe and virtually identical patterns of Native American ancestry, with main contributions from the Embera and Waunana tribes. When the three subcontinental ancestry components are considered jointly, the populations of Chocó and Medellín are shown to be most closely related, to the exclusion of the other admixed American populations that we analyzed. We consider the implications of the existence of shared subcontinental ancestries for Colombian populations that appear, at first glance, to be clearly distinct with respect to competing notions of national identity that emphasize ethnic mixing ( mestizaje ) vs. group-specific identities (multiculturalism). Copyright © 2017 Conley et al.

The prion-ZIP connection: From cousins to partners in iron uptake

PubMed Central

Singh, Neena; Asthana, Abhishek; Baksi, Shounak; Desai, Vilok; Haldar, Swati; Hari, Sahi; Tripathi, Ajai K

2015-01-01

ABSTRACT Converging observations from disparate lines of inquiry are beginning to clarify the cause of brain iron dyshomeostasis in sporadic Creutzfeldt-Jakob disease (sCJD), a neurodegenerative condition associated with the conversion of prion protein (PrPC), a plasma membrane glycoprotein, from α-helical to a β-sheet rich PrP-scrapie (PrPSc) isoform. Biochemical evidence indicates that PrPC facilitates cellular iron uptake by functioning as a membrane-bound ferrireductase (FR), an activity necessary for the transport of iron across biological membranes through metal transporters. An entirely different experimental approach reveals an evolutionary link between PrPC and the Zrt, Irt-like protein (ZIP) family, a group of proteins involved in the transport of zinc, iron, and manganese across the plasma membrane. Close physical proximity of PrPC with certain members of the ZIP family on the plasma membrane and increased uptake of extracellular iron by cells that co-express PrPC and ZIP14 suggest that PrPC functions as a FR partner for certain members of this family. The connection between PrPC and ZIP proteins therefore extends beyond common ancestry to that of functional cooperation. Here, we summarize evidence supporting the facilitative role of PrPC in cellular iron uptake, and implications of this activity on iron metabolism in sCJD brains. PMID:26689487

Variation in a Host-Parasitoid Interaction across Independent Populations.

PubMed

van Nouhuys, Saskya; Niemikapee, Suvi; Hanski, Ilkka

2012-12-05

Antagonistic relationships between parasitoids and their insect hosts involve multiple traits and are shaped by their ecological and evolutionary context. The parasitoid wasp Cotesia melitaearum and its host butterfly Melitaea cinxia occur in several locations around the Baltic sea, with differences in landscape structure, population sizes and the histories of the populations. We compared the virulence of the parasitoid and the susceptibility of the host from five populations in a reciprocal transplant-style experiment using the progeny of five independent host and parasitoid individuals from each population. The host populations showed significant differences in the rate of encapsulation and parasitoid development rate. The parasitoid populations differed in brood size, development rate, pupal size and adult longevity. Some trait differences depended on specific host-parasitoid combinations, but neither species performed systematically better or worse in experiments involving local versus non-local populations of the other species. Furthermore, individuals from host populations with the most recent common ancestry did not perform alike, and there was no negative effect due to a history of inbreeding in the parasitoid. The complex pattern of variation in the traits related to the vulnerability of the host and the ability of the parasitoid to exploit the host may reflect multiple functions of the traits that would hinder simple local adaptation.

Transitive homology-guided structural studies lead to discovery of Cro proteins with 40% sequence identity but different folds

PubMed Central

Roessler, Christian G.; Hall, Branwen M.; Anderson, William J.; Ingram, Wendy M.; Roberts, Sue A.; Montfort, William R.; Cordes, Matthew H. J.

2008-01-01

Proteins that share common ancestry may differ in structure and function because of divergent evolution of their amino acid sequences. For a typical diverse protein superfamily, the properties of a few scattered members are known from experiment. A satisfying picture of functional and structural evolution in relation to sequence changes, however, may require characterization of a larger, well chosen subset. Here, we employ a “stepping-stone” method, based on transitive homology, to target sequences intermediate between two related proteins with known divergent properties. We apply the approach to the question of how new protein folds can evolve from preexisting folds and, in particular, to an evolutionary change in secondary structure and oligomeric state in the Cro family of bacteriophage transcription factors, initially identified by sequence-structure comparison of distant homologs from phages P22 and λ. We report crystal structures of two Cro proteins, Xfaso 1 and Pfl 6, with sequences intermediate between those of P22 and λ. The domains show 40% sequence identity but differ by switching of α-helix to β-sheet in a C-terminal region spanning ≈25 residues. Sedimentation analysis also suggests a correlation between helix-to-sheet conversion and strengthened dimerization. PMID:18227506

The Challenges and Relevance of Exploring the Genetics of North Africa's "Barbary Lion" and the Conservation of Putative Descendants in Captivity.

PubMed

Black, Simon A

2016-01-01

The lions of North Africa were unique in ecological terms as well as from a human cultural perspective and were the definitive lions of Roman and Medieval Europe. Labelled "Barbary" lions, they were once numerous in North Africa but were exterminated by the mid-20th century. Despite subsequent degeneration of the Atlas Mountain ecosystem through human pressures, the feasibility of lion reintroduction has been debated since the 1970s. Research on the long-established captive lion collection traditionally kept by the sultans and kings of Morocco has enabled selective breeding coordinated across Moroccan and European zoos involving a significant number of animals. Molecular genetic research has recently provided insights into lion phylogeny which, despite previous suggestions that all lions share recent common ancestry, now indicates clear distinctions between lions in North, West, and Central Africa, the Middle East, and India versus those in Southern and Eastern Africa. A review of the evolutionary relevance of North African lions highlights the important challenges and opportunities in understanding relationships between Moroccan lions, extinct North African lions, and extant lion populations in India and West and Central Africa and the potential role for lions in ecosystem recovery in those regions.

The Challenges and Relevance of Exploring the Genetics of North Africa's “Barbary Lion” and the Conservation of Putative Descendants in Captivity

PubMed Central

2016-01-01

The lions of North Africa were unique in ecological terms as well as from a human cultural perspective and were the definitive lions of Roman and Medieval Europe. Labelled “Barbary” lions, they were once numerous in North Africa but were exterminated by the mid-20th century. Despite subsequent degeneration of the Atlas Mountain ecosystem through human pressures, the feasibility of lion reintroduction has been debated since the 1970s. Research on the long-established captive lion collection traditionally kept by the sultans and kings of Morocco has enabled selective breeding coordinated across Moroccan and European zoos involving a significant number of animals. Molecular genetic research has recently provided insights into lion phylogeny which, despite previous suggestions that all lions share recent common ancestry, now indicates clear distinctions between lions in North, West, and Central Africa, the Middle East, and India versus those in Southern and Eastern Africa. A review of the evolutionary relevance of North African lions highlights the important challenges and opportunities in understanding relationships between Moroccan lions, extinct North African lions, and extant lion populations in India and West and Central Africa and the potential role for lions in ecosystem recovery in those regions. PMID:27656310

Phylogeny of the "forgotten" cellular slime mold, Fonticula alba, reveals a key evolutionary branch within Opisthokonta.

PubMed

Brown, Matthew W; Spiegel, Frederick W; Silberman, Jeffrey D

2009-12-01

The shared ancestry between Fungi and animals has been unequivocally demonstrated by abundant molecular and morphological data for well over a decade. Along with the animals and Fungi, multiple protists have been placed in the supergroup Opisthokonta making it exceptionally diverse. In an effort to place the cellular slime mold Fonticula alba, an amoeboid protist with aggregative, multicellular fruiting, we sequenced five nuclear encoded genes; small subunit ribosomal RNA, actin, beta-tubulin, elongation factor 1-alpha, and the cytosolic isoform of heat shock protein 70 for phylogenetic analyses. Molecular trees demonstrate that Fonticula is an opisthokont that branches sister to filose amoebae in the genus Nuclearia. Fonticula plus Nuclearia are sister to Fungi. We propose a new name for this well-supported clade, Nucletmycea, incorporating Nuclearia, Fonticula, and Fungi. Fonticula represents the first example of a cellular slime mold morphology within Opisthokonta. Thus, there are four types of multicellularity in the supergroup-animal, fungal, colonial, and now aggregative. Our data indicate that multicellularity in Fonticula evolved independent of that found in the fungal and animal radiations. With the rapidly expanding sequence and genomic data becoming available from many opisthokont lineages, Fonticula may be fundamental to understanding opisthokont evolution as well as any possible commonalities involved with the evolution of multicellularity.

Genetic structure, divergence and admixture of Han Chinese, Japanese and Korean populations.

PubMed

Wang, Yuchen; Lu, Dongsheng; Chung, Yeun-Jun; Xu, Shuhua

2018-01-01

Han Chinese, Japanese and Korean, the three major ethnic groups of East Asia, share many similarities in appearance, language and culture etc., but their genetic relationships, divergence times and subsequent genetic exchanges have not been well studied. We conducted a genome-wide study and evaluated the population structure of 182 Han Chinese, 90 Japanese and 100 Korean individuals, together with the data of 630 individuals representing 8 populations wordwide. Our analyses revealed that Han Chinese, Japanese and Korean populations have distinct genetic makeup and can be well distinguished based on either the genome wide data or a panel of ancestry informative markers (AIMs). Their genetic structure corresponds well to their geographical distributions, indicating geographical isolation played a critical role in driving population differentiation in East Asia. The most recent common ancestor of the three populations was dated back to 3000 ~ 3600 years ago. Our analyses also revealed substantial admixture within the three populations which occurred subsequent to initial splits, and distinct gene introgression from surrounding populations, of which northern ancestral component is dominant. These estimations and findings facilitate to understanding population history and mechanism of human genetic diversity in East Asia, and have implications for both evolutionary and medical studies.

Remarkable ancient divergences amongst neglected lorisiform primates

PubMed Central

Nekaris, K. Anne‐Isola; Perkin, Andrew; Bearder, Simon K.; Pimley, Elizabeth R.; Schulze, Helga; Streicher, Ulrike; Nadler, Tilo; Kitchener, Andrew; Zischler, Hans; Zinner, Dietmar; Roos, Christian

2015-01-01

Lorisiform primates (Primates: Strepsirrhini: Lorisiformes) represent almost 10% of the living primate species and are widely distributed in sub‐Saharan Africa and South/South‐East Asia; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. In this study we report the largest molecular phylogeny in terms of the number of represented taxa. We sequenced the complete mitochondrial cytochrome b gene for 86 lorisiform specimens, including ∼80% of all the species currently recognized. Our results support the monophyly of the Galagidae, but a common ancestry of the Lorisinae and Perodicticinae (family Lorisidae) was not recovered. These three lineages have early origins, with the Galagidae and the Lorisinae diverging in the Oligocene at about 30 Mya and the Perodicticinae emerging in the early Miocene. Our mitochondrial phylogeny agrees with recent studies based on nuclear data, and supports Euoticus as the oldest galagid lineage and the polyphyletic status of Galagoides. Moreover, we have elucidated phylogenetic relationships for several species never included before in a molecular phylogeny. The results obtained in this study suggest that lorisiform diversity remains substantially underestimated and that previously unnoticed cryptic diversity might be present within many lineages, thus urgently requiring a comprehensive taxonomic revision of this primate group. © 2015 The Linnean Society of London PMID:26900177

Amerindian genetic ancestry and INDEL polymorphisms associated with susceptibility of childhood B-cell Leukemia in an admixed population from the Brazilian Amazon.

PubMed

Carvalho, Darlen C; Wanderley, Alayde V; Amador, Marcos A T; Fernandes, Marianne R; Cavalcante, Giovanna C; Pantoja, Karla B C C; Mello, Fernando A R; de Assumpção, Paulo P; Khayat, André S; Ribeiro-Dos-Santos, Ândrea; Santos, Sidney; Dos Santos, Ney P C

2015-08-20

Acute lymphoblastic leukemia (ALL) is a malignant tumor common in children. Studies of genetic susceptibility to cancer using biallelic insertion/deletion (INDEL) type polymorphisms associated with cancer development pathways may help to clarify etymology of ALL. In this study, we investigate the role of eight functional INDEL polymorphisms and influence of genetic ancestry to B-cell ALL susceptibility in children of Brazilian Amazon population, which has a high degree of inter-ethnic admixture. Ancestry analysis was estimated using a panel of 48 autosomal ancestry informative markers. 130 B-cell ALL patients and 125 healthy controls were included in this study. The odds ratios and 95% confidence intervals were adjusted for confounders. The results indicated an association between the investigated INDEL polymorphisms in CASP8 (rs3834129), CYP19A1 (rs11575899) e XRCC1 (rs3213239) genes in the development of B-cell ALL. The carriers of Insertion/Insertion (Ins/Ins) genotype of the polymorphism in CASP8 gene presented reduced chances of developing B-cell ALL (P=0.001; OR=0.353; 95% CI=0.192-0.651). The Deletion/Deletion (Del/Del) genotype of the polymorphism in CYP19A1 gene was associated to a lower chance of developing B-cell ALL (P=3.35×10 -6 ; OR=0.121; 95% CI=0.050-0.295), while Del/Del genotype of the polymorphism in XRCC1 gene was associated to a higher chance of developing B-cell ALL (P=2.01×10 -4 ; OR=6.559; 95% CI=2.433-17.681). We also found that Amerindian ancestry correlates with the risk of B-cell ALL. For each increase of 10% in the Amerindian ancestry results in 1.4-fold chances of developing B-cell ALL (OR=1.406; 95% IC=1.123-1.761), while each increase of 10% in the European ancestry presents a protection effect in the development of B-cell ALL (OR=0.666; 95% IC=0.536-0.827). The results suggest that genetic factors influence leukemogenesis and might be explored in the stratification of B-cell ALL risk in admixed populations. Copyright © 2015 Z. Published by Elsevier Ltd.. All rights reserved.

Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

PubMed

Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Dos Santos Silva, Isabel; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Veer, Laura J Van't; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

2013-04-01

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.

Large-scale genotyping identifies 41 new loci associated with breast cancer risk

PubMed Central

Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Silva, Isabel dos Santos; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Van’t Veer, Laura J; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

2013-01-01

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. PMID:23535729

AD-LIBS: inferring ancestry across hybrid genomes using low-coverage sequence data.

PubMed

Schaefer, Nathan K; Shapiro, Beth; Green, Richard E

2017-04-04

Inferring the ancestry of each region of admixed individuals' genomes is useful in studies ranging from disease gene mapping to speciation genetics. Current methods require high-coverage genotype data and phased reference panels, and are therefore inappropriate for many data sets. We present a software application, AD-LIBS, that uses a hidden Markov model to infer ancestry across hybrid genomes without requiring variant calling or phasing. This approach is useful for non-model organisms and in cases of low-coverage data, such as ancient DNA. We demonstrate the utility of AD-LIBS with synthetic data. We then use AD-LIBS to infer ancestry in two published data sets: European human genomes with Neanderthal ancestry and brown bear genomes with polar bear ancestry. AD-LIBS correctly infers 87-91% of ancestry in simulations and produces ancestry maps that agree with published results and global ancestry estimates in humans. In brown bears, we find more polar bear ancestry than has been published previously, using both AD-LIBS and an existing software application for local ancestry inference, HAPMIX. We validate AD-LIBS polar bear ancestry maps by recovering a geographic signal within bears that mirrors what is seen in SNP data. Finally, we demonstrate that AD-LIBS is more effective than HAPMIX at inferring ancestry when preexisting phased reference data are unavailable and genomes are sequenced to low coverage. AD-LIBS is an effective tool for ancestry inference that can be used even when few individuals are available for comparison or when genomes are sequenced to low coverage. AD-LIBS is therefore likely to be useful in studies of non-model or ancient organisms that lack large amounts of genomic DNA. AD-LIBS can therefore expand the range of studies in which admixture mapping is a viable tool.

From the scala naturae to the symbiogenetic and dynamic tree of life.

PubMed

Kutschera, Ulrich

2011-06-30

All living beings on Earth, from bacteria to humans, are connected through descent from common ancestors and represent the summation of their corresponding, ca. 3500 million year long evolutionary history. However, the evolution of phenotypic features is not predictable, and biologists no longer use terms such as "primitive" or "perfect organisms". Despite these insights, the Bible-based concept of the so-called "ladder of life" or Scala Naturae, i.e., the idea that all living beings can be viewed as representing various degrees of "perfection", with humans at the very top of this biological hierarchy, was popular among naturalists until ca. 1850 (Charles Bonnet, Jean Lamarck and others). Charles Darwin is usually credited with the establishment of a branched evolutionary "Tree of Life". This insight of 1859 was based on his now firmly corroborated proposals of common ancestry and natural selection. In this article I argue that Darwin was still influenced by "ladder thinking", a theological view that prevailed throughout the 19th century and is also part of Ernst Haeckel's famous Oak tree (of Life) of 1866, which is, like Darwin's scheme, static. In 1910, Constantin Mereschkowsky proposed an alternative, "anti-selectionist" concept of biological evolution, which became known as the symbiogenesis-theory. According to the symbiogenesis-scenario, eukaryotic cells evolved on a static Earth from archaic prokaryotes via the fusion and subsequent cooperation of certain microbes. In 1929, Alfred Wegener published his theory of continental drift, which was later corroborated, modified and extended. The resulting theory of plate tectonics is now the principal organizing concept of geology. Over millions of years, plate tectonics and hence the "dynamic Earth" has caused destructive volcanic eruptions and earthquakes. At the same time, it created mountain ranges, deep oceans, novel freshwater habitats, and deserts. As a result, these geologic processes destroyed numerous populations of organisms, and produced the environmental conditions for new species of animals, plants and microbes to adapt and evolve. In this article I propose a tree-like "symbiogenesis, natural selection, and dynamic Earth (synade)-model" of macroevolution that is based on these novel facts and data.

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

PubMed

Lin, Honghuang; van Setten, Jessica; Smith, Albert V; Bihlmeyer, Nathan A; Warren, Helen R; Brody, Jennifer A; Radmanesh, Farid; Hall, Leanne; Grarup, Niels; Müller-Nurasyid, Martina; Boutin, Thibaud; Verweij, Niek; Lin, Henry J; Li-Gao, Ruifang; van den Berg, Marten E; Marten, Jonathan; Weiss, Stefan; Prins, Bram P; Haessler, Jeffrey; Lyytikäinen, Leo-Pekka; Mei, Hao; Harris, Tamara B; Launer, Lenore J; Li, Man; Alonso, Alvaro; Soliman, Elsayed Z; Connell, John M; Huang, Paul L; Weng, Lu-Chen; Jameson, Heather S; Hucker, William; Hanley, Alan; Tucker, Nathan R; Chen, Yii-Der Ida; Bis, Joshua C; Rice, Kenneth M; Sitlani, Colleen M; Kors, Jan A; Xie, Zhijun; Wen, Chengping; Magnani, Jared W; Nelson, Christopher P; Kanters, Jørgen K; Sinner, Moritz F; Strauch, Konstantin; Peters, Annette; Waldenberger, Melanie; Meitinger, Thomas; Bork-Jensen, Jette; Pedersen, Oluf; Linneberg, Allan; Rudan, Igor; de Boer, Rudolf A; van der Meer, Peter; Yao, Jie; Guo, Xiuqing; Taylor, Kent D; Sotoodehnia, Nona; Rotter, Jerome I; Mook-Kanamori, Dennis O; Trompet, Stella; Rivadeneira, Fernando; Uitterlinden, André; Eijgelsheim, Mark; Padmanabhan, Sandosh; Smith, Blair H; Völzke, Henry; Felix, Stephan B; Homuth, Georg; Völker, Uwe; Mangino, Massimo; Spector, Timothy D; Bots, Michiel L; Perez, Marco; Kähönen, Mika; Raitakari, Olli T; Gudnason, Vilmundur; Arking, Dan E; Munroe, Patricia B; Psaty, Bruce M; van Duijn, Cornelia M; Benjamin, Emelia J; Rosand, Jonathan; Samani, Nilesh J; Hansen, Torben; Kääb, Stefan; Polasek, Ozren; van der Harst, Pim; Heckbert, Susan R; Jukema, J Wouter; Stricker, Bruno H; Hayward, Caroline; Dörr, Marcus; Jamshidi, Yalda; Asselbergs, Folkert W; Kooperberg, Charles; Lehtimäki, Terho; Wilson, James G; Ellinor, Patrick T; Lubitz, Steven A; Isaacs, Aaron

2018-05-01

Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability. We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval. We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction ( P <1.2×10 -6 ), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 ( P =5.9×10 -11 ) and SCN5A ( P =1.1×10 -7 ) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus. We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health. © 2018 American Heart Association, Inc.

Investigating Tree Thinking & Ancestry with Cladograms

ERIC Educational Resources Information Center

Davenport, K. D.; Milks, Kirstin Jane; Van Tassell, Rebecca

2015-01-01

Interpreting cladograms is a key skill for biological literacy. In this lesson, students interpret cladograms based on familial relationships and language relationships to build their understanding of tree thinking and to construct a definition of "common ancestor." These skills can then be applied to a true biological cladogram.

Coevolution between flight morphology, vertical stratification and sexual dimorphism: what can we learn from tropical butterflies?

PubMed

Graça, M B; Pequeno, P A C L; Franklin, E; Morais, J W

2017-10-01

Occurrence patterns are partly shaped by the affinity of species with habitat conditions. For winged organisms, flight-related attributes are vital for ecological performance. However, due to the different reproductive roles of each sex, we expect divergence in flight energy budget, and consequently different selection responses between sexes. We used tropical frugivorous butterflies as models to investigate coevolution between flight morphology, sex dimorphism and vertical stratification. We studied 94 species of Amazonian fruit-feeding butterflies sampled in seven sites across 3341 ha. We used wing-thorax ratio as a proxy for flight capacity and hierarchical Bayesian modelling to estimate stratum preference. We detected a strong phylogenetic signal in wing-thorax ratio in both sexes. Stouter fast-flying species preferred the canopy, whereas more slender slow-flying species preferred the understorey. However, this relationship was stronger in females than in males, suggesting that female phenotype associates more intimately with habitat conditions. Within species, males were stouter than females and sexual dimorphism was sharper in understorey species. Because trait-habitat relationships were independent from phylogeny, the matching between flight morphology and stratum preference is more likely to reflect adaptive radiation than shared ancestry. This study sheds light on the impact of flight and sexual dimorphism on the evolution and ecological adaptation of flying organisms. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Phylogenomics of pike cichlids (Cichlidae: Crenicichla): the rapid ecological speciation of an incipient species flock.

PubMed

Burress, E D; Alda, F; Duarte, A; Loureiro, M; Armbruster, J W; Chakrabarty, P

2018-01-01

The rapid rise of phenotypic and ecological diversity in independent lake-dwelling groups of cichlids is emblematic of the East African Great Lakes. In this study, we show that similar ecologically based diversification has occurred in pike cichlids (Crenicichla) throughout the Uruguay River drainage of South America. We collected genomic data from nearly 500 ultraconserved element (UCEs) loci and >260 000 base pairs across 33 species, to obtain a phylogenetic hypothesis for the major species groups and to evaluate the relationships and genetic structure among five closely related, endemic, co-occurring species (the Uruguay River species flock; URSF). Additionally, we evaluated ecological divergence of the URSF based on body and lower pharyngeal jaw (LPJ) shape and gut contents. Across the genus, we recovered novel relationships among the species groups. We found strong support for the monophyly of the URSF; however, relationships among these species remain problematic, likely because of the rapid and recent evolution of this clade. Clustered co-ancestry analysis recovered most species as well delimited genetic groups. The URSF species exhibit species-specific body and LPJ shapes associated with specialized trophic roles. Collectively, our results suggest that the URSF consists of incipient species that arose via ecological speciation associated with the exploration of novel trophic roles. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Ancestry-Shift Refinement Mapping of the C6orf97-ESR1 Breast Cancer Susceptibility Locus

PubMed Central

Stacey, Simon N.; Sulem, Patrick; Zanon, Carlo; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Helgason, Agnar; Jonasdottir, Aslaug; Besenbacher, Soren; Kostic, Jelena P.; Fackenthal, James D.; Huo, Dezheng; Adebamowo, Clement; Ogundiran, Temidayo; Olson, Janet E.; Fredericksen, Zachary S.; Wang, Xianshu; Look, Maxime P.; Sieuwerts, Anieta M.; Martens, John W. M.; Pajares, Isabel; Garcia-Prats, Maria D.; Ramon-Cajal, Jose M.; de Juan, Ana; Panadero, Angeles; Ortega, Eugenia; Aben, Katja K. H.; Vermeulen, Sita H.; Asadzadeh, Fatemeh; van Engelenburg, K. C. Anton; Margolin, Sara; Shen, Chen-Yang; Wu, Pei-Ei; Försti, Asta; Lenner, Per; Henriksson, Roger; Johansson, Robert; Enquist, Kerstin; Hallmans, Göran; Jonsson, Thorvaldur; Sigurdsson, Helgi; Alexiusdottir, Kristin; Gudmundsson, Julius; Sigurdsson, Asgeir; Frigge, Michael L.; Gudmundsson, Larus; Kristjansson, Kristleifur; Halldorsson, Bjarni V.; Styrkarsdottir, Unnur; Gulcher, Jeffrey R.; Hemminki, Kari; Lindblom, Annika; Kiemeney, Lambertus A.; Mayordomo, Jose I.; Foekens, John A.; Couch, Fergus J.; Olopade, Olufunmilayo I.; Gudbjartsson, Daniel F.; Thorsteinsdottir, Unnur; Rafnar, Thorunn; Johannsson, Oskar T.; Stefansson, Kari

2010-01-01

We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor α (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case∶control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2×10−3), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9×10−4) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9×10−7), was without significant heterogeneity between ancestries (Phet = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping. PMID:20661439

A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.

PubMed

Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R; Feingold, Eleanor; Wehby, George; Laurie, Cecelia A; Jain, Deepti; Laurie, Cathy C; Doheny, Kimberly F; McHenry, Toby; Resick, Judith; Sanchez, Carla; Jacobs, Jennifer; Emanuele, Beth; Vieira, Alexandre R; Neiswanger, Katherine; Lidral, Andrew C; Valencia-Ramirez, Luz Consuelo; Lopez-Palacio, Ana Maria; Valencia, Dora Rivera; Arcos-Burgos, Mauricio; Czeizel, Andrew E; Field, L Leigh; Padilla, Carmencita D; Cutiongco-de la Paz, Eva Maria C; Deleyiannis, Frederic; Christensen, Kaare; Munger, Ronald G; Lie, Rolv T; Wilcox, Allen; Romitti, Paul A; Castilla, Eduardo E; Mereb, Juan C; Poletta, Fernando A; Orioli, Iêda M; Carvalho, Flavia M; Hecht, Jacqueline T; Blanton, Susan H; Buxó, Carmen J; Butali, Azeez; Mossey, Peter A; Adeyemo, Wasiu L; James, Olutayo; Braimah, Ramat O; Aregbesola, Babatunde S; Eshete, Mekonen A; Abate, Fikre; Koruyucu, Mine; Seymen, Figen; Ma, Lian; de Salamanca, Javier Enríquez; Weinberg, Seth M; Moreno, Lina; Murray, Jeffrey C; Marazita, Mary L

2016-07-01

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10 -8 ), and 19q13 near RHPN2, a gene involved in organizing the actin cytoskeleton (P = 4.17 × 10 -8 ). Other regions reaching genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and 17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group revealed a novel association with a region on 17q23 (P = 2.92 × 10 -8 ) among individuals with European ancestry. This region included several promising candidates including TANC2, an oncogene required for development, and DCAF7, a scaffolding protein required for craniofacial development. In the Central and South American ancestry group, significant associations with loci previously identified in Asian or European ancestry groups reflected their admixed ancestry. In summary, we have identified novel CL/P risk loci and suggest new genes involved in craniofacial development, confirming the highly heterogeneous etiology of OFCs. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diversity of Wolbachia pipientis strain wPip in a genetically admixtured, above-ground Culex pipiens (Diptera: Culicidae) population: association with form molestus ancestry and host selection patterns.

PubMed

Morningstar, Rebecca J; Hamer, Gabriel L; Goldberg, Tony L; Huang, Shaoming; Andreadis, Theodore G; Walker, Edward D

2012-05-01

Analysis of molecular genetic diversity in nine marker regions of five genes within the bacteriophage WO genomic region revealed high diversity of the Wolbachia pipentis strain wPip in a population of Culex pipiens L. sampled in metropolitan Chicago, IL. From 166 blood fed females, 50 distinct genetic profiles of wPip were identified. Rarefaction analysis suggested a maximum of 110 profiles out of a possible 512 predicted by combinations of the nine markers. A rank-abundance curve showed that few strains were common and most were rare. Multiple regression showed that markers associated with gene Gp2d, encoding a partial putative capsid protein, were significantly associated with ancestry of individuals either to form molestus or form pipiens, as determined by prior microsatellite allele frequency analysis. None of the other eight markers was associated with ancestry to either form, nor to ancestry to Cx. quinquefasciatus Say. Logistic regression of host choice (mammal vs. avian) as determined by bloodmeal analysis revealed that significantly fewer individuals that had fed on mammals had the Gp9a genetic marker (58.5%) compared with avian-fed individuals (88.1%). These data suggest that certain wPip molecular genetic types are associated with genetic admixturing in the Cx. pipiens complex of metropolitan Chicago, IL, and that the association extends to phenotypic variation related to host preference.

Warfarin Pharmacogenomics in Diverse Populations.

PubMed

Kaye, Justin B; Schultz, Lauren E; Steiner, Heidi E; Kittles, Rick A; Cavallari, Larisa H; Karnes, Jason H

2017-09-01

Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin-related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race-specific or admixture-based algorithms may facilitate improved genotype-guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype-guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene-drug pairs and development of clinical recommendations for pharmacogenetic testing. © 2017 Pharmacotherapy Publications, Inc.

Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations

PubMed Central

Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L.; Nalls, Michael A.; Sung, Yun Ju; Tayo, Bamidele O.; Sun, Yan V.; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D.; Young, J. Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L.; Andrews, Jeanette S.; Smith, Jennifer A.; Faul, Jessica D.; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S.; Musani, Solomon K.; Srinivasan, Sathanur; Velez Edwards, Digna R.; Wang, Heming; Becker, Lewis C.; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I.; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W.; Evans, Michele K.; Guo, Xiuqing; Garcia, Melissa E.; Jensen, Rich; Keller, Margaux F.; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W.; Moore, Jason H.; Morrison, Alanna C.; Mosley, Thomas H.; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F.; Ridker, Paul M.; Salako, Babatunde; Singleton, Andrew B.; Shriner, Daniel; Taylor, Kent D.; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M.; Yanek, Lisa R.; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N.; Howard, Virginia J.; Karczewsk, Konrad J.; Lanktree, Matthew B.; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Jeon, Jae-Pil; Kim, Sung Soo; Han, Bok-Ghee; Cho, Yoon Shin; Sim, Xueling; Tay, Wan Ting; Ong, Rick Twee Hee; Seielstad, Mark; Liu, Jian Jun; Aung, Tin; Wong, Tien Yin; Teo, Yik Ying; Tai, E. Shyong; Chen, Chien-Hsiun; Chang, Li-ching; Chen, Yuan-Tsong; Wu, Jer-Yuarn; Kelly, Tanika N.; Gu, Dongfeng; Hixson, James E.; Sung, Yun Ju; He, Jiang; Tabara, Yasuharu; Kokubo, Yoshihiro; Miki, Tetsuro; Iwai, Naoharu; Kato, Norihiro; Takeuchi, Fumihiko; Katsuya, Tomohiro; Nabika, Toru; Sugiyama, Takao; Zhang, Yi; Huang, Wei; Zhang, Xuegong; Zhou, Xueya; Jin, Li; Zhu, Dingliang; Psaty, Bruce M.; Schork, Nicholas J.; Weir, David R.; Rotimi, Charles N.; Sale, Michele M.; Harris, Tamara; Kardia, Sharon L.R.; Hunt, Steven C.; Arnett, Donna; Redline, Susan; Cooper, Richard S.; Risch, Neil J.; Rao, D.C.; Rotter, Jerome I.; Chakravarti, Aravinda; Reiner, Alex P.; Levy, Daniel; Keating, Brendan J.; Zhu, Xiaofeng

2013-01-01

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10−8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability. PMID:23972371

Analysis of Genomic Admixture in Uyghur and Its Implication in Mapping Strategy

PubMed Central

Xu, Shuhua; Huang, Wei; Qian, Ji; Jin, Li

2008-01-01

The Uyghur (UIG) population, settled in Xinjiang, China, is a population presenting a typical admixture of Eastern and Western anthropometric traits. We dissected its genomic structure at population level, individual level, and chromosome level by using 20,177 SNPs spanning nearly the entire chromosome 21. Our results showed that UIG was formed by two-way admixture, with 60% European ancestry and 40% East Asian ancestry. Overall linkage disequilibrium (LD) in UIG was similar to that in its parental populations represented in East Asia and Europe with regard to common alleles, and UIG manifested elevation of LD only within 500 kb and at a level of 0.1 < r2 < 0.8 when ancestry-informative markers (AIMs) were used. The size of chromosomal segments that were derived from East Asian and European ancestries averaged 2.4 cM and 4.1 cM, respectively. Both the magnitude of LD and fragmentary ancestral chromosome segments indicated a long history of Uyghur. Under the assumption of a hybrid isolation (HI) model, we estimated that the admixture event of UIG occurred about 126 [107∼146] generations ago, or 2520 [2140∼2920] years ago assuming 20 years per generation. In spite of the long history and short LD of Uyghur compared with recent admixture populations such as the African-American population, we suggest that mapping by admixture LD (MALD) is still applicable in the Uyghur population but ∼10-fold AIMs are necessary for a whole-genome scan. PMID:18355773

Genetic diversity-seeing the forest through the trees

Treesearch

M. Thompson Conkle

1992-01-01

Forest trees, populations, races, species, and taxonomic groups above the species level display rich variation in biochemical markers. The variation stems from inherited modifications that trace back in time, through converging ancestries, towards common progenitors. Past movements of continents, mountain building events, and climate changes isolated forest populations...

[Genetic aspects of genealogy].

PubMed

Tetushkin, E Iu

2011-11-01

The supplementary historical discipline genealogy is also a supplementary genetic discipline. In its formation, genetics borrowed from genealogy some methods of pedigree analysis. In the 21th century, it started receiving contribution from computer-aided genealogy and genetic (molecular) genealogy. The former provides novel tools for genetics, while the latter, which employing genetic methods, enriches genetics with new evidence. Genealogists formulated three main laws ofgenealogy: the law of three generations, the law of doubling the ancestry number, and the law of declining ancestry. The significance and meaning of these laws can be fully understood only in light of genetics. For instance, a controversy between the exponential growth of the number of ancestors of an individual, i.e., the law of doubling the ancestry number, and the limited number of the humankind is explained by the presence of weak inbreeding because of sibs' interference; the latter causes the pedigrees' collapse, i.e., explains also the law of diminishing ancestry number. Mathematic modeling of pedigrees' collapse presented in a number of studies showed that the number of ancestors of each individual attains maximum in a particular generation termed ancestry saturated generation. All representatives of this and preceding generation that left progeny are common ancestors of all current members of the population. In subdivided populations, these generations are more ancient than in panmictic ones, whereas in small isolates and social strata with limited numbers of partners, they are younger. The genealogical law of three generations, according to which each hundred years contain on average three generation intervals, holds for generation lengths for Y-chromosomal DNA, typically equal to 31-32 years; for autosomal and mtDNA, this time is somewhat shorter. Moving along ascending lineas, the number of genetically effective ancestors transmitting their DNA fragment to descendants increases far slower than the number of common ancestors, because the time to the nearest common ancestor is proportional to log2N, and the time to genetically effective ancestor, to N, where N is the population size. In relatively young populations, the number of genetically effective ancestors does not exceed the number of recombination hot spots, which is equal to 25000-50000. In ancient African populations with weaker linkage disequilibrium, their number may be higher. In genealogy, the degree of kinship is measured by the number of births separating the individuals under comparison, and in genetics, by Wright's coefficients of relationship (R). Genetic frames of a "large family" are limited by the average genomic differences among the members of the human population, which constitute approximately 0.1%. Conventionally it can be assumed that it is limited by relatives, associated with the members of the given nuclear family by the 7th degree of relatedness (R approximately 0.78%). However, in the course of the HapMap project it was established that 10-30% of pairs of individuals from the same population have at least one common genome region, which they inherited from a recent common ancestor. A nuclear family, if it is not consanguinous, unites two lineages, and indirectly, a multitude of them, constituting a "suprafamily" equivalent to a population. Some problems ofgenealogy and related historical issues can be resolved only with the help of genetics. These problems include identification of "true" and "false" Rurikids and the problem of continuity of the Y-chromosomal lineage of the Romanov dynasty. On the other hand, computer-aided genealogy and molecular genealogy seem to be promising in resolving genetic problems connected to recombination and coalescence ofgenomic regions.

Geometric morphometrics as a tool for improving the comparative study of behavioural postures

NASA Astrophysics Data System (ADS)

Fureix, Carole; Hausberger, Martine; Seneque, Emilie; Morisset, Stéphane; Baylac, Michel; Cornette, Raphaël; Biquand, Véronique; Deleporte, Pierre

2011-07-01

Describing postures has always been a central concern when studying behaviour. However, attempts to compare postures objectively at phylogenetical, populational, inter- or intra-individual levels generally either rely upon a few key elements or remain highly subjective. Here, we propose a novel approach, based on well-established geometric morphometrics, to describe and to analyse postures globally (i.e. considering the animal's body posture in its entirety rather than focusing only on a few salient elements, such as head or tail position). Geometric morphometrics is concerned with describing and comparing variation and changes in the form (size and shape) of organisms using the coordinates of a series of homologous landmarks (i.e. positioned in relation to skeletal or muscular cues that are the same for different species for every variety of form and function and that have derived from a common ancestor, i.e. they have a common evolutionary ancestry, e.g. neck, wings, flipper/hand). We applied this approach to horses, using global postures (1) to characterise behaviours that correspond to different arousal levels, (2) to test potential impact of environmental changes on postures. Our application of geometric morphometrics to horse postures showed that this method can be used to characterise behavioural categories, to evaluate the impact of environmental factors (here human actions) and to compare individuals and groups. Beyond its application to horses, this promising approach could be applied to all questions involving the analysis of postures (evolution of displays, expression of emotions, stress and welfare, behavioural repertoires…) and could lead to a whole new line of research.

Effect of Genetic African Ancestry on eGFR and Kidney Disease

PubMed Central

Nadkarni, Girish N.; Belbin, Gillian; Lotay, Vaneet; Wyatt, Christina; Gottesman, Omri; Bottinger, Erwin P.; Kenny, Eimear E.; Peter, Inga

2015-01-01

Self-reported ancestry, genetically determined ancestry, and APOL1 polymorphisms are associated with variation in kidney function and related disease risk, but the relative importance of these factors remains unclear. We estimated the global proportion of African ancestry for 9048 individuals at Mount Sinai Medical Center in Manhattan (3189 African Americans, 1721 European Americans, and 4138 Hispanic/Latino Americans by self-report) using genome-wide genotype data. CKD-EPI eGFR and genotypes of three APOL1 coding variants were available. In admixed African Americans and Hispanic/Latino Americans, serum creatinine values increased as African ancestry increased (per 10% increase in African ancestry, creatinine values increased 1% in African Americans and 0.9% in Hispanic/Latino Americans; P≤1x10−7). eGFR was likewise significantly associated with African genetic ancestry in both populations. In contrast, APOL1 risk haplotypes were significantly associated with CKD, eGFR<45 ml/min per 1.73 m2, and ESRD, with effects increasing with worsening disease states and the contribution of genetic African ancestry decreasing in parallel. Using genetic ancestry in the eGFR equation to reclassify patients as black on the basis of ≥50% African ancestry resulted in higher eGFR for 14.7% of Hispanic/Latino Americans and lower eGFR for 4.1% of African Americans, affecting CKD staging in 4.3% and 1% of participants, respectively. Reclassified individuals had electrolyte values consistent with their newly assigned CKD stage. In summary, proportion of African ancestry was significantly associated with normal-range creatinine and eGFR, whereas APOL1 risk haplotypes drove the associations with CKD. Recalculation of eGFR on the basis of genetic ancestry affected CKD staging and warrants additional investigation. PMID:25349204

ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry

PubMed Central

Borghero, Giuseppe; Pugliatti, Maura; Marrosu, Francesco; Marrosu, Maria Giovanna; Murru, Maria Rita; Floris, Gianluca; Cannas, Antonino; Parish, Leslie D.; Cau, Tea B.; Loi, Daniela; Ticca, Anna; Traccis, Sebastiano; Manera, Umberto; Canosa, Antonio; Moglia, Cristina; Calvo, Andrea; Barberis, Marco; Brunetti, Maura; Renton, Alan E.; Nalls, Mike A.; Traynor, Bryan J.; Restagno, Gabriella; Chiò, Adriano

2016-01-01

Intermediate-length CAG expansions (encoding 27–33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival. PMID:26208502

The (in)famous GWAS P-value threshold revisited and updated for low-frequency variants.

