The prosocial personality and its facets: genetic and environmental architecture of mother-reported behavior of 7-year-old twins

PubMed Central

Knafo-Noam, Ariel; Uzefovsky, Florina; Israel, Salomon; Davidov, Maayan; Zahn-Waxler, Caroyln

2015-01-01

Children vary markedly in their tendency to behave prosocially, and recent research has implicated both genetic and environmental factors in this variability. Yet, little is known about the extent to which different aspects of prosociality constitute a single dimension (the prosocial personality), and to the extent they are intercorrelated, whether these aspects share their genetic and environmental origins. As part of the Longitudinal Israeli Study of Twins (LIST), mothers of 183 monozygotic (MZ) and dizygotic (DZ) 7-year-old twin pairs (51.6% male) reported regarding their children’s prosociality using questionnaires. Five prosociality facets (sharing, social concern, kindness, helping, and empathic concern) were identified. All five facets intercorrelated positively (r > 0.39) suggesting a single-factor structure to the data, consistent with the theoretical idea of a single prosociality trait. Higher MZ than DZ twin correlations indicated genetic contributions to each prosociality facet. A common-factor-common-pathway multivariate model estimated high (69%) heritability for the common prosociality factor, with the non-shared environment and error accounting for the remaining variance. For each facet, unique genetic and environmental contributions were identified as well. The results point to the presence of a broad prosociality phenotype, largely affected by genetics; whereas additional genetic and environmental factors contribute to different aspects of prosociality, such as helping and sharing. PMID:25762952

Routes for breaching and protecting genetic privacy

PubMed Central

Erlich, Yaniv; Narayanan, Arvind

2014-01-01

We are entering an era of ubiquitous genetic information for research, clinical care and personal curiosity. Sharing these datasets is vital for progress in biomedical research. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we present an overview of genetic privacy breaching strategies. We outline the principles of each technique, point to the underlying assumptions, and assess its technological complexity and maturation. We then review potential mitigation methods for privacy-preserving dissemination of sensitive data and highlight different cases that are relevant to genetic applications. PMID:24805122

Routes for breaching and protecting genetic privacy.

PubMed

Erlich, Yaniv; Narayanan, Arvind

2014-06-01

We are entering an era of ubiquitous genetic information for research, clinical care and personal curiosity. Sharing these data sets is vital for progress in biomedical research. However, a growing concern is the ability to protect the genetic privacy of the data originators. Here, we present an overview of genetic privacy breaching strategies. We outline the principles of each technique, indicate the underlying assumptions, and assess their technological complexity and maturation. We then review potential mitigation methods for privacy-preserving dissemination of sensitive data and highlight different cases that are relevant to genetic applications.

Environment dominates over host genetics in shaping human gut microbiota.

PubMed

Rothschild, Daphna; Weissbrod, Omer; Barkan, Elad; Kurilshikov, Alexander; Korem, Tal; Zeevi, David; Costea, Paul I; Godneva, Anastasia; Kalka, Iris N; Bar, Noam; Shilo, Smadar; Lador, Dar; Vila, Arnau Vich; Zmora, Niv; Pevsner-Fischer, Meirav; Israeli, David; Kosower, Noa; Malka, Gal; Wolf, Bat Chen; Avnit-Sagi, Tali; Lotan-Pompan, Maya; Weinberger, Adina; Halpern, Zamir; Carmi, Shai; Fu, Jingyuan; Wijmenga, Cisca; Zhernakova, Alexandra; Elinav, Eran; Segal, Eran

2018-03-08

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

Bivariate Linkage Scan for Reading Disability and Attention-Deficit/Hyperactivity Disorder Localizes Pleiotropic Loci

ERIC Educational Resources Information Center

Gayan, J.; Willcutt, E. G.; Fisher, S. E.; Francks, C.; Cardon, L. R.; Olson, R. K.; Pennington, B. F.; Smith, S. D.; Monaco, A. P.; DeFries, J. C.

2005-01-01

Background: There is a growing interest in the study of the genetic origins of comorbidity, a direct consequence of the recent findings of genetic loci that are seemingly linked to more than one disorder. There are several potential causes for these shared regions of linkage, but one possibility is that these loci may harbor genes with manifold…

Neighborhood Disadvantage Alters the Origins of Children's Nonaggressive Conduct Problems

PubMed Central

Burt, S. Alexandra; Klump, Kelly L.; Gorman-Smith, Deborah; Neiderhiser, Jenae M.

2015-01-01

Neighborhood disadvantage plays a pivotal role in child mental health, including child antisocial behavior (e.g., lying, theft, vandalism; assault, cruelty). Prior studies have indicated that shared environmental influences on youth antisocial behavior increase with increasing disadvantage, but have been unable to confirm that these findings persist once various selection confounds are considered. The current study sought to fill this gap in the literature, examining whether and how neighborhood disadvantage alters the genetic and environmental origins of child antisocial behavior. Our sample consisted of 2,054 child twins participating in the Michigan State University Twin Registry, half of whom were oversampled to reside in modestly-to-severely impoverished neighborhoods. We made use of an innovative set of nuclear twin family models, thereby allowing us to disambiguate between, and simultaneously estimate, multiple elements of the shared environment as well as genetic influences. Although there was no evidence that the etiology of aggressive antisocial behavior was moderated by neighborhood disadvantage, the etiology of non-aggressive antisocial behavior shifted dramatically with increasing neighborhood disadvantage. Sibling-level shared environmental influences were estimated to be near zero in the wealthiest neighborhoods, and increased dramatically in the most impoverished neighborhoods. By contrast, both genetic risk and family-level shared environmental transmission were significantly more influential in middle- and upper-class neighborhoods than in impoverished neighborhoods. Such results collectively highlight the profound role that pervasive neighborhood poverty plays in shaping the etiology of child non-aggressive antisocial behavior. Implications are discussed. PMID:27347447

Speech sound disorder influenced by a locus in 15q14 region.

PubMed

Stein, Catherine M; Millard, Christopher; Kluge, Amy; Miscimarra, Lara E; Cartier, Kevin C; Freebairn, Lisa A; Hansen, Amy J; Shriberg, Lawrence D; Taylor, H Gerry; Lewis, Barbara A; Iyengar, Sudha K

2006-11-01

Despite a growing body of evidence indicating that speech sound disorder (SSD) has an underlying genetic etiology, researchers have not yet identified specific genes predisposing to this condition. The speech and language deficits associated with SSD are shared with several other disorders, including dyslexia, autism, Prader-Willi Syndrome (PWS), and Angelman's Syndrome (AS), raising the possibility of gene sharing. Furthermore, we previously demonstrated that dyslexia and SSD share genetic susceptibility loci. The present study assesses the hypothesis that SSD also shares susceptibility loci with autism and PWS. To test this hypothesis, we examined linkage between SSD phenotypes and microsatellite markers on the chromosome 15q14-21 region, which has been associated with autism, PWS/AS, and dyslexia. Using SSD as the phenotype, we replicated linkage to the 15q14 region (P=0.004). Further modeling revealed that this locus influenced oral-motor function, articulation and phonological memory, and that linkage at D15S118 was potentially influenced by a parent-of-origin effect (LOD score increase from 0.97 to 2.17, P=0.0633). These results suggest shared genetic determinants in this chromosomal region for SSD, autism, and PWS/AS.

Genetic and Environmental Influences on Frontal EEG Asymmetry and Alpha Power in 9–10 Year Old Twins

PubMed Central

Gao, Yu; Tuvblad, Catherine; Raine, Adrian; Lozano, Dora I.; Baker, Laura A.

2008-01-01

Modest genetic influences on frontal EEG asymmetry have been found in adults, but little is known about its genetic origins in children. Resting frontal asymmetry and alpha power were examined in 951 9–10-year-old twins. Results showed that in both males and females: (1) a modest but significant amount of variance in frontal asymmetry was accounted for by genetic factors (11–27%) with the remainder accounted for by non-shared environmental influences, and (2) alpha power were highly heritable, with 70–85% of the variance accounted for by genetic factors. Results suggest that the genetic architecture of frontal asymmetry and alpha power in late childhood are similar to that in adulthood and that the high non-shared environmental influences on frontal asymmetry may reflect environmentally-influenced individual differences in the maturation of frontal cortex as well as state-dependent influences on specific measurements. PMID:19386046

Genetic and environmental influences on thin-ideal internalization.

PubMed

Suisman, Jessica L; O'Connor, Shannon M; Sperry, Steffanie; Thompson, J Kevin; Keel, Pamela K; Burt, S Alexandra; Neale, Michael; Boker, Steven; Sisk, Cheryl; Klump, Kelly L

2012-12-01

Current research on the etiology of thin-ideal internalization focuses on psychosocial influences (e.g., media exposure). The possibility that genetic influences also account for variance in thin-ideal internalization has never been directly examined. This study used a twin design to estimate genetic effects on thin-ideal internalization and examine if environmental influences are primarily shared or nonshared in origin. Participants were 343 postpubertal female twins (ages: 12-22 years; M = 17.61) from the Michigan State University Twin Registry. Thin-ideal internalization was assessed using the Sociocultural Attitudes toward Appearance Questionnaire-3. Twin modeling suggested significant additive genetic and nonshared environmental influences on thin-ideal internalization. Shared environmental influences were small and non-significant. Although prior research focused on psychosocial factors, genetic influences on thin-ideal internalization were significant and moderate in magnitude. Research is needed to investigate possible interplay between genetic and nonshared environmental factors in the development of thin-ideal internalization. Copyright © 2012 Wiley Periodicals, Inc.

Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

PubMed

Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

2015-03-01

The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research.

Replication of a Gene-Environment Interaction via Multimodel Inference: Additive-Genetic Variance in Adolescents’ General Cognitive Ability Increases with Family-of-Origin Socioeconomic Status

PubMed Central

Kirkpatrick, Robert M.; McGue, Matt; Iacono, William G.

2015-01-01

The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES—an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

DOE PAGES

McCluskey, Kevin; Baker, Scott E.

2017-02-17

As model organisms filamentous fungi have been important since the beginning of modern biological inquiry and have benefitted from open data since the earliest genetic maps were shared. From early origins in simple Mendelian genetics of mating types, parasexual genetics of colony colour, and the foundational demonstration of the segregation of a nutritional requirement, the contribution of research systems utilising filamentous fungi has spanned the biochemical genetics era, through the molecular genetics era, and now are at the very foundation of diverse omics approaches to research and development. Fungal model organisms have come from most major taxonomic groups although Ascomycetemore » filamentous fungi have seen the most major sustained effort. In addition to the published material about filamentous fungi, shared molecular tools have found application in every area of fungal biology. Likewise, shared data has contributed to the success of model systems. Furthermore, the scale of data supporting research with filamentous fungi has grown by 10 to 12 orders of magnitude. From genetic to molecular maps, expression databases, and finally genome resources, the open and collaborative nature of the research communities has assured that the rising tide of data has lifted all of the research systems together.« less

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

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

McCluskey, Kevin; Baker, Scott E.

As model organisms filamentous fungi have been important since the beginning of modern biological inquiry and have benefitted from open data since the earliest genetic maps were shared. From early origins in simple Mendelian genetics of mating types, parasexual genetics of colony colour, and the foundational demonstration of the segregation of a nutritional requirement, the contribution of research systems utilising filamentous fungi has spanned the biochemical genetics era, through the molecular genetics era, and now are at the very foundation of diverse omics approaches to research and development. Fungal model organisms have come from most major taxonomic groups although Ascomycetemore » filamentous fungi have seen the most major sustained effort. In addition to the published material about filamentous fungi, shared molecular tools have found application in every area of fungal biology. Likewise, shared data has contributed to the success of model systems. Furthermore, the scale of data supporting research with filamentous fungi has grown by 10 to 12 orders of magnitude. From genetic to molecular maps, expression databases, and finally genome resources, the open and collaborative nature of the research communities has assured that the rising tide of data has lifted all of the research systems together.« less

No evidence from genome-wide data of a Khazar origin for the Ashkenazi Jews.

PubMed

Behar, Doron M; Metspalu, Mait; Baran, Yael; Kopelman, Naama M; Yunusbayev, Bayazit; Gladstein, Ariella; Tzur, Shay; Sahakyan, Hovhannes; Bahmanimehr, Ardeshir; Yepiskoposyan, Levon; Tambets, Kristina; Khusnutdinova, Elza K; Kushniarevich, Alena; Balanovsky, Oleg; Balanovsky, Elena; Kovacevic, Lejla; Marjanovic, Damir; Mihailov, Evelin; Kouvatsi, Anastasia; Triantaphyllidis, Costas; King, Roy J; Semino, Ornella; Torroni, Antonio; Hammer, Michael F; Metspalu, Ene; Skorecki, Karl; Rosset, Saharon; Halperin, Eran; Villems, Richard; Rosenberg, Noah A

2013-12-01

The origin and history of the Ashkenazi Jewish population have long been of great interest, and advances in high-throughput genetic analysis have recently provided a new approach for investigating these topics. We and others have argued on the basis of genome-wide data that the Ashkenazi Jewish population derives its ancestry from a combination of sources tracing to both Europe and the Middle East. It has been claimed, however, through a reanalysis of some of our data, that a large part of the ancestry of the Ashkenazi population originates with the Khazars, a Turkic-speaking group that lived to the north of the Caucasus region ~1,000 years ago. Because the Khazar population has left no obvious modern descendants that could enable a clear test for a contribution to Ashkenazi Jewish ancestry, the Khazar hypothesis has been difficult to examine using genetics. Furthermore, because only limited genetic data have been available from the Caucasus region, and because these data have been concentrated in populations that are genetically close to populations from the Middle East, the attribution of any signal of Ashkenazi-Caucasus genetic similarity to Khazar ancestry rather than shared ancestral Middle Eastern ancestry has been problematic. Here, through integration of genotypes from newly collected samples with data from several of our past studies, we have assembled the largest data set available to date for assessment of Ashkenazi Jewish genetic origins. This data set contains genome-wide single-nucleotide polymorphisms in 1,774 samples from 106 Jewish and non-Jewish populations that span the possible regions of potential Ashkenazi ancestry: Europe, the Middle East, and the region historically associated with the Khazar Khaganate. The data set includes 261 samples from 15 populations from the Caucasus region and the region directly to its north, samples that have not previously been included alongside Ashkenazi Jewish samples in genomic studies. Employing a variety of standard techniques for the analysis of population-genetic structure, we found that Ashkenazi Jews share the greatest genetic ancestry with other Jewish populations and, among non-Jewish populations, with groups from Europe and the Middle East. No particular similarity of Ashkenazi Jews to populations from the Caucasus is evident, particularly populations that most closely represent the Khazar region. Thus, analysis of Ashkenazi Jews together with a large sample from the region of the Khazar Khaganate corroborates the earlier results that Ashkenazi Jews derive their ancestry primarily from populations of the Middle East and Europe, that they possess considerable shared ancestry with other Jewish populations, and that there is no indication of a significant genetic contribution either from within or from north of the Caucasus region. Copyright © 2014 Wayne State University Press, Detroit, Michigan 48201-1309.

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.

Origin and diversity of an underutilized fruit tree crop, cempedak (Artocarpus integer, Moraceae).

PubMed

Wang, Maria M H; Gardner, Elliot M; Chung, Richard C K; Chew, Ming Yee; Milan, Abd Rahman; Pereira, Joan T; Zerega, Nyree J C

2018-06-06

Underutilized crops and their wild relatives are important resources for crop improvement and food security. Cempedak [Artocarpus integer (Thunb). Merr.] is a significant crop in Malaysia but underutilized elsewhere. Here we performed molecular characterization of cempedak and its putative wild relative bangkong (Artocarpus integer (Thunb). Merr. var. silvestris Corner) to address questions regarding the origin and diversity of cempedak. Using data from 12 microsatellite loci, we assessed the genetic diversity and genetic/geographic structure for 353 cempedak and 175 bangkong accessions from Malaysia and neighboring countries and employed clonal analysis to characterize cempedak cultivars. We conducted haplotype network analyses on the trnH-psbA region in a subset of these samples. We also analyzed key vegetative characters that reportedly differentiate cempedak and bangkong. We show that cempedak and bangkong are sister taxa and distinct genetically and morphologically, but the directionality of domestication origin is unclear. Genetic diversity was generally higher in bangkong than in cempedak. We found a distinct genetic cluster for cempedak from Borneo as compared to cempedak from Peninsular Malaysia. Finally, cempedak cultivars with the same names did not always share the same genetic fingerprint. Cempedak origins are complex, with likely admixture and hybridization with bangkong, warranting further investigation. We provide a baseline of genetic diversity of cempedak and bangkong in Malaysia and found that germplasm collections in Malaysia represent diverse coverage of the four cempedak genetic clusters detected. © 2018 Botanical Society of America.

Assembling networks of microbial genomes using linear programming.

PubMed

Holloway, Catherine; Beiko, Robert G

2010-11-20

Microbial genomes exhibit complex sets of genetic affinities due to lateral genetic transfer. Assessing the relative contributions of parent-to-offspring inheritance and gene sharing is a vital step in understanding the evolutionary origins and modern-day function of an organism, but recovering and showing these relationships is a challenging problem. We have developed a new approach that uses linear programming to find between-genome relationships, by treating tables of genetic affinities (here, represented by transformed BLAST e-values) as an optimization problem. Validation trials on simulated data demonstrate the effectiveness of the approach in recovering and representing vertical and lateral relationships among genomes. Application of the technique to a set comprising Aquifex aeolicus and 75 other thermophiles showed an important role for large genomes as 'hubs' in the gene sharing network, and suggested that genes are preferentially shared between organisms with similar optimal growth temperatures. We were also able to discover distinct and common genetic contributors to each sequenced representative of genus Pseudomonas. The linear programming approach we have developed can serve as an effective inference tool in its own right, and can be an efficient first step in a more-intensive phylogenomic analysis.