PubMed

Fadista, João; Manning, Alisa K; Florez, Jose C; Groop, Leif

2016-08-01

Genome-wide association studies (GWAS) have long relied on proposed statistical significance thresholds to be able to differentiate true positives from false positives. Although the genome-wide significance P-value threshold of 5 × 10(-8) has become a standard for common-variant GWAS, it has not been updated to cope with the lower allele frequency spectrum used in many recent array-based GWAS studies and sequencing studies. Using a whole-genome- and -exome-sequencing data set of 2875 individuals of European ancestry from the Genetics of Type 2 Diabetes (GoT2D) project and a whole-exome-sequencing data set of 13 000 individuals from five ancestries from the GoT2D and T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) projects, we describe guidelines for genome- and exome-wide association P-value thresholds needed to correct for multiple testing, explaining the impact of linkage disequilibrium thresholds for distinguishing independent variants, minor allele frequency and ancestry characteristics. We emphasize the advantage of studying recent genetic isolate populations when performing rare and low-frequency genetic association analyses, as the multiple testing burden is diminished due to higher genetic homogeneity.

Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

PubMed Central

Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

2014-01-01

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

PubMed

Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

2014-09-01

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

The Genetic Ancestry of African Americans, Latinos, and European Americans across the United States

PubMed Central

Bryc, Katarzyna; Durand, Eric Y.; Macpherson, J. Michael; Reich, David; Mountain, Joanna L.

2015-01-01

Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical events, such as early Spanish colonization, waves of immigration from many regions of Europe, and forced relocation of Native Americans within the US. This study sheds light on the fine-scale differences in ancestry within and across the United States and informs our understanding of the relationship between racial and ethnic identities and genetic ancestry. PMID:25529636

Spanish genetic admixture is associated with larger V(O2) max decrement from sea level to 4338 m in Peruvian Quechua.

PubMed

Brutsaert, Tom D; Parra, Esteban J; Shriver, Mark D; Gamboa, Alfredo; Palacios, Jose-Antonio; Rivera, Maria; Rodriguez, Ivette; León-Velarde, Fabiola

2003-08-01

Quechua in the Andes may be genetically adapted to altitude and able to resist decrements in maximal O2 consumption in hypoxia (DeltaVo2 max). This hypothesis was tested via repeated measures of Vo2 max (sea level vs. 4338 m) in 30 men of mixed Spanish and Quechua origins. Individual genetic admixture level (%Spanish ancestry) was estimated by using ancestry-informative DNA markers. Genetic admixture explained a significant proportion of the variability in DeltaVo2 max after control for covariate effects, including sea level Vo2 max and the decrement in arterial O2 saturation measured at Vo2 max (DeltaSpO2 max) (R2 for admixture and covariate effects approximately 0.80). The genetic effect reflected a main effect of admixture on DeltaVo2 max (P = 0.041) and an interaction between admixture and DeltaSpO2 max (P = 0.018). Admixture predicted DeltaVo2 max only in subjects with a large DeltaSpO2 max (P = 0.031). In such subjects, DeltaVo2 max was 12-18% larger in a subgroup of subjects with high vs. low Spanish ancestry, with least squares mean values (+/-SE) of 739 +/- 71 vs. 606 +/- 68 ml/min, respectively. A trend for interaction (P = 0.095) was also noted between admixture and the decrease in ventilatory threshold at 4338 m. As previously, admixture predicted DeltaVo2 max only in subjects with a large decrease in ventilatory threshold. These findings suggest that the genetic effect on DeltaVo2 max depends on a subject's aerobic fitness. Genetic effects may be more important (or easier to detect) in athletic subjects who are more likely to show gas-exchange impairment during exercise. The results of this study are consistent with the evolutionary hypothesis and point to a better gas-exchange system in Quechua.

Pregnancy, parturition and preeclampsia in women of African ancestry.

PubMed

Nakimuli, Annettee; Chazara, Olympe; Byamugisha, Josaphat; Elliott, Alison M; Kaleebu, Pontiano; Mirembe, Florence; Moffett, Ashley

2014-06-01

Maternal and associated neonatal mortality rates in sub-Saharan Africa remain unacceptably high. In Mulago Hospital (Kampala, Uganda), 2 major causes of maternal death are preeclampsia and obstructed labor and their complications, conditions occurring at the extremes of the birthweight spectrum, a situation encapsulated as the obstetric dilemma. We have questioned whether the prevalence of these disorders occurs more frequently in indigenous African women and those with African ancestry elsewhere in the world by reviewing available literature. We conclude that these women are at greater risk of preeclampsia than other racial groups. At least part of this susceptibility seems independent of socioeconomic status and likely is due to biological or genetic factors. Evidence for a genetic contribution to preeclampsia is discussed. We go on to propose that the obstetric dilemma in humans is responsible for this situation and discuss how parturition and birthweight are subject to stabilizing selection. Other data we present also suggest that there are particularly strong evolutionary selective pressures operating during pregnancy and delivery in Africans. There is much greater genetic diversity and less linkage disequilibrium in Africa, and the genes responsible for regulating birthweight and placentation may therefore be easier to define than in non-African cohorts. Inclusion of African women into research on preeclampsia is an essential component in tackling this major disparity of maternal health. Copyright © 2014 Mosby, Inc. All rights reserved.

Pregnancy, parturition and preeclampsia in women of African ancestry

PubMed Central

Nakimuli, Annettee; Chazara, Olympe; Byamugisha, Josaphat; Elliott, Alison M.; Kaleebu, Pontiano; Mirembe, Florence; Moffett, Ashley

2014-01-01

Maternal and associated neonatal mortality rates in sub-Saharan Africa remain unacceptably high. In Mulago Hospital (Kampala, Uganda), 2 major causes of maternal death are preeclampsia and obstructed labor and their complications, conditions occurring at the extremes of the birthweight spectrum, a situation encapsulated as the obstetric dilemma. We have questioned whether the prevalence of these disorders occurs more frequently in indigenous African women and those with African ancestry elsewhere in the world by reviewing available literature. We conclude that these women are at greater risk of preeclampsia than other racial groups. At least part of this susceptibility seems independent of socioeconomic status and likely is due to biological or genetic factors. Evidence for a genetic contribution to preeclampsia is discussed. We go on to propose that the obstetric dilemma in humans is responsible for this situation and discuss how parturition and birthweight are subject to stabilizing selection. Other data we present also suggest that there are particularly strong evolutionary selective pressures operating during pregnancy and delivery in Africans. There is much greater genetic diversity and less linkage disequilibrium in Africa, and the genes responsible for regulating birthweight and placentation may therefore be easier to define than in non-African cohorts. Inclusion of African women into research on preeclampsia is an essential component in tackling this major disparity of maternal health. PMID:24184340

PGG.Population: a database for understanding the genomic diversity and genetic ancestry of human populations

PubMed Central

Zhang, Chao; Gao, Yang; Liu, Jiaojiao; Xue, Zhe; Lu, Yan; Deng, Lian; Tian, Lei; Feng, Qidi

2018-01-01

Abstract There are a growing number of studies focusing on delineating genetic variations that are associated with complex human traits and diseases due to recent advances in next-generation sequencing technologies. However, identifying and prioritizing disease-associated causal variants relies on understanding the distribution of genetic variations within and among populations. The PGG.Population database documents 7122 genomes representing 356 global populations from 107 countries and provides essential information for researchers to understand human genomic diversity and genetic ancestry. These data and information can facilitate the design of research studies and the interpretation of results of both evolutionary and medical studies involving human populations. The database is carefully maintained and constantly updated when new data are available. We included miscellaneous functions and a user-friendly graphical interface for visualization of genomic diversity, population relationships (genetic affinity), ancestral makeup, footprints of natural selection, and population history etc. Moreover, PGG.Population provides a useful feature for users to analyze data and visualize results in a dynamic style via online illustration. The long-term ambition of the PGG.Population, together with the joint efforts from other researchers who contribute their data to our database, is to create a comprehensive depository of geographic and ethnic variation of human genome, as well as a platform bringing influence on future practitioners of medicine and clinical investigators. PGG.Population is available at https://www.pggpopulation.org. PMID:29112749

HLA imputation in an admixed population: An assessment of the 1000 Genomes data as a training set.

PubMed

Nunes, Kelly; Zheng, Xiuwen; Torres, Margareth; Moraes, Maria Elisa; Piovezan, Bruno Z; Pontes, Gerlandia N; Kimura, Lilian; Carnavalli, Juliana E P; Mingroni Netto, Regina C; Meyer, Diogo

2016-03-01

Methods to impute HLA alleles based on dense single nucleotide polymorphism (SNP) data provide a valuable resource to association studies and evolutionary investigation of the MHC region. The availability of appropriate training sets is critical to the accuracy of HLA imputation, and the inclusion of samples with various ancestries is an important pre-requisite in studies of admixed populations. We assess the accuracy of HLA imputation using 1000 Genomes Project data as a training set, applying it to a highly admixed Brazilian population, the Quilombos from the state of São Paulo. To assess accuracy, we compared imputed and experimentally determined genotypes for 146 samples at 4 HLA classical loci. We found imputation accuracies of 82.9%, 81.8%, 94.8% and 86.6% for HLA-A, -B, -C and -DRB1 respectively (two-field resolution). Accuracies were improved when we included a subset of Quilombo individuals in the training set. We conclude that the 1000 Genomes data is a valuable resource for construction of training sets due to the diversity of ancestries and the potential for a large overlap of SNPs with the target population. We also show that tailoring training sets to features of the target population substantially enhances imputation accuracy. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

A SNP test to identify Africanized honeybees via proportion of 'African' ancestry.

PubMed

Chapman, Nadine C; Harpur, Brock A; Lim, Julianne; Rinderer, Thomas E; Allsopp, Michael H; Zayed, Amro; Oldroyd, Benjamin P

2015-11-01

The honeybee, Apis mellifera, is the world's most important pollinator and is ubiquitous in most agricultural ecosystems. Four major evolutionary lineages and at least 24 subspecies are recognized. Commercial populations are mainly derived from subspecies originating in Europe (75-95%). The Africanized honeybee is a New World hybrid of A. m. scutellata from Africa and European subspecies, with the African component making up 50-90% of the genome. Africanized honeybees are considered undesirable for bee-keeping in most countries, due to their extreme defensiveness and poor honey production. The international trade in honeybees is restricted, due in part to bans on the importation of queens (and semen) from countries where Africanized honeybees are extant. Some desirable strains from the United States of America that have been bred for traits such as resistance to the mite Varroa destructor are unfortunately excluded from export to countries such as Australia due to the presence of Africanized honeybees in the USA. This study shows that a panel of 95 single nucleotide polymorphisms, chosen to differentiate between the African, Eastern European and Western European lineages, can detect Africanized honeybees with a high degree of confidence via ancestry assignment. Our panel therefore offers a valuable tool to mitigate the risks of spreading Africanized honeybees across the globe and may enable the resumption of queen and bee semen imports from the Americas. © 2015 John Wiley & Sons Ltd.

A Mainly Circum-Mediterranean Origin for West Eurasian and North African mtDNAs in Puerto Rico with Strong Contributions from the Canary Islands and West Africa.

PubMed

Díaz-Zabala, Héctor J; Nieves-Colón, María A; Martínez-Cruzado, Juan C

2017-04-01

Maternal lineages of West Eurasian and North African origin account for 11.5% of total mitochondrial ancestry in Puerto Rico. Historical sources suggest that this ancestry arrived mostly from European migrations that took place during the four centuries of the Spanish colonization of Puerto Rico. This study analyzed 101 mitochondrial control region sequences and diagnostic coding region variants from a sample set randomly and systematically selected using a census-based sampling frame to be representative of the Puerto Rican population, with the goal of defining West Eurasian-North African maternal clades and estimating their possible geographical origin. Median-joining haplotype networks were constructed using hypervariable regions 1 and 2 sequences from various reference populations in search of shared haplotypes. A posterior probability analysis was performed to estimate the percentage of possible origins across wide geographic regions for the entire sample set and for the most common haplogroups on the island. Principal component analyses were conducted to place the Puerto Rican mtDNA set within the variation present among all reference populations. Our study shows that up to 38% of West Eurasian and North African mitochondrial ancestry in Puerto Rico most likely migrated from the Canary Islands. However, most of those haplotypes had previously migrated to the Canary Islands from elsewhere, and there are substantial contributions from various populations across the circum-Mediterranean region and from West African populations related to the modern Wolof and Serer peoples from Senegal and the nomad Fulani who extend up to Cameroon. In conclusion, the West Eurasian mitochondrial ancestry in Puerto Ricans is geographically diverse. However, haplotype diversity seems to be low, and frequencies have been shaped by population bottlenecks, migration waves, and random genetic drift. Consequently, approximately 47% of mtDNAs of West Eurasian and North African ancestry in Puerto Rico probably arrived early in its colonial history.

Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children

PubMed Central

Brehm, John M.; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael; Boutaoui, Nadia; Forno, Erick; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Litonjua, Augusto A.; Cabana, Michael; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa

2012-01-01

Rationale: Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. Objectives: To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. Methods: A cross-sectional study was conducted of 560 children ages 6–14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Measurements and Main Results: Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5–4.9; P = 0.001) and atopy, and a lower FEV1/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2–21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1–4.1; P = 0.04) cases. Conclusions: Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control. PMID:22652028

Known genetic susceptibility factors for chronic pancreatitis in patients of European ancestry are rare in patients of African ancestry.

PubMed

Phillips, Anna Evans; LaRusch, Jessica; Greer, Phil; Abberbock, Judah; Alkaade, Samer; Amann, Stephen T; Anderson, Michelle A; Baillie, John; Banks, Peter A; Brand, Randall E; Conwell, Darwin; Coté, Gregory A; Forsmark, Christopher E; Gardner, Timothy B; Gelrud, Andres; Guda, Nalini; Lewis, Michele; Money, Mary E; Muniraj, Thiruvengadam; Sandhu, Bimaljit S; Sherman, Stuart; Singh, Vikesh K; Slivka, Adam; Tang, Gong; Wilcox, C Mel; Whitcomb, David C; Yadav, Dhiraj

2018-05-19

Multiple pathogenic genetic variants are associated with pancreatitis in patients of European (EA) and Asian ancestries, but studies on patients of African ancestry (AA) are lacking. We evaluated the prevalence of known genetic variations in African-American subjects in the US. We studied prospectively enrolled controls (n = 238) and patients with chronic (CP) (n = 232) or recurrent acute pancreatitis (RAP) (n = 45) in the NAPS2 studies from 2000-2014 of self-identified AA. Demographic and phenotypic information was obtained from structured questionnaires. Ancestry and admixture were evaluated by principal component analysis (PCA). Genotyping was performed for pathogenic genetic variants in PRSS1, SPINK1, CFTR and CTRC. Prevalence of disease-associated variants in NAPS2 subjects of AA and EA was compared. When compared with CP subjects of EA (n = 862), prevalence of established pathogenic genetic variants was infrequent in AA patients with CP, overall (29 vs. 8.19%, OR 4.60, 95% CI 2.74-7.74, p < 0.001), and after stratification by alcohol etiology (p < 0.001). On PCA, AA cases were more heterogeneous but distinct from EA subjects; no difference was observed between AA subjects with and without CP-associated variants. Of 19 A A patients with CP who had pathogenic genetic variants, 2 had variants in PRSS1 (R122H, R122C), 4 in SPINK1 (all N34S heterozygotes), 12 in CFTR (2 CFTR sev , 9 CFTR BD , 1 compound heterozygote with CFTR sev and CFTR BD ), and 1 in CTRC (R254W). Pathogenic genetic variants reported in EA patients are significantly less common in AA patients. Further studies are needed to determine the complex risk factors for AA subjects with pancreatitis. Copyright © 2018. Published by Elsevier B.V.

Identification of genetic risk associated with prostate cancer using ancestry informative markers

PubMed Central

Ricks-Santi, LJ; Apprey, V; Mason, T; Wilson, B; Abbas, M; Hernandez, W; Hooker, S; Doura, M; Bonney, G; Dunston, G; Kittles, R; Ahaghotu, C

2014-01-01

BACKGROUND Prostate cancer (PCa) is a common malignancy and a leading cause of cancer death among men in the United States with African-American (AA) men having the highest incidence and mortality rates. Given recent results from admixture mapping and genome-wide association studies for PCa in AA men, it is clear that many risk alleles are enriched in men with West African genetic ancestry. METHODS A total of 77 ancestry informative markers (AIMs) within surrounding candidate gene regions were genotyped and haplotyped using Pyrosequencing in 358 unrelated men enrolled in a PCa genetic association study at the Howard University Hospital between 2000 and 2004. Sequence analysis of promoter region single-nucleotide polymorphisms (SNPs) to evaluate disruption of transcription factor-binding sites was conducted using in silico methods. RESULTS Eight AIMs were significantly associated with PCa risk after adjusting for age and West African ancestry. SNP rs1993973 (intervening sequences) had the strongest association with PCa using the log-additive genetic model (P = 0.002). SNPs rs1561131 (genotypic, P = 0.007), rs1963562 (dominant, P = 0.01) and rs615382 (recessive, P = 0.009) remained highly significant after adjusting for both age and ancestry. We also tested the independent effect of each significantly associated SNP and rs1561131 (P = 0.04) and rs1963562 (P = 0.04) remained significantly associated with PCa development. After multiple comparisons testing using the false discovery rate, rs1993973 remained significant. Analysis of the rs156113–, rs1963562–rs615382l and rs1993973–rs585224 haplotypes revealed that the least frequently found haplotypes in this population were significantly associated with a decreased risk of PCa (P = 0.032 and 0.0017, respectively). CONCLUSIONS The approach for SNP selection utilized herein showed that AIMs may not only leverage increased linkage disequilibrium in populations to identify risk and protective alleles, but may also be informative in dissecting the biology of PCa and other health disparities. PMID:22801071

Applying Ancestry and Sex Computation as a Quality Control Tool in Targeted Next-Generation Sequencing.

PubMed

Mathias, Patrick C; Turner, Emily H; Scroggins, Sheena M; Salipante, Stephen J; Hoffman, Noah G; Pritchard, Colin C; Shirts, Brian H

2016-03-01

To apply techniques for ancestry and sex computation from next-generation sequencing (NGS) data as an approach to confirm sample identity and detect sample processing errors. We combined a principal component analysis method with k-nearest neighbors classification to compute the ancestry of patients undergoing NGS testing. By combining this calculation with X chromosome copy number data, we determined the sex and ancestry of patients for comparison with self-report. We also modeled the sensitivity of this technique in detecting sample processing errors. We applied this technique to 859 patient samples with reliable self-report data. Our k-nearest neighbors ancestry screen had an accuracy of 98.7% for patients reporting a single ancestry. Visual inspection of principal component plots was consistent with self-report in 99.6% of single-ancestry and mixed-ancestry patients. Our model demonstrates that approximately two-thirds of potential sample swaps could be detected in our patient population using this technique. Patient ancestry can be estimated from NGS data incidentally sequenced in targeted panels, enabling an inexpensive quality control method when coupled with patient self-report. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

PubMed Central

Emery, Leslie S.; Magnaye, Kevin M.; Bigham, Abigail W.; Akey, Joshua M.; Bamshad, Michael J.

2015-01-01

The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

Health and genetic ancestry testing: time to bridge the gap.

PubMed

Smart, Andrew; Bolnick, Deborah A; Tutton, Richard

2017-01-09

It is becoming increasingly difficult to keep information about genetic ancestry separate from information about health, and consumers of genetic ancestry tests are becoming more aware of the potential health risks associated with particular ancestral lineages. Because some of the proposed associations have received little attention from oversight agencies and professional genetic associations, scientific developments are currently outpacing governance regimes for consumer genetic testing. We highlight the recent and unremarked upon emergence of biomedical studies linking markers of genetic ancestry to disease risks, and show that this body of scientific research is becoming part of public discourse connecting ancestry and health. For instance, data on genome-wide ancestry informative markers are being used to assess health risks, and we document over 100 biomedical research articles that propose associations between mitochondrial DNA and Y chromosome markers of genetic ancestry and a wide variety of disease risks. Taking as an example an association between coronary heart disease and British men belonging to Y chromosome haplogroup I, we show how this science was translated into mainstream and online media, and how it circulates among consumers of genetic tests for ancestry. We find wide variations in how the science is interpreted, which suggests the potential for confusion or misunderstanding. We recommend that stakeholders involved in creating and using estimates of genetic ancestry reconsider their policies for communicating with each other and with the public about the health implications of ancestry information.

The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions

PubMed Central

Magalhães da Silva, Thiago; Sandhya Rani, M R; de Oliveira Costa, Gustavo Nunes; Figueiredo, Maria A; Melo, Paulo S; Nascimento, João F; Molyneaux, Neil D; Barreto, Maurício L; Reis, Mitermayer G; Teixeira, M Glória; Blanton, Ronald E

2015-01-01

The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of ‘race' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3–5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry. PMID:25293718

Investigating relationships between ancestry, lifestyle behaviors and perceptions of heart disease and breast cancer among Canadian women with British and with South Asian ancestry.

PubMed

Curtin, Kimberley D; Berry, Tanya R; Courneya, Kerry S; McGannon, Kerry R; Norris, Colleen M; Rodgers, Wendy M; Spence, John C

2018-04-01

Ethnic minority groups including Asians in Canada have different knowledge and perceptions of heart disease and breast cancer compared with the ethnic majority group. Examine relationships between perceptions of heart disease and breast cancer, and lifestyle behaviors for Canadian women with British and with South Asian ancestry. Women with South Asian ( n = 170) and with British ( n = 373) ancestry ( M age = 33.01, SD = 12.86) reported leisure time physical activity, intended fruit and vegetable consumption, disease perceptions (ability to reduce risk, control over getting the diseases, and influence of family history), and demographic information. Mann-Whitney tests and multiple hierarchical linear regressions were used to examine the relationships between lifestyle behaviors and disease perceptions, with ancestry explored as a possible moderator. Participants with South Asian ancestry believed they had greater ability to reduce their risk and have control over getting breast cancer than participants with British ancestry. Family history influences on getting either disease was perceived as higher for women with British ancestry. Age was positively related to all three perceptions in both diseases. Intended fruit and vegetable consumption was positively related to perceptions of ability to reduce risk and control of both diseases, but was stronger for women with South Asian ancestry regarding perceptions of breast cancer. Leisure time physical activity was positively related to perceptions of control over getting heart disease for women with British ancestry. Women's disease perceptions can vary by ancestry and lifestyle behaviors. Accurate representation of diseases is essential in promoting effective preventative behaviors.

Signature Concepts of Key Researchers in North American Higher Education Teaching and Learning

ERIC Educational Resources Information Center

Kandlbinder, Peter

2015-01-01

Universities in the English-speaking world share a common ancestry that extends back to medieval times. From these beginnings universities quickly developed distinctive qualities as they became integrated within different social and cultural systems of their home societies. A number of comparisons of higher education research have shown major…

THE CRYSTAL STRUCTURE AND AMINO ACID SEQUENCE OF DEHALOPEROXIDASE FROM AMPHITRITE ORNATA INDICATE COMMON ANCESTRY WITH GLOBINS. (R827612E02)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Divergent Viruses Discovered in Arthropods and Vertebrates Revise the Evolutionary History of the Flaviviridae and Related Viruses.

PubMed

Shi, Mang; Lin, Xian-Dan; Vasilakis, Nikos; Tian, Jun-Hua; Li, Ci-Xiu; Chen, Liang-Jun; Eastwood, Gillian; Diao, Xiu-Nian; Chen, Ming-Hui; Chen, Xiao; Qin, Xin-Cheng; Widen, Steven G; Wood, Thomas G; Tesh, Robert B; Xu, Jianguo; Holmes, Edward C; Zhang, Yong-Zhen

2016-01-15

Viruses of the family Flaviviridae are important pathogens of humans and other animals and are currently classified into four genera. To better understand their diversity, evolutionary history, and genomic flexibility, we used transcriptome sequencing (RNA-seq) to search for the viruses related to the Flaviviridae in a range of potential invertebrate and vertebrate hosts. Accordingly, we recovered the full genomes of five segmented jingmenviruses and 12 distant relatives of the known Flaviviridae ("flavi-like" viruses) from a range of arthropod species. Although these viruses are highly divergent, they share a similar genomic plan and common ancestry with the Flaviviridae in the NS3 and NS5 regions. Remarkably, although these viruses fill in major gaps in the phylogenetic diversity of the Flaviviridae, genomic comparisons reveal important changes in genome structure, genome size, and replication/gene regulation strategy during evolutionary history. In addition, the wide diversity of flavi-like viruses found in invertebrates, as well as their deep phylogenetic positions, suggests that they may represent the ancestral forms from which the vertebrate-infecting viruses evolved. For the vertebrate viruses, we expanded the previously mammal-only pegivirus-hepacivirus group to include a virus from the graceful catshark (Proscyllium habereri), which in turn implies that these viruses possess a larger host range than is currently known. In sum, our data show that the Flaviviridae infect a far wider range of hosts and exhibit greater diversity in genome structure than previously anticipated. The family Flaviviridae of RNA viruses contains several notorious human pathogens, including dengue virus, West Nile virus, and hepatitis C virus. To date, however, our understanding of the biodiversity and evolution of the Flaviviridae has largely been directed toward vertebrate hosts and their blood-feeding arthropod vectors. Therefore, we investigated an expanded group of potential arthropod and vertebrate host species that have generally been ignored by surveillance programs. Remarkably, these species contained diverse flaviviruses and related viruses that are characterized by major changes in genome size and genome structure, such that these traits are more flexible than previously thought. More generally, these data suggest that arthropods may be the ultimate reservoir of the Flaviviridae and related viruses, harboring considerable genetic and phenotypic diversity. In sum, this study revises the traditional view on the evolutionary history, host range, and genomic structures of a major group of RNA viruses. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Forensic STR loci reveal common genetic ancestry of the Thai-Malay Muslims and Thai Buddhists in the deep Southern region of Thailand.

PubMed

Kutanan, Wibhu; Kitpipit, Thitika; Phetpeng, Sukanya; Thanakiatkrai, Phuvadol

2014-12-01

Among the people living in the five deep Southern Thai provinces, Thai-Malay Muslims (MUS) constitute the majority, while the remaining are Thai Buddhists (BUD). Cultural, linguistic and religious differences between these two populations have been previously reported. However, their biological relationship has never been investigated. In this study, we aimed to reveal the genetic structure and genetic affinity between MUS and BUD by analyzing 15 autosomal short tandem repeats. Both distance and model-based clustering methods showed significant genetic homogeneity between these two populations, suggesting a common biological ancestry. After Islamization in this region during the fourteenth century AD, gradual albeit nonstatistically significant genetic changes occurred within these two populations. Cultural barriers possibly influenced these genetic changes. MUS have closer admixture to Malaysian-Malay Muslims than BUD countrywide. Admixture proportions also support certain degree of genetic dissimilarity between the two studied populations, as shown by the unequal genetic contribution from Malaysian-Malay Muslims. Cultural transformation and recent minor genetic admixture are the likely processes that shaped the genetic structure of both MUS and BUD.

Sex determination, longevity, and the birth and death of reptilian species.

PubMed

Sabath, Niv; Itescu, Yuval; Feldman, Anat; Meiri, Shai; Mayrose, Itay; Valenzuela, Nicole

2016-08-01

Vertebrate sex-determining mechanisms (SDMs) are triggered by the genotype (GSD), by temperature (TSD), or occasionally, by both. The causes and consequences of SDM diversity remain enigmatic. Theory predicts SDM effects on species diversification, and life-span effects on SDM evolutionary turnover. Yet, evidence is conflicting in clades with labile SDMs, such as reptiles. Here, we investigate whether SDM is associated with diversification in turtles and lizards, and whether alterative factors, such as lifespan's effect on transition rates, could explain the relative prevalence of SDMs in turtles and lizards (including and excluding snakes). We assembled a comprehensive dataset of SDM states for squamates and turtles and leveraged large phylogenies for these two groups. We found no evidence that SDMs affect turtle, squamate, or lizard diversification. However, SDM transition rates differ between groups. In lizards TSD-to-GSD surpass GSD-to-TSD transitions, explaining the predominance of GSD lizards in nature. SDM transitions are fewer in turtles and the rates are similar to each other (TSD-to-GSD equals GSD-to-TSD), which, coupled with TSD ancestry, could explain TSD's predominance in turtles. These contrasting patterns can be explained by differences in life history. Namely, our data support the notion that in general, shorter lizard lifespan renders TSD detrimental favoring GSD evolution in squamates, whereas turtle longevity permits TSD retention. Thus, based on the macro-evolutionary evidence we uncovered, we hypothesize that turtles and lizards followed different evolutionary trajectories with respect to SDM, likely mediated by differences in lifespan. Combined, our findings revealed a complex evolutionary interplay between SDMs and life histories that warrants further research that should make use of expanded datasets on unexamined taxa to enable more conclusive analyses.

A comprehensive examination of breast cancer risk loci in African American women

PubMed Central

Feng, Ye; Stram, Daniel O.; Rhie, Suhn Kyong; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F.; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Palmer, Julie R.; Olopade, Olufunmilayo I.; Huo, Dezheng; Adebamowo, Clement A.; Ogundiran, Temidayo; Chen, Gary K.; Stram, Alex; Park, Karen; Rand, Kristin A.; Chanock, Stephen J.; Le Marchand, Loic; Kolonel, Laurence N.; Conti, David V.; Easton, Douglas; Henderson, Brian E.; Haiman, Christopher A.

2014-01-01

Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10−6) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65–70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry. PMID:24852375

Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

PubMed

Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L; Nalls, Michael A; Sung, Yun Ju; Tayo, Bamidele O; Sun, Yan V; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D; Young, J Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L; Andrews, Jeanette S; Smith, Jennifer A; Faul, Jessica D; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S; Musani, Solomon K; Srinivasan, Sathanur; Velez Edwards, Digna R; Wang, Heming; Becker, Lewis C; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W; Evans, Michele K; Guo, Xiuqing; Garcia, Melissa E; Jensen, Rich; Keller, Margaux F; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W; Moore, Jason H; Morrison, Alanna C; Mosley, Thomas H; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F; Ridker, Paul M; Salako, Babatunde; Singleton, Andrew B; Shriner, Daniel; Taylor, Kent D; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M; Yanek, Lisa R; Zhao, Wei; Zonderman, Alan B; Becker, Diane M; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N; Howard, Virginia J; Karczewsk, Konrad J; Lanktree, Matthew B; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Psaty, Bruce M; Schork, Nicholas J; Weir, David R; Rotimi, Charles N; Sale, Michele M; Harris, Tamara; Kardia, Sharon L R; Hunt, Steven C; Arnett, Donna; Redline, Susan; Cooper, Richard S; Risch, Neil J; Rao, D C; Rotter, Jerome I; Chakravarti, Aravinda; Reiner, Alex P; Levy, Daniel; Keating, Brendan J; Zhu, Xiaofeng

2013-09-05

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative.

PubMed

Perez, Marco V; Hoffmann, Thomas J; Tang, Hua; Thornton, Timothy; Stefanick, Marcia L; Larson, Joseph C; Kooperberg, Charles; Reiner, Alex P; Caan, Bette; Iribarren, Carlos; Risch, Neil

2013-09-01

Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk. The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses. Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort. African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans. © 2013.

Conservation genetics and evolution in an endangered species: research in Sonoran topminnows*

PubMed Central

Hedrick, Philip W; Hurt, Carla R

2012-01-01

Conservation genetics of endangered species has primarily focused on using neutral markers to determine units of conservation and estimating evolutionary parameters. Because the endangered Sonoran topminnow can be bred in the laboratory and has a relatively short generation length, experiments to examine both detrimental and adaptive variations are also possible. Here, we discuss over two decades of empirical and experimental observations in the Sonoran topminnow. Results from this research have been used to determine species and evolutionary significant units using neutral markers, document inbreeding and outbreeding depression and genetic load using experimental crosses, and measure adaptive differences in fitness-related traits and variation in pathogen resistance among populations and major histocompatibility complex genotypes. In addition, both premating and postmating reproductive isolation between Gila and Yaqui topminnows have been experimentally determined, and the predicted and observed ancestry of these two species in experimental crosses has been examined over time. Although some have suggested that endangered species are unsuitable for experimentation because of both practical and ethical considerations, these results demonstrate that in this case an endangered species can be employed to examine fundamental questions in conservation and evolution. PMID:23346226

Adaptive genomic evolution of opsins reveals that early mammals flourished in nocturnal environments.

PubMed

Borges, Rui; Johnson, Warren E; O'Brien, Stephen J; Gomes, Cidália; Heesy, Christopher P; Antunes, Agostinho

2018-02-05

Based on evolutionary patterns of the vertebrate eye, Walls (1942) hypothesized that early placental mammals evolved primarily in nocturnal habitats. However, not only Eutheria, but all mammals show photic characteristics (i.e. dichromatic vision, rod-dominated retina) suggestive of a scotopic eye design. Here, we used integrative comparative genomic and phylogenetic methodologies employing the photoreceptive opsin gene family in 154 mammals to test the likelihood of a nocturnal period in the emergence of all mammals. We showed that mammals possess genomic patterns concordant with a nocturnal ancestry. The loss of the RH2, VA, PARA, PARIE and OPN4x opsins in all mammals led us to advance a probable and most-parsimonious hypothesis of a global nocturnal bottleneck that explains the loss of these genes in the emerging lineage (> > 215.5 million years ago). In addition, ancestral character reconstruction analyses provided strong evidence that ancestral mammals possessed a nocturnal lifestyle, ultra-violet-sensitive vision, low visual acuity and low orbit convergence (i.e. panoramic vision). Overall, this study provides insight into the evolutionary history of the mammalian eye while discussing important ecological aspects of the photic paleo-environments ancestral mammals have occupied.

The evolutionary origins of diadromy inferred from a time-calibrated phylogeny for Clupeiformes (herring and allies).

PubMed

Bloom, Devin D; Lovejoy, Nathan R

2014-03-07

One of the most remarkable types of migration found in animals is diadromy, a life-history behaviour in which individuals move between oceans and freshwater habitats for feeding and reproduction. Diadromous fishes include iconic species such as salmon, eels and shad, and have long fascinated biologists because they undergo extraordinary physiological and behavioural modifications to survive in very different habitats. However, the evolutionary origins of diadromy remain poorly understood. Here, we examine the widely accepted productivity hypothesis, which states that differences in productivity between marine and freshwater biomes determine the origins of the different modes of diadromy. Specifically, the productivity hypothesis predicts that anadromous lineages should evolve in temperate areas from freshwater ancestors and catadromous lineages should evolve in tropical areas from marine ancestors. To test this, we generated a time-calibrated phylogeny for Clupeiformes (herrings, anchovies, sardines and allies), an ecologically and economically important group that includes high diversity of diadromous species. Our results do not support the productivity hypothesis. Instead we find that the different modes of diadromy do not have predictable ancestry based on latitude, and that predation, competition and geological history may be at least as important as productivity in determining the origins of diadromy.

Mosaic nature of the mitochondrial proteome: Implications for the origin and evolution of mitochondria.

PubMed

Gray, Michael W

2015-08-18

Comparative studies of the mitochondrial proteome have identified a conserved core of proteins descended from the α-proteobacterial endosymbiont that gave rise to the mitochondrion and was the source of the mitochondrial genome in contemporary eukaryotes. A surprising result of phylogenetic analyses is the relatively small proportion (10-20%) of the mitochondrial proteome displaying a clear α-proteobacterial ancestry. A large fraction of mitochondrial proteins typically has detectable homologs only in other eukaryotes and is presumed to represent proteins that emerged specifically within eukaryotes. A further significant fraction of the mitochondrial proteome consists of proteins with homologs in prokaryotes, but without a robust phylogenetic signal affiliating them with specific prokaryotic lineages. The presumptive evolutionary source of these proteins is quite different in contending models of mitochondrial origin.

Explaining Racial Disparities in Infant Health in Brazil

PubMed Central

Nyarko, Kwame A.; Lopez-Camelo, Jorge; Castilla, Eduardo E.

2015-01-01

Objectives. We sought to quantify how socioeconomic, health care, demographic, and geographic effects explain racial disparities in low birth weight (LBW) and preterm birth (PTB) rates in Brazil. Methods. We employed a sample of 8949 infants born between 1995 and 2009 in 15 cities and 7 provinces in Brazil. We focused on disparities in LBW (< 2500 g) and PTB (< 37 gestational weeks) prevalence between infants of African ancestry alone or African mixed with other ancestries, and European ancestry alone. We used a decomposition model to quantify the contributions of conceptually relevant factors to these disparities. Results. The model explained 45% to 94% of LBW and 64% to 94% of PTB disparities between the African ancestry groups and European ancestry. Differences in prenatal care use and geographic location were the most important contributors, followed by socioeconomic differences. The model explained the majority of the disparities for mixed African ancestry and part of the disparity for African ancestry alone. Conclusions. Public policies to improve children’s health should target prenatal care and geographic location differences to reduce health disparities between infants of African and European ancestries in Brazil. PMID:26313046

Explaining Racial Disparities in Infant Health in Brazil

PubMed Central

Nyarko, Kwame A.; Lopez-Camelo, Jorge; Castilla, Eduardo E.

2013-01-01

Objectives. We sought to quantify how socioeconomic, health care, demographic, and geographic effects explain racial disparities in low birth weight (LBW) and preterm birth (PTB) rates in Brazil. Methods. We employed a sample of 8949 infants born between 1995 and 2009 in 15 cities and 7 provinces in Brazil. We focused on disparities in LBW (< 2500 g) and PTB (< 37 gestational weeks) prevalence between infants of African ancestry alone or African mixed with other ancestries, and European ancestry alone. We used a decomposition model to quantify the contributions of conceptually relevant factors to these disparities. Results. The model explained 45% to 94% of LBW and 64% to 94% of PTB disparities between the African ancestry groups and European ancestry. Differences in prenatal care use and geographic location were the most important contributors, followed by socioeconomic differences. The model explained the majority of the disparities for mixed African ancestry and part of the disparity for African ancestry alone. Conclusions. Public policies to improve children’s health should target prenatal care and geographic location differences to reduce health disparities between infants of African and European ancestries in Brazil. PMID:23409894

Population Genomic Analysis of Ancient and Modern Genomes Yields New Insights into the Genetic Ancestry of the Tyrolean Iceman and the Genetic Structure of Europe

PubMed Central

Sikora, Martin; Carpenter, Meredith L.; Moreno-Estrada, Andres; Henn, Brenna M.; Underhill, Peter A.; Sánchez-Quinto, Federico; Zara, Ilenia; Pitzalis, Maristella; Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Angius, Andrea; Jones, Chris; Mendoza-Revilla, Javier; Nekhrizov, Georgi; Dimitrova, Diana; Theodossiev, Nikola; Harkins, Timothy T.; Keller, Andreas; Maixner, Frank; Zink, Albert; Abecasis, Goncalo; Sanna, Serena; Cucca, Francesco; Bustamante, Carlos D.

2014-01-01

Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture. PMID:24809476

Genomic ancestry and ethnoracial self-classification based on 5,871 community-dwelling Brazilians (The Epigen Initiative)

PubMed Central

Lima-Costa, M. Fernanda; Rodrigues, Laura C.; Barreto, Maurício L.; Gouveia, Mateus; Horta, Bernardo L.; Mambrini, Juliana; Kehdy, Fernanda S. G.; Pereira, Alexandre; Rodrigues-Soares, Fernanda; Victora, Cesar G.; Tarazona-Santos, Eduardo; Cesar, Cibele C.; Conceição, Jackson S.; Costa, Gustavo N.O.; Esteban, Nubia; Fiaccone, Rosemeire L.; Figueiredo, Camila A.; Firmo, Josélia O.A.; Horimoto, Andrea R.V.R.; Leal, Thiago P.; Machado, Moara; Magalhães, Wagner C.S.; de Oliveira, Isabel Oliveira; Peixoto, Sérgio V.; Rodrigues, Maíra R.; Santos, Hadassa C.; Silva, Thiago M.

2015-01-01

Brazil never had segregation laws defining membership of an ethnoracial group. Thus, the composition of the Brazilian population is mixed, and its ethnoracial classification is complex. Previous studies showed conflicting results on the correlation between genome ancestry and ethnoracial classification in Brazilians. We used 370,539 Single Nucleotide Polymorphisms to quantify this correlation in 5,851 community-dwelling individuals in the South (Pelotas), Southeast (Bambui) and Northeast (Salvador) Brazil. European ancestry was predominant in Pelotas and Bambui (median = 85.3% and 83.8%, respectively). African ancestry was highest in Salvador (median = 50.5%). The strength of the association between the phenotype and median proportion of African ancestry varied largely across populations, with pseudo R2 values of 0.50 in Pelotas, 0.22 in Bambui and 0.13 in Salvador. The continuous proportion of African genomic ancestry showed a significant S-shape positive association with self-reported Blacks in the three sites, and the reverse trend was found for self reported Whites, with most consistent classifications in the extremes of the high and low proportion of African ancestry. In self-classified Mixed individuals, the predicted probability of having African ancestry was bell-shaped. Our results support the view that ethnoracial self-classification is affected by both genome ancestry and non-biological factors. PMID:25913126

Genomic ancestry and ethnoracial self-classification based on 5,871 community-dwelling Brazilians (The Epigen Initiative).