Genetic Relatedness of WNIN and WNIN/Ob with Major Rat Strains in Biomedical Research.

PubMed

Battula, Kiran Kumar; Nappanveettil, Giridharan; Nakanishi, Satoshi; Kuramoto, Takashi; Friedman, Jeffry M; Kalashikam, Rajender Rao

2015-06-01

WNIN (Wistar/NIN) is an inbred rat strain maintained at National Institute of Nutrition (NIN) for more than 90 years, and WNIN/Ob is an obese mutant originated from it. To determine their genetic relatedness with major rat strains in biomedical research, they were genotyped at various marker loci. The recently identified markers for albino and hooded mutations which clustered all the known albino rats into a single lineage also included WNIN and WNIN/Ob rats. Genotyping using microsatellite DNA markers and phylogenetic analysis with 49 different rat strains suggested that WNIN shares a common ancestor with many Wistar originated strains. Fst estimates and Fischer's exact test suggest that WNIN rats differed significantly from all other strains tested. WNIN/Ob though shows hyper-leptinemia, like Zucker fatty rat, did not share the Zucker fatty rat mutation. The above analyses suggest WNIN as a highly differentiated rat strain and WNIN/Ob a novel obese mutant evolved from it.

Genetic drift and the population history of the Irish travellers.

PubMed

Relethford, John H; Crawford, Michael H

2013-02-01

The Irish Travellers are an itinerant group in Ireland that has been socially isolated. Two hypotheses have been proposed concerning the genetic origin of the Travellers: (1) they are genetically related to Roma populations in Europe that share a nomadic lifestyle or (2) they are of Irish origin, and genetic differences from the rest of Ireland reflect genetic drift. These hypotheses were tested using data on 33 alleles from 12 red blood cell polymorphism loci. Comparison with other European, Roma, and Indian populations shows that the Travellers are genetically distinct from the Roma and Indian populations and most genetically similar to Ireland, in agreement with earlier genetic analyses of the Travellers. However, the Travellers are still genetically distinct from other Irish populations, which could reflect some external gene flow and/or the action of genetic drift in a small group that was descended from a small number of founders. In order to test the drift hypothesis, we analyzed genetic distances comparing the Travellers to four geographic regions in Ireland. These distances were then compared with adjusted distances that account for differential genetic drift using a method developed by Relethford (Hum Biol 68 (1996) 29-44). The unadjusted distances show the genetic distinctiveness of the Travellers. After adjustment for the expected effects of genetic drift, the Travellers are equidistant from the other Irish samples, showing their Irish origins and population history. The observed genetic differences are thus a reflection of genetic drift, and there is no evidence of any external gene flow. Copyright © 2012 Wiley Periodicals, Inc.

Are there shared environmental influences on attention-deficit/hyperactivity disorder? Reply to Wood, Buitelaar, Rijsdijk, Asherson, and Kuntsi [corrected] (2010).

PubMed

Burt, S Alexandra

2010-05-01

A recent large-scale meta-analysis of twin and adoption studies indicated that shared environmental influences make important contributions to most forms of child and adolescent psychopathology (Burt, 2009b). The sole exception to this robust pattern of results was observed for attention-deficit/hyperactivity disorder (ADHD), which appeared to be largely genetic (and particularly nonadditive genetic) in origin, with no observable influence of the shared environment. The central thesis of Wood, Buitelaar, Rijsdijk, Asherson, and Kuntsi [corrected] (2010) is that, contrary to these findings, shared environmental influences are important for ADHD. As evidence for this thesis, Wood et al. presented a summary of prior twin studies, followed by a discussion of 4 methodological issues that may account for my findings in Burt (2009b). I argue that, although the methodological concerns raised by Wood et al. are very important, they do not undermine my earlier results (Burt, 2009b). I close with a discussion of 2 issues that may allow for some shared environmental influences on ADHD. (c) 2010 APA, all rights reserved.

Southeast Asian origins of five Hill Tribe populations and correlation of genetic to linguistic relationships inferred with genome-wide SNP data

PubMed Central

Listman, JB; Malison, RT; Sanichwankul, K; Ittiwut, C; Mutirangura, A; Gelernter, J

2010-01-01

In Thailand, the term Hill Tribe is used to describe populations whose members traditionally practice slash and burn agriculture and reside in the mountains. These tribes are thought to have migrated throughout Asia for up to 5,000 years, including migrations through Southern China and/or Southeast Asia. There have been continuous migrations southward from China into Thailand for approximately the past thousand years and the present geographic range of any given tribe straddles multiple political borders. As none of these populations have autochthonous scripts, written histories have until recently, been externally produced. Northern Asian, Tibetan, and Siberian origins of Hill Tribes have been proposed. All purport endogamy and have non-mutually intelligible languages. In order to test hypotheses regarding the geographic origins of these populations, relatedness and migrations among them and neighboring populations, and whether their genetic relationships correspond with their linguistic relationships, we analyzed 2445 genome-wide SNP markers in 118 individuals from five Thai Hill Tribe populations (Akha, Hmong, Karen, Lahu, and Lisu), 90 individuals from majority Thai populations, and 826 individuals from Asian and Oceanean HGDP and HapMap populations using a Bayesian clustering method. Considering these results within the context of results of recent large-scale studies of Asian geographic genetic variation allows us to infer a shared Southeast Asian origin of these five Hill Tribe populations as well ancestry components that distinguish among them seen in successive levels of clustering. In addition, the inferred level of shared ancestry among the Hill Tribes corresponds well to relationships among their languages. PMID:20979205

Southeast Asian origins of five Hill Tribe populations and correlation of genetic to linguistic relationships inferred with genome-wide SNP data.

PubMed

Listman, J B; Malison, R T; Sanichwankul, K; Ittiwut, C; Mutirangura, A; Gelernter, J

2011-02-01

In Thailand, the term Hill Tribe is used to describe populations whose members traditionally practice slash and burn agriculture and reside in the mountains. These tribes are thought to have migrated throughout Asia for up to 5,000 years, including migrations through Southern China and/or Southeast Asia. There have been continuous migrations southward from China into Thailand for approximately the past thousand years and the present geographic range of any given tribe straddles multiple political borders. As none of these populations have autochthonous scripts, written histories have until recently, been externally produced. Northern Asian, Tibetan, and Siberian origins of Hill Tribes have been proposed. All purport endogamy and have nonmutually intelligible languages. To test hypotheses regarding the geographic origins of these populations, relatedness and migrations among them and neighboring populations, and whether their genetic relationships correspond with their linguistic relationships, we analyzed 2,445 genome-wide SNP markers in 118 individuals from five Thai Hill Tribe populations (Akha, Hmong, Karen, Lahu, and Lisu), 90 individuals from majority Thai populations, and 826 individuals from Asian and Oceanean HGDP and HapMap populations using a Bayesian clustering method. Considering these results within the context of results ofrecent large-scale studies of Asian geographic genetic variation allows us to infer a shared Southeast Asian origin of these five Hill Tribe populations as well ancestry components that distinguish among them seen in successive levels of clustering. In addition, the inferred level of shared ancestry among the Hill Tribes corresponds well to relationships among their languages. 2010 Wiley-Liss, Inc.

What underlies the diversity of brain tumors?

PubMed Central

Swartling, Fredrik J.; Hede, Sanna-Maria; Weiss, William A.

2012-01-01

Glioma and medulloblastoma represent the most commonly occurring malignant brain tumors in adults and in children respectively. Recent genomic and transcriptional approaches present a complex group of diseases, and delineate a number of molecular subgroups within tumors that share a common histopathology. Differences in cells of origin, regional niches, developmental timing and genetic events all contribute to this heterogeneity. In an attempt to recapitulate the diversity of brain tumors, an increasing array of genetically engineered mouse models (GEMMs) has been developed. These models often utilize promoters and genetic drivers from normal brain development, and can provide insight into specific cells from which these tumors originate. GEMMs show promise in both developmental biology and developmental therapeutics. This review describes numerous murine brain tumor models in the context of normal brain development, and the potential for these animals to impact brain tumor research. PMID:23085857

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

PubMed

Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

2018-03-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

PubMed Central

Gray, Alan; Neyton, Lucile P. A.; Barrett, Jeffrey; Stahl, Eli A.; Tenesa, Albert; Andersson, Robin; Brown, J. Ben; Faulkner, Geoffrey J.; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Kawaji, Hideya; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A.; Hacohen, Nir; Freeman, Thomas C.; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Hume, David A.

2018-01-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits. PMID:29494619

Lederberg on bacterial recombination, Haldane, and cold war genetics: an interview.

PubMed

Sarkar, Sahotra

2014-01-01

Joshua Lederberg (1925-2008), was one of the pioneers of molecular genetics perhaps best known for his discovery of genetic recombination in bacteria which earned him a Nobel Prize in 1958 (shared with George Beadle and Edward Tatum). Lederberg's interests were broad including the origin of life, exobiology (a term that he coined) and emerging diseases and artificial intelligence in his, later years. This article contains the transcription of an interview in excerpts, docu- menting the interactions between Lederberg and fellow biologist J.B.S. Haldane wlich lasted from 1946 until Haldane's death in Kolkata (then Calcutta) in 1964.

The genetic evidence for human origin of Jivaroan shrunken heads in collections from the Polish museums.

PubMed

Piniewska, Danuta; Sanak, Marek; Wojtas, Marta; Polanska, Nina

2017-05-01

Advances in forensic identification using molecular genetics are helpful in resolving some historical mysteries. The aim of this study was to confirm the authenticity of shrunken-head artifacts exhibited by two Polish museums. Shrunken heads, known as tsantsas, were headhunting trophies of South American Indians (Jivaroan). A special preparation preserved their hair and facial appearance. However, it was quite common to offer counterfeit shrunken heads of sloths or monkeys to collectors of curiosities. We sampled small skin specimens of four shrunken-head skin from the museum collection from Warsaw and Krakow, Poland. Following genomic DNA isolation, highly polymorphic short tandem repeats were genotyped using a commercial chemistry and DNA sequencing analyzer. Haplogroups of human Y chromosome were identified. We obtained an informative genetic profile of genomic short tandem repeats from all the samples of shrunken heads. Moreover, amplification of amelogenin loci allowed for sex determination. All four studied shrunken heads were of human origin. In two ones, a shared Y-chromosome haplogroup Q characteristic for Indigenous Americans was detected. Another artifact was counterfeited because Y-chromosome haplogroup I2 was found, characteristic for the Southeastern European origin. Commercial genetic methods of identification can be applied successfully in studies on the origin and authenticity of some unusual collection items.

Origins of domestic dog in southern East Asia is supported by analysis of Y-chromosome DNA.

PubMed

Ding, Z-L; Oskarsson, M; Ardalan, A; Angleby, H; Dahlgren, L-G; Tepeli, C; Kirkness, E; Savolainen, P; Zhang, Y-P

2012-05-01

Global mitochondrial DNA (mtDNA) data indicates that the dog originates from domestication of wolf in Asia South of Yangtze River (ASY), with minor genetic contributions from dog-wolf hybridisation elsewhere. Archaeological data and autosomal single nucleotide polymorphism data have instead suggested that dogs originate from Europe and/or South West Asia but, because these datasets lack data from ASY, evidence pointing to ASY may have been overlooked. Analyses of additional markers for global datasets, including ASY, are therefore necessary to test if mtDNA phylogeography reflects the actual dog history and not merely stochastic events or selection. Here, we analyse 14,437 bp of Y-chromosome DNA sequence in 151 dogs sampled worldwide. We found 28 haplotypes distributed in five haplogroups. Two haplogroups were universally shared and included three haplotypes carried by 46% of all dogs, but two other haplogroups were primarily restricted to East Asia. Highest genetic diversity and virtually complete phylogenetic coverage was found within ASY. The 151 dogs were estimated to originate from 13-24 wolf founders, but there was no indication of post-domestication dog-wolf hybridisations. Thus, Y-chromosome and mtDNA data give strikingly similar pictures of dog phylogeography, most importantly that roughly 50% of the gene pools are shared universally but only ASY has nearly the full range of genetic diversity, such that the gene pools in all other regions may derive from ASY. This corroborates that ASY was the principal, and possibly sole region of wolf domestication, that a large number of wolves were domesticated, and that subsequent dog-wolf hybridisation contributed modestly to the dog gene pool.

Origins of domestic dog in Southern East Asia is supported by analysis of Y-chromosome DNA

PubMed Central

Ding, Z-L; Oskarsson, M; Ardalan, A; Angleby, H; Dahlgren, L-G; Tepeli, C; Kirkness, E; Savolainen, P; Zhang, Y-P

2012-01-01

Global mitochondrial DNA (mtDNA) data indicates that the dog originates from domestication of wolf in Asia South of Yangtze River (ASY), with minor genetic contributions from dog–wolf hybridisation elsewhere. Archaeological data and autosomal single nucleotide polymorphism data have instead suggested that dogs originate from Europe and/or South West Asia but, because these datasets lack data from ASY, evidence pointing to ASY may have been overlooked. Analyses of additional markers for global datasets, including ASY, are therefore necessary to test if mtDNA phylogeography reflects the actual dog history and not merely stochastic events or selection. Here, we analyse 14 437 bp of Y-chromosome DNA sequence in 151 dogs sampled worldwide. We found 28 haplotypes distributed in five haplogroups. Two haplogroups were universally shared and included three haplotypes carried by 46% of all dogs, but two other haplogroups were primarily restricted to East Asia. Highest genetic diversity and virtually complete phylogenetic coverage was found within ASY. The 151 dogs were estimated to originate from 13–24 wolf founders, but there was no indication of post-domestication dog–wolf hybridisations. Thus, Y-chromosome and mtDNA data give strikingly similar pictures of dog phylogeography, most importantly that roughly 50% of the gene pools are shared universally but only ASY has nearly the full range of genetic diversity, such that the gene pools in all other regions may derive from ASY. This corroborates that ASY was the principal, and possibly sole region of wolf domestication, that a large number of wolves were domesticated, and that subsequent dog–wolf hybridisation contributed modestly to the dog gene pool. PMID:22108628

Genetic and environmental influences on adolescent rumination and its association with depressive symptoms.

PubMed

Chen, Jie; Li, Xinying

2013-11-01

Rumination is an important cognitive vulnerability for adolescent and adult depression. However, little is known about the aetiological origins of rumination, as well as its association with depression. Adolescent rumination (self-report) and depressive symptoms (self- and parent-report) were assessed in 674 pairs of same-gender Chinese adolescent twins (11-17 years of age). Females accounted for 53.7 % of the sample. There were significant correlations between self-reported rumination and self-reported depression (r = 0.41), as well as parent-reported adolescent depression (r = 0.22). Genetic influences were significant and modest on all three measures, ranging from 24 % to 42 %. The three measures were also significantly influenced by shared environment, ranging from 20 % to 28 %, and non-shared environmental factors, ranging from 30 % to 56 %. Moreover, the genetic correlations between rumination and depression were significant (within-rater: r(g) = 0.99; cross-rater: r(g) = 0.59) and largely accounted for the phenotypic correlations (within-rater: 68 %; cross-rater: 77 %), while non-shared environmental correlations were also significant (within-rater: r(e) = 0.26; cross-rater: r(e) = 0.12) and accounted for the remainder of the phenotypic correlations (within-rater: 32 %; cross-rater: 23 %). The shared environmental correlations were non-significant. No significant gender and age differences were found in aetiological models. These findings suggest that rumination may be an endophenotype reflecting genetic risk for depression.

Global diversity and distribution of three necrotrophic effectors in Phaeosphaeria nodorum and related species

USDA-ARS?s Scientific Manuscript database

Population genetic and phylogenetic studies showed that P. nodorum is a member of a species-complex that likely shares its center of origin with wheat. We examined the evolutionary history of three known necrotrophic effectors (NEs) produced by Phaeosphaeria nodorum and compared it to neutral loci. ...

Heritable Variation, With Little or No Maternal Effect, Accounts for Recurrence Risk to Autism Spectrum Disorder in Sweden.

PubMed

Yip, Benjamin Hon Kei; Bai, Dan; Mahjani, Behrang; Klei, Lambertus; Pawitan, Yudi; Hultman, Christina M; Grice, Dorothy E; Roeder, Kathryn; Buxbaum, Joseph D; Devlin, Bernie; Reichenberg, Abraham; Sandin, Sven

2018-04-01

Autism spectrum disorder (ASD) has both genetic and environmental origins, including potentially maternal effects. Maternal effects describe the association of one or more maternal phenotypes with liability to ASD in progeny that are independent of maternally transmitted risk alleles. While maternal effects could play an important role, consistent with association to maternal traits such as immune status, no study has estimated maternal, additive genetic, and environmental effects in ASD. Using a population-based sample consisting of all children born in Sweden from 1998 to 2007 and their relatives, we fitted statistical models to family data to estimate the variance in ASD liability originating from maternal, additive genetic, and shared environmental effects. We calculated sibling and cousin family recurrence risk ratio as a direct measure of familial, genetic, and environmental risk factors and repeated the calculations on diagnostic subgroups, specifically autistic disorder (AD) and spectrum disorder (SD), which included Asperger's syndrome and/or pervasive developmental disorder not otherwise specified. The sample consisted of 776,212 children of whom 11,231 had a diagnosis of ASD: 4554 with AD, 6677 with SD. We found support for large additive genetic contribution to liability; heritability (95% confidence interval [CI]) was estimated to 84.8% (95% CI: 73.1-87.3) for ASD, 79.6% (95% CI: 61.2-85.1) for AD, and 76.4% (95% CI: 63.0-82.5) for SD. There was modest, if any, contribution of maternal effects to liability for ASD, including subtypes AD and SD, and there was no support for shared environmental effects. These results show liability to ASD arises largely from additive genetic variation. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Substantial population structure of Plasmodium vivax in Thailand facilitates identification of the sources of residual transmission.