PubMed

Lima-Costa, M Fernanda; Rodrigues, Laura C; Barreto, Maurício L; Gouveia, Mateus; Horta, Bernardo L; Mambrini, Juliana; Kehdy, Fernanda S G; Pereira, Alexandre; Rodrigues-Soares, Fernanda; Victora, Cesar G; Tarazona-Santos, Eduardo

2015-04-27

Brazil never had segregation laws defining membership of an ethnoracial group. Thus, the composition of the Brazilian population is mixed, and its ethnoracial classification is complex. Previous studies showed conflicting results on the correlation between genome ancestry and ethnoracial classification in Brazilians. We used 370,539 Single Nucleotide Polymorphisms to quantify this correlation in 5,851 community-dwelling individuals in the South (Pelotas), Southeast (Bambui) and Northeast (Salvador) Brazil. European ancestry was predominant in Pelotas and Bambui (median = 85.3% and 83.8%, respectively). African ancestry was highest in Salvador (median = 50.5%). The strength of the association between the phenotype and median proportion of African ancestry varied largely across populations, with pseudo R(2) values of 0.50 in Pelotas, 0.22 in Bambui and 0.13 in Salvador. The continuous proportion of African genomic ancestry showed a significant S-shape positive association with self-reported Blacks in the three sites, and the reverse trend was found for self reported Whites, with most consistent classifications in the extremes of the high and low proportion of African ancestry. In self-classified Mixed individuals, the predicted probability of having African ancestry was bell-shaped. Our results support the view that ethnoracial self-classification is affected by both genome ancestry and non-biological factors.

Associations Between Genetic Ancestries and Nicotine Metabolism Biomarkers in the Multiethnic Cohort Study

PubMed Central

Wang, Hansong; Park, Sungshim L.; Stram, Daniel O.; Haiman, Christopher A.; Wilkens, Lynne R.; Hecht, Stephen S.; Kolonel, Laurence N.; Murphy, Sharon E.; Le Marchand, Loïc

2015-01-01

Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) and 19 tobacco-derived biomarkers in smokers from 3 admixed groups in the Multiethnic Cohort Study (1993–present), namely, African ancestry in African Americans (n = 362), Amerindian ancestry in Latinos (n = 437), and Asian and Native Hawaiian ancestries in Native Hawaiians (n = 300). After multiple comparison adjustment, both African and Asian ancestries were significantly related to a greater level of free cotinine; African ancestry was also significantly related to lower cotinine glucuronidation (P's < 0.00156). The predicted decrease in cotinine glucuronidation was 8.6% (P = 4.5 × 10−6) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4q was related to lower cotinine glucuronidation (P's < 2.7 × 10−7, smallest P = 1.5 × 10−9), although this is the same region reported in our previous genome-wide association study. Our results implicate a genetic ancestral component in the observed ethnic/racial variation in nicotine metabolism. Further studies are needed to identify the underlying genetic variation that could potentially be ethnic/racial specific. PMID:26568573

European ancestry as a risk factor for atrial fibrillation in African Americans.

PubMed

Marcus, Gregory M; Alonso, Alvaro; Peralta, Carmen A; Lettre, Guillaume; Vittinghoff, Eric; Lubitz, Steven A; Fox, Ervin R; Levitzky, Yamini S; Mehra, Reena; Kerr, Kathleen F; Deo, Rajat; Sotoodehnia, Nona; Akylbekova, Meggie; Ellinor, Patrick T; Paltoo, Dina N; Soliman, Elsayed Z; Benjamin, Emelia J; Heckbert, Susan R

2010-11-16

Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown whether the higher risk is due to genetic or environmental factors. Because African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. We studied whites (n=4543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517). Percent European ancestry in African Americans was estimated with 1747 ancestry informative markers from the Illumina custom ITMAT-Broad-CARe array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (hazard ratio, 1.13; 95% confidence interval, 1.03 to 1.23; P=0.007). After adjustment for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% confidence interval, 1.07 to 1.29; P=0.001). A second analysis using 3192 ancestry informative markers from a genome-wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative.

The role of ancestry in TB susceptibility of an admixed South African population.

PubMed

Daya, Michelle; van der Merwe, Lize; van Helden, Paul D; Möller, Marlo; Hoal, Eileen G

2014-07-01

Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ancestry and dental development: A geographic and genetic perspective

PubMed Central

Dhamo, Brunilda; Kragt, Lea; Grgic, Olja; Vucic, Strahinja; Medina‐Gomez, Carolina; Rivadeneira, Fernando; Jaddoe, Vincent W.V.; Wolvius, Eppo B.

2017-01-01

Abstract Objective In this study, we investigated the influence of ancestry on dental development in the Generation R Study. Methods Information on geographic ancestry was available in 3,600 children (1,810 boys and 1,790 girls, mean age 9.81 ± 0.35 years) and information about genetic ancestry was available in 2,786 children (1,387 boys and 1,399 girls, mean age 9.82 ± 0.34 years). Dental development was assessed in all children using the Demirjian method. The associations of geographic ancestry (Cape Verdean, Moroccan, Turkish, Dutch Antillean, Surinamese Creole and Surinamese Hindustani vs Dutch as the reference group) and genetic content of ancestry (European, African or Asian) with dental development was analyzed using linear regression models. Results In a geographic perspective of ancestry, Moroccan (β = 0.18; 95% CI: 0.07, 0.28), Turkish (β = 0.22; 95% CI: 0.12, 0.32), Dutch Antillean (β = 0.27; 95% CI: 0.12, 0.41), and Surinamese Creole (β = 0.16; 95% CI: 0.03, 0.30) preceded Dutch children in dental development. Moreover, in a genetic perspective of ancestry, a higher proportion of European ancestry was associated with decelerated dental development (β = −0.32; 95% CI: –.44, –.20). In contrast, a higher proportion of African ancestry (β = 0.29; 95% CI: 0.16, 0.43) and a higher proportion of Asian ancestry (β = 0.28; 95% CI: 0.09, 0.48) were associated with accelerated dental development. When investigating only European children, these effect estimates increased to twice as large in absolute value. Conclusion Based on a geographic and genetic perspective, differences in dental development exist in a population of heterogeneous ancestry and should be considered when describing the physiological growth in children. PMID:29139104

Ancestry and dental development: A geographic and genetic perspective.

PubMed

Dhamo, Brunilda; Kragt, Lea; Grgic, Olja; Vucic, Strahinja; Medina-Gomez, Carolina; Rivadeneira, Fernando; Jaddoe, Vincent W V; Wolvius, Eppo B; Ongkosuwito, Edwin M

2018-02-01

In this study, we investigated the influence of ancestry on dental development in the Generation R Study. Information on geographic ancestry was available in 3,600 children (1,810 boys and 1,790 girls, mean age 9.81 ± 0.35 years) and information about genetic ancestry was available in 2,786 children (1,387 boys and 1,399 girls, mean age 9.82 ± 0.34 years). Dental development was assessed in all children using the Demirjian method. The associations of geographic ancestry (Cape Verdean, Moroccan, Turkish, Dutch Antillean, Surinamese Creole and Surinamese Hindustani vs Dutch as the reference group) and genetic content of ancestry (European, African or Asian) with dental development was analyzed using linear regression models. In a geographic perspective of ancestry, Moroccan (β = 0.18; 95% CI: 0.07, 0.28), Turkish (β = 0.22; 95% CI: 0.12, 0.32), Dutch Antillean (β = 0.27; 95% CI: 0.12, 0.41), and Surinamese Creole (β = 0.16; 95% CI: 0.03, 0.30) preceded Dutch children in dental development. Moreover, in a genetic perspective of ancestry, a higher proportion of European ancestry was associated with decelerated dental development (β = -0.32; 95% CI: -.44, -.20). In contrast, a higher proportion of African ancestry (β = 0.29; 95% CI: 0.16, 0.43) and a higher proportion of Asian ancestry (β = 0.28; 95% CI: 0.09, 0.48) were associated with accelerated dental development. When investigating only European children, these effect estimates increased to twice as large in absolute value. Based on a geographic and genetic perspective, differences in dental development exist in a population of heterogeneous ancestry and should be considered when describing the physiological growth in children. © 2017 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

The impact of self-reported ethnicity versus genetic ancestry on phenotypic characteristics of polycystic ovary syndrome (PCOS).

PubMed

Louwers, Y V; Lao, O; Fauser, B C J M; Kayser, M; Laven, J S E

2014-10-01

It is well established that ethnicity is associated with the phenotype of polycystic ovary syndrome (PCOS). Self-reported ethnicity was shown to be an inaccurate proxy for ethnic origin in other disease traits, and it remains unclear how in PCOS patients self-reported ethnicity compares with a biological proxy such as genetic ancestry. We compared the impact of self-reported ethnicity versus genetic ancestry on PCOS and tested which of these 2 classifications better predicts the variability in phenotypic characteristics of PCOS. A total of 1499 PCOS patients from The Netherlands, comprising 11 self-reported ethnic groups of European, African, American, and Asian descent were genotyped with the Illumina 610K Quad BeadChip and merged with the data genotyped with the Illumina HumanHap650K available for the reference panel collected by the Human Genome Diversity Project (HGDP), in a collaboration with the Centre Etude Polymorphism Humain (CEPH), including 53 populations for ancestry reference. Algorithms for inferring genetic relationships among individuals, including multidimensional scaling and ADMIXTURE, were applied to recover genetic ancestry for each individual. Regression analysis was used to determine the best predictor for the variability in PCOS characteristics. The association between self-reported ethnicity and genetic ancestry was moderate. For amenorrhea, total follicle count, body mass index, SHBG, dehydroepiandrosterone sulfate, and insulin, mainly genetic ancestry clusters ended up in the final models (P values < .004), indicating that they explain a larger proportion of variability of these PCOS characteristics compared with self-reported ethnicity. Especially variability of insulin levels seems predominantly explained by genetic ancestry. Self-reported ancestry is not a perfect proxy for genetic ancestry in patients with PCOS, emphasizing that by using genetic ancestry data instead of self-reported ethnicity, PCOS-relevant misclassification can be avoided. Moreover, because genetic ancestry explained a larger proportion of phenotypic variability associated with PCOS than self-reported ethnicity, future studies should focus on genetic ancestry verification of PCOS patients for research questions and treatment as well as preventive strategies in these women.

Dissecting the Within-Africa Ancestry of Populations of African Descent in the Americas

PubMed Central

Stefflova, Klara; Dulik, Matthew C.; Barnholtz-Sloan, Jill S.; Pai, Athma A.; Walker, Amy H.; Rebbeck, Timothy R.

2011-01-01

Background The ancestry of African-descended Americans is known to be drawn from three distinct populations: African, European, and Native American. While many studies consider this continental admixture, few account for the genetically distinct sources of ancestry within Africa – the continent with the highest genetic variation. Here, we dissect the within-Africa genetic ancestry of various populations of the Americas self-identified as having primarily African ancestry using uniparentally inherited mitochondrial DNA. Methods and Principal Findings We first confirmed that our results obtained using uniparentally-derived group admixture estimates are correlated with the average autosomal-derived individual admixture estimates (hence are relevant to genomic ancestry) by assessing continental admixture using both types of markers (mtDNA and Y-chromosome vs. ancestry informative markers). We then focused on the within-Africa maternal ancestry, mining our comprehensive database of published mtDNA variation (∼5800 individuals from 143 African populations) that helped us thoroughly dissect the African mtDNA pool. Using this well-defined African mtDNA variation, we quantified the relative contributions of maternal genetic ancestry from multiple W/WC/SW/SE (West to South East) African populations to the different pools of today's African-descended Americans of North and South America and the Caribbean. Conclusions Our analysis revealed that both continental admixture and within-Africa admixture may be critical to achieving an adequate understanding of the ancestry of African-descended Americans. While continental ancestry reflects gender-specific admixture processes influenced by different socio-historical practices in the Americas, the within-Africa maternal ancestry reflects the diverse colonial histories of the slave trade. We have confirmed that there is a genetic thread connecting Africa and the Americas, where each colonial system supplied their colonies in the Americas with slaves from African colonies they controlled or that were available for them at the time. This historical connection is reflected in different relative contributions from populations of W/WC/SW/SE Africa to geographically distinct Africa-derived populations of the Americas, adding to the complexity of genomic ancestry in groups ostensibly united by the same demographic label. PMID:21253579

Dissecting the within-Africa ancestry of populations of African descent in the Americas.

PubMed

Stefflova, Klara; Dulik, Matthew C; Barnholtz-Sloan, Jill S; Pai, Athma A; Walker, Amy H; Rebbeck, Timothy R

2011-01-06

The ancestry of African-descended Americans is known to be drawn from three distinct populations: African, European, and Native American. While many studies consider this continental admixture, few account for the genetically distinct sources of ancestry within Africa--the continent with the highest genetic variation. Here, we dissect the within-Africa genetic ancestry of various populations of the Americas self-identified as having primarily African ancestry using uniparentally inherited mitochondrial DNA. We first confirmed that our results obtained using uniparentally-derived group admixture estimates are correlated with the average autosomal-derived individual admixture estimates (hence are relevant to genomic ancestry) by assessing continental admixture using both types of markers (mtDNA and Y-chromosome vs. ancestry informative markers). We then focused on the within-Africa maternal ancestry, mining our comprehensive database of published mtDNA variation (∼5800 individuals from 143 African populations) that helped us thoroughly dissect the African mtDNA pool. Using this well-defined African mtDNA variation, we quantified the relative contributions of maternal genetic ancestry from multiple W/WC/SW/SE (West to South East) African populations to the different pools of today's African-descended Americans of North and South America and the Caribbean. Our analysis revealed that both continental admixture and within-Africa admixture may be critical to achieving an adequate understanding of the ancestry of African-descended Americans. While continental ancestry reflects gender-specific admixture processes influenced by different socio-historical practices in the Americas, the within-Africa maternal ancestry reflects the diverse colonial histories of the slave trade. We have confirmed that there is a genetic thread connecting Africa and the Americas, where each colonial system supplied their colonies in the Americas with slaves from African colonies they controlled or that were available for them at the time. This historical connection is reflected in different relative contributions from populations of W/WC/SW/SE Africa to geographically distinct Africa-derived populations of the Americas, adding to the complexity of genomic ancestry in groups ostensibly united by the same demographic label.

Phylogenomic analysis demonstrates a pattern of rare and ancient horizontal gene transfer between plants and fungi.

PubMed

Richards, Thomas A; Soanes, Darren M; Foster, Peter G; Leonard, Guy; Thornton, Christopher R; Talbot, Nicholas J

2009-07-01

Horizontal gene transfer (HGT) describes the transmission of genetic material across species boundaries and is an important evolutionary phenomenon in the ancestry of many microbes. The role of HGT in plant evolutionary history is, however, largely unexplored. Here, we compare the genomes of six plant species with those of 159 prokaryotic and eukaryotic species and identify 1689 genes that show the highest similarity to corresponding genes from fungi. We constructed a phylogeny for all 1689 genes identified and all homolog groups available from the rice (Oryza sativa) genome (3177 gene families) and used these to define 14 candidate plant-fungi HGT events. Comprehensive phylogenetic analyses of these 14 data sets, using methods that account for site rate heterogeneity, demonstrated support for nine HGT events, demonstrating an infrequent pattern of HGT between plants and fungi. Five HGTs were fungi-to-plant transfers and four were plant-to-fungi HGTs. None of the fungal-to-plant HGTs involved angiosperm recipients. These results alter the current view of organismal barriers to HGT, suggesting that phagotrophy, the consumption of a whole cell by another, is not necessarily a prerequisite for HGT between eukaryotes. Putative functional annotation of the HGT candidate genes suggests that two fungi-to-plant transfers have added phenotypes important for life in a soil environment. Our study suggests that genetic exchange between plants and fungi is exceedingly rare, particularly among the angiosperms, but has occurred during their evolutionary history and added important metabolic traits to plant lineages.

Genetic and morphological structure of a spruce hybrid (Picea sitchensis x P. glauca) zone along a climatic gradient.

PubMed

Hamilton, Jill A; Aitken, Sally N

2013-08-01

Historic colonization and contemporary evolutionary processes contribute to patterns of genetic variation and differentiation among populations. However, separating the respective influences of these processes remains a challenge, particularly for natural hybrid zones, where standing genetic variation may result from evolutionary processes both preceding and following contact, influencing the evolutionary trajectory of hybrid populations. Where adaptation to novel environments may be facilitated by interspecific hybridization, teasing apart these processes will have practical implications for forest management in changing environments. We evaluated the neutral genetic architecture of the Picea sitchensis (Sitka spruce) × P. glauca (white spruce) hybrid zone along the Nass and Skeena river valleys in northwestern British Columbia using chloroplast, mitochondrial, and nuclear microsatellite markers, in combination with cone morphological traits. Sitka spruce mitotype "capture", evidenced by this species dominating the maternal lineage, is consistent with earlier colonization of the region by Sitka spruce. This "capture" differs from the spatial distribution of chloroplast haplotypes, indicating pollen dispersal and its contribution to geographic structure. Genetic ancestry, based on nuclear markers, was strongly influenced by climate and geography. Highly parallel results for replicate transects along environmental gradients provide support for the bounded hybrid superiority model of hybrid zone maintenance. • This broad-scale analysis of neutral genetic structure indicates the importance of historic and contemporary gene flow, environmental selection, and their interaction in shaping neutral genetic variation within this hybrid zone, informative to seed transfer development and reforestation for future climates.

Evolution of RNA- and DNA-guided antivirus defense systems in prokaryotes and eukaryotes: common ancestry vs convergence.

PubMed

Koonin, Eugene V

2017-02-10

Complementarity between nucleic acid molecules is central to biological information transfer processes. Apart from the basal processes of replication, transcription and translation, complementarity is also employed by multiple defense and regulatory systems. All cellular life forms possess defense systems against viruses and mobile genetic elements, and in most of them some of the defense mechanisms involve small guide RNAs or DNAs that recognize parasite genomes and trigger their inactivation. The nucleic acid-guided defense systems include prokaryotic Argonaute (pAgo)-centered innate immunity and CRISPR-Cas adaptive immunity as well as diverse branches of RNA interference (RNAi) in eukaryotes. The archaeal pAgo machinery is the direct ancestor of eukaryotic RNAi that, however, acquired additional components, such as Dicer, and enormously diversified through multiple duplications. In contrast, eukaryotes lack any heritage of the CRISPR-Cas systems, conceivably, due to the cellular toxicity of some Cas proteins that would get activated as a result of operon disruption in eukaryotes. The adaptive immunity function in eukaryotes is taken over partly by the PIWI RNA branch of RNAi and partly by protein-based immunity. In this review, I briefly discuss the interplay between homology and analogy in the evolution of RNA- and DNA-guided immunity, and attempt to formulate some general evolutionary principles for this ancient class of defense systems. This article was reviewed by Mikhail Gelfand and Bojan Zagrovic.

CpG Dinucleotide Frequencies Reveal the Role of Host Methylation Capabilities in Parvovirus Evolution

PubMed Central

Upadhyay, Mohita; Samal, Jasmine; Kandpal, Manish; Vasaikar, Suhas; Biswas, Banhi; Gomes, James

2013-01-01

Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to “fractional” methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses. PMID:24109231

CpG dinucleotide frequencies reveal the role of host methylation capabilities in parvovirus evolution.

PubMed

Upadhyay, Mohita; Samal, Jasmine; Kandpal, Manish; Vasaikar, Suhas; Biswas, Banhi; Gomes, James; Vivekanandan, Perumal

2013-12-01

Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to "fractional" methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses.

Ancient genomic architecture for mammalian olfactory receptor clusters

PubMed Central

Aloni, Ronny; Olender, Tsviya; Lancet, Doron

2006-01-01

Background Mammalian olfactory receptor (OR) genes reside in numerous genomic clusters of up to several dozen genes. Whole-genome sequence alignment nets of five mammals allow their comprehensive comparison, aimed at reconstructing the ancestral olfactory subgenome. Results We developed a new and general tool for genome-wide definition of genomic gene clusters conserved in multiple species. Syntenic orthologs, defined as gene pairs showing conservation of both genomic location and coding sequence, were subjected to a graph theory algorithm for discovering CLICs (clusters in conservation). When applied to ORs in five mammals, including the marsupial opossum, more than 90% of the OR genes were found within a framework of 48 multi-species CLICs, invoking a general conservation of gene order and composition. A detailed analysis of individual CLICs revealed multiple differences among species, interpretable through species-specific genomic rearrangements and reflecting complex mammalian evolutionary dynamics. One significant instance involves CLIC #1, which lacks a human member, implying the human-specific deletion of an OR cluster, whose mouse counterpart has been tentatively associated with isovaleric acid odorant detection. Conclusion The identified multi-species CLICs demonstrate that most of the mammalian OR clusters have a common ancestry, preceding the split between marsupials and placental mammals. However, only two of these CLICs were capable of incorporating chicken OR genes, parsimoniously implying that all other CLICs emerged subsequent to the avian-mammalian divergence. PMID:17010214

Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren's Syndrome According to Ancestry.

PubMed

Taylor, Kimberly E; Wong, Quenna; Levine, David M; McHugh, Caitlin; Laurie, Cathy; Doheny, Kimberly; Lam, Mi Y; Baer, Alan N; Challacombe, Stephen; Lanfranchi, Hector; Schiødt, Morten; Srinivasan, M; Umehara, Hisanori; Vivino, Frederick B; Zhao, Yan; Shiboski, Stephen C; Daniels, Troy E; Greenspan, John S; Shiboski, Caroline H; Criswell, Lindsey A

2017-06-01

The Sjögren's International Collaborative Clinical Alliance (SICCA) is an international data registry and biorepository derived from a multisite observational study of participants in whom genotyping was performed on the Omni2.5M platform and who had undergone deep phenotyping using common protocol-directed methods. The aim of this study was to examine the genetic etiology of Sjögren's syndrome (SS) across ancestry and disease subsets. We performed genome-wide association study analyses using SICCA subjects and external controls obtained from dbGaP data sets, one using all participants (1,405 cases, 1,622 SICCA controls, and 3,125 external controls), one using European participants (585, 966, and 580, respectively), and one using Asian participants (460, 224, and 901, respectively) with ancestry adjustments via principal components analyses. We also investigated whether subphenotype distributions differ by ethnicity, and whether this contributes to the heterogeneity of genetic associations. We observed significant associations in established regions of the major histocompatibility complex (MHC), IRF5, and STAT4 (P = 3 × 10 -42 , P = 3 × 10 -14 , and P = 9 × 10 -10 , respectively), and several novel suggestive regions (those with 2 or more associations at P < 1 × 10 -5 ). Two regions have been previously implicated in autoimmune disease: KLRG1 (P = 6 × 10 -7 [Asian cluster]) and SH2D2A (P = 2 × 10 -6 [all participants]). We observed striking differences between the associations in Europeans and Asians, with high heterogeneity especially in the MHC; representative single-nucleotide polymorphisms from established and suggestive regions had highly significant differences in the allele frequencies in the study populations. We showed that SSA/SSB autoantibody production and the labial salivary gland focus score criteria were associated with the first worldwide principal component, indicative of higher non-European ancestry (P = 4 × 10 -15 and P = 4 × 10 -5 , respectively), but that subphenotype differences did not explain most of the ancestry differences in genetic associations. Genetic associations with SS differ markedly according to ancestry; however, this is not explained by differences in subphenotypes. © 2017, The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Ancestry, Socioeconomic Status, and Age-Related Cataract in Asians: The Singapore Epidemiology of Eye Diseases Study.

PubMed

Chua, Jacqueline; Koh, Jia Yu; Tan, Ava Grace; Zhao, Wanting; Lamoureux, Ecosse; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Yin; Cheng, Ching-Yu

2015-11-01

To determine the prevalence of age-related cataract and its ancestral and socioeconomic risk factors in a multi-ethnic Asian population. Population-based, cross-sectional study. A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years in the Singapore Epidemiology of Eye Diseases Study. Study participants were invited for a structured interview and received a standardized comprehensive eye examination. Digital lens photographs were taken from eyes of each participant and graded for nuclear, cortical, and posterior subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System. Prevalence data were compared with the Blue Mountains Eye Study (BMES) in Australia. Information on medical and lifestyle factors was collected using questionnaires and blood samples. To increase the precision of racial definition, genetic ancestry was derived from genome-wide single nucleotide polymorphism markers using principal component analysis. Regression models were used to investigate the association of cataract with socioeconomic factors (education and income) and genetic ancestry. Age-related cataract. A total of 8750 participants (94.0%) had gradable lens photographs. The age-standardized prevalence of cataract surgery in Chinese (16.0%), Malays (10.6%), and Indians (20.2%) was higher than in white subjects (4.1%). We found the age-standardized cataract prevalence in Chinese (30.4%), Malays (37.8%), and Indians (33.1%) was higher than in whites (18.5%). Cataract was 1.5 to 2 times more common in Asians and began 10 years earlier than in white subjects. Malays had significantly higher age-standardized prevalence of nuclear, cortical, and PSC cataract than Chinese (P<0.001). The severity of nuclear, cortical, and PSC cataract was significantly correlated with genetic ancestry in our South East Asian population. Less education and lower income were associated with cataract for Chinese and Indians but not Malays. The presence of visual impairment associated with cataract was higher in people aged ≥60 years and Malays. We showed that people of different Asian ethnicities had a higher prevalence and earlier age of onset of cataract than Europeans. People of Malay ancestry have a greater severity for all cataract subtypes than people of Chinese ancestry. Education and income were associated with cataract for certain Asian subgroups. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Phylogenetic reconstruction using four low-copy nuclear loci strongly supports a polyphyletic origin of the genus Sorghum

PubMed Central

Hawkins, Jennifer S.; Ramachandran, Dhanushya; Henderson, Ashley; Freeman, Jasmine; Carlise, Michael; Harris, Alex; Willison-Headley, Zachary

2015-01-01

Background and Aims Sorghum is an essential grain crop whose evolutionary placement within the Andropogoneae has been the subject of scrutiny for decades. Early studies using cytogenetic and morphological data point to a poly- or paraphyletic origin of the genus; however, acceptance of poly- or paraphyly has been met with resistance. This study aimed to address the species relationships within Sorghum, in addition to the placement of Sorghum within the tribe, using a phylogenetic approach and employing broad taxon sampling. Methods From 16 diverse Sorghum species, eight low-copy nuclear loci were sequenced that are known to play a role in morphological diversity and have been previously used to study evolutionary relationships in grasses. Further, the data for four of these loci were combined with those from 57 members of the Andropogoneae in order to determine the placement of Sorghum within the tribe. Both maximum likelihood and Bayesian analyses were performed on multilocus concatenated data matrices. Key Results The Sorghum-specific topology provides strong support for two major lineages, in alignment with earlier studies employing chloroplast and internal transcribed spacer (ITS) markers. Clade I is composed of the Eu-, Chaeto- and Heterosorghum, while clade II contains the Stipo- and Parasorghum. When combined with data from the Andropogoneae, Clade II resolves as sister to a clade containing Miscanthus and Saccharum with high posterior probability and bootstrap support, and to the exclusion of Clade I. Conclusions The results provide compelling evidence for a two-lineage polyphyletic ancestry of Sorghum within the larger Andropogoneae, i.e. the derivation of the two major Sorghum clades from a unique common ancestor. Rejection of monophyly in previous molecular studies is probably due to limited taxon sampling outside of the genus. The clade consisting of Para- and Stiposorghum resolves as sister to Miscanthus and Saccharum with strong node support. PMID:26141132

Pulotu: Database of Austronesian Supernatural Beliefs and Practices

PubMed Central

Watts, Joseph; Sheehan, Oliver; Greenhill, Simon J.; Gomes-Ng, Stephanie; Atkinson, Quentin D.; Bulbulia, Joseph; Gray, Russell D.

2015-01-01

Scholars have debated naturalistic theories of religion for thousands of years, but only recently have scientists begun to test predictions empirically. Existing databases contain few variables on religion, and are subject to Galton’s Problem because they do not sufficiently account for the non-independence of cultures or systematically differentiate the traditional states of cultures from their contemporary states. Here we present Pulotu: the first quantitative cross-cultural database purpose-built to test evolutionary hypotheses of supernatural beliefs and practices. The Pulotu database documents the remarkable diversity of the Austronesian family of cultures, which originated in Taiwan, spread west to Madagascar and east to Easter Island–a region covering over half the world’s longitude. The focus of Austronesian beliefs range from localised ancestral spirits to powerful creator gods. A wide range of practices also exist, such as headhunting, elaborate tattooing, and the construction of impressive monuments. Pulotu is freely available, currently contains 116 cultures, and has 80 variables describing supernatural beliefs and practices, as well as social and physical environments. One major advantage of Pulotu is that it has separate sections on the traditional states of cultures, the post-contact history of cultures, and the contemporary states of cultures. A second major advantage is that cultures are linked to a language-based family tree, enabling the use phylogenetic methods, which can be used to address Galton’s Problem by accounting for common ancestry, to infer deep prehistory, and to model patterns of trait evolution over time. We illustrate the power of phylogenetic methods by performing an ancestral state reconstruction on the Pulotu variable “headhunting", finding evidence that headhunting was practiced in proto-Austronesian culture. Quantitative cross-cultural databases explicitly linking cultures to a phylogeny have the potential to revolutionise the field of comparative religious studies in the same way that genetic databases have revolutionised the field of evolutionary biology. PMID:26398231

Pulotu: Database of Austronesian Supernatural Beliefs and Practices.

PubMed

Watts, Joseph; Sheehan, Oliver; Greenhill, Simon J; Gomes-Ng, Stephanie; Atkinson, Quentin D; Bulbulia, Joseph; Gray, Russell D

2015-01-01

Scholars have debated naturalistic theories of religion for thousands of years, but only recently have scientists begun to test predictions empirically. Existing databases contain few variables on religion, and are subject to Galton's Problem because they do not sufficiently account for the non-independence of cultures or systematically differentiate the traditional states of cultures from their contemporary states. Here we present Pulotu: the first quantitative cross-cultural database purpose-built to test evolutionary hypotheses of supernatural beliefs and practices. The Pulotu database documents the remarkable diversity of the Austronesian family of cultures, which originated in Taiwan, spread west to Madagascar and east to Easter Island-a region covering over half the world's longitude. The focus of Austronesian beliefs range from localised ancestral spirits to powerful creator gods. A wide range of practices also exist, such as headhunting, elaborate tattooing, and the construction of impressive monuments. Pulotu is freely available, currently contains 116 cultures, and has 80 variables describing supernatural beliefs and practices, as well as social and physical environments. One major advantage of Pulotu is that it has separate sections on the traditional states of cultures, the post-contact history of cultures, and the contemporary states of cultures. A second major advantage is that cultures are linked to a language-based family tree, enabling the use phylogenetic methods, which can be used to address Galton's Problem by accounting for common ancestry, to infer deep prehistory, and to model patterns of trait evolution over time. We illustrate the power of phylogenetic methods by performing an ancestral state reconstruction on the Pulotu variable "headhunting", finding evidence that headhunting was practiced in proto-Austronesian culture. Quantitative cross-cultural databases explicitly linking cultures to a phylogeny have the potential to revolutionise the field of comparative religious studies in the same way that genetic databases have revolutionised the field of evolutionary biology.

Population Ancestry and Genetic Risk for Diabetes and Kidney, Cardiovascular, and Bone Disease: Modifiable Environmental Factors May Produce the Cures

PubMed Central

Freedman, Barry I.; Divers, Jasmin; Palmer, Nicholette D.

2013-01-01

Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This manuscript provides evidence in support of differential allele frequency distributions that underlie the higher rates of non-diabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biologic factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The current era of precision medicine will couple one’s genetic make-up with specific therapies to reduce rates of disease based on presence of disease-specific alleles. PMID:23896482

Genetic evidence for an East Asian origin of Chinese Muslim populations Dongxiang and Hui

PubMed Central

Yao, Hong-Bing; Wang, Chuan-Chao; Tao, Xiaolan; Shang, Lei; Wen, Shao-Qing; Zhu, Bofeng; Kang, Longli; Jin, Li; Li, Hui

2016-01-01

There is a long-going debate on the genetic origin of Chinese Muslim populations, such as Uygur, Dongxiang, and Hui. However, genetic information for those Muslim populations except Uygur is extremely limited. In this study, we investigated the genetic structure and ancestry of Chinese Muslims by analyzing 15 autosomal short tandem repeats in 652 individuals from Dongxiang, Hui, and Han Chinese populations in Gansu province. Both genetic distance and Bayesian-clustering methods showed significant genetic homogeneity between the two Muslim populations and East Asian populations, suggesting a common genetic ancestry. Our analysis found no evidence of substantial gene flow from Middle East or Europe into Dongxiang and Hui people during their Islamization. The dataset generated in present study are also valuable for forensic identification and paternity tests in China. PMID:27924949

Multi-ethnic genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

PubMed Central

Waage, Johannes; Baurecht, Hansjörg; Hotze, Melanie; Strachan, David P; Curtin, John A; Bønnelykke, Klaus; Tian, Chao; Takahashi, Atsushi; Esparza-Gordillo, Jorge; Alves, Alexessander Couto; Thyssen, Jacob P; den Dekker, Herman T; Ferreira, Manuel A; Altmaier, Elisabeth; Sleiman, Patrick MA; Xiao, Feng Li; Gonzalez, Juan R; Marenholz, Ingo; Kalb, Birgit; Yanes, Maria Pino; Xu, Cheng-Jian; Carstensen, Lisbeth; Groen-Blokhuis, Maria M; Venturini, Cristina; Pennell, Craig E; Barton, Sheila J; Levin, Albert M; Curjuric, Ivan; Bustamante, Mariona; Kreiner-Møller, Eskil; Lockett, Gabrielle A; Bacelis, Jonas; Bunyavanich, Supinda; Myers, Rachel A; Matanovic, Anja; Kumar, Ashish; Tung, Joyce Y; Hirota, Tomomitsu; Kubo, Michiaki; McArdle, Wendy L; Henderson, A J; Kemp, John P; Zheng, Jie; Smith, George Davey; Rüschendorf, Franz; Bauerfeind, Anja; Lee-Kirsch, Min Ae; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Mangold, Elisabeth; Cichon, Sven; Keil, Thomas; Rodríguez, Elke; Peters, Annette; Franke, Andre; Lieb, Wolfgang; Novak, Natalija; Fölster-Holst, Regina; Horikoshi, Momoko; Pekkanen, Juha; Sebert, Sylvain; Husemoen, Lise L; Grarup, Niels; de Jongste, Johan C; Rivadeneira, Fernando; Hofman, Albert; Jaddoe, Vincent WV; Pasmans, Suzanne GMA; Elbert, Niels J; Uitterlinden, André G; Marks, Guy B; Thompson, Philip J; Matheson, Melanie C; Robertson, Colin F; Ried, Janina S; Li, Jin; Zuo, Xian Bo; Zheng, Xiao Dong; Yin, Xian Yong; Sun, Liang Dan; McAleer, Maeve A; O'Regan, Grainne M; Fahy, Caoimhe MR; Campbell, Linda E; Macek, Milan; Kurek, Michael; Hu, Donglei; Eng, Celeste; Postma, Dirkje S; Feenstra, Bjarke; Geller, Frank; Hottenga, Jouke Jan; Middeldorp, Christel M; Hysi, Pirro; Bataille, Veronique; Spector, Tim; Tiesler, Carla MT; Thiering, Elisabeth; Pahukasahasram, Badri; Yang, James J; Imboden, Medea; Huntsman, Scott; Vilor-Tejedor, Natàlia; Relton, Caroline L; Myhre, Ronny; Nystad, Wenche; Custovic, Adnan; Weiss, Scott T; Meyers, Deborah A; Söderhäll, Cilla; Melén, Erik; Ober, Carole; Raby, Benjamin A; Simpson, Angela; Jacobsson, Bo; Holloway, John W; Bisgaard, Hans; Sunyer, Jordi; Hensch, Nicole M Probst; Williams, L Keoki; Godfrey, Keith M; Wang, Carol A; Boomsma, Dorret I; Melbye, Mads; Koppelman, Gerard H; Jarvis, Deborah; McLean, WH Irwin; Irvine, Alan D; Zhang, Xue Jun; Hakonarson, Hakon; Gieger, Christian; Burchard, Esteban G; Martin, Nicholas G; Duijts, Liesbeth; Linneberg, Allan; Jarvelin, Marjo-Riitta; Noethen, Markus M; Lau, Susanne; Hübner, Norbert; Lee, Young-Ae; Tamari, Mayumi; Hinds, David A; Glass, Daniel; Brown, Sara J; Heinrich, Joachim; Evans, David M; Weidinger, Stephan

2015-01-01

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified 10 novel risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with novel secondary signals at 4 of these). Notably, the new loci include candidate genes with roles in regulation of innate host defenses and T-cell function, underscoring the important contribution of (auto-)immune mechanisms to atopic dermatitis pathogenesis. PMID:26482879

Reuniting Art and Nature in the Life of the Child

ERIC Educational Resources Information Center

Strauch-Nelson, Wendy

2012-01-01

Sometimes looking at the history of education can be a bit frustrating. Examination of the past is necessary, however, if people are to move forward responsibly for the sake of the child. In this article, the author examines the common ancestry of the kindergarten, art, and nature study. As the founder of the kindergarten, Friedrich Froebel played…

How Theories on Origins Can Be Taught in Public Schools without Controversy.

ERIC Educational Resources Information Center

Sunderland, Luther D.

The two general concepts of how living organisms originated are defined: namely, common ancestry evolution and the abrupt appearance of completed organisms on earth. The fossil record is examined from the deepest first fossil-bearing rocks to the top of the geologic column. Evidence obtained from fossil museums is presented so students can…

Genetic Ancestry-Smoking Interactions and Lung Function in African Americans: A Cohort Study

PubMed Central

Colangelo, Laura A.; Williams, L. Keoki; Sen, Saunak; Kritchevsky, Stephen B.; Meibohm, Bernd; Galanter, Joshua; Hu, Donglei; Gignoux, Christopher R.; Liu, Yongmei; Harris, Tamara B.; Ziv, Elad; Zmuda, Joseph; Garcia, Melissa; Leak, Tennille S.; Foreman, Marilyn G.; Smith, Lewis J.; Fornage, Myriam; Liu, Kiang; Burchard, Esteban G.

2012-01-01

Background Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans. Methodology/Principal Findings We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value  = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA. Conclusions/Significance African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking. PMID:22737244

HGDP and HapMap Analysis by Ancestry Mapper Reveals Local and Global Population Relationships

PubMed Central

Magalhães, Tiago R.; Casey, Jillian P.; Conroy, Judith; Regan, Regina; Fitzpatrick, Darren J.; Shah, Naisha; Sobral, João; Ennis, Sean

2012-01-01

Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population. As a consequence, the Ancestry Mapper Id (AMid) has intrinsic biological meaning and provides a tool to measure similarity between world populations. We applied Ancestry Mapper to a dataset comprised of the HGDP and HapMap data. The results show distinctions at the continental level, while simultaneously giving details at the population level. We clustered AMids of HGDP/HapMap and observe a recapitulation of human migrations: for a small number of clusters, individuals are grouped according to continental origins; for a larger number of clusters, regional and population distinctions are evident. Calculating distances between AMids allows us to infer ancestry. The number of coordinates is expandable, increasing the power of Ancestry Mapper. An R package called Ancestry Mapper is available to apply this method to any high density genomic data set. PMID:23189146

HGDP and HapMap analysis by Ancestry Mapper reveals local and global population relationships.

PubMed

Magalhães, Tiago R; Casey, Jillian P; Conroy, Judith; Regan, Regina; Fitzpatrick, Darren J; Shah, Naisha; Sobral, João; Ennis, Sean

2012-01-01

Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population. As a consequence, the Ancestry Mapper Id (AMid) has intrinsic biological meaning and provides a tool to measure similarity between world populations. We applied Ancestry Mapper to a dataset comprised of the HGDP and HapMap data. The results show distinctions at the continental level, while simultaneously giving details at the population level. We clustered AMids of HGDP/HapMap and observe a recapitulation of human migrations: for a small number of clusters, individuals are grouped according to continental origins; for a larger number of clusters, regional and population distinctions are evident. Calculating distances between AMids allows us to infer ancestry. The number of coordinates is expandable, increasing the power of Ancestry Mapper. An R package called Ancestry Mapper is available to apply this method to any high density genomic data set.