PubMed

Kittichai, Veerayuth; Koepfli, Cristian; Nguitragool, Wang; Sattabongkot, Jetsumon; Cui, Liwang

2017-10-01

Plasmodium vivax transmission in Thailand has been substantially reduced over the past 10 years, yet it remains highly endemic along international borders. Understanding the genetic relationship of residual parasite populations can help track the origins of the parasites that are reintroduced into malaria-free regions within the country. A total of 127 P. vivax isolates were genotyped from two western provinces (Tak and Kanchanaburi) and one eastern province (Ubon Ratchathani) of Thailand using 10 microsatellite markers. Genetic diversity was high, but recent clonal expansion was detected in all three provinces. Substantial population structure and genetic differentiation of parasites among provinces suggest limited gene flow among these sites. There was no haplotype sharing among the three sites, and a reduced panel of four microsatellite markers was sufficient to assign the parasites to their provincial origins. Significant parasite genetic differentiation between provinces shows successful interruption of parasite spread within Thailand, but high diversity along international borders implies a substantial parasite population size in these regions. The provincial origin of P. vivax cases can be reliably determined by genotyping four microsatellite markers, which should be useful for monitoring parasite reintroduction after malaria elimination.

Y-STR Haplogroup Diversity in the Jat Population Reveals Several Different Ancient Origins.

PubMed

Mahal, David G; Matsoukas, Ianis G

2017-01-01

The Jats represent a large ethnic community that has inhabited the northwest region of India and Pakistan for several thousand years. It is estimated the community has a population of over 123 million people. Many historians and academics have asserted that the Jats are descendants of Aryans, Scythians, or other ancient people that arrived and lived in northern India at one time. Essentially, the specific origin of these people has remained a matter of contention for a long time. This study demonstrated that the origins of Jats can be clarified by identifying their Y-chromosome haplogroups and tracing their genetic markers on the Y-DNA haplogroup tree. A sample of 302 Y-chromosome haplotypes of Jats in India and Pakistan was analyzed. The results showed that the sample population had several different lines of ancestry and emerged from at least nine different geographical regions of the world. It also became evident that the Jats did not have a unique set of genes, but shared an underlying genetic unity with several other ethnic communities in the Indian subcontinent. A startling new assessment of the genetic ancient origins of these people was revealed with DNA science.

Inferring modes of colonization for pest species using heterozygosity comparisons and a shared-allele test.

PubMed

Sved, J A; Yu, H; Dominiak, B; Gilchrist, A S

2003-02-01

Long-range dispersal of a species may involve either a single long-distance movement from a core population or spreading via unobserved intermediate populations. Where the new populations originate as small propagules, genetic drift may be extreme and gene frequency or assignment methods may not prove useful in determining the relation between the core population and outbreak samples. We describe computationally simple resampling methods for use in this situation to distinguish between the different modes of dispersal. First, estimates of heterozygosity can be used to test for direct sampling from the core population and to estimate the effective size of intermediate populations. Second, a test of sharing of alleles, particularly rare alleles, can show whether outbreaks are related to each other rather than arriving as independent samples from the core population. The shared-allele statistic also serves as a genetic distance measure that is appropriate for small samples. These methods were applied to data on a fruit fly pest species, Bactrocera tryoni, which is quarantined from some horticultural areas in Australia. We concluded that the outbreaks in the quarantine zone came from a heterogeneous set of genetically differentiated populations, possibly ones that overwinter in the vicinity of the quarantine zone.

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

Population genetics structure of glyphosate-resistant Johnsongrass (Sorghum halepense L. Pers) does not support a single origin of the resistance

PubMed Central

Fernández, Luis; de Haro, Luis Alejandro; Distefano, Ana J; Carolina Martínez, Maria; Lía, Verónica; Papa, Juan C; Olea, Ignacio; Tosto, Daniela; Esteban Hopp, Horacio

2013-01-01

Single sequence repeats (SSR) developed for Sorghum bicolor were used to characterize the genetic distance of 46 different Sorghum halepense (Johnsongrass) accessions from Argentina some of which have evolved toward glyphosate resistance. Since Johnsongrass is an allotetraploid and only one subgenome is homologous to cultivated sorghum, some SSR loci amplified up to two alleles while others (presumably more conserved loci) amplified up to four alleles. Twelve SSR providing information of 24 loci representative of Johnsongrass genome were selected for genetic distance characterization. All of them were highly polymorphic, which was evidenced by the number of different alleles found in the samples studied, in some of them up to 20. UPGMA and Mantel analysis showed that Johnsongrass glyphosate-resistant accessions that belong to different geographic regions do not share similar genetic backgrounds. In contrast, they show closer similarity to their neighboring susceptible counterparts. Discriminant Analysis of Principal Components using the clusters identified by K-means support the lack of a clear pattern of association among samples and resistance status or province of origin. Consequently, these results do not support a single genetic origin of glyphosate resistance. Nucleotide sequencing of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) encoding gene from glyphosate-resistant and susceptible accessions collected from different geographic origins showed that none presented expected mutations in aminoacid positions 101 and 106 which are diagnostic of target-site resistance mechanism. PMID:24223277

Asymmetry in scientific method and limits to cross-disciplinary dialogue: toward a shared language and science policy in pharmacogenomics and human disease genetics.

PubMed

Ozdemir, Vural; Williams-Jones, Bryn; Graham, Janice E; Preskorn, Sheldon H; Gripeos, Dimitrios; Glatt, Stephen J; Friis, Robert H; Reist, Christopher; Szabo, Sandor; Lohr, James B; Someya, Toshiyuki

2007-04-01

Pharmacogenomics is a hybrid field of experimental science at the intersection of human disease genetics and clinical pharmacology sharing applications of the new genomic technologies. But this hybrid field is not yet stable or fully integrated, nor is science policy in pharmacogenomics fully equipped to resolve the challenges of this emerging hybrid field. The disciplines of human disease genetics and clinical pharmacology contain significant differences in their scientific practices. Whereas clinical pharmacology originates as an experimental science, human disease genetics is primarily observational in nature. The result is a significant asymmetry in scientific method that can differentially impact the degree to which gene-environment interactions are discerned and, by extension, the study sample size required in each discipline. Because the number of subjects enrolled in observational genetic studies of diseases is characteristically viewed as an important criterion of scientific validity and reliability, failure to recognize discipline-specific requirements for sample size may lead to inappropriate dismissal or silencing of meritorious, although smaller-scale, craft-based pharmacogenomic investigations using an experimental study design. Importantly, the recognition that pharmacogenomics is an experimental science creates an avenue for systematic policy response to the ethical imperative to prospectively pursue genetically customized therapies before regulatory approval of pharmaceuticals. To this end, we discuss the critical role of interdisciplinary engagement between medical sciences, policy, and social science. We emphasize the need for development of shared standards across scientific, methodologic, and socioethical epistemologic divides in the hybrid field of pharmacogenomics to best serve the interests of public health.

A national Swedish longitudinal twin-sibling study of criminal convictions from adolescence through early adulthood.

PubMed

Kendler, Kenneth S; Lönn, Sara Larsson; Maes, Hermine H; Morris, Nancy A; Lichtenstein, Paul; Sundquist, Jan; Sundquist, Kristina

2015-06-01

Prior twin and adoption studies have demonstrated the importance of both genetic and shared environmental factors in the etiology of criminal behavior (CB). However, despite substantial interest in life-course theories of CB, few genetically informative studies have examined CB in a developmental context. In 69,767 male-male twin pairs and full-sibling pairs with ≤ 2 years' difference in age, born 1958-1976 and ascertained from the Swedish Twin and Population Registries, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. We fitted a Cholesky structural model, using the OpenMx package, to CB in these pairs over three age periods: 15-19, 20-24, and 25-29. The Cholesky model had two main genetic factors. The first began at ages 15-19 and declined in importance over development. The second started at ages 20-24 and was stable over time. Only one major shared environmental factor was seen, beginning at ages 15-19. Heritability for CB declined from ages 15-29, as did shared environmental effects, although at a slower rate. Genetic risk factors for CB in males are developmentally dynamic, demonstrating both innovation and attenuation. These results are consistent with theories of adolescent-limited and life-course persistent CB subtypes. Heritability for CB did not increase over time as might be predicted from active gene-environmental correlation. However, consistent with expectation, the proportion of variability explained by shared environmental effects declined slightly as individuals aged and moved away from their original homes and neighborhoods.

Allele Sharing and Evidence for Sexuality in a Mitochondrial Clade of Bdelloid Rotifers.

PubMed

Signorovitch, Ana; Hur, Jae; Gladyshev, Eugene; Meselson, Matthew

2015-06-01

Rotifers of Class Bdelloidea are common freshwater invertebrates of ancient origin whose apparent asexuality has posed a challenge to the view that sexual reproduction is essential for long-term evolutionary success in eukaryotes and to hypotheses for the advantage of sex. The possibility nevertheless exists that bdelloids reproduce sexually under unknown or inadequately investigated conditions. Although certain methods of population genetics offer definitive means for detecting infrequent or atypical sex, they have not previously been applied to bdelloid rotifers. We conducted such a test with bdelloids belonging to a mitochondrial clade of Macrotrachela quadricornifera. This revealed a striking pattern of allele sharing consistent with sexual reproduction and with meiosis of an atypical sort, in which segregation occurs without requiring homologous chromosome pairs. Copyright © 2015 by the Genetics Society of America.

The genetic legacy of the expansion of Turkic-speaking nomads across Eurasia.

PubMed

Yunusbayev, Bayazit; Metspalu, Mait; Metspalu, Ene; Valeev, Albert; Litvinov, Sergei; Valiev, Ruslan; Akhmetova, Vita; Balanovska, Elena; Balanovsky, Oleg; Turdikulova, Shahlo; Dalimova, Dilbar; Nymadawa, Pagbajabyn; Bahmanimehr, Ardeshir; Sahakyan, Hovhannes; Tambets, Kristiina; Fedorova, Sardana; Barashkov, Nikolay; Khidiyatova, Irina; Mihailov, Evelin; Khusainova, Rita; Damba, Larisa; Derenko, Miroslava; Malyarchuk, Boris; Osipova, Ludmila; Voevoda, Mikhail; Yepiskoposyan, Levon; Kivisild, Toomas; Khusnutdinova, Elza; Villems, Richard

2015-04-01

The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic languages. These groups have dispersed across a vast area, including Siberia, Northwest China, Central Asia, East Europe, the Caucasus, Anatolia, the Middle East, and Afghanistan. The origin and early dispersal history of the Turkic peoples is disputed, with candidates for their ancient homeland ranging from the Transcaspian steppe to Manchuria in Northeast Asia. Previous genetic studies have not identified a clear-cut unifying genetic signal for the Turkic peoples, which lends support for language replacement rather than demic diffusion as the model for the Turkic language's expansion. We addressed the genetic origin of 373 individuals from 22 Turkic-speaking populations, representing their current geographic range, by analyzing genome-wide high-density genotype data. In agreement with the elite dominance model of language expansion most of the Turkic peoples studied genetically resemble their geographic neighbors. However, western Turkic peoples sampled across West Eurasia shared an excess of long chromosomal tracts that are identical by descent (IBD) with populations from present-day South Siberia and Mongolia (SSM), an area where historians center a series of early Turkic and non-Turkic steppe polities. While SSM matching IBD tracts (> 1cM) are also observed in non-Turkic populations, Turkic peoples demonstrate a higher percentage of such tracts (p-values ≤ 0.01) compared to their non-Turkic neighbors. Finally, we used the ALDER method and inferred admixture dates (~9th-17th centuries) that overlap with the Turkic migrations of the 5th-16th centuries. Thus, our results indicate historical admixture among Turkic peoples, and the recent shared ancestry with modern populations in SSM supports one of the hypothesized homelands for their nomadic Turkic and related Mongolic ancestors.

The Genetic Legacy of the Expansion of Turkic-Speaking Nomads across Eurasia

PubMed Central

Metspalu, Ene; Valeev, Albert; Litvinov, Sergei; Valiev, Ruslan; Akhmetova, Vita; Balanovska, Elena; Balanovsky, Oleg; Turdikulova, Shahlo; Dalimova, Dilbar; Nymadawa, Pagbajabyn; Bahmanimehr, Ardeshir; Sahakyan, Hovhannes; Tambets, Kristiina; Fedorova, Sardana; Barashkov, Nikolay; Khidiyatova, Irina; Mihailov, Evelin; Khusainova, Rita; Damba, Larisa; Derenko, Miroslava; Malyarchuk, Boris; Osipova, Ludmila; Voevoda, Mikhail; Yepiskoposyan, Levon; Kivisild, Toomas; Khusnutdinova, Elza; Villems, Richard

2015-01-01

The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic languages. These groups have dispersed across a vast area, including Siberia, Northwest China, Central Asia, East Europe, the Caucasus, Anatolia, the Middle East, and Afghanistan. The origin and early dispersal history of the Turkic peoples is disputed, with candidates for their ancient homeland ranging from the Transcaspian steppe to Manchuria in Northeast Asia. Previous genetic studies have not identified a clear-cut unifying genetic signal for the Turkic peoples, which lends support for language replacement rather than demic diffusion as the model for the Turkic language’s expansion. We addressed the genetic origin of 373 individuals from 22 Turkic-speaking populations, representing their current geographic range, by analyzing genome-wide high-density genotype data. In agreement with the elite dominance model of language expansion most of the Turkic peoples studied genetically resemble their geographic neighbors. However, western Turkic peoples sampled across West Eurasia shared an excess of long chromosomal tracts that are identical by descent (IBD) with populations from present-day South Siberia and Mongolia (SSM), an area where historians center a series of early Turkic and non-Turkic steppe polities. While SSM matching IBD tracts (> 1cM) are also observed in non-Turkic populations, Turkic peoples demonstrate a higher percentage of such tracts (p-values ≤ 0.01) compared to their non-Turkic neighbors. Finally, we used the ALDER method and inferred admixture dates (~9th–17th centuries) that overlap with the Turkic migrations of the 5th–16th centuries. Thus, our results indicate historical admixture among Turkic peoples, and the recent shared ancestry with modern populations in SSM supports one of the hypothesized homelands for their nomadic Turkic and related Mongolic ancestors. PMID:25898006

Origins of Eukaryotic Sexual Reproduction

PubMed Central

2014-01-01

Sexual reproduction is a nearly universal feature of eukaryotic organisms. Given its ubiquity and shared core features, sex is thought to have arisen once in the last common ancestor to all eukaryotes. Using the perspectives of molecular genetics and cell biology, we consider documented and hypothetical scenarios for the instantiation and evolution of meiosis, fertilization, sex determination, uniparental inheritance of organelle genomes, and speciation. PMID:24591519

Neuroticism and Extraversion Share Genetic and Environmental Effects with Negative and Positive Mood Spillover in a Nationally Representative Sample

PubMed Central

Horwitz, Briana N.; Luong, Gloria; Charles, Susan T.

2008-01-01

Work-family spillover research focuses on how negative and positive moods in one life domain carry over to another domain. Domain-specific etiologies (e.g., family conflict) are often emphasized to explain spillover. Yet, strong correlations exist between spillover variables of the same emotional valence and originating from different domains, suggesting individual differences in the tendencies to prolong mood-states. The current study (N=1143 individuals) examined whether these general tendencies are associated with neuroticism and extraversion, and how genetic and environmental effects contribute to these associations. Findings revealed that neuroticism and extraversion are related to these tendencies through genetic and environmental pathways. PMID:19430588

The ethics of contacting family members of a subject in a genetic research study to return results for an autosomal dominant syndrome.

PubMed

Taylor, Holly A; Wilfond, Benjamin S

2013-01-01

This case explores the ethical landscape around recontacting a subject's relatives to return genetic research results when the informed consent form signed by the original cohort of subjects is silent on whether investigators may share new information with the research subject's family. As a result of rapid advances in genetic technology, methods to identify genetic markers can mature during the life course of a study. In this case, the investigators identified the genetic mutation responsible for the disorder after a number of their original subjects had died. The researchers now have the ability to inform relatives of the subject about their risk of developing the same disease. Mark Rothstein, JD, from the University of Louisville School of Medicine, provides an overview of the medical/scientific, legal, and ethical issues underlying this case. Lauren Milner, PhD, and colleagues at Stanford University explore how the relationship between researcher and subject affect this debate. Seema Shah, JD, and colleagues at the National Institutes of Health and University of California, Los Angeles (UCLA) discuss whether and how requirements of the duty to warn are applicable in this case.

Inferring modes of colonization for pest species using heterozygosity comparisons and a shared-allele test.