Socioeconomic Status and Lung Cancer: Unraveling the Contribution of Genetic Admixture

PubMed Central

Selvin, Steve; Wrensch, Margaret R.; Sison, Jennette D.; Hansen, Helen M.; Quesenberry, Charles P.; Seldin, Michael F.; Barcellos, Lisa F.; Buffler, Patricia A.; Wiencke, John K.

2013-01-01

Objectives. We examined the relationship between genetic ancestry, socioeconomic status (SES), and lung cancer among African Americans and Latinos. Methods. We evaluated SES and genetic ancestry in a Northern California lung cancer case–control study (1998–2003) of African Americans and Latinos. Lung cancer case and control participants were frequency matched on age, gender, and race/ethnicity. We assessed case–control differences in individual admixture proportions using the 2-sample t test and analysis of covariance. Logistic regression models examined associations among genetic ancestry, socioeconomic characteristics, and lung cancer. Results. Decreased Amerindian ancestry was associated with higher education among Latino control participants and greater African ancestry was associated with decreased education among African lung cancer case participants. Education was associated with lung cancer among both Latinos and African Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry was not associated with lung cancer among African Americans. Conclusions. Findings suggest that socioeconomic factors may have a greater impact than genetic ancestry on lung cancer among African Americans. The genetic heterogeneity and recent dynamic migration and acculturation of Latinos complicate recruitment; thus, epidemiological analyses and findings should be interpreted cautiously. PMID:23948011

AncestrySNPminer: A bioinformatics tool to retrieve and develop ancestry informative SNP panels

PubMed Central

Amirisetty, Sushil; Khurana Hershey, Gurjit K.; Baye, Tesfaye M.

2012-01-01

A wealth of genomic information is available in public and private databases. However, this information is underutilized for uncovering population specific and functionally relevant markers underlying complex human traits. Given the huge amount of SNP data available from the annotation of human genetic variation, data mining is a faster and cost effective approach for investigating the number of SNPs that are informative for ancestry. In this study, we present AncestrySNPminer, the first web-based bioinformatics tool specifically designed to retrieve Ancestry Informative Markers (AIMs) from genomic data sets and link these informative markers to genes and ontological annotation classes. The tool includes an automated and simple “scripting at the click of a button” functionality that enables researchers to perform various population genomics statistical analyses methods with user friendly querying and filtering of data sets across various populations through a single web interface. AncestrySNPminer can be freely accessed at https://research.cchmc.org/mershalab/AncestrySNPminer/login.php. PMID:22584067

Parasitism and mutualism in Wolbachia: what the phylogenomic trees can and cannot say.

PubMed

Bordenstein, Seth R; Paraskevopoulos, Charalampos; Dunning Hotopp, Julie C; Sapountzis, Panagiotis; Lo, Nathan; Bandi, Claudio; Tettelin, Hervé; Werren, John H; Bourtzis, Kostas

2009-01-01

Ecological and evolutionary theories predict that parasitism and mutualism are not fixed endpoints of the symbiotic spectrum. Rather, parasitism and mutualism may be host or environment dependent, induced by the same genetic machinery, and shifted due to selection. These models presume the existence of genetic or environmental variation that can spur incipient changes in symbiotic lifestyle. However, for obligate intracellular bacteria whose genomes are highly reduced, studies specify that discrete symbiotic associations can be evolutionarily stable for hundreds of millions of years. Wolbachia is an inherited obligate, intracellular infection of invertebrates containing taxa that act broadly as both parasites in arthropods and mutualists in certain roundworms. Here, we analyze the ancestry of mutualism and parasitism in Wolbachia and the evolutionary trajectory of this variation in symbiotic lifestyle with a comprehensive, phylogenomic analysis. Contrary to previous claims, we show unequivocally that the transition in lifestyle cannot be reconstructed with current methods due to long-branch attraction (LBA) artifacts of the distant Anaplasma and Ehrlichia outgroups. Despite the use of 1) site-heterogenous phylogenomic methods that can overcome systematic error, 2) a taxonomically rich set of taxa, and 3) statistical assessments of the genes, tree topologies, and models of evolution, we conclude that the LBA artifact is serious enough to afflict past and recent claims including the root lies in the middle of the Wolbachia mutualists and parasites. We show that different inference methods yield different results and high bootstrap support did not equal phylogenetic accuracy. Recombination was rare among this taxonomically diverse data set, indicating that elevated levels of recombination in Wolbachia are restricted to specific coinfecting groups. In conclusion, we attribute the inability to root the tree to rate heterogeneity between the ingroup and outgroup. Site-heterogenous models of evolution did improve the placement of aberrant taxa in the ingroup phylogeny. Finally, in the unrooted topology, the distribution of parasitism and mutualism across the tree suggests that at least two interphylum transfers shaped the origins of nematode mutualism and arthropod parasitism. We suggest that the ancestry of mutualism and parasitism is not resolvable without more suitable outgroups or complete genome sequences from all Wolbachia supergroups.

Evidence for wild waterfowl origin of H7N3 influenza A virus detected in captive-reared New Jersey pheasants

USGS Publications Warehouse

Ramey, Andrew M.; Kim Torchetti, Mia; Poulson, Rebecca L.; Carter, Deborah L.; Reeves, Andrew B.; Link, Paul; Walther, Patrick; Lebarbenchon, Camille; Stallknecht, David E.

2016-01-01

In August 2014, a low-pathogenic H7N3 influenza A virus was isolated from pheasants at a New Jersey gamebird farm and hunting preserve. In this study, we use phylogenetic analyses and calculations of genetic similarity to gain inference into the genetic ancestry of this virus and to identify potential routes of transmission. Results of maximum-likelihood (ML) and maximum-clade-credibility (MCC) phylogenetic analyses provide evidence that A/pheasant/New Jersey/26996-2/2014 (H7N3) had closely related H7 hemagglutinin (HA) and N3 neuraminidase (NA) gene segments as compared to influenza A viruses circulating among wild waterfowl in the central and eastern USA. The estimated time of the most recent common ancestry (TMRCA) between the pheasant virus and those most closely related from wild waterfowl was early 2013 for both the H7 HA and N3 NA gene segments. None of the viruses from waterfowl identified as being most closely related to A/pheasant/New Jersey/26996-2/2014 at the HA and NA gene segments in ML and MCC phylogenetic analyses shared ≥99 % nucleotide sequence identity for internal gene segment sequences. This result indicates that specific viral strains identified in this study as being closely related to the HA and NA gene segments of A/pheasant/New Jersey/26996-2/2014 were not the direct predecessors of the etiological agent identified during the New Jersey outbreak. However, the recent common ancestry of the H7 and N3 gene segments of waterfowl-origin viruses and the virus isolated from pheasants suggests that viral diversity maintained in wild waterfowl likely played an important role in the emergence of A/pheasant/New Jersey/26996-2/2014.

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.

PubMed

Horikoshi, Momoko; Mӓgi, Reedik; van de Bunt, Martijn; Surakka, Ida; Sarin, Antti-Pekka; Mahajan, Anubha; Marullo, Letizia; Thorleifsson, Gudmar; Hӓgg, Sara; Hottenga, Jouke-Jan; Ladenvall, Claes; Ried, Janina S; Winkler, Thomas W; Willems, Sara M; Pervjakova, Natalia; Esko, Tõnu; Beekman, Marian; Nelson, Christopher P; Willenborg, Christina; Wiltshire, Steven; Ferreira, Teresa; Fernandez, Juan; Gaulton, Kyle J; Steinthorsdottir, Valgerdur; Hamsten, Anders; Magnusson, Patrik K E; Willemsen, Gonneke; Milaneschi, Yuri; Robertson, Neil R; Groves, Christopher J; Bennett, Amanda J; Lehtimӓki, Terho; Viikari, Jorma S; Rung, Johan; Lyssenko, Valeriya; Perola, Markus; Heid, Iris M; Herder, Christian; Grallert, Harald; Müller-Nurasyid, Martina; Roden, Michael; Hypponen, Elina; Isaacs, Aaron; van Leeuwen, Elisabeth M; Karssen, Lennart C; Mihailov, Evelin; Houwing-Duistermaat, Jeanine J; de Craen, Anton J M; Deelen, Joris; Havulinna, Aki S; Blades, Matthew; Hengstenberg, Christian; Erdmann, Jeanette; Schunkert, Heribert; Kaprio, Jaakko; Tobin, Martin D; Samani, Nilesh J; Lind, Lars; Salomaa, Veikko; Lindgren, Cecilia M; Slagboom, P Eline; Metspalu, Andres; van Duijn, Cornelia M; Eriksson, Johan G; Peters, Annette; Gieger, Christian; Jula, Antti; Groop, Leif; Raitakari, Olli T; Power, Chris; Penninx, Brenda W J H; de Geus, Eco; Smit, Johannes H; Boomsma, Dorret I; Pedersen, Nancy L; Ingelsson, Erik; Thorsteinsdottir, Unnur; Stefansson, Kari; Ripatti, Samuli; Prokopenko, Inga; McCarthy, Mark I; Morris, Andrew P

2015-07-01

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation

PubMed Central

van de Bunt, Martijn; Surakka, Ida; Sarin, Antti-Pekka; Mahajan, Anubha; Marullo, Letizia; Thorleifsson, Gudmar; Hӓgg, Sara; Hottenga, Jouke-Jan; Ladenvall, Claes; Ried, Janina S.; Winkler, Thomas W.; Willems, Sara M.; Pervjakova, Natalia; Esko, Tõnu; Beekman, Marian; Nelson, Christopher P.; Willenborg, Christina; Ferreira, Teresa; Fernandez, Juan; Gaulton, Kyle J.; Steinthorsdottir, Valgerdur; Hamsten, Anders; Magnusson, Patrik K. E.; Willemsen, Gonneke; Milaneschi, Yuri; Robertson, Neil R.; Groves, Christopher J.; Bennett, Amanda J.; Lehtimӓki, Terho; Viikari, Jorma S.; Rung, Johan; Lyssenko, Valeriya; Perola, Markus; Heid, Iris M.; Herder, Christian; Grallert, Harald; Müller-Nurasyid, Martina; Roden, Michael; Hypponen, Elina; Isaacs, Aaron; van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Mihailov, Evelin; Houwing-Duistermaat, Jeanine J.; de Craen, Anton J. M.; Deelen, Joris; Havulinna, Aki S.; Blades, Matthew; Hengstenberg, Christian; Erdmann, Jeanette; Schunkert, Heribert; Kaprio, Jaakko; Tobin, Martin D.; Samani, Nilesh J.; Lind, Lars; Salomaa, Veikko; Lindgren, Cecilia M.; Slagboom, P. Eline; Metspalu, Andres; van Duijn, Cornelia M.; Eriksson, Johan G.; Peters, Annette; Gieger, Christian; Jula, Antti; Groop, Leif; Raitakari, Olli T.; Power, Chris; Penninx, Brenda W. J. H.; de Geus, Eco; Smit, Johannes H.; Boomsma, Dorret I.; Pedersen, Nancy L.; Ingelsson, Erik; Thorsteinsdottir, Unnur; Stefansson, Kari; Ripatti, Samuli; Prokopenko, Inga; McCarthy, Mark I.; Morris, Andrew P.

2015-01-01

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated. PMID:26132169

Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world

PubMed Central

Morrison, Margaux A.; Magalhaes, Tiago R.; Ramke, Jacqueline; Smith, Silvia E.; Ennis, Sean; Simpson, Claire L.; Portas, Laura; Murgia, Federico; Ahn, Jeeyun; Dardenne, Caitlin; Mayne, Katie; Robinson, Rosann; Morgan, Denise J.; Brian, Garry; Lee, Lucy; Woo, Se J.; Zacharaki, Fani; Tsironi, Evangelia E.; Miller, Joan W.; Kim, Ivana K.; Park, Kyu H.; Bailey-Wilson, Joan E.; Farrer, Lindsay A.; Stambolian, Dwight; DeAngelis, Margaret M.

2015-01-01

We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus. PMID:26217379

Genome-wide association study of Tourette Syndrome

PubMed Central

Scharf, Jeremiah M.; Yu, Dongmei; Mathews, Carol A.; Neale, Benjamin M.; Stewart, S. Evelyn; Fagerness, Jesen A; Evans, Patrick; Gamazon, Eric; Edlund, Christopher K.; Service, Susan; Tikhomirov, Anna; Osiecki, Lisa; Illmann, Cornelia; Pluzhnikov, Anna; Konkashbaev, Anuar; Davis, Lea K; Han, Buhm; Crane, Jacquelyn; Moorjani, Priya; Crenshaw, Andrew T.; Parkin, Melissa A.; Reus, Victor I.; Lowe, Thomas L.; Rangel-Lugo, Martha; Chouinard, Sylvain; Dion, Yves; Girard, Simon; Cath, Danielle C; Smit, Jan H; King, Robert A.; Fernandez, Thomas; Leckman, James F.; Kidd, Kenneth K.; Kidd, Judith R.; Pakstis, Andrew J.; State, Matthew; Herrera, Luis Diego; Romero, Roxana; Fournier, Eduardo; Sandor, Paul; Barr, Cathy L; Phan, Nam; Gross-Tsur, Varda; Benarroch, Fortu; Pollak, Yehuda; Budman, Cathy L.; Bruun, Ruth D.; Erenberg, Gerald; Naarden, Allan L; Lee, Paul C; Weiss, Nicholas; Kremeyer, Barbara; Berrío, Gabriel Bedoya; Campbell, Desmond; Silgado, Julio C. Cardona; Ochoa, William Cornejo; Restrepo, Sandra C. Mesa; Muller, Heike; Duarte, Ana V. Valencia; Lyon, Gholson J; Leppert, Mark; Morgan, Jubel; Weiss, Robert; Grados, Marco A.; Anderson, Kelley; Davarya, Sarah; Singer, Harvey; Walkup, John; Jankovic, Joseph; Tischfield, Jay A.; Heiman, Gary A.; Gilbert, Donald L.; Hoekstra, Pieter J.; Robertson, Mary M.; Kurlan, Roger; Liu, Chunyu; Gibbs, J. Raphael; Singleton, Andrew; Hardy, John; Strengman, Eric; Ophoff, Roel; Wagner, Michael; Moessner, Rainald; Mirel, Daniel B.; Posthuma, Danielle; Sabatti, Chiara; Eskin, Eleazar; Conti, David V.; Knowles, James A.; Ruiz-Linares, Andres; Rouleau, Guy A.; Purcell, Shaun; Heutink, Peter; Oostra, Ben A.; McMahon, William; Freimer, Nelson; Cox, Nancy J.; Pauls, David L.

2012-01-01

Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder. PMID:22889924

Evolutionary engineering of industrial microorganisms-strategies and applications.

PubMed

Zhu, Zhengming; Zhang, Juan; Ji, Xiaomei; Fang, Zhen; Wu, Zhimeng; Chen, Jian; Du, Guocheng

2018-06-01

Microbial cells have been widely used in the industry to obtain various biochemical products, and evolutionary engineering is a common method in biological research to improve their traits, such as high environmental tolerance and improvement of product yield. To obtain better integrate functions of microbial cells, evolutionary engineering combined with other biotechnologies have attracted more attention in recent years. Classical laboratory evolution has been proven effective to letting more beneficial mutations occur in different genes but also has some inherent limitations such as a long evolutionary period and uncontrolled mutation frequencies. However, recent studies showed that some new strategies may gradually overcome these limitations. In this review, we summarize the evolutionary strategies commonly used in industrial microorganisms and discuss the combination of evolutionary engineering with other biotechnologies such as systems biology and inverse metabolic engineering. Finally, we prospect the importance and application prospect of evolutionary engineering as a powerful tool especially in optimization of industrial microbial cell factories.

Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case–control study

PubMed Central

Traylor, Matthew; Curtis, Charles; Patel, Hamel; Breen, Gerome; Hyuck Lee, Sang; Xu, Xiaohui; Newhouse, Stephen; Dobson, Richard; Steer, Sophia; Cope, Andrew P.; Markus, Hugh S.; Lewis, Cathryn M.

2017-01-01

Abstract Objectives. To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals. Methods. A case–control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture. Results. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 −7). HLA haplotype ORs in European and African ancestry individuals were highly correlated (r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 −4). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 −4) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 −5) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 −3). Conclusion. Gene–environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable. PMID:28407095

Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases.

PubMed

Lopera, Esteban A; Baena, Armando; Florez, Victor; Montiel, Jehidys; Duque, Constanza; Ramirez, Tatiana; Borrero, Mauricio; Cordoba, Carlos M; Rojas, Fredy; Pareja, Rene; Bedoya, Astrid M; Bedoya, Gabriel; Sanchez, Gloria I

2014-12-01

European (E) variants of HPV 16 are evenly distributed among world regions, meanwhile Non-European variants such as European-Asian (EAs), Asian American (AA) and African (Af) are mostly confined to Eastern Asia, The Americas and African regions respectively. Several studies have shown that genetic variation of HPV 16 is associated with the risk of cervical cancer, which also seems to be dependent on the population. This relationship between ethnicity and variants have led to the suggestion that there is co-evolution of variants with humankind. Our aim was to evaluate the relationship between the individual ancestry proportion and infection with HPV 16 variants in cervical cancer. We examined the association between ancestry and HPV 16 variants in samples of 82 cervical cancer cases from different regions of Colombia. Individual ancestry proportions (European, African and Native American) were estimated by genotyping 106 ancestry informative markers. Variants were identified by PCR amplification of the E6 gene, followed by reverse line blot hybridization (RLB) with variants specific probes. Overall European (E) and Asian American (AA) variants frequency was 66.5% and 33.5% respectively. Similar distribution was observed in cases with higher proportions of European or African ancestry. A higher Native American ancestry was significantly associated with higher frequency of E variants (median ancestry>23.6%, Age and place of birth adjusted OR: 3.55, 95% CI: 1.26-10.03, p=0.01). Even further, an inverse geographic correlation between Native American ancestry and frequency of infections with AA variants was observed (ρ=-0.825, p=0.008). Regions with higher proportion of Native American ancestry had a lower frequency of AA variants of HPV 16. This study suggests replacement of AA variants by E variants of human papillomavirus 16 in cervical cancer cases with high Native American ancestry. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study.

PubMed

Traylor, Matthew; Curtis, Charles; Patel, Hamel; Breen, Gerome; Hyuck Lee, Sang; Xu, Xiaohui; Newhouse, Stephen; Dobson, Richard; Steer, Sophia; Cope, Andrew P; Markus, Hugh S; Lewis, Cathryn M; Scott, Ian C

2017-08-01

To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals. A case-control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 - 7 ). HLA haplotype ORs in European and African ancestry individuals were highly correlated ( r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 - 4 ). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 - 4 ) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 - 5 ) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 - 3 ). Gene-environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Studying the Genetics of Complex Disease With Ancestry-Specific Human Phenotype Networks: The Case of Type 2 Diabetes in East Asian Populations.

PubMed

Qiu, Jingya; Moore, Jason H; Darabos, Christian

2016-05-01

Genome-wide association studies (GWAS) have led to the discovery of over 200 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM). Additionally, East Asians develop T2DM at a higher rate, younger age, and lower body mass index than their European ancestry counterparts. The reason behind this occurrence remains elusive. With comprehensive searches through the National Human Genome Research Institute (NHGRI) GWAS catalog literature, we compiled a database of 2,800 ancestry-specific SNPs associated with T2DM and 70 other related traits. Manual data extraction was necessary because the GWAS catalog reports statistics such as odds ratio and P-value, but does not consistently include ancestry information. Currently, many statistics are derived by combining initial and replication samples from study populations of mixed ancestry. Analysis of all-inclusive data can be misleading, as not all SNPs are transferable across diverse populations. We used ancestry data to construct ancestry-specific human phenotype networks (HPN) centered on T2DM. Quantitative and visual analysis of network models reveal the genetic disparities between ancestry groups. Of the 27 phenotypes in the East Asian HPN, six phenotypes were unique to the network, revealing the underlying ancestry-specific nature of some SNPs associated with T2DM. We studied the relationship between T2DM and five phenotypes unique to the East Asian HPN to generate new interaction hypotheses in a clinical context. The genetic differences found in our ancestry-specific HPNs suggest different pathways are involved in the pathogenesis of T2DM among different populations. Our study underlines the importance of ancestry in the development of T2DM and its implications in pharmocogenetics and personalized medicine. © 2016 The Authors. *Genetic Epidemiology Published by Wiley Periodicals, Inc.

Update of the GJB2/DFNB1 mutation spectrum in Russia: a founder Ingush mutation del(GJB2-D13S175) is the most frequent among other large deletions

PubMed Central

Bliznetz, Elena A; Lalayants, Maria R; Markova, Tatiana G; Balanovsky, Oleg P; Balanovska, Elena V; Skhalyakho, Roza A; Pocheshkhova, Elvira A; Nikitina, Natalya V; Voronin, Sergey V; Kudryashova, Elena K; Glotov, Oleg S; Polyakov, Alexander V

2017-01-01

Although mutations in the GJB2 gene sequence make up the majority of variants causing autosomal-recessive non-syndromic hearing loss, few large deletions have been shown to contribute to DFNB1 deafness. Currently, genetic testing for DFNB1 hearing loss includes GJB2 sequencing and DFNB1 deletion analysis for two common large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854). Here, we report frequency in Russia, clinical significance and evolutionary origins of a 101 kb deletion, del(GJB2-D13S175), recently identified by us. In multiethnic cohort of 1104 unrelated hearing loss patients with biallelic mutations at the DFNB1 locus, the del(GJB2-D13S175) allele frequency of up to 0.5% (11/2208) was determined and this allele was shown to be predominantly associated with profound sensorineural hearing loss. Additionally, eight previously unpublished GJB2 mutations were described in this study. All patients carrying del(GJB2-D13S175) were of the Ingush ancestry. Among normal hearing individuals, del(GJB2-D13S175) was observed in Russian Republic of Ingushetia with a carrier rate of ~1% (2/241). Analysis of haplotypes associated with the deletion revealed a common founder in the Ingushes, with age of the deletion being ~3000 years old. Since del(GJB2-D13S175) was missed by standard methods of GJB2 analysis, del(GJB2-D13S175) detection has been added to our routine testing strategy for DFNB1 hearing loss. PMID:28405014

Phylogeography and genetic ancestry of tigers (Panthera tigris).

PubMed

Luo, Shu-Jin; Kim, Jae-Heup; Johnson, Warren E; van der Walt, Joelle; Martenson, Janice; Yuhki, Naoya; Miquelle, Dale G; Uphyrkina, Olga; Goodrich, John M; Quigley, Howard B; Tilson, Ronald; Brady, Gerald; Martelli, Paolo; Subramaniam, Vellayan; McDougal, Charles; Hean, Sun; Huang, Shi-Qiang; Pan, Wenshi; Karanth, Ullas K; Sunquist, Melvin; Smith, James L D; O'Brien, Stephen J

2004-12-01

Eight traditional subspecies of tiger (Panthera tigris),of which three recently became extinct, are commonly recognized on the basis of geographic isolation and morphological characteristics. To investigate the species' evolutionary history and to establish objective methods for subspecies recognition, voucher specimens of blood, skin, hair, and/or skin biopsies from 134 tigers with verified geographic origins or heritage across the whole distribution range were examined for three molecular markers: (1) 4.0 kb of mitochondrial DNA (mtDNA) sequence; (2) allele variation in the nuclear major histocompatibility complex class II DRB gene; and (3) composite nuclear microsatellite genotypes based on 30 loci. Relatively low genetic variation with mtDNA,DRB,and microsatellite loci was found, but significant population subdivision was nonetheless apparent among five living subspecies. In addition, a distinct partition of the Indochinese subspecies P. t. corbetti in to northern Indochinese and Malayan Peninsula populations was discovered. Population genetic structure would suggest recognition of six taxonomic units or subspecies: (1) Amur tiger P. t. altaica; (2) northern Indochinese tiger P. t. corbetti; (3) South China tiger P. t. amoyensis; (4) Malayan tiger P. t. jacksoni, named for the tiger conservationist Peter Jackson; (5) Sumatran tiger P. t. sumatrae; and (6) Bengal tiger P. t. tigris. The proposed South China tiger lineage is tentative due to limited sampling. The age of the most recent common ancestor for tiger mtDNA was estimated to be 72,000-108,000 y, relatively younger than some other Panthera species. A combination of population expansions, reduced gene flow, and genetic drift following the last genetic diminution, and the recent anthropogenic range contraction, have led to the distinct genetic partitions. These results provide an explicit basis for subspecies recognition and will lead to the improved management and conservation of these recently isolated but distinct geographic populations of tigers.

Association of African genetic ancestry with fasting glucose and HbA1c levels in non-diabetic individuals: the Boston Area Community Health (BACH) Prediabetes Study.

PubMed

Meigs, James B; Grant, Richard W; Piccolo, Rebecca; López, Lenny; Florez, Jose C; Porneala, Bianca; Marceau, Lisa; McKinlay, John B

2014-09-01

To test among diabetes-free urban community-dwelling adults the hypothesis that the proportion of African genetic ancestry is positively associated with glycaemia, after accounting for other continental ancestry proportions, BMI and socioeconomic status (SES). The Boston Area Community Health cohort is a multi-stage 1:1:1 stratified random sample of self-identified African-American, Hispanic and white adults from three Boston inner city areas. We measured 62 ancestry informative markers, fasting glucose (FG), HbA1c, BMI and SES (income, education, occupation and insurance status) and analysed 1,387 eligible individuals (379 African-American, 411 Hispanic, 597 white) without clinical or biochemical evidence of diabetes. We used three-heritage multinomial linear regression models to test the association of FG or HbA1c with genetic ancestry proportion adjusted for: (1) age and sex; (2) age, sex and BMI; and (3) age, sex, BMI and SES. Mean age- and sex-adjusted FG levels were 5.73 and 5.54 mmol/l among those with 100% African or European ancestry, respectively. Using per cent European ancestry as the referent, each 1% increase in African ancestry proportion was associated with an age- and sex-adjusted FG increase of 0.0019 mmol/l (p = 0.01). In the BMI- and SES-adjusted model the slope was 0.0019 (p = 0.02). Analysis of HbA1c gave similar results. A greater proportion of African genetic ancestry is independently associated with higher FG levels in a non-diabetic community-based cohort, even accounting for other ancestry proportions, obesity and SES. The results suggest that differences between African-Americans and whites in type 2 diabetes risk may include genetically mediated differences in glucose homeostasis.

European Ancestry as a Risk Factor for Atrial Fibrillation in African Americans

PubMed Central

Marcus, Gregory M.; Alonso, Alvaro; Peralta, Carmen A.; Lettre, Guillaume; Vittinghoff, Eric; Lubitz, Steven A.; Fox, Ervin R.; Levitzky, Yamini S.; Mehra, Reena; Kerr, Kathleen F.; Deo, Rajat; Sotoodehnia, Nona; Akylbekova, Meggie; Ellinor, Patrick T.; Paltoo, Dina N.; Soliman, Elsayed Z.; Benjamin, Emelia J.; Heckbert, Susan R.

2010-01-01

Background Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown if the higher riskis due to genetic or environmental factors. As African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. Methods and Results We studied whites (n=4,543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10,902) and Africa Americans (n=3,517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3,517). Percent European ancestry in African Americans was estimated using 1,747 ancestry informative markers (AIMs) from the Illumina custom ITMAT-Broad-CARe (IBC) array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3,517 ARIC participants developed incident AF. A meta-analysis from the two studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (HR 1.13, 95% CI 1.03–1.23, p=0.007). After adjusting for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% CI 1.07–1.29, p=0.001). A second analysis using 3,192 AIMs from a genome wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. Conclusion European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative. PMID:21098467

Ancestry as a potential modifier of gene expression in breast tumors from Colombian women

PubMed Central

Serrano-Gómez, Silvia J.; Sanabria-Salas, María Carolina; Garay, Jone; Baddoo, Melody C.; Hernández-Suarez, Gustavo; Mejía, Juan Carlos; García, Oscar; Miele, Lucio

2017-01-01

Background Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padj<0.01), GRB7 (log2FC = 2.327, padj<0.01), GSDMB (log2FC = 1.723, padj<0.01, MIEN1 (log2FC = 2.195, padj<0.01 and ONECUT2 (log2FC = 2.204, padj<0.01). In the replication set we found a statistical significant association between ERBB2 expression with Indigenous American ancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value. PMID:28832682

A minimum set of ancestry informative markers for determining admixture proportions in a mixed American population: the Brazilian set

PubMed Central

Santos, Hadassa C; Horimoto, Andréa V R; Tarazona-Santos, Eduardo; Rodrigues-Soares, Fernanda; Barreto, Mauricio L; Horta, Bernardo L; Lima-Costa, Maria F; Gouveia, Mateus H; Machado, Moara; Silva, Thiago M; Sanches, José M; Esteban, Nubia; Magalhaes, Wagner CS; Rodrigues, Maíra R; Kehdy, Fernanda S G; Pereira, Alexandre C

2016-01-01

The Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost- and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using ~370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals. PMID:26395555

European genetic ancestry is associated with a decreased risk of lupus nephritis.

PubMed

Richman, Ilana B; Taylor, Kimberly E; Chung, Sharon A; Trupin, Laura; Petri, Michelle; Yelin, Edward; Graham, Robert R; Lee, Annette; Behrens, Timothy W; Gregersen, Peter K; Seldin, Michael F; Criswell, Lindsey A

2012-10-01

African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82-0.87; P = 1.9 × 10(-30) ). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB1*0301 and DRB1*1501) did not substantively alter this relationship. European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors. Copyright © 2012 by the American College of Rheumatology.

Impact of Genetic Ancestry and Socio-Demographic Status on the Clinical Expression of Systemic Lupus Erythematosus in Amerindian-European Populations

PubMed Central

Sánchez, Elena; Rasmussen, Astrid; Riba, Laura; Acevedo, Eduardo; Kelly, Jennifer A.; Langefeld, Carl D.; García-De La Torre, Ignacio; Maradiaga-Ceceña, Marco A.; Cardiel, Mario H.; Esquivel-Valerio, Jorge A.; Rodriguez-Amado, Jacqueline; Moctezuma, José Francisco; Miranda, Pedro; Perandones, Carlos; Castel, Cecilia; Laborde, Hugo A.; Alba, Paula; Musuruana, Jorge; Goecke, Annelise; Anaya, Juan-Manuel; Kaufman, Kenneth M.; Adler, Adam; Brown, Elizabeth E.; Alarcón, Graciela S.; Kimberly, Robert P.; Edberg, Jeffrey C.; Criswell, Lindsey A.; Gilkeson, Gary S.; Niewold, Timothy B.; Martin, Javier; Vyse, Timothy J.; Ramsey-Goldman, Rosalind; Petri, Michelle; Merrill, Joan T.; Reveille, John D.; Tsao, Betty P.; Orozco, Lorena; Baca, Vicente; James, Judith A.; Harley, John B.; Tusié-Luna, Teresa; Pons-Estel, Bernardo A.; Jacob, Chaim O.; Alarcón-Riquelme, Marta E.

2012-01-01

Objective Amerindian-Europeans, Asians and African-Americans have an excess morbidity from SLE and higher prevalence of lupus nephritis than Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and socio-demographic characteristics and clinical features in a large cohort of Amerindian-European SLE patients. Methods A total of 2116 SLE patients of Amerindian-European origin and 4001 SLE patients of European descent with clinical data were used in the study. Genotyping of 253 continental ancestry informative markers was performed on the Illumina platform. The STRUCTURE and ADMIXTURE software were used to determine genetic ancestry of each individual. Correlation between ancestry and socio-demographic and clinical data were analyzed using logistic regression. Results The average Amerindian genetic ancestry of 2116 SLE patients was 40.7%. There was an increased risk of having renal involvement (P<0.0001, OR= 3.50 95%CI 2.63-4.63) and an early age of onset with the presence of Amerindian genetic ancestry (P<0.0001). Amerindian ancestry protected against photosensitivity (P<0.0001, OR= 0.58 95%CI 0.44-0.76), oral ulcers (P<0.0001, OR= 0.55 95%CI 0.42-0.72), and serositis (P<0.0001, OR= 0.56 95%CI 0.41-0.75) after adjustment by age, gender and age of onset. However, gender and age of onset had stronger effects on malar rash, discoid rash, arthritis and neurological involvement than genetic ancestry. Conclusion In general, genetic Amerindian ancestry correlates with lower socio-demographic status and increases the risk for developing renal involvement and SLE at an earlier age of onset. PMID:22886787

African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations

PubMed Central

Vergara, Candelaria; Murray, Tanda; Rafaels, Nicholas; Lewis, Rachel; Campbell, Monica; Foster, Cassandra; Gao, Li; Faruque, Mezbah; Oliveira, Ricardo Riccio; Carvalho, Edgar; Araujo, Maria Ilma; Cruz, Alvaro A.; Watson, Harold; Mercado, Dilia; Knight-Madden, Jennifer; Ruczinski, Ingo; Dunston, Georgia; Ford, Jean; Caraballo, Luis; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.

2014-01-01

Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels. PMID:23554133

Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study.

PubMed

Slattery, Martha L; Lundgreen, Abbie; Hines, Lisa; Wolff, Roger K; Torres-Mejia, Gabriella; Baumgartner, Kathy N; John, Esther M

2015-12-01

Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship. We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women. Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size. There were no significant associations with breast cancer risk between genes and SNPs overall. However, LEPR was significantly associated with breast cancer risk among women with low IA ancestry (PARTP=0.024); POMC was significantly associated with breast cancer risk among women with intermediate (PARTP=0.015) and high (PARTP=0.012) IA ancestry. The overall pathway was statistically significant for pre-menopausal women with low IA ancestry (PARTP=0.05), as was cocaine and amphetamine regulated transcript protein (CARTPT) (PARTP=0.014) and ghrelin (GHRL) (PARTP=0.007). POMC was significantly associated with breast cancer risk among post-menopausal women with higher IA ancestry (PARTP=0.005). Three SNPs in LEPR (rs6704167, rs17412175, and rs7626141), and adiponectin (ADIPOQ); rs822391) showed significant 4-way interactions (GxExMenopausexAncestry) for multiple indicators of body size among pre-menopausal women. Energy homeostasis genes were associated with breast cancer risk; menopausal status, body size, and genetic ancestry influenced this relationship. Copyright © 2015 Elsevier Ltd. All rights reserved.

Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Hines, Lisa; Wolff, Roger K.; Torres-Mejia, Gabriella; Baumgartner, Kathy N.; John, Esther M.

2015-01-01

Background Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship. Methods We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women. Results Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size. There were no significant associations with breast cancer risk between genes and SNPs overall. However, LEPR was significantly associated with breast cancer risk among women with low IA ancestry (PARTP = 0.024); POMC was significantly associated with breast cancer risk among women with intermediate (PARTP = 0.015) and high (PARTP = 0.012) IA ancestry. The overall pathway was statistically significant for pre-menopausal women with low IA ancestry (PARTP = 0.05), as was cocaine and amphetamine regulated transcript protein (CARTPT) (PARTP = 0.014) and ghrelin (GHRL) (PARTP = 0.007). POMC was significantly associated with breast cancer risk among post-menopausal women with higher IA ancestry (PARTP = 0.005). Three SNPs in LEPR (rs6704167, rs17412175, and rs7626141), and adiponectin (ADIPOQ); rs822391) showed significant 4-way interactions (GxExMenopausexAncestry) for multiple indicators of body size among pre-menopausal women. Conclusions Energy homeostasis genes were associated with breast cancer risk; menopausal status, body size, and genetic ancestry influenced this relationship. PMID:26395295

Early Back-to-Africa Migration into the Horn of Africa

PubMed Central

Hodgson, Jason A.; Mulligan, Connie J.; Al-Meeri, Ali; Raaum, Ryan L.

2014-01-01

Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive of earlier episodes of admixture. To investigate this further, we generated new genome-wide SNP data for a Yemeni population sample and merged these new data with published genome-wide genetic data from the HOA and a broad selection of surrounding populations. We used multidimensional scaling and ADMIXTURE methods in an exploratory data analysis to develop hypotheses on admixture and population structure in HOA populations. These analyses suggested that there might be distinct, differentiated African and non-African ancestries in the HOA. After partitioning the SNP data into African and non-African origin chromosome segments, we found support for a distinct African (Ethiopic) ancestry and a distinct non-African (Ethio-Somali) ancestry in HOA populations. The African Ethiopic ancestry is tightly restricted to HOA populations and likely represents an autochthonous HOA population. The non-African ancestry in the HOA, which is primarily attributed to a novel Ethio-Somali inferred ancestry component, is significantly differentiated from all neighboring non-African ancestries in North Africa, the Levant, and Arabia. The Ethio-Somali ancestry is found in all admixed HOA ethnic groups, shows little inter-individual variance within these ethnic groups, is estimated to have diverged from all other non-African ancestries by at least 23 ka, and does not carry the unique Arabian lactase persistence allele that arose about 4 ka. Taking into account published mitochondrial, Y chromosome, paleoclimate, and archaeological data, we find that the time of the Ethio-Somali back-to-Africa migration is most likely pre-agricultural. PMID:24921250

African Ancestry Influences CCR5 –2459G>A Genotype-Associated Virologic Success of Highly Active Antiretroviral Therapy

PubMed Central

Cheruvu, Vinay K.; Igo, Robert P.; Jurevic, Richard J.; Serre, David; Zimmerman, Peter A.; Rodriguez, Benigno; Mehlotra, Rajeev K.

2014-01-01

Introduction In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) –2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients. Methods Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 –2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry. Results We found that the interaction between CCR5 –2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and <0.71 vs. ≥0.71) was significantly associated with TVLS (GG compared with AA, P = 0.044 and 0.018, respectively). Furthermore, the association between CCR5 –2459G>A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan-Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% CI, 1.27–5.22; P = 0.01] and 2.26 [95% CI, 1.18–4.32; P = 0.01], respectively) analyses. Conclusions We observed that the association between CCR5 –2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical, and requires further studies. PMID:24714069

Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study.

PubMed

Wassertheil-Smoller, Sylvia; Qi, Qibin; Dave, Tushar; Mitchell, Braxton D; Jackson, Rebecca D; Liu, Simin; Park, Ki; Salinas, Joel; Dunn, Erin C; Leira, Enrique C; Xu, Huichun; Ryan, Kathleen; Smoller, Jordan W

2018-03-01

Although depression is a risk factor for stroke in large prospective studies, it is unknown whether these conditions have a shared genetic basis. We applied a polygenic risk score (PRS) for major depressive disorder derived from European ancestry analyses by the Psychiatric Genomics Consortium to a genome-wide association study of ischemic stroke in the Stroke Genetics Network of National Institute of Neurological Disorders and Stroke. Included in separate analyses were 12 577 stroke cases and 25 643 controls of European ancestry and 1353 cases and 2383 controls of African ancestry. We examined the association between depression PRS and ischemic stroke overall and with pathogenic subtypes using logistic regression analyses. The depression PRS was associated with higher risk of ischemic stroke overall in both European ( P =0.025) and African ancestry ( P =0.011) samples from the Stroke Genetics Network. Ischemic stroke risk increased by 3.0% (odds ratio, 1.03; 95% confidence interval, 1.00-1.05) for every 1 SD increase in PRS for those of European ancestry and by 8% (odds ratio, 1.08; 95% confidence interval, 1.04-1.13) for those of African ancestry. Among stroke subtypes, elevated risk of small artery occlusion was observed in both European and African ancestry samples. Depression PRS was also associated with higher risk of cardioembolic stroke in European ancestry and large artery atherosclerosis in African ancestry persons. Higher polygenic risk for major depressive disorder is associated with increased risk of ischemic stroke overall and with small artery occlusion. Additional associations with ischemic stroke subtypes differed by ancestry. © 2018 American Heart Association, Inc.

Body Composition Remodeling and Incident Mobility Limitations in African Ancestry Men.

PubMed

Santanasto, Adam J; Miljkovic, Iva; Cvejkus, Ryan C; Gordon, Christopher L; Bunker, Clareann H; Patrick, Allen L; Wheeler, Victor W; Zmuda, Joseph M

2018-04-05

Mobility limitations are common, with higher prevalence in African Americans compared to whites, and are associated with disability, institutionalization and death. Aging is associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African Ancestry. Seven-year changes in body composition were measured using peripheral computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African Ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models. Seventy-five men (14.9%) developed incident mobility limitations over 6.2±0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations a (OR: 1.60; 95% CI: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87). Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men.

Differences in vaginal microbiome in African American women versus women of European ancestry

PubMed Central

Fettweis, Jennifer M.; Brooks, J. Paul; Serrano, Myrna G.; Sheth, Nihar U.; Girerd, Philippe H.; Edwards, David J.; Strauss, Jerome F.; Jefferson, Kimberly K.