PubMed Central

Sved, J A; Yu, H; Dominiak, B; Gilchrist, A S

2003-01-01

Long-range dispersal of a species may involve either a single long-distance movement from a core population or spreading via unobserved intermediate populations. Where the new populations originate as small propagules, genetic drift may be extreme and gene frequency or assignment methods may not prove useful in determining the relation between the core population and outbreak samples. We describe computationally simple resampling methods for use in this situation to distinguish between the different modes of dispersal. First, estimates of heterozygosity can be used to test for direct sampling from the core population and to estimate the effective size of intermediate populations. Second, a test of sharing of alleles, particularly rare alleles, can show whether outbreaks are related to each other rather than arriving as independent samples from the core population. The shared-allele statistic also serves as a genetic distance measure that is appropriate for small samples. These methods were applied to data on a fruit fly pest species, Bactrocera tryoni, which is quarantined from some horticultural areas in Australia. We concluded that the outbreaks in the quarantine zone came from a heterogeneous set of genetically differentiated populations, possibly ones that overwinter in the vicinity of the quarantine zone. PMID:12618417

Lifestyle, Genetics, and Disease in Sami

PubMed Central

Ross, Alastair B.; Johansson, Åsa; Ingman, Max; Gyllensten, Ulf

2006-01-01

Aim To present a summary of the lifestyle, genetic origin, diet, and disease in the population of Sami, indigenous people of northern Fennoscandia. Method A survey of the available scientific literature and preliminary results from our own study of the Swedish Sami population. Results The Sami probably have a heterogeneous genetic origin, with a major contribution of continental or Eastern European tribes and a smaller contribution from Asia. The traditional Sami diet, high in animal products, persists in Sami groups still involved with reindeer herding, but others have adopted a diet typical of Western cultures. Early reports indicated a lower prevalence of heart disease and most cancers, except stomach cancer. Recent studies have not found a lower risk of heart disease, but have consistently shown an overall reduced cancer risk. Sami have been reported to share some specific health-related genetic polymorphisms with other European populations, but none that would explain the observed differences in disease risk. Conclusion The genetic structure of the Sami population makes it suitable for studies of the genetic and environmental factors influencing the development of common diseases. The difference in incidence of heart disease between studies may reflect the ongoing transition from a traditional to a more Westernized lifestyle. The ability to compare population segments with different lifestyles, combined with the genetic structure of the population, creates unusual possibilities for studies of the genetic and environmental factors involved in the development of common disease. PMID:16909452

Genetic islands in pome fruit pathogenic and non-pathogenic Erwinia species and related plasmids

PubMed Central

Llop, Pablo

2015-01-01

New pathogenic bacteria belonging to the genus Erwinia associated with pome fruit trees (Erwinia, E. piriflorinigrans, E. uzenensis) have been increasingly described in the last years, and comparative analyses have found that all these species share several genetic characteristics. Studies at different level (whole genome comparison, virulence genes, plasmid content, etc.) show a high intraspecies homogeneity (i.e., among E. amylovora strains) and also abundant similarities appear between the different Erwinia species: presence of plasmids of similar size in the pathogenic species; high similarity in several genes associated with exopolysaccharide production and hence, with virulence, as well as in some other genes, in the chromosomes. Many genetic similarities have been observed also among some of the plasmids (and genomes) from the pathogenic species and E. tasmaniensis or E. billingiae, two epiphytic species on the same hosts. The amount of genetic material shared in this genus varies from individual genes to clusters, genomic islands and genetic material that even may constitute a whole plasmid. Recent research on evolution of erwinias point out the horizontal transfer acquisition of some genomic islands that were subsequently lost in some species and several pathogenic traits that are still present. How this common material has been obtained and is efficiently maintained in different species belonging to the same genus sharing a common ecological niche provides an idea of the origin and evolution of the pathogenic Erwinia and the interaction with non-pathogenic species present in the same niche, and the role of the genes that are conserved in all of them. PMID:26379649

Editorial overview: Molecular and genetic bases of disease: the double life of DNA.

PubMed

McMurray, Cynthia T; Vijg, Jan

2014-06-01

This issue of Current Opinions focuses on the dual role of DNA in life and death. In ancient Roman religion and myth, Janus is the god who looks both to the past and to the future. He guides the beginnings of life, its progression from one condition to another, and he foresees distant events. The analogy to DNA could not be stronger. Closely interacting with the environment, our basic genetics provides the origin of life, guides the quality of health with age, predicts disease, and ultimately foresees our end. A shared and deep interest with the origin of life has long prompted our desire to define aging, and, ultimately, to understand whether it can be reversed. In this special issue, the authors collectively review concepts of normative aging, DNA instability, DNA repair, the genetic contribution of age and diet to disease, and how the basic molecular transactions of DNA guide both the transitions to life as well as the transitions to death. Published by Elsevier Ltd.

Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution

PubMed Central

Kim, Hoon; Zheng, Siyuan; Amini, Seyed S.; Virk, Selene M.; Mikkelsen, Tom; Brat, Daniel J.; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E.; Cohen, Mark L.; Van Meir, Erwin G.; Scarpace, Lisa; Laird, Peter W.; Weinstein, John N.; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S.

2015-01-01

Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. PMID:25650244

The genetic and environmental aetiology of spatial, mathematics and general anxiety

PubMed Central

Malanchini, Margherita; Rimfeld, Kaili; Shakeshaft, Nicholas G.; Rodic, Maja; Schofield, Kerry; Selzam, Saskia; Dale, Philip S.; Petrill, Stephen A.; Kovas, Yulia

2017-01-01

Individuals differ in their level of general anxiety as well as in their level of anxiety towards specific activities, such as mathematics and spatial tasks. Both specific anxieties correlate moderately with general anxiety, but the aetiology of their association remains unexplored. Moreover, the factor structure of spatial anxiety is to date unknown. The present study investigated the factor structure of spatial anxiety, its aetiology, and the origins of its association with general and mathematics anxiety in a sample of 1,464 19-21-year-old twin pairs from the UK representative Twins Early Development Study. Participants reported their general, mathematics and spatial anxiety as part of an online battery of tests. We found that spatial anxiety is a multifactorial construct, including two components: navigation anxiety and rotation/visualization anxiety. All anxiety measures were moderately heritable (30% to 41%), and non-shared environmental factors explained the remaining variance. Multivariate genetic analysis showed that, although some genetic and environmental factors contributed to all anxiety measures, a substantial portion of genetic and non-shared environmental influences were specific to each anxiety construct. This suggests that anxiety is a multifactorial construct phenotypically and aetiologically, highlighting the importance of studying anxiety within specific contexts. PMID:28220830

The genetic and environmental aetiology of spatial, mathematics and general anxiety.

PubMed

Malanchini, Margherita; Rimfeld, Kaili; Shakeshaft, Nicholas G; Rodic, Maja; Schofield, Kerry; Selzam, Saskia; Dale, Philip S; Petrill, Stephen A; Kovas, Yulia

2017-02-21

Individuals differ in their level of general anxiety as well as in their level of anxiety towards specific activities, such as mathematics and spatial tasks. Both specific anxieties correlate moderately with general anxiety, but the aetiology of their association remains unexplored. Moreover, the factor structure of spatial anxiety is to date unknown. The present study investigated the factor structure of spatial anxiety, its aetiology, and the origins of its association with general and mathematics anxiety in a sample of 1,464 19-21-year-old twin pairs from the UK representative Twins Early Development Study. Participants reported their general, mathematics and spatial anxiety as part of an online battery of tests. We found that spatial anxiety is a multifactorial construct, including two components: navigation anxiety and rotation/visualization anxiety. All anxiety measures were moderately heritable (30% to 41%), and non-shared environmental factors explained the remaining variance. Multivariate genetic analysis showed that, although some genetic and environmental factors contributed to all anxiety measures, a substantial portion of genetic and non-shared environmental influences were specific to each anxiety construct. This suggests that anxiety is a multifactorial construct phenotypically and aetiologically, highlighting the importance of studying anxiety within specific contexts.

Cis-regulatory changes in Kit ligand expression and parallel evolution of pigmentation in sticklebacks and humans

PubMed Central

Miller, Craig T.; Beleza, Sandra; Pollen, Alex A.; Schluter, Dolph; Kittles, Rick A.; Shriver, Mark D.; Kingsley, David M.

2010-01-01

SUMMARY Dramatic pigmentation changes have evolved within most vertebrate groups, including fish and humans. Here we use genetic crosses in sticklebacks to investigate the parallel origin of pigmentation changes in natural populations. High-resolution mapping and expression experiments show that light gills and light ventrums map to a divergent regulatory allele of the Kit ligand (Kitlg) gene. The divergent allele reduces expression in gill and skin tissue, and is shared by multiple derived freshwater populations with reduced pigmentation. In humans, Europeans and East Asians also share derived alleles at the KITLG locus. Strong signatures of selection map to regulatory regions surrounding the gene, and admixture mapping shows that the KITLG genomic region has a significant effect on human skin color. These experiments suggest that regulatory changes in Kitlg contribute to natural variation in vertebrate pigmentation, and that similar genetic mechanisms may underlie rapid evolutionary change in fish and humans. PMID:18083106

Genetic history of an archaic hominin group from Denisova Cave in Siberia

PubMed Central

Reich, David; Green, Richard E.; Kircher, Martin; Krause, Johannes; Patterson, Nick; Durand, Eric Y.; Viola, Bence; Briggs, Adrian W.; Stenzel, Udo; Johnson, Philip L. F.; Maricic, Tomislav; Good, Jeffrey M.; Marques-Bonet, Tomas; Alkan, Can; Fu, Qiaomei; Mallick, Swapan; Li, Heng; Meyer, Matthias; Eichler, Evan E.; Stoneking, Mark; Richards, Michael; Talamo, Sahra; Shunkov, Michael V.; Derevianko, Anatoli P.; Hublin, Jean-Jacques; Kelso, Janet; Slatkin, Montgomery; Pääbo, Svante

2015-01-01

Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4–6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population ‘Denisovans’ and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans. PMID:21179161

Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia.