2014-01-01

Women of European ancestry are more likely to harbour a Lactobacillus-dominated microbiome, whereas African American women are more likely to exhibit a diverse microbial profile. African American women are also twice as likely to be diagnosed with bacterial vaginosis and are twice as likely to experience preterm birth. The objective of this study was to further characterize and contrast the vaginal microbial profiles in African American versus European ancestry women. Through the Vaginal Human Microbiome Project at Virginia Commonwealth University, 16S rRNA gene sequence analysis was used to compare the microbiomes of vaginal samples from 1268 African American women and 416 women of European ancestry. The results confirmed significant differences in the vaginal microbiomes of the two groups and identified several taxa relevant to these differences. Major community types were dominated by Gardnerella vaginalis and the uncultivated bacterial vaginosis-associated bacterium-1 (BVAB1) that were common among African Americans. Moreover, the prevalence of multiple bacterial taxa that are associated with microbial invasion of the amniotic cavity and preterm birth, including Mycoplasma, Gardnerella, Prevotella and Sneathia, differed between the two ethnic groups. We investigated the contributions of intrinsic and extrinsic factors, including pregnancy, body mass index, diet, smoking and alcohol use, number of sexual partners, and household income, to vaginal community composition. Ethnicity, pregnancy and alcohol use correlated significantly with the relative abundance of bacterial vaginosis-associated species. Trends between microbial profiles and smoking and number of sexual partners were observed; however, these associations were not statistically significant. These results support and extend previous findings that there are significant differences in the vaginal microbiome related to ethnicity and demonstrate that these differences are pronounced even in healthy women. PMID:25073854

A comprehensive examination of breast cancer risk loci in African American women.

PubMed

Feng, Ye; Stram, Daniel O; Rhie, Suhn Kyong; Millikan, Robert C; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Palmer, Julie R; Olopade, Olufunmilayo I; Huo, Dezheng; Adebamowo, Clement A; Ogundiran, Temidayo; Chen, Gary K; Stram, Alex; Park, Karen; Rand, Kristin A; Chanock, Stephen J; Le Marchand, Loic; Kolonel, Laurence N; Conti, David V; Easton, Douglas; Henderson, Brian E; Haiman, Christopher A

2014-10-15

Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10(-6)) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65-70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetic Ancestry is Associated with Measures of Subclinical Atherosclerosis in African Americans: The Jackson Heart Study

PubMed Central

Gebreab, Samson Y; Riestra, Pia; Khan, Rumana J; Xu, Ruihua; Musani, Solomon K; Tekola-Ayele, Fasil; Correa, Adolfo; Wilson, James G; Rotimi, Charles N; Davis, Sharon K

2015-01-01

Objective To determine whether genetic ancestry was associated with subclinical atherosclerosis measures after adjustment for traditional CVD risk factors, inflammatory marker, socioeconomic status (SES) and psychosocial factors in a large admixed African American population. Approach and Results Participants were drawn from Jackson Heart Study (JHS). Participant’s percent of European Ancestry (PEA) was estimated based on 1747 genetic markers using HAPMIX. Association of PEA with peripheral arterial disease (PAD) and common carotid intima media thickness (cCIMT) were investigated among 2168 participants and with coronary artery calcification (CAC >0) and abdominal aortic calcification (AAC >0) among 1139 participants. The associations were evaluated using multivariable regression models. Our results showed a 1 standard deviation increase in PEA was associated with a lower PAD prevalence after adjusting for age and gender [Prevalence ratio (PR) = 0. 90 (95% CI: 0.82, 0.99); p=0.036]. Adjustments for traditional CVD risk factors, SES, and psychosocial factors attenuated this association [PR=0.91 (0.82, 1.00); p=0.046]. There was also a non-linear association between PEA and CAC and AAC. The lowest PEA was associated with a lower CAC [PR=0.75 (0.58, 0.96); p=0.022] and a lower AAC [PR=0. 80 (0.67, 0.96); p=0.016] compared to the reference group (10th–90th percentile) after adjusting for traditional CVD risk factors, inflammatory marker, SES and psychosocial factors. However, we found no significant association between PEA and cCIMT. Conclusions Overall, our findings indicate that genetic ancestry was associated with subclinical atherosclerosis, suggesting unmeasured risk factors and/or interactions with genetic factors might contribute to the distribution of subclinical atherosclerosis among African Americans. PMID:25745061

Genomic ancestry and education level independently influence abdominal fat distributions in a Brazilian admixed population.

PubMed

França, Giovanny Vinícius Araújo de; De Lucia Rolfe, Emanuella; Horta, Bernardo Lessa; Gigante, Denise Petrucci; Yudkin, John S; Ong, Ken K; Victora, Cesar Gomes

2017-01-01

We aimed to identify the independent associations of genomic ancestry and education level with abdominal fat distributions in the 1982 Pelotas birth cohort study, Brazil. In 2,890 participants (1,409 men and 1,481 women), genomic ancestry was assessed using genotype data on 370,539 genome-wide variants to quantify ancestral proportions in each individual. Years of completed education was used to indicate socio-economic position. Visceral fat depth and subcutaneous abdominal fat thickness were measured by ultrasound at age 29-31y; these measures were adjusted for BMI to indicate abdominal fat distributions. Linear regression models were performed, separately by sex. Admixture was observed between European (median proportion 85.3), African (6.6), and Native American (6.3) ancestries, with a strong inverse correlation between the African and European ancestry scores (ρ = -0.93; p<0.001). Independent of education level, African ancestry was inversely associated with both visceral and subcutaneous abdominal fat distributions in men (both P = 0.001), and inversely associated with subcutaneous abdominal fat distribution in women (p = 0.009). Independent of genomic ancestry, higher education level was associated with lower visceral fat, but higher subcutaneous fat, in both men and women (all p<0.001). Our findings, from an admixed population, indicate that both genomic ancestry and education level were independently associated with abdominal fat distribution in adults. African ancestry appeared to lower abdominal fat distributions, particularly in men.

Analysis of ancestry informative markers in three main ethnic groups from Ecuador supports a trihybrid origin of Ecuadorians.

PubMed

Santangelo, Roberta; González-Andrade, Fabricio; Børsting, Claus; Torroni, Antonio; Pereira, Vania; Morling, Niels

2017-11-01

Ancestry inference is traditionally done using autosomal SNPs that present great allele frequency differences among populations from different geographic regions. These ancestry informative markers (AIMs) are useful for determining the most likely biogeographic ancestry or population of origin of an individual. Due to the growing interest in AIMs and their applicability in different fields, commercial companies have started to develop AIM multiplexes targeted for Massive Parallel Sequencing platforms. This project focused on the study of three main ethnic groups from Ecuador (Kichwa, Mestizo, and Afro-Ecuadorian) using the Precision ID Ancestry panel (Thermo Fisher Scientific). In total, 162 Ecuadorian individuals were investigated. The Afro-Ecuadorian and Mestizo showed higher average genetic diversities compared to the Kichwa. These results are consistent with the highly admixed nature of the first two groups. The Kichwa showed the highest proportion of Native Amerindian (NAM) ancestry relative to the other two groups. The Mestizo had an admixed ancestry of NAM and European with a larger European component, whereas the Afro-Ecuadorian were highly admixed presenting proportions of African, Native Amerindian, and European ancestries. The comparison of our results with previous studies based on uniparental markers (i.e. Y chromosome and mtDNA) highlighted the sex-biased admixture process in the Ecuadorian Mestizo. Overall, the data generated in this work represent one important step to assess the application of ancestry inference in admixed populations in a forensic context. Copyright © 2017 Elsevier B.V. All rights reserved.

Genomic ancestry and education level independently influence abdominal fat distributions in a Brazilian admixed population

PubMed Central

De Lucia Rolfe, Emanuella; Horta, Bernardo Lessa; Gigante, Denise Petrucci; Yudkin, John S.; Ong, Ken K.; Victora, Cesar Gomes

2017-01-01

We aimed to identify the independent associations of genomic ancestry and education level with abdominal fat distributions in the 1982 Pelotas birth cohort study, Brazil. In 2,890 participants (1,409 men and 1,481 women), genomic ancestry was assessed using genotype data on 370,539 genome-wide variants to quantify ancestral proportions in each individual. Years of completed education was used to indicate socio-economic position. Visceral fat depth and subcutaneous abdominal fat thickness were measured by ultrasound at age 29–31y; these measures were adjusted for BMI to indicate abdominal fat distributions. Linear regression models were performed, separately by sex. Admixture was observed between European (median proportion 85.3), African (6.6), and Native American (6.3) ancestries, with a strong inverse correlation between the African and European ancestry scores (ρ = -0.93; p<0.001). Independent of education level, African ancestry was inversely associated with both visceral and subcutaneous abdominal fat distributions in men (both P = 0.001), and inversely associated with subcutaneous abdominal fat distribution in women (p = 0.009). Independent of genomic ancestry, higher education level was associated with lower visceral fat, but higher subcutaneous fat, in both men and women (all p<0.001). Our findings, from an admixed population, indicate that both genomic ancestry and education level were independently associated with abdominal fat distribution in adults. African ancestry appeared to lower abdominal fat distributions, particularly in men. PMID:28582437

Genetic Ancestry, Serum Interferon-α Activity, and Autoantibodies in Systemic Lupus Erythematosus

PubMed Central

Ko, Kichul; Franek, Beverly S.; Marion, Miranda; Kaufman, Kenneth M.; Langefeld, Carl D.; Harley, John B.; Niewold, Timothy B.

2012-01-01

Objective To investigate and refine the relationships among systemic lupus erythematosus (SLE) and related autoantibodies, interferon-α (IFN-α), and various ancestral backgrounds. Methods We investigated quantitatively defined genetic ancestry through principal component analysis in place of self-reported ancestry. Results African ancestry was found to be associated with presence of anti-RNP antibody (p = 0.0026), and anti-RNP was correlated with high levels of IFN-α (p = 2.8 × 10−5). Conclusion Our data support a model in which African ancestry increases the likelihood of SLE-associated autoantibody formation, which subsequently results in higher levels of serum IFN-α. PMID:22505704

Identifying the rooted species tree from the distribution of unrooted gene trees under the coalescent.

PubMed

Allman, Elizabeth S; Degnan, James H; Rhodes, John A

2011-06-01

Gene trees are evolutionary trees representing the ancestry of genes sampled from multiple populations. Species trees represent populations of individuals-each with many genes-splitting into new populations or species. The coalescent process, which models ancestry of gene copies within populations, is often used to model the probability distribution of gene trees given a fixed species tree. This multispecies coalescent model provides a framework for phylogeneticists to infer species trees from gene trees using maximum likelihood or Bayesian approaches. Because the coalescent models a branching process over time, all trees are typically assumed to be rooted in this setting. Often, however, gene trees inferred by traditional phylogenetic methods are unrooted. We investigate probabilities of unrooted gene trees under the multispecies coalescent model. We show that when there are four species with one gene sampled per species, the distribution of unrooted gene tree topologies identifies the unrooted species tree topology and some, but not all, information in the species tree edges (branch lengths). The location of the root on the species tree is not identifiable in this situation. However, for 5 or more species with one gene sampled per species, we show that the distribution of unrooted gene tree topologies identifies the rooted species tree topology and all its internal branch lengths. The length of any pendant branch leading to a leaf of the species tree is also identifiable for any species from which more than one gene is sampled.

The Bos taurus–Bos indicus balance in fertility and milk related genes

PubMed Central

Lehnert, Sigrid A.; Mudadu, Mauricio A.; Coutinho, Luiz; Regitano, Luciana; George, Andrew; Reverter, Antonio

2017-01-01

Numerical approaches to high-density single nucleotide polymorphism (SNP) data are often employed independently to address individual questions. We linked independent approaches in a bioinformatics pipeline for further insight. The pipeline driven by heterozygosity and Hardy-Weinberg equilibrium (HWE) analyses was applied to characterize Bos taurus and Bos indicus ancestry. We infer a gene co-heterozygosity network that regulates bovine fertility, from data on 18,363 cattle with genotypes for 729,068 SNP. Hierarchical clustering separated populations according to Bos taurus and Bos indicus ancestry. The weights of the first principal component were subjected to Normal mixture modelling allowing the estimation of a gene’s contribution to the Bos taurus-Bos indicus axis. We used deviation from HWE, contribution to Bos indicus content and association to fertility traits to select 1,284 genes. With this set, we developed a co-heterozygosity network where the group of genes annotated as fertility-related had significantly higher Bos indicus content compared to other functional classes of genes, while the group of genes associated with milk production had significantly higher Bos taurus content. The network analysis resulted in capturing novel gene associations of relevance to bovine domestication events. We report transcription factors that are likely to regulate genes associated with cattle domestication and tropical adaptation. Our pipeline can be generalized to any scenarios where population structure requires scrutiny at the molecular level, particularly in the presence of a priori set of genes known to impact a phenotype of evolutionary interest such as fertility. PMID:28763475

PGG.Population: a database for understanding the genomic diversity and genetic ancestry of human populations.

PubMed

Zhang, Chao; Gao, Yang; Liu, Jiaojiao; Xue, Zhe; Lu, Yan; Deng, Lian; Tian, Lei; Feng, Qidi; Xu, Shuhua

2018-01-04

There are a growing number of studies focusing on delineating genetic variations that are associated with complex human traits and diseases due to recent advances in next-generation sequencing technologies. However, identifying and prioritizing disease-associated causal variants relies on understanding the distribution of genetic variations within and among populations. The PGG.Population database documents 7122 genomes representing 356 global populations from 107 countries and provides essential information for researchers to understand human genomic diversity and genetic ancestry. These data and information can facilitate the design of research studies and the interpretation of results of both evolutionary and medical studies involving human populations. The database is carefully maintained and constantly updated when new data are available. We included miscellaneous functions and a user-friendly graphical interface for visualization of genomic diversity, population relationships (genetic affinity), ancestral makeup, footprints of natural selection, and population history etc. Moreover, PGG.Population provides a useful feature for users to analyze data and visualize results in a dynamic style via online illustration. The long-term ambition of the PGG.Population, together with the joint efforts from other researchers who contribute their data to our database, is to create a comprehensive depository of geographic and ethnic variation of human genome, as well as a platform bringing influence on future practitioners of medicine and clinical investigators. PGG.Population is available at https://www.pggpopulation.org. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

SNPs and Haplotypes in Native American Populations

PubMed Central

Kidd, Judith R.; Friedlaender, Françoise; Pakstis, Andrew J.; Furtado, Manohar; Fang, Rixun; Wang, Xudong; Nievergelt, Caroline M.; Kidd, Kenneth K.

2013-01-01

Autosomal DNA polymorphisms can provide new information and understanding of both the origins of and relationships among modern Native American populations. At the same time that autosomal markers can be highly informative, they are also susceptible to ascertainment biases in the selection of the markers to use. Identifying markers that can be used for ancestry inference among Native American populations can be considered separate from identifying markers to further the quest for history. In the current study we are using data on nine Native American populations to compare the results based on a large haplotype-based dataset with relatively small independent sets of SNPs. We are interested in what types of limited datasets an individual laboratory might be able to collect are best for addressing two different questions of interest. First, how well can we differentiate the Native American populations and/or infer ancestry by assigning an individual to her population(s) of origin? Second, how well can we infer the historical/evolutionary relationships among Native American populations and their Eurasian origins. We conclude that only a large comprehensive dataset involving multiple autosomal markers on multiple populations will be able to answer both questions; different small sets of markers are able to answer only one or the other of these questions. Using our largest dataset we see a general increasing distance from Old World populations from North to South in the New World except for an unexplained close relationship between our Maya and Quechua samples. PMID:21913176

Molecular phylogeography of the Chagas' disease vector Triatoma infestans in Argentina

PubMed Central

Pérez de Rosas, A R; Segura, E L; García, B A

2011-01-01

Triatoma infestans is the main vector of Chagas' disease in South America between latitudes 10°S and 46°S. A multilocus microsatellite data set of 836 individuals from 27 populations of T. infestans, from all its range of distribution in Argentina, was analyzed. Our results favor the hypothesis of two independent migration events of colonization in Argentina and secondary contacts. The majority of the populations of the western provinces of Catamarca, La Rioja, San Juan and the west of Cordoba province, had almost no shared ancestry with the rest of the populations analyzed. Probably those populations, belonging to localities close to the Andean region, could have been established by the dispersal line of T. infestans that would have arrived to Argentina through the Andes, whereas most of the rest of the populations analyzed may have derived from the dispersal line of T. infestans in non-Andean lowlands. Among them, those from the provinces of Formosa, Chaco, Santiago del Estero and Santa Fe shared different percentages of ancestry and presented lower degree of genetic differentiation. The migratory movement linked to regional economies and possibly associated with passive dispersal, would allow a higher genetic exchange among these populations of T. infestans. This study, using microsatellite markers, provides a new approach for evaluating the validity of the different hypotheses concerning the evolutionary history of this species. Two major lineages of T. infestans, an Andean and non-Andean, are suggested. PMID:21224874

Toward a unifying framework for evolutionary processes.

PubMed

Paixão, Tiago; Badkobeh, Golnaz; Barton, Nick; Çörüş, Doğan; Dang, Duc-Cuong; Friedrich, Tobias; Lehre, Per Kristian; Sudholt, Dirk; Sutton, Andrew M; Trubenová, Barbora

2015-10-21

The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

From the scala naturae to the symbiogenetic and dynamic tree of life

PubMed Central

2011-01-01

All living beings on Earth, from bacteria to humans, are connected through descent from common ancestors and represent the summation of their corresponding, ca. 3500 million year long evolutionary history. However, the evolution of phenotypic features is not predictable, and biologists no longer use terms such as "primitive" or "perfect organisms". Despite these insights, the Bible-based concept of the so-called "ladder of life" or Scala Naturae, i.e., the idea that all living beings can be viewed as representing various degrees of "perfection", with humans at the very top of this biological hierarchy, was popular among naturalists until ca. 1850 (Charles Bonnet, Jean Lamarck and others). Charles Darwin is usually credited with the establishment of a branched evolutionary "Tree of Life". This insight of 1859 was based on his now firmly corroborated proposals of common ancestry and natural selection. In this article I argue that Darwin was still influenced by "ladder thinking", a theological view that prevailed throughout the 19th century and is also part of Ernst Haeckel's famous Oak tree (of Life) of 1866, which is, like Darwin's scheme, static. In 1910, Constantin Mereschkowsky proposed an alternative, "anti-selectionist" concept of biological evolution, which became known as the symbiogenesis-theory. According to the symbiogenesis-scenario, eukaryotic cells evolved on a static Earth from archaic prokaryotes via the fusion and subsequent cooperation of certain microbes. In 1929, Alfred Wegener published his theory of continental drift, which was later corroborated, modified and extended. The resulting theory of plate tectonics is now the principal organizing concept of geology. Over millions of years, plate tectonics and hence the "dynamic Earth" has caused destructive volcanic eruptions and earthquakes. At the same time, it created mountain ranges, deep oceans, novel freshwater habitats, and deserts. As a result, these geologic processes destroyed numerous populations of organisms, and produced the environmental conditions for new species of animals, plants and microbes to adapt and evolve. In this article I propose a tree-like "symbiogenesis, natural selection, and dynamic Earth (synade)-model" of macroevolution that is based on these novel facts and data. Reviewers This article was reviewed by Mark Ragan, W. Ford Doolittle, and Staffan Müller-Wille. PMID:21714937

Neutral Evolution of Multiple Quantitative Characters: A Genealogical Approach

PubMed Central

Griswold, Cortland K.; Logsdon, Benjamin; Gomulkiewicz, Richard

2007-01-01

The G matrix measures the components of phenotypic variation that are genetically heritable. The structure of G, that is, its principal components and their associated variances, determines, in part, the direction and speed of multivariate trait evolution. In this article we present a framework and results that give the structure of G under the assumption of neutrality. We suggest that a neutral expectation of the structure of G is important because it gives a null expectation for the structure of G from which the unique consequences of selection can be determined. We demonstrate how the processes of mutation, recombination, and drift shape the structure of G. Furthermore, we demonstrate how shared common ancestry between segregating alleles shapes the structure of G. Our results show that shared common ancestry, which manifests itself in the form of a gene genealogy, causes the structure of G to be nonuniform in that the variances associated with the principal components of G decline at an approximately exponential rate. Furthermore we show that the extent of the nonuniformity in the structure of G is enhanced with declines in mutation rates, recombination rates, and numbers of loci and is dependent on the pattern and modality of mutation. PMID:17339224

Mitochondrial Evolution

PubMed Central

Gray, Michael W.

2012-01-01

Viewed through the lens of the genome it contains, the mitochondrion is of unquestioned bacterial ancestry, originating from within the bacterial phylum α-Proteobacteria (Alphaproteobacteria). Accordingly, the endosymbiont hypothesis—the idea that the mitochondrion evolved from a bacterial progenitor via symbiosis within an essentially eukaryotic host cell—has assumed the status of a theory. Yet mitochondrial genome evolution has taken radically different pathways in diverse eukaryotic lineages, and the organelle itself is increasingly viewed as a genetic and functional mosaic, with the bulk of the mitochondrial proteome having an evolutionary origin outside Alphaproteobacteria. New data continue to reshape our views regarding mitochondrial evolution, particularly raising the question of whether the mitochondrion originated after the eukaryotic cell arose, as assumed in the classical endosymbiont hypothesis, or whether this organelle had its beginning at the same time as the cell containing it. PMID:22952398

Ancient Ethiopian genome reveals extensive Eurasian admixture throughout the African continent.

PubMed

Gallego Llorente, M; Jones, E R; Eriksson, A; Siska, V; Arthur, K W; Arthur, J W; Curtis, M C; Stock, J T; Coltorti, M; Pieruccini, P; Stretton, S; Brock, F; Higham, T; Park, Y; Hofreiter, M; Bradley, D G; Bhak, J; Pinhasi, R; Manica, A

2015-11-13

Characterizing genetic diversity in Africa is a crucial step for most analyses reconstructing the evolutionary history of anatomically modern humans. However, historic migrations from Eurasia into Africa have affected many contemporary populations, confounding inferences. Here, we present a 12.5× coverage ancient genome of an Ethiopian male ("Mota") who lived approximately 4500 years ago. We use this genome to demonstrate that the Eurasian backflow into Africa came from a population closely related to Early Neolithic farmers, who had colonized Europe 4000 years earlier. The extent of this backflow was much greater than previously reported, reaching all the way to Central, West, and Southern Africa, affecting even populations such as Yoruba and Mbuti, previously thought to be relatively unadmixed, who harbor 6 to 7% Eurasian ancestry. Copyright © 2015, American Association for the Advancement of Science.

Ancestry and demography and descendants of Iron Age nomads of the Eurasian Steppe

NASA Astrophysics Data System (ADS)

Unterländer, Martina; Palstra, Friso; Lazaridis, Iosif; Pilipenko, Aleksandr; Hofmanová, Zuzana; Groß, Melanie; Sell, Christian; Blöcher, Jens; Kirsanow, Karola; Rohland, Nadin; Rieger, Benjamin; Kaiser, Elke; Schier, Wolfram; Pozdniakov, Dimitri; Khokhlov, Aleksandr; Georges, Myriam; Wilde, Sandra; Powell, Adam; Heyer, Evelyne; Currat, Mathias; Reich, David; Samashev, Zainolla; Parzinger, Hermann; Molodin, Vyacheslav I.; Burger, Joachim

2017-03-01

During the 1st millennium before the Common Era (BCE), nomadic tribes associated with the Iron Age Scythian culture spread over the Eurasian Steppe, covering a territory of more than 3,500 km in breadth. To understand the demographic processes behind the spread of the Scythian culture, we analysed genomic data from eight individuals and a mitochondrial dataset of 96 individuals originating in eastern and western parts of the Eurasian Steppe. Genomic inference reveals that Scythians in the east and the west of the steppe zone can best be described as a mixture of Yamnaya-related ancestry and an East Asian component. Demographic modelling suggests independent origins for eastern and western groups with ongoing gene-flow between them, plausibly explaining the striking uniformity of their material culture. We also find evidence that significant gene-flow from east to west Eurasia must have occurred early during the Iron Age.

Characterization of European-ancestry NAFLD-Associated Variants in Individuals of African and Hispanic Descent

PubMed Central

Palmer, Nicholette D; Musani, Solomon K; Yerges-Armstrong, Laura M; Feitosa, Mary F; Bielak, Lawrence F; Hernaez, Ruben; Kahali, Bratati; Carr, J Jeffrey; Harris, Tamara B; Jhun, Min A; Kardia, Sharon LR; Langefeld, Carl D; Mosley, Thomas H; Norris, Jill M; Smith, Albert V; Taylor, Herman A; Wagenknecht, Lynne E; Liu, Jiankang; Borecki, Ingrid B; Peyser, Patricia A; Speliotes, Elizabeth K

2013-01-01

Nonalcoholic Fatty Liver Disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European-ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African and/or Hispanic Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African-American (n=3124) and one Hispanic-American (n=849) cohorts. All analyses controlled for variation in age, age2, gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African-American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9kg/m2, respectively. Hepatic steatosis was 0.20–0.34 heritable in African-and Hispanic-American families (p<0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1. Conclusions We show for the first time that multiple genetic variants are associated with hepatic steatosis across ancestries and explain a substantial proportion of the genetic predisposition in African and Hispanic Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries. PMID:23564467

An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans

PubMed Central

Kelley, James M.; Hughes, Laura B.; Faggard, Jeffrey D.; Danila, Maria I.; Crawford, Monica H.; Edberg, Yuanqing; Padilla, Miguel A.; Tiwari, Hemant K.; Westfall, Andrew O.; Alarcón, Graciela S.; Conn, Doyt L.; Jonas, Beth L.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard D.; Allison, David B.; Kimberly, Robert P.; Moreland, Larry W.; Edberg, Jeffrey C.; Bridges, S. Louis

2009-01-01

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ∼1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462×10−26, Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13–0.26, p = 2.4×10−28, Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF = 0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations. PMID:19300490

Characterization of European ancestry nonalcoholic fatty liver disease-associated variants in individuals of African and Hispanic descent.

PubMed

Palmer, Nicholette D; Musani, Solomon K; Yerges-Armstrong, Laura M; Feitosa, Mary F; Bielak, Lawrence F; Hernaez, Ruben; Kahali, Bratati; Carr, J Jeffrey; Harris, Tamara B; Jhun, Min A; Kardia, Sharon L R; Langefeld, Carl D; Mosley, Thomas H; Norris, Jill M; Smith, Albert V; Taylor, Herman A; Wagenknecht, Lynne E; Liu, Jiankang; Borecki, Ingrid B; Peyser, Patricia A; Speliotes, Elizabeth K

2013-09-01

Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African- and/or Hispanic-Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African American (n = 3,124) and one Hispanic American (n = 849) cohorts. All analyses controlled for variation in age, age(2) , gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9 kg/m(2) , respectively. Hepatic steatosis was 0.20-0.34 heritable in African- and Hispanic-American families (P < 0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1. Multiple genetic variants are associated with hepatic steatosis across ancestries. This explains a substantial proportion of the genetic predisposition in African- and Hispanic-Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries. © 2013 by the American Association for the Study of Liver Diseases.

Genetic structure characterization of Chileans reflects historical immigration patterns.

PubMed

Eyheramendy, Susana; Martinez, Felipe I; Manevy, Federico; Vial, Cecilia; Repetto, Gabriela M

2015-03-17

Identifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography.

Genetic structure characterization of Chileans reflects historical immigration patterns

PubMed Central

Eyheramendy, Susana; Martinez, Felipe I.; Manevy, Federico; Vial, Cecilia; Repetto, Gabriela M.

2015-01-01

Identifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography. PMID:25778948

How to Identify and Interpret Evolutionary Tree Diagrams

ERIC Educational Resources Information Center

Kong, Yi; Anderson, Trevor; Pelaez, Nancy

2016-01-01

Evolutionary trees are key tools for modern biology and are commonly portrayed in textbooks to promote learning about biological evolution. However, many people have difficulty in understanding what evolutionary trees are meant to portray. In fact, some ideas that current professional biologists depict with evolutionary trees are neither clearly…

Ancestry prediction in Singapore population samples using the Illumina ForenSeq kit.

PubMed

Ramani, Anantharaman; Wong, Yongxun; Tan, Si Zhen; Shue, Bing Hong; Syn, Christopher

2017-11-01

The ability to predict bio-geographic ancestry can be valuable to generate investigative leads towards solving crimes. Ancestry informative marker (AIM) sets include large numbers of SNPs to predict an ancestral population. Massively parallel sequencing has enabled forensic laboratories to genotype a large number of such markers in a single assay. Illumina's ForenSeq DNA Signature Kit includes the ancestry informative SNPs reported by Kidd et al. In this study, the ancestry prediction capabilities of the ForenSeq kit through sequencing on the MiSeq FGx were evaluated in 1030 unrelated Singapore population samples of Chinese, Malay and Indian origin. A total of 59 ancestry SNPs and phenotypic SNPs with AIM properties were selected. The bio-geographic ancestry of the 1030 samples, as predicted by Illumina's ForenSeq Universal Analysis Software (UAS), was determined. 712 of the genotyped samples were used as a training sample set for the generation of an ancestry prediction model using STRUCTURE and Snipper. The performance of the prediction model was tested by both methods with the remaining 318 samples. Ancestry prediction in UAS was able to correctly classify the Singapore Chinese as part of the East Asian cluster, while Indians clustered with Ad-mixed Americans and Malays clustered in-between these two reference populations. Principal component analyses showed that the 59 SNPs were only able to account for 26% of the variation between the Singapore sub-populations. Their discriminatory potential was also found to be lower (G ST =0.085) than that reported in ALFRED (F ST =0.357). The Snipper algorithm was able to correctly predict bio-geographic ancestry in 91% of Chinese and Indian, and 88% of Malay individuals, while the success rates for the STRUCTURE algorithm were 94% in Chinese, 80% in Malay, and 91% in Indian individuals. Both these algorithms were able to provide admixture proportions when present. Ancestry prediction accuracy (in terms of likelihood ratio) was generally high in the absence of admixture. Misclassification occurred in admixed individuals, who were likely offspring of inter-ethnic marriages, and hence whose self-reported bio-geographic ancestries were dependent on that of their fathers, and in individuals of minority sub-populations with inter-ethnic beliefs. The ancestry prediction capabilities of the 59 SNPs on the ForenSeq kit were reasonably effective in differentiating the Singapore Chinese, Malay and Indian sub-populations, and will be of use for investigative purposes. However, there is potential for more accurate prediction through the evaluation of other AIM sets. Copyright © 2017 Elsevier B.V. All rights reserved.

History Shaped the Geographic Distribution of Genomic Admixture on the Island of Puerto Rico

PubMed Central

Via, Marc; Gignoux, Christopher R.; Roth, Lindsey A.; Fejerman, Laura; Galanter, Joshua; Choudhry, Shweta; Toro-Labrador, Gladys; Viera-Vera, Jorge; Oleksyk, Taras K.; Beckman, Kenneth; Ziv, Elad; Risch, Neil

2011-01-01

Contemporary genetic variation among Latin Americans human groups reflects population migrations shaped by complex historical, social and economic factors. Consequently, admixture patterns may vary by geographic regions ranging from countries to neighborhoods. We examined the geographic variation of admixture across the island of Puerto Rico and the degree to which it could be explained by historic and social events. We analyzed a census-based sample of 642 Puerto Rican individuals that were genotyped for 93 ancestry informative markers (AIMs) to estimate African, European and Native American ancestry. Socioeconomic status (SES) data and geographic location were obtained for each individual. There was significant geographic variation of ancestry across the island. In particular, African ancestry demonstrated a decreasing East to West gradient that was partially explained by historical factors linked to the colonial sugar plantation system. SES also demonstrated a parallel decreasing cline from East to West. However, at a local level, SES and African ancestry were negatively correlated. European ancestry was strongly negatively correlated with African ancestry and therefore showed patterns complementary to African ancestry. By contrast, Native American ancestry showed little variation across the island and across individuals and appears to have played little social role historically. The observed geographic distributions of SES and genetic variation relate to historical social events and mating patterns, and have substantial implications for the design of studies in the recently admixed Puerto Rican population. More generally, our results demonstrate the importance of incorporating social and geographic data with genetics when studying contemporary admixed populations. PMID:21304981

A rapid screening of ancestry for genetic association studies in an admixed population from Pernambuco, Brazil.

PubMed

Coelho, A V C; Moura, R R; Cavalcanti, C A J; Guimarães, R L; Sandrin-Garcia, P; Crovella, S; Brandão, L A C

2015-03-31

Genetic association studies determine how genes influence traits. However, non-detected population substructure may bias the analysis, resulting in spurious results. One method to detect substructure is to genotype ancestry informative markers (AIMs) besides the candidate variants, quantifying how much ancestral populations contribute to the samples' genetic background. The present study aimed to use a minimum quantity of markers, while retaining full potential to estimate ancestries. We tested the feasibility of a subset of the 12 most informative markers from a previously established study to estimate influence from three ancestral populations: European, African and Amerindian. The results showed that in a sample with a diverse ethnicity (N = 822) derived from 1000 Genomes database, the 12 AIMs had the same capacity to estimate ancestries when compared to the original set of 128 AIMs, since estimates from the two panels were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The ancestry estimates from Recife subjects were in accordance with previous studies, showing that Northeastern Brazilian populations show great influence from European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%) ancestries. Ethnicity self-classification according to skin-color was confirmed to be a poor indicator of population substructure in Brazilians, since ancestry estimates overlapped between classifications. Thus, our streamlined panel of 12 markers may substitute panels with more markers, while retaining the capacity to control for population substructure and admixture, thereby reducing sample processing time.

Human and Helicobacter pylori coevolution shapes the risk of gastric disease.

PubMed

Kodaman, Nuri; Pazos, Alvaro; Schneider, Barbara G; Piazuelo, M Blanca; Mera, Robertino; Sobota, Rafal S; Sicinschi, Liviu A; Shaffer, Carrie L; Romero-Gallo, Judith; de Sablet, Thibaut; Harder, Reed H; Bravo, Luis E; Peek, Richard M; Wilson, Keith T; Cover, Timothy L; Williams, Scott M; Correa, Pelayo

2014-01-28

Helicobacter pylori is the principal cause of gastric cancer, the second leading cause of cancer mortality worldwide. However, H. pylori prevalence generally does not predict cancer incidence. To determine whether coevolution between host and pathogen influences disease risk, we examined the association between the severity of gastric lesions and patterns of genomic variation in matched human and H. pylori samples. Patients were recruited from two geographically distinct Colombian populations with significantly different incidences of gastric cancer, but virtually identical prevalence of H. pylori infection. All H. pylori isolates contained the genetic signatures of multiple ancestries, with an ancestral African cluster predominating in a low-risk, coastal population and a European cluster in a high-risk, mountain population. The human ancestry of the biopsied individuals also varied with geography, with mostly African ancestry in the coastal region (58%), and mostly Amerindian ancestry in the mountain region (67%). The interaction between the host and pathogen ancestries completely accounted for the difference in the severity of gastric lesions in the two regions of Colombia. In particular, African H. pylori ancestry was relatively benign in humans of African ancestry but was deleterious in individuals with substantial Amerindian ancestry. Thus, coevolution likely modulated disease risk, and the disruption of coevolved human and H. pylori genomes can explain the high incidence of gastric disease in the mountain population.

A Genomic Approach for Distinguishing between Recent and Ancient Admixture as Applied to Cattle

PubMed Central

Hillis, David M.

2014-01-01

Genomic data facilitate opportunities to track complex population histories of divergence and gene flow. We developed a metric, scaled block size (SBS), which uses the nonrecombined block size of introgressed regions of chromosomes to differentiate between recent and ancient types of admixture, and applied it to the reconstruction of admixture in cattle. Cattle are descendants of 2 independently domesticated lineages, taurine and indicine, which diverged more than 200 000 years ago. Several breeds have hybrid ancestry between these divergent lineages. Using 47 506 single-nucleotide polymorphisms, we analyzed the genomic architecture of the ancestry of 1369 individuals. We focused on 4 groups with admixed ancestry, including 2 anciently admixed African breeds (n = 58; n = 43), New World cattle of Spanish origin (n = 51), and known recent hybrids (n = 46). We estimated the ancestry of chromosomal regions for each individual and used the SBS metric to differentiate the timing of admixture among groups and among individuals within groups. By comparing SBS values of test individuals with standards with known recent hybrid ancestry, we were able to differentiate individuals of recent hybrid origin from other admixed cattle. We also estimated ancestry at the chromosomal scale. The X chromosome exhibits reduced indicine ancestry in recent hybrid, New World, and western African cattle, with virtually no evidence of indicine ancestry in New World cattle. PMID:24510946

Single Motherhood, Alcohol Dependence, and Smoking During Pregnancy: A Propensity Score Analysis.

PubMed

Waldron, Mary; Bucholz, Kathleen K; Lian, Min; Lessov-Schlaggar, Christina N; Miller, Ruth Huang; Lynskey, Michael T; Knopik, Valerie S; Madden, Pamela A F; Heath, Andrew C

2017-09-01

Few studies linking single motherhood and maternal smoking during pregnancy consider correlated risk from problem substance use beyond history of smoking and concurrent use of alcohol. In the present study, we used propensity score methods to examine whether the risk of smoking during pregnancy associated with single motherhood is the result of potential confounders, including alcohol dependence. Data were drawn from mothers participating in a birth cohort study of their female like-sex twin offspring (n = 257 African ancestry; n = 1,711 European or other ancestry). We conducted standard logistic regression models predicting smoking during pregnancy from single motherhood at twins' birth, followed by propensity score analyses comparing single-mother and two-parent families stratified by predicted probability of single motherhood. In standard models, single motherhood predicted increased risk of smoking during pregnancy in European ancestry but not African ancestry families. In propensity score analyses, rates of smoking during pregnancy were elevated in single-mother relative to two-parent European ancestry families across much of the spectrum a priori risk of single motherhood. Among African ancestry families, within-strata comparisons of smoking during pregnancy by single-mother status were nonsignificant. These findings highlight single motherhood as a unique risk factor for smoking during pregnancy in European ancestry mothers, over and above alcohol dependence. Additional research is needed to identify risks, beyond single motherhood, associated with smoking during pregnancy in African ancestry mothers.

Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

PubMed Central

Browning, Sharon R.; Grinde, Kelsey; Plantinga, Anna; Gogarten, Stephanie M.; Stilp, Adrienne M.; Kaplan, Robert C.; Avilés-Santa, M. Larissa; Browning, Brian L.; Laurie, Cathy C.

2016-01-01

We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ancestry-specific PCA, we found significant population structure within African, European, and Amerindian ancestries in the Hispanic/Latino individuals in our study. In the African ancestral component of the admixed individuals, individuals whose grandparents were from Central America clustered separately from individuals whose grandparents were from the Caribbean, and also from reference Yoruba and Mandenka West African individuals. In the European component, individuals whose grandparents were from Puerto Rico diverged partially from other background groups. In the Amerindian ancestral component, individuals clustered into multiple different groups depending on the grandparental country of origin. Therefore, local ancestry estimation provides further insight into the complex genetic structure of US Hispanic/Latino populations, which must be properly accounted for in genotype-phenotype association studies. It also provides a basis for admixture mapping and ancestry-specific allele frequency estimation, which are useful in the identification of risk factors for disease. PMID:27172203

Evidence for past and present hybridization in three Antarctic icefish species provides new perspectives on an evolutionary radiation.

PubMed

Marino, I A M; Benazzo, A; Agostini, C; Mezzavilla, M; Hoban, S M; Patarnello, T; Zane, L; Bertorelle, G

2013-10-01

Determining the timing, extent and underlying causes of interspecific gene exchange during or following speciation is central to understanding species' evolution. Antarctic notothenioid fish, thanks to the acquisition of antifreeze glycoproteins during Oligocene transition to polar conditions, experienced a spectacular radiation to >100 species during Late Miocene cooling events. The impact of recent glacial cycles on this group is poorly known, but alternating warming and cooling periods may have affected species' distributions, promoted ecological divergence into recurrently opening niches and/or possibly brought allopatric species into contact. Using microsatellite markers and statistical methods including Approximate Bayesian Computation, we investigated genetic differentiation, hybridization and the possible influence of the last glaciation/deglaciation events in three icefish species of the genus Chionodraco. Our results provide strong evidence of contemporary and past introgression by showing that: (i) a substantial fraction of contemporary individuals in each species has mixed ancestry, (ii) evolutionary scenarios excluding hybridization or including it only in ancient times have small or zero posterior probabilities, (iii) the data support a scenario of interspecific gene flow associated with the two most recent interglacial periods. Glacial cycles might therefore have had a profound impact on the genetic composition of Antarctic fauna, as newly available shelf areas during the warmer intervals might have favoured secondary contacts and hybridization between diversified groups. If our findings are confirmed in other notothenioids, they offer new perspectives for understanding evolutionary dynamics of Antarctic fish and suggest a need for new predictions on the effects of global warming in this group. © 2013 John Wiley & Sons Ltd.

Evolutionary relationships of Fusobacterium nucleatum based on phylogenetic analysis and comparative genomics

PubMed Central

Mira, Alex; Pushker, Ravindra; Legault, Boris A; Moreira, David; Rodríguez-Valera, Francisco

2004-01-01

Background The phylogenetic position and evolutionary relationships of Fusobacteria remain uncertain. Especially intriguing is their relatedness to low G+C Gram positive bacteria (Firmicutes) by ribosomal molecular phylogenies, but their possession of a typical gram negative outer membrane. Taking advantage of the recent completion of the Fusobacterium nucleatum genome sequence we have examined the evolutionary relationships of Fusobacterium genes by phylogenetic analysis and comparative genomics tools. Results The data indicate that Fusobacterium has a core genome of a very different nature to other bacterial lineages, and branches out at the base of Firmicutes. However, depending on the method used, 35–56% of Fusobacterium genes appear to have a xenologous origin from bacteroidetes, proteobacteria, spirochaetes and the Firmicutes themselves. A high number of hypothetical ORFs with unusual codon usage and short lengths were found and hypothesized to be remnants of transferred genes that were discarded. Some proteins and operons are also hypothesized to be of mixed ancestry. A large portion of the Gram-negative cell wall-related genes seems to have been transferred from proteobacteria. Conclusions Many instances of similarity to other inhabitants of the dental plaque that have been sequenced were found. This suggests that the close physical contact found in this environment might facilitate horizontal gene transfer, supporting the idea of niche-specific gene pools. We hypothesize that at a point in time, probably associated to the rise of mammals, a strong selective pressure might have existed for a cell with a Clostridia-like metabolic apparatus but with the adhesive and immune camouflage features of Proteobacteria. PMID:15566569

Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations.

PubMed

Sánchez, Elena; Rasmussen, Astrid; Riba, Laura; Acevedo-Vasquez, Eduardo; Kelly, Jennifer A; Langefeld, Carl D; Williams, Adrianne H; Ziegler, Julie T; Comeau, Mary E; Marion, Miranda C; García-De La Torre, Ignacio; Maradiaga-Ceceña, Marco A; Cardiel, Mario H; Esquivel-Valerio, Jorge A; Rodriguez-Amado, Jacqueline; Moctezuma, José Francisco; Miranda, Pedro; Perandones, Carlos E; Castel, Cecilia; Laborde, Hugo A; Alba, Paula; Musuruana, Jorge L; Goecke, I Annelise; Anaya, Juan-Manuel; Kaufman, Kenneth M; Adler, Adam; Glenn, Stuart B; Brown, Elizabeth E; Alarcón, Graciela S; Kimberly, Robert P; Edberg, Jeffrey C; Vilá, Luis M; Criswell, Lindsey A; Gilkeson, Gary S; Niewold, Timothy B; Martín, Javier; Vyse, Timothy J; Boackle, Susan A; Ramsey-Goldman, Rosalind; Scofield, R Hal; Petri, Michelle; Merrill, Joan T; Reveille, John D; Tsao, Betty P; Orozco, Lorena; Baca, Vicente; Moser, Kathy L; Gaffney, Patrick M; James, Judith A; Harley, John B; Tusié-Luna, Teresa; Pons-Estel, Bernardo A; Jacob, Chaim O; Alarcón-Riquelme, Marta E

2012-11-01

American Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients. A total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). The average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement. In general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age. Copyright © 2012 by the American College of Rheumatology.

African ancestry, early life exposures, and respiratory morbidity in early childhood.

PubMed

Kumar, R; Tsai, H-J; Hong, X; Gignoux, C; Pearson, C; Ortiz, K; Fu, M; Pongracic, J A; Burchard, E G; Bauchner, H; Wang, X

2012-02-01

Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05-1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and early life risk factors associated with childhood recurrent wheezing. © 2011 Blackwell Publishing Ltd.

The evolutionary origins of diadromy inferred from a time-calibrated phylogeny for Clupeiformes (herring and allies)

PubMed Central

Bloom, Devin D.; Lovejoy, Nathan R.

2014-01-01

One of the most remarkable types of migration found in animals is diadromy, a life-history behaviour in which individuals move between oceans and freshwater habitats for feeding and reproduction. Diadromous fishes include iconic species such as salmon, eels and shad, and have long fascinated biologists because they undergo extraordinary physiological and behavioural modifications to survive in very different habitats. However, the evolutionary origins of diadromy remain poorly understood. Here, we examine the widely accepted productivity hypothesis, which states that differences in productivity between marine and freshwater biomes determine the origins of the different modes of diadromy. Specifically, the productivity hypothesis predicts that anadromous lineages should evolve in temperate areas from freshwater ancestors and catadromous lineages should evolve in tropical areas from marine ancestors. To test this, we generated a time-calibrated phylogeny for Clupeiformes (herrings, anchovies, sardines and allies), an ecologically and economically important group that includes high diversity of diadromous species. Our results do not support the productivity hypothesis. Instead we find that the different modes of diadromy do not have predictable ancestry based on latitude, and that predation, competition and geological history may be at least as important as productivity in determining the origins of diadromy. PMID:24430843

Conserved antigenic sites between MERS-CoV and Bat-coronavirus are revealed through sequence analysis.

PubMed

Sharmin, Refat; Islam, Abul B M M K

2016-01-01

MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein's antigenic sites are found to be conserved with those in HKU4 and HKU5. This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity.

Mitogenomes from The 1000 Genome Project reveal new Near Eastern features in present-day Tuscans.

PubMed

Gómez-Carballa, Alberto; Pardo-Seco, Jacobo; Amigo, Jorge; Martinón-Torres, Federico; Salas, Antonio

2015-01-01

Genetic analyses have recently been carried out on present-day Tuscans (Central Italy) in order to investigate their presumable recent Near East ancestry in connection with the long-standing debate on the origins of the Etruscan civilization. We retrieved mitogenomes and genome-wide SNP data from 110 Tuscans analyzed within the context of The 1000 Genome Project. For phylogeographic and evolutionary analysis we made use of a large worldwide database of entire mitogenomes (>26,000) and partial control region sequences (>180,000). Different analyses reveal the presence of typical Near East haplotypes in Tuscans representing isolated members of various mtDNA phylogenetic branches. As a whole, the Near East component in Tuscan mitogenomes can be estimated at about 8%; a proportion that is comparable to previous estimates but significantly lower than admixture estimates obtained from autosomal SNP data (21%). Phylogeographic and evolutionary inter-population comparisons indicate that the main signal of Near Eastern Tuscan mitogenomes comes from Iran. Mitogenomes of recent Near East origin in present-day Tuscans do not show local or regional variation. This points to a demographic scenario that is compatible with a recent arrival of Near Easterners to this region in Italy with no founder events or bottlenecks.

Manipulation of Fgf and Bmp signaling in teleost fishes suggests potential pathways for the evolutionary origin of multicuspid teeth

PubMed Central

Jackman, William R; Davies, Shelby H; Lyons, David B; Stauder, Caitlin K; Denton-Schneider, Benjamin R; Jowdry, Andrea; Aigler, Sharon R; Vogel, Scott A; Stock, David W

2014-01-01

Teeth with two or more cusps have arisen independently from an ancestral unicuspid condition in a variety of vertebrate lineages, including sharks, teleost fishes, amphibians, lizards, and mammals. One potential explanation for the repeated origins of multicuspid teeth is the existence of multiple adaptive pathways leading to them, as suggested by their different uses in these lineages. Another is that the addition of cusps required only minor changes in genetic pathways regulating tooth development. Here we provide support for the latter hypothesis by demonstrating that manipulation of the levels of Fibroblast growth factor (Fgf) or Bone morphogenetic protein (Bmp) signaling produces bicuspid teeth in the zebrafish (Danio rerio), a species lacking multicuspid teeth in its ancestry. The generality of these results for teleosts is suggested by the conversion of unicuspid pharyngeal teeth into bicuspid teeth by similar manipulations of the Mexican Tetra (Astyanax mexicanus). That these manipulations also produced supernumerary teeth in both species supports previous suggestions of similarities in the molecular control of tooth and cusp number. We conclude that despite their apparent complexity, the evolutionary origin of multicuspid teeth is positively constrained, likely requiring only slight modifications of a pre-existing mechanism for patterning the number and spacing of individual teeth. PMID:25098636

Manipulation of Fgf and Bmp signaling in teleost fishes suggests potential pathways for the evolutionary origin of multicuspid teeth.

PubMed

Jackman, William R; Davies, Shelby H; Lyons, David B; Stauder, Caitlin K; Denton-Schneider, Benjamin R; Jowdry, Andrea; Aigler, Sharon R; Vogel, Scott A; Stock, David W

2013-01-01

Teeth with two or more cusps have arisen independently from an ancestral unicuspid condition in a variety of vertebrate lineages, including sharks, teleost fishes, amphibians, lizards, and mammals. One potential explanation for the repeated origins of multicuspid teeth is the existence of multiple adaptive pathways leading to them, as suggested by their different uses in these lineages. Another is that the addition of cusps required only minor changes in genetic pathways regulating tooth development. Here we provide support for the latter hypothesis by demonstrating that manipulation of the levels of Fibroblast growth factor (Fgf) or Bone morphogenetic protein (Bmp) signaling produces bicuspid teeth in the zebrafish (Danio rerio), a species lacking multicuspid teeth in its ancestry. The generality of these results for teleosts is suggested by the conversion of unicuspid pharyngeal teeth into bicuspid teeth by similar manipulations of the Mexican Tetra (Astyanax mexicanus). That these manipulations also produced supernumerary teeth in both species supports previous suggestions of similarities in the molecular control of tooth and cusp number. We conclude that despite their apparent complexity, the evolutionary origin of multicuspid teeth is positively constrained, likely requiring only slight modifications of a pre-existing mechanism for patterning the number and spacing of individual teeth. © 2013 Wiley Periodicals, Inc.

Mitogenomes from The 1000 Genome Project Reveal New Near Eastern Features in Present-Day Tuscans

PubMed Central

Pardo-Seco, Jacobo; Amigo, Jorge; Martinón-Torres, Federico

2015-01-01

Background Genetic analyses have recently been carried out on present-day Tuscans (Central Italy) in order to investigate their presumable recent Near East ancestry in connection with the long-standing debate on the origins of the Etruscan civilization. We retrieved mitogenomes and genome-wide SNP data from 110 Tuscans analyzed within the context of The 1000 Genome Project. For phylogeographic and evolutionary analysis we made use of a large worldwide database of entire mitogenomes (>26,000) and partial control region sequences (>180,000). Results Different analyses reveal the presence of typical Near East haplotypes in Tuscans representing isolated members of various mtDNA phylogenetic branches. As a whole, the Near East component in Tuscan mitogenomes can be estimated at about 8%; a proportion that is comparable to previous estimates but significantly lower than admixture estimates obtained from autosomal SNP data (21%). Phylogeographic and evolutionary inter-population comparisons indicate that the main signal of Near Eastern Tuscan mitogenomes comes from Iran. Conclusions Mitogenomes of recent Near East origin in present-day Tuscans do not show local or regional variation. This points to a demographic scenario that is compatible with a recent arrival of Near Easterners to this region in Italy with no founder events or bottlenecks. PMID:25786119

Genome-Wide Association Studies of the PR Interval in African Americans

PubMed Central

Palmer, Cameron; Meng, Yan A.; Soliman, Elsayed Z.; Musani, Solomon K.; Kerr, Kathleen F.; Schnabel, Renate B.; Lubitz, Steven A.; Sotoodehnia, Nona; Redline, Susan; Pfeufer, Arne; Müller, Martina; Evans, Daniel S.; Nalls, Michael A.; Liu, Yongmei; Newman, Anne B.; Zonderman, Alan B.; Evans, Michele K.; Deo, Rajat; Ellinor, Patrick T.; Paltoo, Dina N.

2011-01-01

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10−8) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta  = 5.1 msec per minor allele, 95% CI  = 4.1–6.1, p = 3×10−23). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8–3.0, p = 3×10−16) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans. PMID:21347284

Evaluating Self-declared Ancestry of U.S. Americans with Autosomal, Y-chromosomal and Mitochondrial DNA

PubMed Central

Lao, Oscar; Vallone, Peter M; Coble, Michael D; Diegoli, Toni M; van Oven, Mannis; van der Gaag, Kristiaan J; Pijpe, Jeroen; de Knijff, Peter; Kayser, Manfred

2010-01-01

The current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with self-declared ancestry we have analyzed paternally, maternally and bi-parentally inherited DNA markers sensitive for indicating continental genetic ancestry in all four major U.S. American groups. We found that self-declared U.S. Hispanics and U.S. African Americans tend to show variable degrees of continental genetic admixture among the three genetic systems, with evidence for a marked sex-biased admixture history. Moreover, for these two groups we observed significant regional variation across the country in genetic admixture. In contrast, self-declared U.S. European and U.S. Asian Americans were genetically more homogeneous at the continental ancestry level. Two autosomal ancestry-sensitive markers located in skin pigmentation candidate genes showed significant differences in self-declared U.S. African Americans or U.S. European Americans, relative to their assumed parental populations from Africa or Europe. This provides genetic support for the importance of skin color in the complex process of ancestry identification. © 2010 Wiley-Liss, Inc. PMID:20886636

Deep cultural ancestry and human development indicators across nation states

PubMed Central

Sookias, Roland B.; Passmore, Samuel

2018-01-01

How historical connections, events and cultural proximity can influence human development is being increasingly recognized. One aspect of history that has only recently begun to be examined is deep cultural ancestry, i.e. the vertical relationships of descent between cultures, which can be represented by a phylogenetic tree of descent. Here, we test whether deep cultural ancestry predicts the United Nations Human Development Index (HDI) for 44 Eurasian countries, using language ancestry as a proxy for cultural relatedness and controlling for three additional factors—geographical proximity, religion and former communism. While cultural ancestry alone predicts HDI and its subcomponents (income, health and education indices), when geographical proximity is included only income and health indices remain significant and the effect is small. When communism and religion variables are included, cultural ancestry is no longer a significant predictor; communism significantly negatively predicts HDI, income and health indices, and Muslim percentage of the population significantly negatively predicts education index, although the latter result may not be robust. These findings indicate that geographical proximity and recent cultural history—especially communism—are more important than deep cultural factors in current human development and suggest the efficacy of modern policy initiatives is not tightly constrained by cultural ancestry. PMID:29765628

Deep cultural ancestry and human development indicators across nation states.

PubMed

Sookias, Roland B; Passmore, Samuel; Atkinson, Quentin D

2018-04-01

How historical connections, events and cultural proximity can influence human development is being increasingly recognized. One aspect of history that has only recently begun to be examined is deep cultural ancestry, i.e. the vertical relationships of descent between cultures, which can be represented by a phylogenetic tree of descent. Here, we test whether deep cultural ancestry predicts the United Nations Human Development Index (HDI) for 44 Eurasian countries, using language ancestry as a proxy for cultural relatedness and controlling for three additional factors-geographical proximity, religion and former communism. While cultural ancestry alone predicts HDI and its subcomponents (income, health and education indices), when geographical proximity is included only income and health indices remain significant and the effect is small. When communism and religion variables are included, cultural ancestry is no longer a significant predictor; communism significantly negatively predicts HDI, income and health indices, and Muslim percentage of the population significantly negatively predicts education index, although the latter result may not be robust. These findings indicate that geographical proximity and recent cultural history-especially communism-are more important than deep cultural factors in current human development and suggest the efficacy of modern policy initiatives is not tightly constrained by cultural ancestry.

European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus

PubMed Central

Chung, Sharon A.; Tian, Chao; Taylor, Kimberly E.; Lee, Annette T.; Ortmann, Ward A.; Hom, Geoffrey; Graham, Robert R.; Nititham, Joanne; Kelly, Jennifer A.; Morrisey, Jean; Wu, Hui; Yin, Hong; Alarcón-Riquelme, Marta E.; Tsao, Betty P.; Harley, John B.; Gaffney, Patrick M.; Moser, Kathy L.; Manzi, Susan; Petri, Michelle; Gregersen, Peter K.; Langefeld, Carl D.; Behrens, Timothy W.; Seldin, Michael F.; Criswell, Lindsey A.

2009-01-01

Objective To determine whether genetic substructure in European-derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease. Methods SLE patients of European descent (n=1754) from 8 case collections were genotyped for over 1,400 ancestry informative markers that define a north/south gradient of European substructure. Based on these genetic markers, we used the STRUCTURE program to characterize each SLE patient in terms of percent northern (vs. southern) European ancestry. Non-parametric methods, including tests of trend, were used to identify associations between northern European ancestry and specific SLE manifestations. Results In multivariate analyses, increasing levels of northern European ancestry were significantly associated with photosensitivity (ptrend=0.0021, OR for highest quartile of northern European ancestry compared to lowest quartile 1.64, 95% CI 1.13–2.35) and discoid rash (ptrend=0.014, ORhigh-low 1.93, 95% CI 0.98–3.83). In contrast, northern European ancestry was protective for anticardiolipin (ptrend=1.6 × 10−4, ORhigh-low 0.46, 95% CI 0.30–0.69) and anti-dsDNA (ptrend=0.017, ORhigh-low 0.67, 95% CI 0.46–0.96) autoantibody production. Conclusions This study demonstrates that specific SLE manifestations vary according to northern vs. southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure due to genetic ancestry. PMID:19644962

Genetic ancestry and lower extremity peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis.

PubMed

Allison, Matthew A; Peralta, Carmen A; Wassel, Christina L; Aboyans, Victor; Arnett, Donna K; Cushman, Mary; Eng, John; Ix, Joachim; Rich, Stephen S; Criqui, Michael H

2010-10-01

Using self-report of race/ethnicity, African Americans consistently have a higher prevalence of peripheral artery disease (PAD) compared to other ethnic groups. We aimed to determine the associations between estimated genetic admixture and PAD among African and Hispanic Americans. We studied the association between genetic ancestry and PAD among 1417 African and Hispanic American participants in the Multi-Ethnic Study of Atherosclerosis who were genotyped for ancestry informative markers (AIMs). PAD was defined as an ankle-brachial index (ABI) < 0.90. The overall prevalence of PAD among the 712 self-identified African American subjects was 15.2% and 4.6% among the 705 self-identified Hispanic Americans. A one standard deviation increment in European ancestry was associated with non-significant reductions in the odds for PAD among African (OR: 0.96 [95% CI: 0.78-1.18]) and Hispanic Americans (0.84 [0.58-1.23]), while the same increment in Native American ancestry was significantly associated with a lower odds of PAD in Hispanic Americans (0.56 [0.36-0.96]). Adjustment for demographic variables, field center, cardiovascular disease (CVD) risk factors and inflammatory markers strengthened the odds for European ancestry among African (0.85 [0.66-1.10]) and Hispanic Americans (0.68 [0.41-1.11]). The magnitude of the association for Native American ancestry among Hispanic Americans did not materially change (0.56 [0.29-1.09]). In conclusion, a higher percent Native American ancestry in Hispanics is associated with a lower odds of PAD while in both Hispanics and African Americans, greater European ancestry does not appear to be associated with lower odds for PAD.

Race, Genetic West African Ancestry, and Prostate Cancer Prediction by PSA in Prospectively Screened High-Risk Men

PubMed Central

Giri, Veda N.; Egleston, Brian; Ruth, Karen; Uzzo, Robert G.; Chen, David Y.T.; Buyyounouski, Mark; Raysor, Susan; Hooker, Stanley; Torres, Jada Benn; Ramike, Teniel; Mastalski, Kathleen; Kim, Taylor Y.; Kittles, Rick

2008-01-01

Introduction “Race-specific” PSA needs evaluation in men at high-risk for prostate cancer (PCA) for optimizing early detection. Baseline PSA and longitudinal prediction for PCA was examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Materials and Methods Eligibility criteria are age 35–69 years, FH of PCA, African American (AA) race, or BRCA1/2 mutations. Biopsies have been performed at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for PCA. Results 646 men (63% AA) were analyzed. Individual WA ancestry estimates varied widely among self-reported AA men. “Race-specific” differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with ≥ 1 follow-up visit (405 total, 54% AA), three-year prediction for PCA with a PSA of 1.5–4.0 ng/mL was higher in AA men with age in the model (p=0.025) compared to EA men. Hazard ratios of PSA for PCA were also higher by self-reported race (1.59 for AA vs. 1.32 for EA, p=0.04). There was a trend for increasing prediction for PCA with increasing genetic WA ancestry. Conclusions “Race-specific” PSA may need to be redefined as higher prediction for PCA at any given PSA in AA men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing PCA early detection. PMID:19240249

Genomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium.

PubMed

Morrison, Alanna C; Felix, Janine F; Cupples, L Adrienne; Glazer, Nicole L; Loehr, Laura R; Dehghan, Abbas; Demissie, Serkalem; Bis, Joshua C; Rosamond, Wayne D; Aulchenko, Yurii S; Wang, Ying A; Haritunians, Talin; Folsom, Aaron R; Rivadeneira, Fernando; Benjamin, Emelia J; Lumley, Thomas; Couper, David; Stricker, Bruno H; O'Donnell, Christopher J; Rice, Kenneth M; Chang, Patricia P; Hofman, Albert; Levy, Daniel; Rotter, Jerome I; Fox, Ervin R; Uitterlinden, Andre G; Wang, Thomas J; Psaty, Bruce M; Willerson, James T; van Duijn, Cornelia M; Boerwinkle, Eric; Witteman, Jacqueline C M; Vasan, Ramachandran S; Smith, Nicholas L

2010-06-01

Prognosis and survival are significant concerns for individuals with heart failure (HF). To better understand the pathophysiology of HF prognosis, the association between 2,366,858 single-nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Participants were 2526 individuals of European ancestry and 466 individuals of African ancestry who experienced an incident HF event during follow-up in the respective cohorts. Within each study, the association between genetic variants and time to mortality among individuals with HF was assessed by Cox proportional hazards models that included adjustment for sex and age at the time of the HF event. Prospective fixed-effect meta-analyses were conducted for the 4 study populations of European ancestry (N=1645 deaths) and for the 2 populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0x10(-7). Meta-analytic findings among individuals of European ancestry revealed 1 genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, P=3.2x10(-7)). Eight additional loci in individuals of European ancestry and 4 loci in individuals of African ancestry were identified by high-signal SNPs (P<1.0x10(-5)) but did not meet genome-wide significance. This study identified a novel locus associated with all-cause mortality among individuals of European ancestry with HF. This finding warrants additional investigation, including replication, in other studies of HF.

European ancestry is positively associated with breast cancer risk in Mexican women

PubMed Central

Fejerman, Laura; Romieu, Isabelle; John, Esther M.; Lazcano-Ponce, Eduardo; Huntsman, Scott; Beckman, Kenneth B.; Pérez-Stable, Eliseo J.; Burchard, Esteban Gonzalez; Ziv, Elad; Torres-Mejía, Gabriela

2010-01-01

The incidence of breast cancer is 35% lower in Hispanic women living in the San Francisco Bay Area than in non-Hispanic white women. We have previously described a significant association between genetic ancestry and risk of breast cancer in a sample of US Hispanics/Latinas. We re-tested the association in women residing in Mexico because of the possibility that the original finding may be confounded by US specific unmeasured environmental exposures. We genotyped a set of 106 ancestry informative markers (AIMs) in 846 Mexican women with breast cancer and 1,035 unaffected controls and estimated genetic ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (CI) for ancestry modeled as a categorical and continuous variable were estimated using logistic regression and adjusted for reproductive and other known risk factors. Greater European ancestry was associated with increased breast cancer risk in this new and independent sample of Mexican women residing in Mexico. Compared to women with 0-25% European ancestry, the risk was increased for women with 51-75% and 76-100% European ancestry (OR=1.35, 95% CI: 0.96-1.91 and 2.44, 95% CI: 0.94-6.35 respectively, p for trend=0.044). For every 25% increase in European ancestry (modeled as a continuous variable) there was a 20% increase in risk of breast cancer (95% CI: 1.03-1.41, p=0.019). These results suggest that non-genetic factors play a crucial role in explaining the difference in breast cancer incidence between Latinas and non-Latina white women and it also points out to the possibility of a genetic component to this difference. PMID:20332279

Differences in Allergic Sensitization by Self-reported Race and Genetic Ancestry

PubMed Central

Yang, James J.; Burchard, Esteban G.; Choudhry, Shweta; Johnson, Christine C.; Ownby, Dennis R.; Favro, David; Chen, Justin; Akana, Matthew; Ha, Connie; Kwok, Pui-Yan; Krajenta, Richard; Havstad, Suzanne L.; Joseph, Christine L.; Seibold, Max A.; Shriver, Mark D.; Williams, L. Keoki

2010-01-01

Background Many allergic conditions occur more frequently in African-American patients when compared with white patients; however it is not known whether this represents genetic predisposition or disparate environmental exposures. Objective To assess the relationship of self-reported race and genetic ancestry to allergic sensitization. Methods We included 601 women enrolled in a population-based cohort study whose self-reported race was African-American or white. Genetic ancestry was estimated using markers that differentiate West African and European ancestry. We assessed the relationship between allergic sensitization (defined as ≥1 allergen-specific IgE result) and both self-reported race and genetic ancestry. Regression models adjusted for socio-demographic variables, environmental exposures, and location of residence. Results The average proportion of West African ancestry in African-American participants was 0.69, whereas the mean proportion of European ancestry in white participants was 0.79. Self-reported African-American race was associated with allergic sensitization when compared with those who reported being white (adjusted odds ratio [aOR] 2.19; 95% confidence interval [CI] 1.22 – 3.93) even after adjusting for other variables. Genetic ancestry was not significantly associated with allergic sensitization after accounting for location of residence (aOR 2.09 for urban vs. suburban residence, 95% CI 1.32 −3.31). Conclusion Self-reported race and location of residence appeared to be more important predictors of allergic sensitization when compared with genetic ancestry, suggesting that the disparity in allergic sensitization by race may be primarily due to environmental factors rather than genetic differences. Clinical Implications These data suggest that efforts to eliminate disparities in allergic sensitization should focus on contributing environmental factors. PMID:19014772

Ancestry analysis reveals a predominant Native American component with moderate European admixture in Bolivians.

PubMed

Heinz, Tanja; Alvarez-Iglesias, Vanesa; Pardo-Seco, Jacobo; Taboada-Echalar, Patricia; Gómez-Carballa, Alberto; Torres-Balanza, Antonio; Rocabado, Omar; Carracedo, Angel; Vullo, Carlos; Salas, Antonio

2013-09-01

We have genotyped 46 Ancestry Informative Markers (AIMs) in two of the most populated areas in Bolivia, namely, La Paz (Andean region; n=105), and Chuquisaca (Sub-Andean region; n=73). Using different analytical tools, we inferred admixture proportions of these two American communities by comparing the genetic profiles with those publicly available from the CEPH (Centre d'Etude du Polymorphisme Humain) panel representing three main continental groups (Africa, Europe, and America). By way of simulations, we first evaluated the minimum sample size needed in order to obtain accurate estimates of ancestry proportions. The results indicated that sample sizes above 30 individuals could be large enough to estimate main continental ancestry proportions using the 46 AIMs panel. With the exception of a few individuals, the results also indicated that Bolivians showed a predominantly Native American ancestry with variable levels of European admixture. The proportions of ancestry were statistically different in La Paz and Chuquisaca: the Native American component was 86% and 77% (Mann-Whitney U-test: un-adjusted P-value=2.1×10(-5)), while the European ancestry was 13% and 21% (Mann-Whitney U-test: un-adjusted P-value=3.6×10(-5)), respectively. The African ancestry in Bolivians captured by the AIMs analyzed in the present study was below 2%. The inferred ancestry of Bolivians fits well with previous studies undertaken on haplotype data, indicating a major proportion of Native American lineages. The genetic differences observed in these two groups suggest that forensic genetic analysis should be better performed based on local databases built in the main Bolivian areas. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents

PubMed Central

McCormack, Shana E; Chesi, Alessandra; Mitchell, Jonathan A; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Mahboubi, Soroosh; Winer, Karen K; Kelly, Andrea; Grant, Struan FA; Zemel, Babette S

2017-01-01

More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (~0.33 years, p<0.001) and boys (~0.43 years, p<0.001). Boys and girls of all ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.12 years (ancestry by self-report, p = 0.12) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.0038) or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. PMID:27419386

DNA from the Past Informs Ex Situ Conservation for the Future: An “Extinct” Species of Galápagos Tortoise Identified in Captivity

PubMed Central

Russello, Michael A.; Poulakakis, Nikos; Gibbs, James P.; Tapia, Washington; Benavides, Edgar; Powell, Jeffrey R.; Caccone, Adalgisa

2010-01-01

Background Although not unusual to find captive relicts of species lost in the wild, rarely are presumed extinct species rediscovered outside of their native range. A recent study detected living descendents of an extinct Galápagos tortoise species (Chelonoidis elephantopus) once endemic to Floreana Island on the neighboring island of Isabela. This finding adds to the growing cryptic diversity detected among these species in the wild. There also exists a large number of Galápagos tortoises in captivity of ambiguous origin. The recently accumulated population-level haplotypic and genotypic data now available for C. elephantopus add a critical reference population to the existing database of 11 extant species for investigating the origin of captive individuals of unknown ancestry. Methodology/Findings We reanalyzed mitochondrial DNA control region haplotypes and microsatellite genotypes of 156 captive individuals using an expanded reference database that included all extant Galápagos tortoise species as well as the extinct species from Floreana. Nine individuals (six females and three males) exhibited strong signatures of Floreana ancestry and a high probability of assignment to C. elephantopus as detected by Bayesian assignment and clustering analyses of empirical and simulated data. One male with high assignment probability to C. elephantopus based on microsatellite genotypic data also possessed a “Floreana-like” mitochondrial DNA haplotype. Significance Historical DNA analysis of museum specimens has provided critical spatial and temporal components to ecological, evolutionary, taxonomic and conservation-related research, but rarely has it informed ex situ species recovery efforts. Here, the availability of population-level genotypic data from the extinct C. elephantopus enabled the identification of nine Galápagos tortoise individuals of substantial conservation value that were previously misassigned to extant species of varying conservation status. As all captive individuals of C. elephantopus ancestry currently reside at a centralized breeding facility on Santa Cruz, these findings permit breeding efforts to commence in support of the reestablishment of this extinct species to its native range. PMID:20084268

Providing Contexts for Understanding Musical Narratives of Power in the Classroom: Music, Politics, and Power in Grenada, West Indies

ERIC Educational Resources Information Center

Sirek, Danielle

2016-01-01

The role of music in Grenada, West Indies has traditionally been to pass on knowledges, values, and ideals; and to provide a means of connecting to one another through expressing commonality of experience, ancestry, and nationhood. This paper explores how Eric Matthew Gairy, during his era of political leadership in Grenada (1951-1979), exploited…

Ancestry estimation and control of population stratification for sequence-based association studies.

PubMed

Wang, Chaolong; Zhan, Xiaowei; Bragg-Gresham, Jennifer; Kang, Hyun Min; Stambolian, Dwight; Chew, Emily Y; Branham, Kari E; Heckenlively, John; Fulton, Robert; Wilson, Richard K; Mardis, Elaine R; Lin, Xihong; Swaroop, Anand; Zöllner, Sebastian; Abecasis, Gonçalo R

2014-04-01

Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysis of off-target sequence reads, and implement our method in the publicly available LASER software. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry when used with sequencing data sets with whole-genome shotgun coverage as low as 0.001×. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1×. On an even finer scale, the method improves discrimination between exome-sequenced study participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and to reduce the risk of spurious findings due to population structure.

Effects of Sample Selection Bias on the Accuracy of Population Structure and Ancestry Inference

PubMed Central

Shringarpure, Suyash; Xing, Eric P.

2014-01-01

Population stratification is an important task in genetic analyses. It provides information about the ancestry of individuals and can be an important confounder in genome-wide association studies. Public genotyping projects have made a large number of datasets available for study. However, practical constraints dictate that of a geographical/ethnic population, only a small number of individuals are genotyped. The resulting data are a sample from the entire population. If the distribution of sample sizes is not representative of the populations being sampled, the accuracy of population stratification analyses of the data could be affected. We attempt to understand the effect of biased sampling on the accuracy of population structure analysis and individual ancestry recovery. We examined two commonly used methods for analyses of such datasets, ADMIXTURE and EIGENSOFT, and found that the accuracy of recovery of population structure is affected to a large extent by the sample used for analysis and how representative it is of the underlying populations. Using simulated data and real genotype data from cattle, we show that sample selection bias can affect the results of population structure analyses. We develop a mathematical framework for sample selection bias in models for population structure and also proposed a correction for sample selection bias using auxiliary information about the sample. We demonstrate that such a correction is effective in practice using simulated and real data. PMID:24637351

Cranial index in a modern people of Thai ancestry

PubMed Central

Jung, Hyunwoo

2018-01-01

The present research aims to examine the cranial index in a modern people of Thai ancestry. Ultimately, this study will help to create a databank containing a cranial index for the classifications of the people from Asia. In this study, 185 modern crania of people of supposed Thai ancestry were examined. They were collected from the Department of Anatomy at Chulalongkorn University in Bangkok, Thailand. The maximum cranial length and breadth were measured using standard anthropometric instruments based on Martin's methods. The cranial index was calculated using the equation ([maximum cranial breadth/maximum cranial length]×100). The mean cranial indices for the male and female skulls examined were 81.81±4.23 and 82.99±4.37, respectively. The most common type of skull in the modern Thai people in this study was the brachycranic type with a frequency of 42.7%, followed by the mesocranic (27.03%) and hyperbrachycranic types (25.59%). The rarest type observed in this study was the dolichocranic type (4.32%). The present study provides valuable data pertaining to the cranial index in a modern Thai population and reveals that modern Thai males and females belong to the brachycranic group. The results of this study will be of forensic anthropological importance to populations in close proximity to the location where the skulls studied here were sourced. PMID:29644107

Frequency and spectrum of hemoglobinopathy mutations in a Uruguayan pediatric population

PubMed Central

Luz, Julio Da; Ávila, Amalia; Icasuriaga, Sandra; Gongóra, María; Castillo, Luis; Serrón, Alejandra; Kimura, Elza Miyuki; Costa, Fernando Ferreira; Sans, Mónica; Sonati, Maria de Fátima

2013-01-01

Hemoglobinopathies are the most common recessive diseases worldwide but their prevalence in Uruguay has not been investigated. In this study, 397 unrelated outpatient children from the Pereira Rosell Hospital Center (CHPR), as well as 31 selected patients with microcytic anemia and 28 β-thalassemia carriers were analyzed for hemoglobinopathies by using biochemical and molecular biology methods. Parametric and non-parametric methods were used to compare the hematological indices between groups of genotypes. Of the 397 patients in the first group, approximately 1% (0.76% HbS and 0.25% β-thalassemia) had a mutation in the HBB gene and 3.3% had β-thalassemia. These mutations had a heterogeneous distribution that varied according to individual ancestry. HbS was found exclusively in individuals with declared African ancestry and had a carrier frequency of 2.2%. The frequency of α-thalassemia carriers in outpatients of European and African ancestry was 1.2% and 6.5%, respectively. In contrast, the frequency of α-thalassemia carriers in patients with microcytic anemia was 25.8%, significantly higher (p < 0.01) than that observed in the sample as a whole and in Afro-descendants and Euro-descendants. Significant differences were observed in the hematological parameters between individuals with thalassemia genotypes and those with a normal genotype. These results indicate that hemoglobinopathies are a relevant health problem in Uruguay. PMID:24130436

Association of cocaine- and amphetamine-related transcript, leptin and leptin receptor gene polymorphisms with anthropometric obesity phenotype indicators in South African learners.

PubMed

Yako, Y Y; Fanampe, B L; Hassan, M S; Erasmus, R T; van der Merwe, L; van Rensburg, S J; Matsha, T E

2011-01-01

Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys(109)Arg G allele was associated with an average reduction of 2.36 kg/m(2) in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. Our findings suggest that c.517A→G and Lys(109)Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group. Copyright © 2011 S. Karger AG, Basel.

Genetic ancestry as an effect modifier of naltrexone in smoking cessation among African Americans: an analysis of a randomized controlled trial

PubMed Central

Bress, Adam; Kittles, Rick; Wing, Coady; Hooker, Stanley E; King, Andrea

2015-01-01

Objectives To determine if there were differential quit rates between AA and European Americans (EA) with the experimental treatment naltrexone, and examine the role of genetic ancestry on these outcomes among AAs. Methods Data from a previous randomized trial of 315 smokers to naltrexone vs. placebo were reanalyzed using West African (WA) genetic ancestry to define sub-populations. Logistic regression models were used to estimate treatment effects on early and end of treatment quit rates, by race and WA ancestry. Results Among EAs (n=136), naltrexone significantly increased quit rates at four weeks (62% vs. 43%, p=0.03) with directional, but not statistically significant effects at 12 weeks (30% vs. 18%, p=0.12). In contrast, among the AAs (n=95), quit rates did not differ between naltrexone and placebo groups at either interval (four weeks: 43% vs. 32%, p=0.27; 12 weeks: 22% vs. 18%, p=0.60). A median split was conducted in AAs for WA ancestry. Among AAs with low WA ancestry, quit rates were significantly higher with naltrexone compared with placebo (60% vs. 27%, p=0.03). There was no advantage in quit rates with naltrexone for the high WA ancestry group. Conclusions Naltrexone efficacy for smoking cessation varies across AA subjects with different levels of WA ancestry. These results suggest that genetic background may partially explain racial differences in drug response. PMID:25918964

Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

PubMed

Browning, Sharon R; Grinde, Kelsey; Plantinga, Anna; Gogarten, Stephanie M; Stilp, Adrienne M; Kaplan, Robert C; Avilés-Santa, M Larissa; Browning, Brian L; Laurie, Cathy C

2016-06-01

We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ancestry-specific PCA, we found significant population structure within African, European, and Amerindian ancestries in the Hispanic/Latino individuals in our study. In the African ancestral component of the admixed individuals, individuals whose grandparents were from Central America clustered separately from individuals whose grandparents were from the Caribbean, and also from reference Yoruba and Mandenka West African individuals. In the European component, individuals whose grandparents were from Puerto Rico diverged partially from other background groups. In the Amerindian ancestral component, individuals clustered into multiple different groups depending on the grandparental country of origin. Therefore, local ancestry estimation provides further insight into the complex genetic structure of US Hispanic/Latino populations, which must be properly accounted for in genotype-phenotype association studies. It also provides a basis for admixture mapping and ancestry-specific allele frequency estimation, which are useful in the identification of risk factors for disease. Copyright © 2016 Browning et al.

The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.

PubMed

Amos, Christopher I; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R; Gayther, Simon A; Casey, Graham; Hunter, David J; Sellers, Thomas A; Gruber, Stephen B; Dunning, Alison M; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A; Hazelett, Dennis J; Bojesen, Stig E; Caga-Anan, Charlisse; Haiman, Christopher A; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E; Couch, Fergus J; Forman, Judith L; Giles, Graham G; Conti, David V; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske-Hohlfeld, Irene; Hicks, Belynda D; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline; Soucy, Penny; Manz, Judith; Cunningham, Julie M; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel; Lindström, Sara; Adams, Marcia; McKay, James D; Phelan, Catherine M; Benlloch, Sara; Kelemen, Linda E; Brennan, Paul; Riggan, Marjorie; O'Mara, Tracy A; Shen, Hongbing; Shi, Yongyong; Thompson, Deborah J; Goodman, Marc T; Nielsen, Sune F; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L; Shelford, Tameka; Edlund, Christopher K; Taylor, Jack A; Field, John K; Park, Sue K; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J; Marchini, Jonathan; Amin Al Olama, Ali; Peters, Ulrike; Eeles, Rosalind A; Seldin, Michael F; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C; Pharoah, Paul D P; Chenevix-Trench, Georgia; Chanock, Stephen J; Simard, Jacques; Easton, Douglas F

2017-01-01

Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures. Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126-35. ©2016 AACR. ©2016 American Association for Cancer Research.

The OncoArray Consortium: a Network for Understanding the Genetic Architecture of Common Cancers

PubMed Central

Amos, Christopher I.; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R.; Gayther, Simon A.; Casey, Graham; Hunter, David J.; Sellers, Thomas A.; Gruber, Stephen B.; Dunning, Alison M.; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B.; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A.; Hazelett, Dennis J.; Bojesen, Stig E.; Caga-Anan, Charlisse; Haiman, Christopher A.; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J.; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E.; Couch, Fergus J.; Forman, Judith L.; Giles, Graham G.; Conti, David V.; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske, Irene; Hicks, Belynda D.; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline B.; Soucy, Penny; Manz, Judith; Cunningham, Julie M.; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel M.; Lindström, Sara; Adams, Marcia; McKay, James D.; Phelan, Catherine M.; Benlloch, Sara; Kelemen, Linda E.; Brennan, Paul; Riggan, Marjorie; O’Mara, Tracy A.; Shen, Hongbin; Shi, Yongyong; Thompson, Deborah J.; Goodman, Marc T.; Nielsen, Sune F.; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L.; Shelford, Tameka; Edlund, Christopher K.; Taylor, Jack A.; Field, John K.; Park, Sue K.; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J.; Marchini, Jonathan; Al Olama, Ali Amin; Peters, Ulrike; Eeles, Rosalind A.; Seldin, Michael F.; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C.; Pharoah, Paul D.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Simard, Jacques; Easton, Douglas F.

2016-01-01

Background Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. Methods The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. Impact Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. PMID:27697780

Education of Non-European Ancestry Immigrant Students in Suburban High Schools

ERIC Educational Resources Information Center

Shodavaram, Mary P.; Jones, Lisa A.; Weaver, Laurie R.; Marquez, Judith A.; Ensle, Anne L.

2009-01-01

The purpose of this study was to examine suburban high school teachers' beliefs about non-European ancestry immigrant students; more specifically, suburban teachers' beliefs regarding the impact of students' cultural backgrounds on academic performance were examined. Non-European ancestry immigrant students are those students whose ancestral…

Multi-InDel Analysis for Ancestry Inference of Sub-Populations in China

PubMed Central

Sun, Kuan; Ye, Yi; Luo, Tao; Hou, Yiping

2016-01-01

Ancestry inference is of great interest in diverse areas of scientific researches, including the forensic biology, medical genetics and anthropology. Various methods have been published for distinguishing populations. However, few reports refer to sub-populations (like ethnic groups) within Asian populations for the limitation of markers. Several InDel loci located very tightly in physical positions were treated as one marker by us, which is multi-InDel. The multi-InDel shows potential as Ancestry Inference Marker (AIM). In this study, we performed a genome-wide scan for multi-InDels as AIM. After examining the FST distributions in the 1000 Genomes Database, 12 candidates were selected and validated for eastern Asian populations. A multiplexed assay was developed as a panel to genotype 12 multi-InDel markers simultaneously. Ancestry component analysis with STRUCTURE and principal component analysis (PCA) were employed to estimate its capability for ancestry inference. Furthermore, ancestry assignments of trial individuals were conducted. It proved to be very effective when 210 samples from Han and Tibetan individuals in China were tested. The panel consisting of multi-InDel markers exhibited considerable potency in ancestry inference, and was suggested to be applied in forensic practices and genetic population studies. PMID:28004788

Genetic Population Structure Analysis in New Hampshire Reveals Eastern European Ancestry

PubMed Central

Sloan, Chantel D.; Andrew, Angeline D.; Duell, Eric J.; Williams, Scott M.; Karagas, Margaret R.; Moore, Jason H.

2009-01-01

Genetic structure due to ancestry has been well documented among many divergent human populations. However, the ability to associate ancestry with genetic substructure without using supervised clustering has not been explored in more presumably homogeneous and admixed US populations. The goal of this study was to determine if genetic structure could be detected in a United States population from a single state where the individuals have mixed European ancestry. Using Bayesian clustering with a set of 960 single nucleotide polymorphisms (SNPs) we found evidence of population stratification in 864 individuals from New Hampshire that can be used to differentiate the population into six distinct genetic subgroups. We then correlated self-reported ancestry of the individuals with the Bayesian clustering results. Finnish and Russian/Polish/Lithuanian ancestries were most notably found to be associated with genetic substructure. The ancestral results were further explained and substantiated using New Hampshire census data from 1870 to 1930 when the largest waves of European immigrants came to the area. We also discerned distinct patterns of linkage disequilibrium (LD) between the genetic groups in the growth hormone receptor gene (GHR). To our knowledge, this is the first time such an investigation has uncovered a strong link between genetic structure and ancestry in what would otherwise be considered a homogenous US population. PMID:19738909

Genetic population structure analysis in New Hampshire reveals Eastern European ancestry.

PubMed

Sloan, Chantel D; Andrew, Angeline D; Duell, Eric J; Williams, Scott M; Karagas, Margaret R; Moore, Jason H

2009-09-07

Genetic structure due to ancestry has been well documented among many divergent human populations. However, the ability to associate ancestry with genetic substructure without using supervised clustering has not been explored in more presumably homogeneous and admixed US populations. The goal of this study was to determine if genetic structure could be detected in a United States population from a single state where the individuals have mixed European ancestry. Using Bayesian clustering with a set of 960 single nucleotide polymorphisms (SNPs) we found evidence of population stratification in 864 individuals from New Hampshire that can be used to differentiate the population into six distinct genetic subgroups. We then correlated self-reported ancestry of the individuals with the Bayesian clustering results. Finnish and Russian/Polish/Lithuanian ancestries were most notably found to be associated with genetic substructure. The ancestral results were further explained and substantiated using New Hampshire census data from 1870 to 1930 when the largest waves of European immigrants came to the area. We also discerned distinct patterns of linkage disequilibrium (LD) between the genetic groups in the growth hormone receptor gene (GHR). To our knowledge, this is the first time such an investigation has uncovered a strong link between genetic structure and ancestry in what would otherwise be considered a homogenous US population.

The genomic ancestry, landscape genetics and invasion history of introduced mice in New Zealand

PubMed Central

Russell, James C.; King, Carolyn M.

2018-01-01

The house mouse (Mus musculus) provides a fascinating system for studying both the genomic basis of reproductive isolation, and the patterns of human-mediated dispersal. New Zealand has a complex history of mouse invasions, and the living descendants of these invaders have genetic ancestry from all three subspecies, although most are primarily descended from M. m. domesticus. We used the GigaMUGA genotyping array (approximately 135 000 loci) to describe the genomic ancestry of 161 mice, sampled from 34 locations from across New Zealand (and one Australian city—Sydney). Of these, two populations, one in the south of the South Island, and one on Chatham Island, showed complete mitochondrial lineage capture, featuring two different lineages of M. m. castaneus mitochondrial DNA but with only M. m. domesticus nuclear ancestry detectable. Mice in the northern and southern parts of the North Island had small traces (approx. 2–3%) of M. m. castaneus nuclear ancestry, and mice in the upper South Island had approximately 7–8% M. m. musculus nuclear ancestry including some Y-chromosomal ancestry—though no detectable M. m. musculus mitochondrial ancestry. This is the most thorough genomic study of introduced populations of house mice yet conducted, and will have relevance to studies of the isolation mechanisms separating subspecies of mice. PMID:29410804

Forensic ancestry analysis in two Chinese minority populations using massively parallel sequencing of 165 ancestry-informative SNPs.

PubMed

He, Guanglin; Wang, Zheng; Wang, Mengge; Luo, Tao; Liu, Jing; Zhou, You; Gao, Bo; Hou, Yiping

2018-06-04

Ancestry inference based on single nucleotide polymorphism (SNP) with marked allele frequency differences in diverse populations (called ancestry-informative SNP, AISNP) is rapidly developed with the technology advancements of massively parallel sequencing (MPS). Despite the decade of exploration and broad public interest in the peopling of East-Asians, the genetic landscape of Chinese Silk Road populations based on the AISNPs is still little known. In this work, 206 unrelated individuals from Chinese Uyghur and Hui populations were firstly genotyped by 165 AISNPs (The Precision ID Ancestry Panel) using the Ion Torrent PGM system. The ethnic origin of two investigated populations and population structures and genetic relationships were subsequently investigated. The 165 AISNPs panel not only can differentiate Uyghur and Hui populations but also has potential applications in individual identification. Comprehensive population comparisons and admixture estimates demonstrated a predominantly higher European-related ancestry (36.30%) in Uyghurs than Huis (3.66%). Overall, the Precision ID Ancestry Panel can provide good resolution at the intercontinental level, but has limitations on the genetic homogeneous populations, such as the Hui and Han. Additional population-specific AISNPs remain necessary to get better-scale resolution within geographically proximate populations in East Asia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Did the notochord evolve from an ancient axial muscle? The axochord hypothesis

PubMed Central

Brunet, Thibaut; Lauri, Antonella

2015-01-01

The origin of the notochord is one of the key remaining mysteries of our evolutionary ancestry. Here, we present a multi‐level comparison of the chordate notochord to the axochord, a paired axial muscle spanning the ventral midline of annelid worms and other invertebrates. At the cellular level, comparative molecular profiling in the marine annelids P. dumerilii and C. teleta reveals expression of similar, specific gene sets in presumptive axochordal and notochordal cells. These cells also occupy corresponding positions in a conserved anatomical topology and undergo similar morphogenetic movements. At the organ level, a detailed comparison of bilaterian musculatures reveals that most phyla form axochord‐like muscles, suggesting that such a muscle was already present in urbilaterian ancestors. Integrating comparative evidence at the cell and organ level, we propose that the notochord evolved by modification of a ventromedian muscle followed by the assembly of an axial complex supporting swimming in vertebrate ancestors. PMID:26172338

African ancestry, early life exposures, and respiratory morbidity in early childhood

PubMed Central

Kumar, R.; Tsai, H.-J.; Hong, X.; Gignoux, C.; Pearson, C.; Ortiz, K.; Fu, M.; Pongracic, J. A.; Burchard, E. G.; Bauchner, H.; Wang, X.

2012-01-01

Summary Background Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. Objective To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. Methods We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Results Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02–1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19–1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14–1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05–1.34) and European ancestry (OR: 0.84, 95% CI: 0.74–0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (ORwhites: 0.31, 95% CI: 0.09–1.14; ORhispanic: 0.47, 95% CI: 0.20–1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. Conclusions and Clinical Relevance In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and early life risk factors associated with childhood recurrent wheezing. PMID:22093077

Admixture mapping of pelvic organ prolapse in African Americans from the Women’s Health Initiative Hormone Therapy trial

PubMed Central

Hartmann, Katherine E.; Aldrich, Melinda C.; Ward, Renee M.; Wu, Jennifer M.; Park, Amy J.; Graff, Mariaelisa; Qi, Lihong; Nassir, Rami; Wallace, Robert B.; O'Sullivan, Mary J.; North, Kari E.; Velez Edwards, Digna R.; Edwards, Todd L.

2017-01-01

Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women’s Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ≥2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk. PMID:28582460

Cooperative combinatorial optimization: evolutionary computation case study.

PubMed

Burgin, Mark; Eberbach, Eugene

2008-01-01

This paper presents a formalization of the notion of cooperation and competition of multiple systems that work toward a common optimization goal of the population using evolutionary computation techniques. It is proved that evolutionary algorithms are more expressive than conventional recursive algorithms, such as Turing machines. Three classes of evolutionary computations are introduced and studied: bounded finite, unbounded finite, and infinite computations. Universal evolutionary algorithms are constructed. Such properties of evolutionary algorithms as completeness, optimality, and search decidability are examined. A natural extension of evolutionary Turing machine (ETM) model is proposed to properly reflect phenomena of cooperation and competition in the whole population.

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations.

PubMed

Kehdy, Fernanda S G; Gouveia, Mateus H; Machado, Moara; Magalhães, Wagner C S; Horimoto, Andrea R; Horta, Bernardo L; Moreira, Rennan G; Leal, Thiago P; Scliar, Marilia O; Soares-Souza, Giordano B; Rodrigues-Soares, Fernanda; Araújo, Gilderlanio S; Zamudio, Roxana; Sant Anna, Hanaisa P; Santos, Hadassa C; Duarte, Nubia E; Fiaccone, Rosemeire L; Figueiredo, Camila A; Silva, Thiago M; Costa, Gustavo N O; Beleza, Sandra; Berg, Douglas E; Cabrera, Lilia; Debortoli, Guilherme; Duarte, Denise; Ghirotto, Silvia; Gilman, Robert H; Gonçalves, Vanessa F; Marrero, Andrea R; Muniz, Yara C; Weissensteiner, Hansi; Yeager, Meredith; Rodrigues, Laura C; Barreto, Mauricio L; Lima-Costa, M Fernanda; Pereira, Alexandre C; Rodrigues, Maíra R; Tarazona-Santos, Eduardo

2015-07-14

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

Association of substance use disorders with childhood trauma but not African genetic heritage in an African American cohort.

PubMed

Ducci, Francesca; Roy, Alec; Shen, Pei-Hong; Yuan, Qiaoping; Yuan, Nicole P; Hodgkinson, Colin A; Goldman, Lynn R; Goldman, David

2009-09-01

Genetic variation influences differential vulnerability to addiction within populations. However, it remains unclear whether differences in frequencies of vulnerability alleles contribute to disparities between populations and to what extent ancestry correlates with differential exposure to environmental risk factors, including poverty and trauma. The authors used 186 ancestry-informative markers to measure African ancestry in 407 addicts and 457 comparison subjects self-identified as African Americans. The reference group was 1,051 individuals from the Human Genome Diversity Cell Line Panel, which includes 51 diverse populations representing most worldwide genetic diversity. African Americans varied in degrees of African, European, Middle Eastern, and Central Asian genetic heritage. The overall level of African ancestry was actually smaller among cocaine, opiate, and alcohol addicts (proportion=0.76-0.78) than nonaddicted African American comparison subjects (proportion=0.81). African ancestry was associated with living in impoverished neighborhoods, a factor previously associated with risk. There was no association between African ancestry and exposure to childhood abuse or neglect, a factor that strongly predicted all types of addictions. These results suggest that African genetic heritage does not increase the likelihood of genetic risk for addictions. They highlight the complex interrelation between genetic ancestry and social, economic, and environmental conditions and the strong relation of those factors to addiction. Studies of epidemiological samples characterized for genetic ancestry and social, psychological, demographic, economic, cultural, and historical factors are needed to better disentangle the effects of genetic and environmental factors underlying interpopulation differences in vulnerability to addiction and other health disparities.

Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation.

PubMed

Kidd, Jeffrey M; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F; Peckham, Heather E; Omberg, Larsson; Bormann Chung, Christina A; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G; Russell, Archie; Reynolds, Andy; Clark, Andrew G; Reese, Martin G; Lincoln, Stephen E; Butte, Atul J; De La Vega, Francisco M; Bustamante, Carlos D

2012-10-05

Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations

PubMed Central

Kehdy, Fernanda S. G.; Gouveia, Mateus H.; Machado, Moara; Magalhães, Wagner C. S.; Horimoto, Andrea R.; Horta, Bernardo L.; Moreira, Rennan G.; Leal, Thiago P.; Scliar, Marilia O.; Soares-Souza, Giordano B.; Rodrigues-Soares, Fernanda; Araújo, Gilderlanio S.; Zamudio, Roxana; Sant Anna, Hanaisa P.; Santos, Hadassa C.; Duarte, Nubia E.; Fiaccone, Rosemeire L.; Figueiredo, Camila A.; Silva, Thiago M.; Costa, Gustavo N. O.; Beleza, Sandra; Berg, Douglas E.; Cabrera, Lilia; Debortoli, Guilherme; Duarte, Denise; Ghirotto, Silvia; Gilman, Robert H.; Gonçalves, Vanessa F.; Marrero, Andrea R.; Muniz, Yara C.; Weissensteiner, Hansi; Yeager, Meredith; Rodrigues, Laura C.; Barreto, Mauricio L.; Lima-Costa, M. Fernanda; Pereira, Alexandre C.; Rodrigues, Maíra R.; Tarazona-Santos, Eduardo

2015-01-01

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6–8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes. PMID:26124090

A Novel Test for Gene-Ancestry Interactions in Genome-Wide Association Data

PubMed Central

Dunlop, Malcolm G.; Houlston, Richard S.; Tomlinson, Ian P.; Holmes, Chris C.

2012-01-01

Genome-wide association study (GWAS) data on a disease are increasingly available from multiple related populations. In this scenario, meta-analyses can improve power to detect homogeneous genetic associations, but if there exist ancestry-specific effects, via interactions on genetic background or with a causal effect that co-varies with genetic background, then these will typically be obscured. To address this issue, we have developed a robust statistical method for detecting susceptibility gene-ancestry interactions in multi-cohort GWAS based on closely-related populations. We use the leading principal components of the empirical genotype matrix to cluster individuals into “ancestry groups” and then look for evidence of heterogeneous genetic associations with disease or other trait across these clusters. Robustness is improved when there are multiple cohorts, as the signal from true gene-ancestry interactions can then be distinguished from gene-collection artefacts by comparing the observed interaction effect sizes in collection groups relative to ancestry groups. When applied to colorectal cancer, we identified a missense polymorphism in iron-absorption gene CYBRD1 that associated with disease in individuals of English, but not Scottish, ancestry. The association replicated in two additional, independently-collected data sets. Our method can be used to detect associations between genetic variants and disease that have been obscured by population genetic heterogeneity. It can be readily extended to the identification of genetic interactions on other covariates such as measured environmental exposures. We envisage our methodology being of particular interest to researchers with existing GWAS data, as ancestry groups can be easily defined and thus tested for interactions. PMID:23236349

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

PubMed Central

Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

Enhanced Methods for Local Ancestry Assignment in Sequenced Admixed Individuals

PubMed Central

Brown, Robert; Pasaniuc, Bogdan

2014-01-01

Inferring the ancestry at each locus in the genome of recently admixed individuals (e.g., Latino Americans) plays a major role in medical and population genetic inferences, ranging from finding disease-risk loci, to inferring recombination rates, to mapping missing contigs in the human genome. Although many methods for local ancestry inference have been proposed, most are designed for use with genotyping arrays and fail to make use of the full spectrum of data available from sequencing. In addition, current haplotype-based approaches are very computationally demanding, requiring large computational time for moderately large sample sizes. Here we present new methods for local ancestry inference that leverage continent-specific variants (CSVs) to attain increased performance over existing approaches in sequenced admixed genomes. A key feature of our approach is that it incorporates the admixed genomes themselves jointly with public datasets, such as 1000 Genomes, to improve the accuracy of CSV calling. We use simulations to show that our approach attains accuracy similar to widely used computationally intensive haplotype-based approaches with large decreases in runtime. Most importantly, we show that our method recovers comparable local ancestries, as the 1000 Genomes consensus local ancestry calls in the real admixed individuals from the 1000 Genomes Project. We extend our approach to account for low-coverage sequencing and show that accurate local ancestry inference can be attained at low sequencing coverage. Finally, we generalize CSVs to sub-continental population-specific variants (sCSVs) and show that in some cases it is possible to determine the sub-continental ancestry for short chromosomal segments on the basis of sCSVs. PMID:24743331

Association of Substance Use Disorders With Childhood Trauma but not African Genetic Heritage in an African American Cohort

PubMed Central

Ducci, Francesca; Roy, Alec; Shen, Pei-Hong; Yuan, Qiaoping; Yuan, Nicole P.; Hodgkinson, Colin A.; Goldman, Lynn R.; Goldman, David

2009-01-01

Objective Genetic variation influences differential vulnerability to addiction within populations. However, it remains unclear whether differences in frequencies of vulnerability alleles contribute to disparities between populations and to what extent ancestry correlates with differential exposure to environmental risk factors, including poverty and trauma. Method The authors used 186 ancestry-informative markers to measure African ancestry in 407 addicts and 457 comparison subjects self-identified as African Americans. The reference group was 1,051 individuals from the Human Genome Diversity Cell Line Panel, which includes 51 diverse populations representing most worldwide genetic diversity. Results African Americans varied in degrees of African, European, Middle Eastern, and Central Asian genetic heritage. The overall level of African ancestry was actually smaller among cocaine, opiate, and alcohol addicts (proportion=0.76–0.78) than nonaddicted African American comparison subjects (proportion=0.81). African ancestry was associated with living in impoverished neighborhoods, a factor previously associated with risk. There was no association between African ancestry and exposure to childhood abuse or neglect, a factor that strongly predicted all types of addictions. Conclusions These results suggest that African genetic heritage does not increase the likelihood of genetic risk for addictions. They highlight the complex interrelation between genetic ancestry and social, economic, and environmental conditions and the strong relation of those factors to addiction. Studies of epidemiological samples characterized for genetic ancestry and social, psychological, demographic, economic, cultural, and historical factors are needed to better disentangle the effects of genetic and environmental factors underlying interpopulation differences in vulnerability to addiction and other health disparities. PMID:19605534

Population Genetic Inference from Personal Genome Data: Impact of Ancestry and Admixture on Human Genomic Variation

PubMed Central

Kidd, Jeffrey M.; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D.; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F.; Peckham, Heather E.; Omberg, Larsson; Bormann Chung, Christina A.; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G.; Russell, Archie; Reynolds, Andy; Clark, Andrew G.; Reese, Martin G.; Lincoln, Stephen E.; Butte, Atul J.; De La Vega, Francisco M.; Bustamante, Carlos D.

2012-01-01

Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas—70% of the European ancestry in today’s African Americans dates back to European gene flow happening only 7–8 generations ago. PMID:23040495

Ancestry informative markers in Amerindians from Brazilian Amazon.

PubMed

Luizon, Marcelo Rizzatti; Mendes-Junior, Celso Teixeira; De Oliveira, Silviene Fabiana; Simões, Aguinaldo Luiz

2008-01-01

Ancestry informative markers (AIMs) are genetic loci with large frequency differences between the major ethnic groups and are very useful in admixture estimation. However, their frequencies are poorly known within South American indigenous populations, making it difficult to use them in admixture studies with Latin American populations, such as the trihybrid Brazilian population. To minimize this problem, the frequencies of the AIMs FY-null, RB2300, LPL, AT3-I/D, Sb19.3, APO, and PV92 were determined via PCR and PCR-RFLP in four tribes from Brazilian Amazon (Tikúna, Kashinawa, Baníwa, and Kanamarí), to evaluate their potential for discriminating indigenous populations from Europeans and Africans, as well as discriminating each tribe from the others. Although capable of differentiating tribes, as evidenced by the exact test of population differentiation, a neighbor-joining tree suggests that the AIMs are useless in obtaining reliable reconstructions of the biological relationships and evolutionary history that characterize the villages and tribes studied. The mean allele frequencies from these AIMs were very similar to those observed for North American natives. They discriminated Amerindians from Africans, but not from Europeans. On the other hand, the neighbor-joining dendrogram separated Africans and Europeans from Amerindians with a high statistical support (bootstrap = 0.989). The relatively low diversity (G(ST) = 0.042) among North American natives and Amerindians from Brazilian Amazon agrees with the lack of intra-ethnic variation previously reported for these markers. Despite genetic drift effects, the mean allelic frequencies herein presented could be used as Amerindian parental frequencies in admixture estimates in urban Brazilian populations. (c) 2007 Wiley-Liss, Inc.

Forensic genetic analysis of bio-geographical ancestry.

PubMed

Phillips, Chris

2015-09-01

With the great strides made in the last ten years in the understanding of human population variation and the detailed characterization of the genome, it is now possible to identify sets of ancestry informative markers suitable for relatively small-scale PCR-based assays and use them to analyze the ancestry of an individual from forensic DNA. This review outlines some of the current understanding of past human population structure and how it may have influenced the complex distribution of contemporary human diversity. A simplified description of human diversity can provide a suitable basis for choosing the best ancestry-informative markers, which is important given the constraints of multiplex sizes in forensic DNA tests. It is also important to decide the level of geographic resolution that is realistic to ensure the balance between informativeness and an over-simplification of complex human diversity patterns. A detailed comparison is made of the most informative ancestry markers suitable for forensic use and assessments are made of the data analysis regimes that can provide statistical inferences of a DNA donor's bio-geographical ancestry. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry

PubMed Central

Kessler, Michael D.; Yerges-Armstrong, Laura; Taub, Margaret A.; Shetty, Amol C.; Maloney, Kristin; Jeng, Linda Jo Bone; Ruczinski, Ingo; Levin, Albert M.; Williams, L. Keoki; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Boorgula, Meher Preethi; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Scott, Alan F.; Vergara, Candelaria; Gao, Jingjing; Hu, Yijuan; Johnston, Henry Richard; Qin, Zhaohui S.; Padhukasahasram, Badri; Dunston, Georgia M.; Faruque, Mezbah U.; Kenny, Eimear E.; Gietzen, Kimberly; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-YounA; Kumar, Rajesh; Schleimer, Robert; Bustamante, Carlos; De La Vega, Francisco M.; Gignoux, Chris R.; Shringarpure, Suyash S.; Musharoff, Shaila; Wojcik, Genevieve; Burchard, Esteban G.; Eng, Celeste; Gourraud, Pierre-Antoine; Hernandez, Ryan D.; Lizee, Antoine; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O.; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Abecasis, Goncalo; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Pissamai, Maul R. N.; Trevor, Maul R. N.; Watson, Harold; Araujo, Maria Ilma; Oliveira, Ricardo Riccio; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Herrera-Paz, Edwin Francisco; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Vasquez, Olga Marina; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria; O'Connor, Timothy D.

2016-01-01

To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVar's correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=−0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations. PMID:27725664

Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

PubMed Central

Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

2017-01-01

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001 PMID:28044981

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

PubMed Central

Agarwal, D; Pineda, S; Michailidou, K; Herranz, J; Pita, G; Moreno, L T; Alonso, M R; Dennis, J; Wang, Q; Bolla, M K; Meyer, K B; Menéndez-Rodríguez, P; Hardisson, D; Mendiola, M; González-Neira, A; Lindblom, A; Margolin, S; Swerdlow, A; Ashworth, A; Orr, N; Jones, M; Matsuo, K; Ito, H; Iwata, H; Kondo, N; Hartman, M; Hui, M; Lim, W Y; T-C Iau, P; Sawyer, E; Tomlinson, I; Kerin, M; Miller, N; Kang, D; Choi, J-Y; Park, S K; Noh, D-Y; Hopper, J L; Schmidt, D F; Makalic, E; Southey, M C; Teo, S H; Yip, C H; Sivanandan, K; Tay, W-T; Brauch, H; Brüning, T; Hamann, U; Dunning, A M; Shah, M; Andrulis, I L; Knight, J A; Glendon, G; Tchatchou, S; Schmidt, M K; Broeks, A; Rosenberg, E H; van't Veer, L J; Fasching, P A; Renner, S P; Ekici, A B; Beckmann, M W; Shen, C-Y; Hsiung, C-N; Yu, J-C; Hou, M-F; Blot, W; Cai, Q; Wu, A H; Tseng, C-C; Van Den Berg, D; Stram, D O; Cox, A; Brock, I W; Reed, M W R; Muir, K; Lophatananon, A; Stewart-Brown, S; Siriwanarangsan, P; Zheng, W; Deming-Halverson, S; Shrubsole, M J; Long, J; Shu, X-O; Lu, W; Gao, Y-T; Zhang, B; Radice, P; Peterlongo, P; Manoukian, S; Mariette, F; Sangrajrang, S; McKay, J; Couch, F J; Toland, A E; Yannoukakos, D; Fletcher, O; Johnson, N; Silva, I dos Santos; Peto, J; Marme, F; Burwinkel, B; Guénel, P; Truong, T; Sanchez, M; Mulot, C; Bojesen, S E; Nordestgaard, B G; Flyer, H; Brenner, H; Dieffenbach, A K; Arndt, V; Stegmaier, C; Mannermaa, A; Kataja, V; Kosma, V-M; Hartikainen, J M; Lambrechts, D; Yesilyurt, B T; Floris, G; Leunen, K; Chang-Claude, J; Rudolph, A; Seibold, P; Flesch-Janys, D; Wang, X; Olson, J E; Vachon, C; Purrington, K; Giles, G G; Severi, G; Baglietto, L; Haiman, C A; Henderson, B E; Schumacher, F; Le Marchand, L; Simard, J; Dumont, M; Goldberg, M S; Labrèche, F; Winqvist, R; Pylkäs, K; Jukkola-Vuorinen, A; Grip, M; Devilee, P; Tollenaar, R A E M; Seynaeve, C; García-Closas, M; Chanock, S J; Lissowska, J; Figueroa, J D; Czene, K; Eriksson, M; Humphreys, K; Darabi, H; Hooning, M J; Kriege, M; Collée, J M; Tilanus-Linthorst, M; Li, J; Jakubowska, A; Lubinski, J; Jaworska-Bieniek, K; Durda, K; Nevanlinna, H; Muranen, T A; Aittomäki, K; Blomqvist, C; Bogdanova, N; Dörk, T; Hall, P; Chenevix-Trench, G; Easton, D F; Pharoah, P D P; Arias-Perez, J I; Zamora, P; Benítez, J; Milne, R L

2014-01-01

Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. PMID:24548884

Classification of Obesity Varies between Body Mass Index and Direct Measures of Body Fat in Boys and Girls of Asian and European Ancestry

ERIC Educational Resources Information Center

McConnell-Nzunga, J.; Naylor, P. J.; Macdonald, H.; Rhodes, R. E.; Hofer, S. M.; McKay, H.

2018-01-01

Body mass index is a common proxy for proportion of body fat. However, body mass index may not classify youth similarly across ages and ethnicities. We used sex- and ethnic-specific receiver operating characteristic curves to determine how obesity classifications compared between body mass index and dual energy x-ray absorptiometry-based body fat…

Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls

PubMed Central

Zheng, Wei; Zhang, Ben; Cai, Qiuyin; Sung, Hyuna; Michailidou, Kyriaki; Shi, Jiajun; Choi, Ji-Yeob; Long, Jirong; Dennis, Joe; Humphreys, Manjeet K.; Wang, Qin; Lu, Wei; Gao, Yu-Tang; Li, Chun; Cai, Hui; Park, Sue K.; Yoo, Keun-Young; Noh, Dong-Young; Han, Wonshik; Dunning, Alison M.; Benitez, Javier; Vincent, Daniel; Bacot, Francois; Tessier, Daniel; Kim, Sung-Won; Lee, Min Hyuk; Lee, Jong Won; Lee, Jong-Young; Xiang, Yong-Bing; Zheng, Ying; Wang, Wenjin; Ji, Bu-Tian; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Teo, Soo Hwang; Yip, Cheng Har; Kang, In Nee; Wong, Tien Y.; Shen, Chen-Yang; Yu, Jyh-Cherng; Huang, Chiun-Sheng; Hou, Ming-Feng; Hartman, Mikael; Miao, Hui; Lee, Soo Chin; Putti, Thomas Choudary; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Sangrajrang, Suleeporn; Shen, Hongbing; Chen, Kexin; Wu, Pei-Ei; Ren, Zefang; Haiman, Christopher A.; Sueta, Aiko; Kim, Mi Kyung; Khoo, Ui Soon; Iwasaki, Motoki; Pharoah, Paul D.P.; Wen, Wanqing; Hall, Per; Shu, Xiao-Ou; Easton, Douglas F.; Kang, Daehee

2013-01-01

In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations. PMID:23535825

Association of Aldosterone Synthase Polymorphism (CYP11B2 -344T>C) and Genetic Ancestry with Atrial Fibrillation and Serum Aldosterone in African Americans with Heart Failure

PubMed Central

Bress, Adam; Han, Jin; Patel, Shitalben R.; Desai, Ankit A.; Mansour, Ibrahim; Groo, Vicki; Progar, Kristin; Shah, Ebony; Stamos, Thomas D.; Wing, Coady; Garcia, Joe G. N.; Kittles, Rick; Cavallari, Larisa H.

2013-01-01

The objective of this study was to examine the extent to which aldosterone synthase genotype (CYP11B2) and genetic ancestry correlate with atrial fibrillation (AF) and serum aldosterone in African Americans with heart failure. Clinical data, echocardiographic measurements, and a genetic sample for determination of CYP11B2 -344T>C (rs1799998) genotype and genetic ancestry were collected from 194 self-reported African Americans with chronic, ambulatory heart failure. Genetic ancestry was determined using 105 autosomal ancestry informative markers. In a sub-set of patients (n = 126), serum was also collected for determination of circulating aldosterone. The CYP11B2 −344C allele frequency was 18% among the study population, and 19% of patients had AF. Multiple logistic regression revealed that the CYP11B2 −344CC genotype was a significant independent predictor of AF (OR 12.7, 95% CI 1.60–98.4, p = 0.0150, empirical p = 0.011) while holding multiple clinical factors, left atrial size, and percent European ancestry constant. Serum aldosterone was significantly higher among patients with AF (p = 0.036), whereas increased West African ancestry was inversely correlated with serum aldosterone (r = −0.19, p = 0.037). The CYP11B2 −344CC genotype was also overrepresented among patients with extreme aldosterone elevation (≥90th percentile, p = 0.0145). In this cohort of African Americans with chronic ambulatory heart failure, the CYP11B2 −344T>C genotype was a significant independent predictor of AF while holding clinical, echocardiographic predictors, and genetic ancestry constant. In addition, increased West African ancestry was associated with decreased serum aldosterone levels, potentially providing an explanation for the lower risk for AF observed among African Americans. PMID:23936266

African ancestry and lung function in Puerto Rican children.

PubMed

Brehm, John M; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael M; Boutaoui, Nadia; Forno, Erick; Cloutier, Michelle M; Datta, Soma; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Calvert, Deanna; Thornton-Thompson, Sherell; Wakefield, Dorothy; Litonjua, Augusto A; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2012-06-01

Puerto Rican and African American subjects share a significant proportion of African ancestry. Recent findings suggest that African ancestry influences lung function in African American adults. We sought to examine whether a greater proportion of African ancestry is associated with lower FEV(1) and forced vital capacity (FVC) in Puerto Rican children independently of socioeconomic status, health care access, or key environmental/lifestyle factors. We performed a cross-sectional case-control study of 943 Puerto Rican children aged 6 to 14 years with (n= 520) and without (n= 423) asthma (defined as physician-diagnosed asthma and wheeze in the prior year) living in Hartford, Connecticut (n= 383), and San Juan, Puerto Rico (n= 560). We estimated the percentage of African racial ancestry in study participants using genome-wide genotypic data. We tested whether African ancestry is associated with FEV(1) and FVC using linear regression. Multivariate models were adjusted for indicators of socioeconomic status and health care and selected environmental/lifestyle exposures. After adjustment for household income and other covariates, each 20% increment in African ancestry was significantly associated with lower prebronchodilator FEV(1) (-105 mL; 95% CI, -159 to -51 mL; P< .001) and FVC (-133 mL; 95% CI, -197 to -69 mL; P< .001) and postbronchodilator FEV(1) (-152 mL; 95% CI, -210 to -94 mL; P< .001) and FVC (-145 mL; 95% CI, -211 to -79 mL; P< .001) in children with asthma. Similar but weaker associations were found for prebronchodilator and postbronchodilator FEV(1) (change for each 20% increment in African ancestry, -78 mL; 95% CI, -131 to -25 mL; P= .004) and for postbronchodilator FVC among children without asthma. Genetic factors, environmental/lifestyle factors, or both correlated with African ancestry might influence childhood lung function in Puerto Rican subjects. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

African Ancestry and Lung Function in Puerto Rican Children

PubMed Central

Brehm, John M.; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael; Boutaoui, Nadia; Forno, Erick; Cloutier, Michelle; Datta, Soma; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Calvert, Deanna; Thornton-Thompson, Sherell; Wakefield, Dorothy; Litonjua, Augusto A.; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C.

2012-01-01

Background Puerto Ricans and African Americans share a significant proportion of African ancestry. Recent findings suggest that African ancestry influences lung function in African American adults. Objective To examine whether a greater proportion of African ancestry is associated with lower FEV1 and FVC in Puerto Rican children, independently of socioeconomic status (SES), healthcare access or key environmental/lifestyle (EL) factors. Methods Cross-sectional case-control study of 943 Puerto Rican children ages 6 to 14 years with (n=520) and without (n=423) asthma (defined as physician-diagnosed asthma and wheeze in the prior year) living in Hartford (CT, n=383) and San Juan (PR, n=560). We estimated the percentage of African racial ancestry in study participants using genome-wide genotypic data. We tested whether African ancestry is associated with FEV1 and FVC using linear regression. Multivariate models were adjusted for indicators of SES and healthcare, and selected EL exposures. Results After adjustment for household income and other covariates, each 20% increment in African ancestry was significantly associated with lower pre-bronchodilator(BD) FEV1 (−105 ml, 95% confidence interval [CI] = −159 ml to −51 ml, P <0.001) and FVC (−133 ml, 95% CI −197 ml to −69 ml, P <0.001), and post-BD FEV1 (−152 ml, 95% CI=−210 ml to −94 ml, P <0.001) and FVC (−145 ml, 95% CI= −211 to −79 ml, P <0.001) in children with asthma. Similar but weaker associations were found for pre- and post-BD FEV1 (change for each 20% increment in African ancestry= −78 ml, 95% CI= −131 to −25 ml, P=0.004), and for post-BD FVC among children without asthma. Conclusions Genetic and/or EL factors correlated with African ancestry may influence childhood lung function in Puerto Ricans. PMID:22560959

The Genomic Ancestry of Individuals from Different Geographical Regions of Brazil Is More Uniform Than Expected

PubMed Central

Pena, Sérgio D. J.; Di Pietro, Giuliano; Fuchshuber-Moraes, Mateus; Genro, Julia Pasqualini; Hutz, Mara H.; Kehdy, Fernanda de Souza Gomes; Kohlrausch, Fabiana; Magno, Luiz Alexandre Viana; Montenegro, Raquel Carvalho; Moraes, Manoel Odorico; de Moraes, Maria Elisabete Amaral; de Moraes, Milene Raiol; Ojopi, Élida B.; Perini, Jamila A.; Racciopi, Clarice; Ribeiro-dos-Santos, Ândrea Kely Campos; Rios-Santos, Fabrício; Romano-Silva, Marco A.; Sortica, Vinicius A.; Suarez-Kurtz, Guilherme

2011-01-01

Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a “total ancestry” estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries - a phenomenon described and intended as the “whitening of Brazil” - is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations. PMID:21359226

Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans

PubMed Central

Bentley, Amy R.; Chen, Guanjie; Shriner, Daniel; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Mullikin, James C.; Blakesley, Robert W.; Hansen, Nancy F.; Bouffard, Gerard G.; Cherukuri, Praveen F.; Maskeri, Baishali; Young, Alice C.; Adeyemo, Adebowale; Rotimi, Charles N.

2014-01-01

Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a “European” vs. “African” genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2–3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA. PMID:24603370

Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents.

PubMed

McCormack, Shana E; Chesi, Alessandra; Mitchell, Jonathan A; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Mahboubi, Soroosh; Winer, Karen K; Kelly, Andrea; Grant, Struan Fa; Zemel, Babette S

2017-01-01

More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p < 0.001) and boys (∼0.43 years, p < 0.001). Boys and girls of all ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Comparative Analysis of Breast Cancer Phenotypes in African American, White American, and West Versus East African patients: Correlation Between African Ancestry and Triple-Negative Breast Cancer.

PubMed

Jiagge, Evelyn; Jibril, Aisha Souleiman; Chitale, Dhananjay; Bensenhaver, Jessica M; Awuah, Baffour; Hoenerhoff, Mark; Adjei, Ernest; Bekele, Mahteme; Abebe, Engida; Nathanson, S David; Gyan, Kofi; Salem, Barbara; Oppong, Joseph; Aitpillah, Francis; Kyei, Ishmael; Bonsu, Ernest Osei; Proctor, Erica; Merajver, Sofia D; Wicha, Max; Stark, Azadeh; Newman, Lisa A

2016-11-01

Triple-negative breast cancer (TNBC) is more common among African American (AA) and western sub-Saharan African breast cancer (BC) patients compared with White/Caucasian Americans (WA) and Europeans. Little is known about TNBC in east Africa. Invasive BC diagnosed 1998-2014 were evaluated: WA and AA patients from the Henry Ford Health System in Detroit, Michigan; Ghanaian/west Africans from the Komfo Anokye Teaching Hospital in Kumasi, Ghana; and Ethiopian/east Africans from the St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia. Histopathology and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), and HER2/neu expression was performed in Michigan on formalin-fixed, paraffin-embedded samples from all cases. A total of 234 Ghanaian (mean age 49 years), 94 Ethiopian (mean age 43 years), 272 AA (mean age 60 years), and 321 WA (mean age 62 years; p = 0.001) patients were compared. ER-negative and TNBC were more common among Ghanaian and AA compared with WA and Ethiopian cases (frequency ER-negativity 71.1 and 37.1 % vs. 19.8 and 28.6 % respectively, p < 0.0001; frequency TNBC 53.2 and 29.8 % vs. 15.5 and 15.0 %, respectively, p < 0.0001). Among patients younger than 50 years, prevalence of TNBC remained highest among Ghanaians (50.8 %) and AA (34.3 %) compared with WA and Ethiopians (approximately 16 % in each; p = 0.0002). This study confirms an association between TNBC and West African ancestry; TNBC frequency among AA patients is intermediate between WA and Ghanaian/West Africans consistent with genetic admixture following the west Africa-based trans-Atlantic slave trade. TNBC frequency was low among Ethiopians/East Africans; this may reflect less shared ancestry between AA and Ethiopians.

Mitochondrial DNA Analysis of Mazahua and Otomi Indigenous Populations from Estado de México Suggests a Distant Common Ancestry.

PubMed

González-Oliver, Angélica; Garfias-Morales, Ernesto; Smith, David Glenn; Quinto-Sánchez, Mirsha

2017-07-01

The indigenous Mazahua and Otomi have inhabited the same localities in Estado de México since pre-Columbian times. Their languages, Mazahua and Otomi, belong to the Oto-Manguean linguistic family, and although they share cultural traditions and a regional history that suggest close genetic relationships and common ancestry, the historical records concerning their origin are confusing. To understand the biological relationships between Mazahua and Otomi, we analyzed mitochondrial DNA (mtDNA) genetic variation. We identified the mtDNA haplogroups by restriction fragment length polymorphism typing and sequenced hypervariable region 1 of the mtDNA control region in 141 Mazahua and 100 Otomi. These results showed that Otomi exhibit a higher frequency of haplogroup A than B, whereas Mazahua exhibit the opposite pattern. In the Otomi EM population the most frequent subhaplogroups are, in order of frequency, A2, B2, and C1, whereas in the Mazahua 1 population they are B2, D1, and A2. The most frequent haplotypes (Ht) of haplogroups A and B are Ht2 (A) and Ht58 (B2g1) in Mazahua 1 and Ht8 (A2), Ht22 (A2ao1), and Ht53 (B2c2b) in Otomi EM. The genetic differences between the Mazahua 1 and Otomi EM suggest a distant shared ancestry and a moderate degree of maternal admixture that has not obscured the difference of their mtDNA patterns. These unexpected results suggest the Mazahua and Otomi probably descend from the same group but separated very early and admixed with other Mesoamerican populations before their arrival in Central Mexico. The historical evidence of conflicting relations between the Mazahua and Otomi and the almost nonexistence of marriage between them could be responsible for maintaining only a moderate degree of maternal admixture.

Biodiversity and evolution of the Myxozoa.

PubMed

Canning, Elizabeth U; Okamura, Beth

2004-01-01

Myxozoans (phylum Myxozoa) are metazoan parasites utilizing invertebrate and (mainly) aquatic vertebrate hosts. They have in common with cnidarians the possession of virtually identical, highly complex organelles, namely the polar capsules in myxozoan spores, serving for attachment to new hosts and the nematocysts in surface epithelia of cnidarians, serving for food capture. Although myxozoan spores are multicellular, the simple trophic body forms of almost all species, reduced to syncytial plasmodia or single cells, reveal no clues to myxozoan ancestry or phylogenetic relationships. The myxozoan genus Buddenbrockia is one of only two known genera belonging to a clade which diverged early in the evolution of the Myxozoa. Today the Myxozoa are represented by two classes, the Myxosporea, containing all the better-known genera, which alternate between fish and annelids, and the Malacosporea, containing Buddenbrockia and Tetracapsuloides, parasitising bryozoans. The latter genus also infects salmonid fish, causing proliferative kidney disease (PKD). The enigmatic Buddenbrockia has retained some of its ancestral features in a body wall of two cell layers and a worm-like shape, maintained by four longitudinally-running muscle blocks, similar to a gutless nematode and suggestive of a bilaterian ancestry. Although some analyses of 18S rDNA sequences tend towards a cnidarian (diploblast) affinity for myxozoans, the majority of these studies place them within, or sister to, the Bilateria. The latter view is supported by their possession of central class Hox genes, so far considered to be synapomorphic for Bilateria. The simple body form is, therefore, an extreme example of simplification due to parasitism. Various hypotheses for the occurrence of identical complex organelles (nematocysts and polar capsules) in diploblast and triploblast phyla are evaluated: common ancestry, convergent evolution, gene transfer and, especially, endosymbiosis. A theory of the evolution of their digenetic life cycles is proposed, with the invertebrate as primary host and secondary acquisition of the vertebrate host serving for asexual population increase.

Ethnic Admixture Affects Diabetes Risk in Native Hawaiians: The Multiethnic Cohort

PubMed Central

Maskarinec, Gertraud; Morimoto, Yukiko; Jacobs, Simone; Grandinetti, Andrew; Mau, Marjorie K.; Kolonel, Laurence N.

2016-01-01

Background/Objectives Obesity and diabetes rates are high in Native Hawaiians (NH) who commonly have mixed ancestries. Persons of Asian ancestry experience a high risk of type 2 diabetes despite the relatively low body weight. We evaluated the impact of ethnic admixture on diabetes risk among NH in the Multiethnic Cohort (MEC). Methods/Subjects Based on self-reports, 11,521 eligible men and women were categorized into NH/white, NH/other, NH alone, NH/Asian, and the most common three ancestry admixture, NH/Chinese/white. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with the NH/white category as the reference group; covariates included known confounders, i.e., body mass index (BMI), dietary and other life-style factors. Results The NH alone category had the highest proportion of overweight and obese individuals and the NH/Asian category the lowest proportion. During 12 years of follow-up after cohort entry at 56 years, 2,072 incident cases were ascertained through questionnaires and health plan linkages. All NH categories had higher HRs than the NH/white category before and after adjustment for BMI. In fully-adjusted models, the NH/Asian category showed the highest risk (HR=1.45; 95%CI: 1.27–1.65), followed by NH/other (HR=1.20; 95%CI: 1.03–1.39), NH/Chinese/white (HR=1.19; 95%CI: 1.04–1.37), and NH alone (HR=1.19; 95%CI: 1.03–1.37). The elevated risk by Asian admixture was more pronounced in normal weight than overweight/obese individuals. Conclusions These findings indicate that Asian admixture in NHs is associated with higher risk for type 2 diabetes independent of known risk factors and suggest a role for ethnicity-related genetic factors in the development of this disease. PMID:27026423

Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population

PubMed Central

Friedrich, Deise C.; Santos, Sidney E. B.; Ribeiro-dos-Santos, Ândrea K. C.; Hutz, Mara H.

2012-01-01

Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The −13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The −13779*C,−13910*T, −13937*A, −14010*C, −14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was −13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The −13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the −13910*T allele is an oversimplification. PMID:23029545

Ancestry, admixture and fitness in Colombian genomes

PubMed Central

Rishishwar, Lavanya; Conley, Andrew B.; Wigington, Charles H.; Wang, Lu; Valderrama-Aguirre, Augusto; King Jordan, I.

2015-01-01

The human dimension of the Columbian Exchange entailed substantial genetic admixture between ancestral source populations from Africa, the Americas and Europe, which had evolved separately for many thousands of years. We sought to address the implications of the creation of admixed American genomes, containing novel allelic combinations, for human health and fitness via analysis of an admixed Colombian population from Medellin. Colombian genomes from Medellin show a wide range of three-way admixture contributions from ancestral source populations. The primary ancestry component for the population is European (average = 74.6%, range = 45.0%–96.7%), followed by Native American (average = 18.1%, range = 2.1%–33.3%) and African (average = 7.3%, range = 0.2%–38.6%). Locus-specific patterns of ancestry were evaluated to search for genomic regions that are enriched across the population for particular ancestry contributions. Adaptive and innate immune system related genes and pathways are particularly over-represented among ancestry-enriched segments, including genes (HLA-B and MAPK10) that are involved in defense against endemic pathogens such as malaria. Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous glands (EDAR) are also found in regions with anomalous ancestry patterns. These results suggest the possibility that ancestry-specific loci were differentially retained in the modern admixed Colombian population based on their utility in the New World environment. PMID:26197429

Differentiation of African components of ancestry to stratify groups in a case-control study of a Brazilian urban population.

PubMed

Silbiger, Vivian N; Hirata, Mario H; Luchessi, Andre D; Genvigir, Fabiana D V; Cerda, Alvaro; Rodrigues, Alice C; Willrich, Maria A V; Arazi, Simone S; Dorea, Egidio L; Bernik, Marcia M S; Faludi, Andre A; Bertolami, Marcelo C; Santos, Carla; Carracedo, Angel; Salas, Antonio; Freire, Ana; Lareu, Maria Victoria; Phillips, Christopher; Porras-Hurtado, Liliana; Fondevila, Manuel; Hirata, Rosario D C

2012-06-01

Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA <0.25 and >0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA <0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.

The imprint of the Slave Trade in an African American population: mitochondrial DNA, Y chromosome and HTLV-1 analysis in the Noir Marron of French Guiana

PubMed Central

2010-01-01

Background Retracing the genetic histories of the descendant populations of the Slave Trade (16th-19th centuries) is particularly challenging due to the diversity of African ethnic groups involved and the different hybridisation processes with Europeans and Amerindians, which have blurred their original genetic inheritances. The Noir Marron in French Guiana are the direct descendants of maroons who escaped from Dutch plantations in the current day Surinam. They represent an original ethnic group with a highly blended culture. Uniparental markers (mtDNA and NRY) coupled with HTLV-1 sequences (env and LTR) were studied to establish the genetic relationships linking them to African American and African populations. Results All genetic systems presented a high conservation of the African gene pool (African ancestry: mtDNA = 99.3%; NRY = 97.6%; HTLV-1 env = 20/23; HTLV-1 LTR = 6/8). Neither founder effect nor genetic drift was detected and the genetic diversity is within a range commonly observed in Africa. Higher genetic similarities were observed with the populations inhabiting the Bight of Benin (from Ivory Coast to Benin). Other ancestries were identified but they presented an interesting sex-bias. Whilst male origins spread throughout the north of the bight (from Benin to Senegal), female origins were spread throughout the south (from the Ivory Coast to Angola). Conclusions The Noir Marron are unique in having conserved their African genetic ancestry, despite major cultural exchanges with Amerindians and Europeans through inhabiting the same region for four centuries. Their maroon identity and the important number of slaves deported in this region have maintained the original African diversity. All these characteristics permit to identify a major origin located in the former region of the Gold Coast and the Bight of Benin; regions highly impacted by slavery, from which goes a sex-biased longitudinal gradient of ancestry. PMID:20958967

More comprehensive forensic genetic marker analyses for accurate human remains identification using massively parallel DNA sequencing.

PubMed

Ambers, Angie D; Churchill, Jennifer D; King, Jonathan L; Stoljarova, Monika; Gill-King, Harrell; Assidi, Mourad; Abu-Elmagd, Muhammad; Buhmeida, Abdelbaset; Al-Qahtani, Mohammed; Budowle, Bruce

2016-10-17

Although the primary objective of forensic DNA analyses of unidentified human remains is positive identification, cases involving historical or archaeological skeletal remains often lack reference samples for comparison. Massively parallel sequencing (MPS) offers an opportunity to provide biometric data in such cases, and these cases provide valuable data on the feasibility of applying MPS for characterization of modern forensic casework samples. In this study, MPS was used to characterize 140-year-old human skeletal remains discovered at a historical site in Deadwood, South Dakota, United States. The remains were in an unmarked grave and there were no records or other metadata available regarding the identity of the individual. Due to the high throughput of MPS, a variety of biometric markers could be typed using a single sample. Using MPS and suitable forensic genetic markers, more relevant information could be obtained from a limited quantity and quality sample. Results were obtained for 25/26 Y-STRs, 34/34 Y SNPs, 166/166 ancestry-informative SNPs, 24/24 phenotype-informative SNPs, 102/102 human identity SNPs, 27/29 autosomal STRs (plus amelogenin), and 4/8 X-STRs (as well as ten regions of mtDNA). The Y-chromosome (Y-STR, Y-SNP) and mtDNA profiles of the unidentified skeletal remains are consistent with the R1b and H1 haplogroups, respectively. Both of these haplogroups are the most common haplogroups in Western Europe. Ancestry-informative SNP analysis also supported European ancestry. The genetic results are consistent with anthropological findings that the remains belong to a male of European ancestry (Caucasian). Phenotype-informative SNP data provided strong support that the individual had light red hair and brown eyes. This study is among the first to genetically characterize historical human remains with forensic genetic marker kits specifically designed for MPS. The outcome demonstrates that substantially more genetic information can be obtained from the same initial quantities of DNA as that of current CE-based analyses.

The imprint of the Slave Trade in an African American population: mitochondrial DNA, Y chromosome and HTLV-1 analysis in the Noir Marron of French Guiana.

PubMed

Brucato, Nicolas; Cassar, Olivier; Tonasso, Laure; Tortevoye, Patricia; Migot-Nabias, Florence; Plancoulaine, Sabine; Guitard, Evelyne; Larrouy, Georges; Gessain, Antoine; Dugoujon, Jean-Michel

2010-10-19

Retracing the genetic histories of the descendant populations of the Slave Trade (16th-19th centuries) is particularly challenging due to the diversity of African ethnic groups involved and the different hybridisation processes with Europeans and Amerindians, which have blurred their original genetic inheritances. The Noir Marron in French Guiana are the direct descendants of maroons who escaped from Dutch plantations in the current day Surinam. They represent an original ethnic group with a highly blended culture. Uniparental markers (mtDNA and NRY) coupled with HTLV-1 sequences (env and LTR) were studied to establish the genetic relationships linking them to African American and African populations. All genetic systems presented a high conservation of the African gene pool (African ancestry: mtDNA = 99.3%; NRY = 97.6%; HTLV-1 env = 20/23; HTLV-1 LTR = 6/8). Neither founder effect nor genetic drift was detected and the genetic diversity is within a range commonly observed in Africa. Higher genetic similarities were observed with the populations inhabiting the Bight of Benin (from Ivory Coast to Benin). Other ancestries were identified but they presented an interesting sex-bias. Whilst male origins spread throughout the north of the bight (from Benin to Senegal), female origins were spread throughout the south (from the Ivory Coast to Angola). The Noir Marron are unique in having conserved their African genetic ancestry, despite major cultural exchanges with Amerindians and Europeans through inhabiting the same region for four centuries. Their maroon identity and the important number of slaves deported in this region have maintained the original African diversity. All these characteristics permit to identify a major origin located in the former region of the Gold Coast and the Bight of Benin; regions highly impacted by slavery, from which goes a sex-biased longitudinal gradient of ancestry.

Interrogation of the platelet-derived growth factor receptor alpha locus and corneal astigmatism in Australians of Northern European ancestry: results of a genome-wide association study.

PubMed

Yazar, Seyhan; Mishra, Aniket; Ang, Wei; Kearns, Lisa S; Mountain, Jenny A; Pennell, Craig; Montgomery, Grant W; Young, Terri L; Hammond, Christopher J; Macgregor, Stuart; Mackey, David A; Hewitt, Alex W

2013-01-01

Corneal astigmatism is a common eye disorder characterized by irregularities in corneal curvature. Recently, the rs7677751 single nucleotide polymorphism (SNP) at the platelet-derived growth factor receptor alpha (PDGFRA) locus was found to be associated with corneal astigmatism in people of Asian ancestry. In the present study, we sought to replicate this finding and identify other genetic markers of corneal astigmatism in an Australian population of Northern European ancestry. Data from two cohorts were included in this study. The first cohort consisted of 1,013 individuals who were part of the Western Australian Pregnancy Cohort (Raine) Study: 20-year follow-up Eye Study. The second cohort comprised 1,788 individuals of 857 twin families who were recruited through the Twins Eye Study in Tasmania and the Brisbane Adolescent Twin Study. Corneal astigmatism was calculated as the absolute difference between the keratometry readings in two meridians, and genotype data were extracted from genome-wide arrays. Initially, each cohort was analyzed separately, before being combined for meta- and subsequent genome-wide pathway analysis. Following meta-analysis, SNP rs7677751 at the PDGFRA locus had a combined p=0.32. No variant was found to be statistically significantly associated with corneal astigmatism at the genome-wide level (p<5.0×10(-8)). The SNP with strongest association was rs1164064 (p=1.86×10(-6)) on chromosome 3q13. Gene-based pathway analysis identified a significant association between the Gene Ontology "segmentation" (GO:0035282) pathway, corrected p=0.009. Our data suggest that the PDGFRA locus does not transfer a major risk of corneal astigmatism in people of Northern European ancestry. Better-powered studies are required to validate the novel putative findings of our study.

Growth gains from selective breeding in a spruce hybrid zone do not compromise local adaptation to climate.

PubMed

MacLachlan, Ian R; Yeaman, Sam; Aitken, Sally N

2018-02-01

Hybrid zones contain extensive standing genetic variation that facilitates rapid responses to selection. The Picea glauca  ×  Picea engelmannii hybrid zone in western Canada is the focus of tree breeding programs that annually produce ~90 million reforestation seedlings. Understanding the direct and indirect effects of selective breeding on adaptive variation is necessary to implement assisted gene flow (AGF) polices in Alberta and British Columbia that match these seedlings with future climates. We decomposed relationships among hybrid ancestry, adaptive traits, and climate to understand the implications of selective breeding for climate adaptations and AGF strategies. The effects of selection on associations among hybrid index estimated from ~6,500 SNPs, adaptive traits, and provenance climates were assessed for ~2,400 common garden seedlings. Hybrid index differences between natural and selected seedlings within breeding zones were small in Alberta (average +2%), but larger and more variable in BC (average -7%, range -24% to +1%), slightly favoring P. glauca ancestry. The average height growth gain of selected seedlings over natural seedlings within breeding zones was 36% (range 12%-86%). Clines in growth with temperature-related variables were strong, but differed little between selected and natural populations. Seedling hybrid index and growth trait associations with evapotranspiration-related climate variables were stronger in selected than in natural seedlings, indicating possible preadaptation to drier future climates. Associations among cold hardiness, hybrid ancestry, and cold-related climate variables dominated signals of local adaptation and were preserved in breeding populations. Strong hybrid ancestry-phenotype-climate associations suggest that AGF will be necessary to match interior spruce breeding populations with shifting future climates. The absence of antagonistic selection responses among traits and maintenance of cold adaptation in selected seedlings suggests breeding populations can be safely redeployed using AGF prescriptions similar to those of natural populations.

Genomic adaptation of admixed dairy cattle in East Africa

PubMed Central

Kim, Eui-Soo; Rothschild, Max F.

2014-01-01

Dairy cattle in East Africa imported from the U.S. and Europe have been adapted to new environments. In small local farms, cattle have generally been maintained by crossbreeding that could increase survivability under a severe environment. Eventually, genomic ancestry of a specific breed will be nearly fixed in genomic regions of local breeds or crossbreds when it is advantageous for survival or production in harsh environments. To examine this situation, 25 Friesians and 162 local cattle produced by crossbreeding of dairy breeds in Kenya were sampled and genotyped using 50K SNPs. Using principal component analysis (PCA), the admixed local cattle were found to consist of several imported breeds, including Guernsey, Norwegian Red, and Holstein. To infer the influence of parental breeds on genomic regions, local ancestry mapping was performed based on the similarity of haplotypes. As a consequence, it appears that no genomic region has been under the complete influence of a specific parental breed. Nonetheless, the ancestry of Holstein-Friesians was substantial in most genomic regions (>80%). Furthermore, we examined the frequency of the most common haplotypes from parental breeds that have changed substantially in Kenyan crossbreds during admixture. The frequency of these haplotypes from parental breeds, which were likely to be selected in temperate regions, has deviated considerably from expected frequency in 11 genomic regions. Additionally, extended haplotype homozygosity (EHH) based methods were applied to identify the regions responding to recent selection in crossbreds, called candidate regions, resulting in seven regions that appeared to be affected by Holstein-Friesians. However, some signatures of selection were less dependent on Holsteins-Friesians, suggesting evidence of adaptation in East Africa. The analysis of local ancestry is a useful approach to understand the detailed genomic structure and may reveal regions of the genome required for specialized adaptation when combined with methods for searching for the recent changes of haplotype frequency in an admixed population. PMID:25566325

Elucidating the genetic architecture of reproductive ageing in the Japanese population.

PubMed

Horikoshi, Momoko; Day, Felix R; Akiyama, Masato; Hirata, Makoto; Kamatani, Yoichiro; Matsuda, Koichi; Ishigaki, Kazuyoshi; Kanai, Masahiro; Wright, Hollis; Toro, Carlos A; Ojeda, Sergio R; Lomniczi, Alejandro; Kubo, Michiaki; Ong, Ken K; Perry, John R B

2018-05-17

Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, we report 26 loci (all P < 5 × 10 -8 ) for reproductive ageing, i.e. puberty timing or age at menopause, in a non-European population (up to 67,029 women of Japanese ancestry). Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause. For puberty timing, we demonstrate an aetiological role for receptor-like protein tyrosine phosphatases by combining evidence across population genetics and pre- and peri-pubertal changes in hypothalamic gene expression in rodent and primate models. Furthermore, our findings demonstrate widespread differences in allele frequencies and effect estimates between Japanese and European associated variants, highlighting the benefits and challenges of large-scale trans-ethnic approaches.

Ancestral effect on HOMA-IR levels quantitated in an American population of Mexican origin.

PubMed

Qu, Hui-Qi; Li, Quan; Lu, Yang; Hanis, Craig L; Fisher-Hoch, Susan P; McCormick, Joseph B

2012-12-01

An elevated insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) is more commonly seen in the Mexican American population than in European populations. We report quantitative ancestral effects within a Mexican American population, and we correlate ancestral components with HOMA-IR. We performed ancestral analysis in 1,551 participants of the Cameron County Hispanic Cohort by genotyping 103 ancestry-informative markers (AIMs). These AIMs allow determination of the percentage (0-100%) ancestry from three major continental populations, i.e., European, African, and Amerindian. We observed that predominantly Amerindian ancestral components were associated with increased HOMA-IR (β = 0.124, P = 1.64 × 10(-7)). The correlation was more significant in males (Amerindian β = 0.165, P = 5.08 × 10(-7)) than in females (Amerindian β = 0.079, P = 0.019). This unique study design demonstrates how genomic markers for quantitative ancestral information can be used in admixed populations to predict phenotypic traits such as insulin resistance.

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations.

PubMed

Kopelman, Naama M; Stone, Lewi; Wang, Chaolong; Gefel, Dov; Feldman, Marcus W; Hillel, Jossi; Rosenberg, Noah A

2009-12-08

Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent.

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations

PubMed Central

2009-01-01

Background Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. Results We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. Conclusion These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent. PMID:19995433

Resolving the ancestry of Austronesian-speaking populations.

PubMed

Soares, Pedro A; Trejaut, Jean A; Rito, Teresa; Cavadas, Bruno; Hill, Catherine; Eng, Ken Khong; Mormina, Maru; Brandão, Andreia; Fraser, Ross M; Wang, Tse-Yi; Loo, Jun-Hun; Snell, Christopher; Ko, Tsang-Ming; Amorim, António; Pala, Maria; Macaulay, Vincent; Bulbeck, David; Wilson, James F; Gusmão, Leonor; Pereira, Luísa; Oppenheimer, Stephen; Lin, Marie; Richards, Martin B

2016-03-01

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion.

Revisiting the Genetic Ancestry of Brazilians Using Autosomal AIM-Indels

PubMed Central

Saloum de Neves Manta, Fernanda; Pereira, Rui; Vianna, Romulo; Rodolfo Beuttenmüller de Araújo, Alfredo; Leite Góes Gitaí, Daniel; Aparecida da Silva, Dayse; de Vargas Wolfgramm, Eldamária; da Mota Pontes, Isabel; Ivan Aguiar, José; Ozório Moraes, Milton; Fagundes de Carvalho, Elizeu; Gusmão, Leonor

2013-01-01

There are many different studies that contribute to the global picture of the ethnic heterogeneity in Brazilian populations. These studies use different types of genetic markers and are focused on the comparison of populations at different levels. In some of them, each geographical region is treated as a single homogeneous population, whereas other studies create different subdivisions: political (e.g., pooling populations by State), demographic (e.g., urban and rural), or ethnic (e.g., culture, self-declaration, or skin colour). In this study, we performed an enhanced reassessment of the genetic ancestry of ~ 1,300 Brazilians characterised for 46 autosomal Ancestry Informative Markers (AIMs). In addition, 798 individuals from twelve Brazilian populations representing the five geographical macro-regions of Brazil were newly genotyped, including a Native American community and a rural Amazonian community. Following an increasing North to South gradient, European ancestry was the most prevalent in all urban populations (with values up to 74%). The populations in the North consisted of a significant proportion of Native American ancestry that was about two times higher than the African contribution. Conversely, in the Northeast, Center-West and Southeast, African ancestry was the second most prevalent. At an intrapopulation level, all urban populations were highly admixed, and most of the variation in ancestry proportions was observed between individuals within each population rather than among population. Nevertheless, individuals with a high proportion of Native American ancestry are only found in the samples from Terena and Santa Isabel. Our results allowed us to further refine the genetic landscape of Brazilians while establishing the basis for the effective application of an autosomal AIM panel in forensic casework and clinical association studies within the highly admixed Brazilian populations. PMID:24073242

Gun Violence, African Ancestry, and Asthma: A Case-Control Study in Puerto Rican Children.

PubMed

Rosas-Salazar, Christian; Han, Yueh-Ying; Brehm, John M; Forno, Erick; Acosta-Pérez, Edna; Cloutier, Michelle M; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2016-06-01

Exposure to gun violence and African ancestry have been separately associated with increased risk of asthma in Puerto Rican children. The objective of this study was to examine whether African ancestry and gun violence interact on asthma and total IgE in school-aged Puerto Rican children. This is a case-control study of 747 Puerto Rican children aged 9 to 14 years living in San Juan, Puerto Rico (n = 472), and Hartford, Connecticut (n = 275). Exposure to gun violence was defined as the child's report of hearing gunshots more than once, and the percentage of African ancestry was estimated using genome-wide genotypic data. Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. Serum total IgE (IU/mL) was measured in study participants. Multivariate logistic and linear regressions were used for the analysis of asthma and total IgE, respectively. In multivariate analyses, there was a significant interaction between exposure to gun violence and African ancestry on asthma (P = .001) and serum total IgE (P = .04). Among children exposed to gun violence, each quartile increase in the percentage of African ancestry was associated with approximately 45% higher odds of asthma (95% CI, 1.15-1.84; P = .002) and an approximately 19% increment in total IgE (95% , 0.60-40.65, P = .04). In contrast, there was no significant association between African ancestry and asthma or total IgE in children not exposed to gun violence. Our results suggest that exposure to gun violence modifies the estimated effect of African ancestry on asthma and atopy in Puerto Rican children. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Haemoglobin A1c as a screening tool for type 2 diabetes and prediabetes in populations of Swedish and Middle-East ancestry.

PubMed

Hellgren, Margareta; Hjörleifsdottir Steiner, Kristin; Bennet, Louise

2017-08-01

To explore and compare sensitivity and specificity for HbA1c ≥48mmol/mol as a predictor for type 2 diabetes mellitus (T2DM) in two populations with different ethnicity and to examine the predictive value of two levels of HbA1c (≥42mmol/mol, ≥39mmol/mol) for prediabetes in these populations. Four cohorts were examined with an oral glucose tolerance test. (1) The MEDIM Study (n=1991 individuals of Swedish and Iraqi ancestry); (2) The Skaraborg Project (n=1327 individuals of Swedish ancestry); (3) The 4-D study (n=424 individuals of Swedish, Iraqi and Turkish ancestry); (4) The Flemingsberg study (n=212 participants of Turkish ancestry). HbA1c ≥48mmol/mol had a sensitivity for T2DM of 31% and 25% respectively in individuals of Middle-East and Swedish ancestry. The positive and negative predictive value was high in both populations (70.3, 96.4 and 96.2, 97.6 respectively). Using HbA1c ≥42mmol/mol and ≥39mmol/mol as a predictor for prediabetes gave a sensitivity of 17% and 36% in individuals of Middle-East and 15% and 34% in individuals of Swedish ancestry. Even if HbA1c ≥48mmol/mol is a valuable diagnostic tool, it is a blunt and insensitive tool for screening and would exclude most people with T2DM, independent of ancestry and age. HbA1c is an inefficient way to detect individuals with prediabetes. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry

PubMed Central

Huo, Dezheng; Zheng, Yonglan; Ogundiran, Temidayo O.; Adebamowo, Clement; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Simon, Michael S.; John, Esther M.; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M.Cristina; Ambs, Stefan; Niu, Qun; Zhang, Jing; Cox, Nancy J.; Olopade, Olufunmilayo I.

2012-01-01

Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case–control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04–1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10–1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00–1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer. PMID:22357627

Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes

PubMed Central

Florez, J. C.; Price, A. L.; Campbell, D.; Riba, L.; Parra, M. V.; Yu, F.; Duque, C.; Saxena, R.; Gallego, N.; Tello-Ruiz, M.; Franco, L.; Rodríguez-Torres, M.; Villegas, A.; Bedoya, G.; Aguilar-Salinas, C. A.; Tusié-Luna, M. T.; Ruiz-Linares, A.; Reich, D.

2011-01-01

Aims/hypothesis Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. Methods We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Results Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02–0.21], p=2.0 × 10−5) and Colombians (OR 0.26 [0.08–0.78], p=0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19–2.12], p=0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04–0.71], p=0.02). Adjustment for BMI did not change the results. Conclusions/interpretation The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects. PMID:19526211

Genomic African and Native American Ancestry and Chagas Disease: The Bambui (Brazil) Epigen Cohort Study of Aging

PubMed Central

2016-01-01

Background The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown. Methodology/Principal Findings We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual proportions of African, European and Native American genomic ancestry with T. cruzi infection and related outcomes in 1,341 participants (aged ≥ 60 years) of the Bambui (Brazil) population-based cohort study of aging. Potential confounding variables included sociodemographic characteristics and an array of health measures. The prevalence of T. cruzi infection was 37.5% and 56.3% of those infected had a major ECG abnormality. Baseline T. cruzi infection was correlated with higher levels of African and Native American ancestry, which in turn were strongly associated with poor socioeconomic circumstances. Cardiomyopathy in infected persons was not significantly associated with African or Native American ancestry levels. Infected persons with a major ECG abnormality were at increased risk of 15-year mortality relative to their counterparts with no such abnormalities (adjusted hazard ratio = 1.80; 95% 1.41, 2.32). African and Native American ancestry levels had no significant effect modifying this association. Conclusions/Significance Our findings indicate that African and Native American ancestry have no influence on the presence of major ECG abnormalities and had no influence on the ability of an ECG abnormality to predict mortality in older people infected with T. cruzi. In contrast, our results revealed a strong and independent association between prevalent T. cruzi infection and higher levels of African and Native American ancestry. Whether this association is a consequence of genetic background or differential exposure to infection remains to be determined. PMID:27182885

Genomic ancestry, self-reported "color" and quantitative measures of skin pigmentation in Brazilian admixed siblings.

PubMed

Leite, Tailce K M; Fonseca, Rômulo M C; de França, Nanci M; Parra, Esteban J; Pereira, Rinaldo W

2011-01-01

A current concern in genetic epidemiology studies in admixed populations is that population stratification can lead to spurious results. The Brazilian census classifies individuals according to self-reported "color", but several studies have demonstrated that stratifying according to "color" is not a useful strategy to control for population structure, due to the dissociation between self-reported "color" and genomic ancestry. We report the results of a study in a group of Brazilian siblings in which we measured skin pigmentation using a reflectometer, and estimated genomic ancestry using 21 Ancestry Informative Markers (AIMs). Self-reported "color", according to the Brazilian census, was also available for each participant. This made it possible to evaluate the relationship between self-reported "color" and skin pigmentation, self-reported "color" and genomic ancestry, and skin pigmentation and genomic ancestry. We observed that, although there were significant differences between the three "color" groups in genomic ancestry and skin pigmentation, there was considerable dispersion within each group and substantial overlap between groups. We also saw that there was no good agreement between the "color" categories reported by each member of the sibling pair: 30 out of 86 sibling pairs reported different "color", and in some cases, the sibling reporting the darker "color" category had lighter skin pigmentation. Socioeconomic status was significantly associated with self-reported "color" and genomic ancestry in this sample. This and other studies show that subjective classifications based on self-reported "color", such as the one that is used in the Brazilian census, are inadequate to describe the population structure present in recently admixed populations. Finally, we observed that one of the AIMs included in the panel (rs1426654), which is located in the known pigmentation gene SLC24A5, was strongly associated with skin pigmentation in this sample.

Eurasiaplex: a forensic SNP assay for differentiating European and South Asian ancestries.

PubMed

Phillips, C; Freire Aradas, A; Kriegel, A K; Fondevila, M; Bulbul, O; Santos, C; Serrulla Rech, F; Perez Carceles, M D; Carracedo, Á; Schneider, P M; Lareu, M V

2013-05-01

We have selected a set of single nucleotide polymorphisms (SNPs) with the specific aim of differentiating European and South Asian ancestries. The SNPs were combined into a 23-plex SNaPshot primer extension assay: Eurasiaplex, designed to complement an existing 34-plex forensic ancestry test with both marker sets occupying well-spaced genomic positions, enabling their combination as single profile submissions to the Bayesian Snipper forensic ancestry inference system. We analyzed the ability of Eurasiaplex plus 34plex SNPs to assign ancestry to a total 1648 profiles from 16 European, 7 Middle East, 13 Central-South Asian and 21 East Asian populations. Ancestry assignment likelihoods were estimated from Snipper using training sets of five-group data (three Eurasian groups, East Asian and African genotypes) and four-group data (Middle East genotypes removed). Five-group differentiations gave assignment success of 91% for NW European populations, 72% for Middle East populations and 39% for Central-South Asian populations, indicating Middle East individuals are not reliably differentiated from either Europeans or Central-South Asians. Four-group differentiations provided markedly improved assignment success rates of 97% for most continental Europeans tested (excluding Turkish and Adygei at the far eastern edge of Europe) and 95% for Central-South Asians, despite applying a probability threshold for the highest likelihood ratio above '100 times more likely'. As part of the assessment of the sensitivity of Eurasiaplex to analyze challenging forensic material we detail Eurasiaplex and 34-plex SNP typing to infer ancestry of a cranium recovered from the sea, achieving 82% SNP genotype completeness. Therefore, Eurasiaplex provides an informative and forensically robust approach to the differentiation of European and South Asian ancestries amongst Eurasian populations. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Genomic Insights into the Ancestry and Demographic History of South America

PubMed Central

Homburger, Julian R.; Moreno-Estrada, Andrés; Gignoux, Christopher R.; Nelson, Dominic; Sanchez, Elena; Ortiz-Tello, Patricia; Pons-Estel, Bernardo A.; Acevedo-Vasquez, Eduardo; Miranda, Pedro; Langefeld, Carl D.; Gravel, Simon; Alarcón-Riquelme, Marta E.; Bustamante, Carlos D.

2015-01-01

South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina) to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9–14 generations ago), with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform future medical genetic studies in the region. PMID:26636962

Genomic Insights into the Ancestry and Demographic History of South America.

PubMed

Homburger, Julian R; Moreno-Estrada, Andrés; Gignoux, Christopher R; Nelson, Dominic; Sanchez, Elena; Ortiz-Tello, Patricia; Pons-Estel, Bernardo A; Acevedo-Vasquez, Eduardo; Miranda, Pedro; Langefeld, Carl D; Gravel, Simon; Alarcón-Riquelme, Marta E; Bustamante, Carlos D

2015-12-01

South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina) to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9-14 generations ago), with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform future medical genetic studies in the region.

Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection

PubMed Central

Hulgan, Todd; Samuels, David C.; Bush, William; Ellis, Ronald J.; Letendre, Scott L.; Heaton, Robert K.; Franklin, Donald R.; Straub, Peter; Murdock, Deborah G.; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin B.; Marra, Christina M.; McArthur, Justin C.; McCutchan, J. Allen; Morgello, Susan; Simpson, David M.; Grant, Igor; Kallianpur, Asha R.

2015-01-01

Background. Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Methods. CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir. Results. Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm3, 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P < .001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = −0.34; P = .008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval, .04, .63; P = .009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry. Conclusions. In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons. PMID:26129753

Evolutionary Psychology and Intelligence Research Cannot Be Integrated the Way Kanazawa (2010) Suggested

ERIC Educational Resources Information Center

Penke, Lars; Borsboom, Denny; Johnson, Wendy; Kievit, Rogier A.; Ploeger, Annemie; Wicherts, Jelte M.

2011-01-01

This article shares the authors' comments on a record by Kanazawa. Evolutionary psychologists search for human universals, differential psychologists for variation around common human themes. So far, evolutionary psychology and differential psychology seem somewhat disparate and unconnected, although Kanazawa is certainly not the first to attempt…

Origins and evolution of viruses of eukaryotes: The ultimate modularity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koonin, Eugene V., E-mail: koonin@ncbi.nlm.nih.gov; Dolja, Valerian V., E-mail: doljav@science.oregonstate.edu; Krupovic, Mart, E-mail: krupovic@pasteur.fr

2015-05-15

Viruses and other selfish genetic elements are dominant entities in the biosphere, with respect to both physical abundance and genetic diversity. Various selfish elements parasitize on all cellular life forms. The relative abundances of different classes of viruses are dramatically different between prokaryotes and eukaryotes. In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well. Phylogenomic analysis yields tangiblemore » clues for the origins of major classes of eukaryotic viruses and in particular their likely roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA viruses of eukaryotes might have been assembled de novo from genes derived from prokaryotic retroelements and bacteria although a primordial origin of this class of viruses cannot be ruled out. Different groups of double-stranded RNA viruses derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The eukaryotic ssDNA viruses apparently evolved via a fusion of genes from prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses. Different families of eukaryotic dsDNA viruses appear to have originated from specific groups of bacteriophages on at least two independent occasions. Polintons, the largest known eukaryotic transposons, predicted to also form virus particles, most likely, were the evolutionary intermediates between bacterial tectiviruses and several groups of eukaryotic dsDNA viruses including the proposed order “Megavirales” that unites diverse families of large and giant viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to have involved fusion between structural and replicative gene modules derived from different sources along with additional acquisitions of diverse genes. - Highlights: • Eukaryotic virome dramatically differs from the viromes of bacteria and archaea. • Eukaryotic virome is dominated by RNA viruses and retroelements. • All classes of eukaryotic viruses evolved by gene module exchange. • Prokaryotic ancestry is traceable for core gene modules of most eukaryotic viruses. • Evolutionary histories of viruses and transposable elements are tightly linked.« less

Racial differences in venous thromboembolism.

PubMed

Zakai, N A; McClure, L A

2011-10-01

The incidence of venous thrombosis (VTE) varies by race, with African-Americans having over 5-fold greater incidence than Asian-ancestry populations, and an intermediate risk for European and Hispanic populations. Known racial differences in genetic polymorphisms associated with thrombosis do not account for this gradient of risk, nor do known racial variations in environmental risk factors. Data on the incidence of and risk factors for VTE outside of Europe and North America and in non-European ancestry populations are sparse. Common genetic polymorphisms in European-Ancestry populations, such as factor V Leiden and prothrombin G20210A, and environmental risk factors, such as obesity, may account for some of the increased risk in European populations, and high factor VIII, high von Willebrand factor and low protein C levels and increased prevalence of obesity may explain some of the increased risk in African-Americans. The low rates in Asian populations may be partially explained by low clinical suspicion in a perceived low-risk population and lack of access to healthcare in other populations. As risk factors for thrombosis, such as surgery and treatment for cancer, are applicable to more people, as obesity increases in prevalence in the developing world, and as surveillance systems for VTE improve, VTE may increase in previously low-risk populations. While differences in VTE by race due to genetic predisposition will probably always be present, understanding the reasons for racial differences in VTE will help providers develop strategies to minimize VTE in all populations. © 2011 International Society on Thrombosis and Haemostasis.

Accounting for linkage disequilibrium in association analysis of diverse populations.

PubMed

Charles, Bashira A; Shriner, Daniel; Rotimi, Charles N

2014-04-01

The National Human Genome Research Institute's catalog of published genome-wide association studies (GWAS) lists over 10,000 genetic variants collectively associated with over 800 human diseases or traits. Most of these GWAS have been conducted in European-ancestry populations. Findings gleaned from these studies have led to identification of disease-associated loci and biologic pathways involved in disease etiology. In multiple instances, these genomic findings have led to the development of novel medical therapies or evidence for prescribing a given drug as the appropriate treatment for a given individual beyond phenotypic appearances or socially defined constructs of race or ethnicity. Such findings have implications for populations throughout the globe and GWAS are increasingly being conducted in more diverse populations. A major challenge for investigators seeking to follow up genomic findings between diverse populations is discordant patterns of linkage disequilibrium (LD). We provide an overview of common measures of LD and opportunities for their use in novel methods designed to address challenges associated with following up GWAS conducted in European-ancestry populations in African-ancestry populations or, more generally, between populations with discordant LD patterns. We detail the strengths and weaknesses associated with different approaches. We also describe application of these strategies in follow-up studies of populations with concordant LD patterns (replication) or discordant LD patterns (transferability) as well as fine-mapping studies. We review application of these methods to a variety of traits and diseases. © 2014 WILEY PERIODICALS, INC.

"Do You Know Your Language?" How Teachers of Punjabi and Chinese Ancestries Construct Their Family Languages in Their Personal and Professional Lives.

ERIC Educational Resources Information Center

Beynon, June; Ilieva, Roumiana; Dichupa, Marela; Hirji, Shemina

2003-01-01

Focuses on how teachers of minority ancestries construct and represent their family language identities. Drawing on poststructural, postcolonial and sociocultural theory on culture, identity, and language, examined the complex nature of linguistic identities of 25 teachers of Chinese and 20 teachers of Punjabi ancestries. (Author/VWL)