PubMed

Klütsch, C F C; Seppälä, E H; Fall, T; Uhlén, M; Hedhammar, A; Lohi, H; Savolainen, P

2011-02-01

The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60-100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480-3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage. © 2010 The Authors, Animal Genetics © 2010 Stichting International Foundation for Animal Genetics.

Functions and origin of plasmids in Erwinia species that are pathogenic to or epiphytically associated with pome fruit trees.

PubMed

Llop, Pablo; Barbé, Silvia; López, María M

The genus Erwinia includes plant-associated pathogenic and non-pathogenic species. Among them, all species pathogenic to pome fruit trees ( E. amylovora, E. pyrifoliae, E. piriflorinigrans, Erwinia sp. from Japan) cause similar symptoms, but differ in their degrees of aggressiveness, i.e. in symptoms, host range or both. The presence of plasmids of similar size, in the range of 30 kb, is a common characteristic that they possess. Besides, they share some genetic content with high homology in several genes associated with exopolysaccharide production and hence, with virulence, as well as in some other genes. Knowledge of the content of these plasmids and comparative genetic analyses may provide interesting new clues to understanding the origin and evolution of these pathogens and the level of symptoms they produce. Furthermore, genetic similarities observed among some of the plasmids (and genomes) from the above indicated pathogenic species and E. tasmaniensis or E. billingiae , which are epiphytic on the same hosts, may reveal associations that could expose the mechanisms of origin of pathogens. A summary of the current information on their plasmids and the relationships among them is presented here.

Ah, Sweet Mystery of Life, OSIRIS-REx May Find You

NASA Technical Reports Server (NTRS)

Dworkin, Jason P.

2015-01-01

The nature of the origin of life is a topic that has engaged people since ancient times. Where did we come from? What was the first life? How are we related? Are we alone? The study of biologic remains and environments preserved in rocks (fossils) and biochemical pathways and structures found across organisms (molecular fossils) can address these questions. Molecular evidence shows that all life on Earth is related fundamentally, biology shares a genetic language, related molecular machinery, and common chemistry By looking at the details of genetic and protein sequences more detailed relationships can be determined for modern organisms.

Equality in Educational Policy and the Heritability of Educational Attainment

PubMed Central

Colodro-Conde, Lucía; Rijsdijk, Frühling; Tornero-Gómez, María J.; Sánchez-Romera, Juan F.; Ordoñana, Juan R.

2015-01-01

Secular variation in the heritability of educational attainment are proposed to be due to the implementation of more egalitarian educational policies leading to increased equality in educational opportunities in the second part of the 20th century. The action of effect is hypothesized to be a decrease of shared environmental (e.g., family socioeconomic status or parents’ education) influences on educational attainment, giving more room for genetic differences between individuals to impact on the variation of the trait. However, this hypothesis has not yet found consistent evidence. Support for this effect relies mainly on comparisons between countries adopting different educational systems or between different time periods within a country reflecting changes in general policy. Using a population-based sample of 1271 pairs of adult twins, we analyzed the effect of the introduction of a specific educational policy in Spain in 1970. The shared-environmental variance decreased, leading to an increase in heritability in the post-reform cohort (44 vs. 67%) for males. Unstandardized estimates of genetic variance were of a similar magnitude (.56 vs. .57) between cohorts, while shared environmental variance decreased from .56 to .04. Heritability remained in the same range for women (40 vs. 34%). Our results support the role of educational policy in affecting the relative weight of genetic and environmental factors on educational attainment, such that increasing equality in educational opportunities increases heritability estimates by reducing variation of non-genetic familial origin. PMID:26618539

Looking for the Primordial Genetic Honeycomb

NASA Astrophysics Data System (ADS)

Gallori, Enzo; Biondi, Elisa; Branciamore, Sergio

2006-12-01

All life forms on Earth share the same biological program based on the DNA/RNA genomes and proteins. The genetic information, recorded in the nucleotide sequence of the DNA and RNA molecule, supplies the language of life which is transferred through the different generations, thus ensuring the perpetuation of genetic information on Earth. The presence of a genetic system is absolutely essential to life. Thus, the appearance in an ancestral era of a nucleic acid-like polymer able to undergo Darwinian evolution indicates the beginning of life on our planet. The building of primordial genetic molecules, whatever they were, required the presence of a protected environment, allowing the synthesis and concentration of precursors (nucleotides), their joining into larger molecules (polynucleotides), the protection of forming polymers against degradation (i.e. by cosmic and UV radiation), thus ensuring their persistence in a changing environment, and the expression of the “biological” potential of the molecule (its capacity to self-replicate and evolve). Determining how these steps occurred and how the primordial genetic molecules originated on Earth is a very difficult problem that still must be resolved. It has long been proposed that surface chemistry, i.e. on clay minerals, could have played a crucial role in the prebiotic formation of molecules basic to life. In the present work, we discuss results obtained in different fields that strengthen the hypothesis of a clay-surface-mediated origin of genetic material.

Genetic structure provides insights into the geographic origins and temporal change in the invasive charru mussel (Sururu) in the southeastern United States

PubMed Central

Walters, Linda J.; Fernandes, Flavio C.; Ferreira, Carlos E. L.

2017-01-01

In 2004, Mytella charruana (d'Orbigny, 1842) (Mollusca: Bivalvia: Mytilidae) became established along the coast of the southeastern United States (SE-US). Using mitochondrial DNA sequencing (cytochrome c oxidase subunit I), we compared genetic variation throughout its native range in South America to its invasive range in the SE-US. Samples from the SE-US were collected in 2006 and 2010 enabling a temporal comparison to evaluate possible genetic changes of the invasive population. We addressed two questions. First, what are the potential source populations (or geographic regions) for the SE-US invasion? Second, how has genetic diversity changed between the two sampling periods within the SE-US? We identified a total of 72 haplotypes, 64 of which were isolated to geographic sites and only 8 were shared among sites. The highly structured native range provides insight into the origin of invasive populations where our results suggest that the introduced SE-US population originated from multiple source populations with the Panama region as the primary source. Additionally, our results indicate that genetic composition of the non-native populations was unchanged between the two sampling periods. Mytella charruana exhibit a significant pattern of genetic structure among natural populations, owing to biogeographic barriers that limit natural dispersal, and an ability to persist in novel habitats, owing to a suite of life-history characters that favor survival under variable conditions. Overall, this study explains why M. charruana may become an increasing threat to locations founded by anthropogenic transportation. PMID:28686694

Genetic Diversity within a Global Panel of Durum Wheat (Triticum durum) Landraces and Modern Germplasm Reveals the History of Alleles Exchange.

PubMed

Kabbaj, Hafssa; Sall, Amadou T; Al-Abdallat, Ayed; Geleta, Mulatu; Amri, Ahmed; Filali-Maltouf, Abdelkarim; Belkadi, Bouchra; Ortiz, Rodomiro; Bassi, Filippo M

2017-01-01

Durum wheat is the 10th most important crop in the world, and its use traces back to the origin of agriculture. Unfortunately, in the last century only part of the genetic diversity available for this species has been captured in modern varieties through breeding. Here, the population structure and genetic diversity shared among elites and landraces collected from 32 countries was investigated. A total of 370 entries were genotyped with Axiom 35K array to identify 8,173 segregating single nucleotide polymorphisms (SNPs). Of these, 500 were selected as highly informative with a PIC value above 0.32 and used to test population structure via DAPC, STRUCTURE, and neighbor joining tree. A total of 10 sub-populations could be identified, six constituted by modern germplasm and four by landraces of different geographical origin. Interestingly, genomic comparison among groups indicated that Middle East and Ethiopia had the lowest level of allelic diversity, while breeding programs and landraces collected outside these regions were the richest in rare alleles. Further, phylogenetic analysis among landraces indicated that Ethiopia might represent a second center of origin of durum wheat, rather than a second domestication site as previously believed. Together, the analyses carried here provide a global picture of the available genetic diversity for this crop and shall guide its targeted use by breeders.

New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling.

PubMed

Martín-Subero, José I; Kreuz, Markus; Bibikova, Marina; Bentink, Stefan; Ammerpohl, Ole; Wickham-Garcia, Eliza; Rosolowski, Maciej; Richter, Julia; Lopez-Serra, Lidia; Ballestar, Esteban; Berger, Hilmar; Agirre, Xabier; Bernd, Heinz-Wolfram; Calvanese, Vincenzo; Cogliatti, Sergio B; Drexler, Hans G; Fan, Jian-Bing; Fraga, Mario F; Hansmann, Martin L; Hummel, Michael; Klapper, Wolfram; Korn, Bernhard; Küppers, Ralf; Macleod, Roderick A F; Möller, Peter; Ott, German; Pott, Christiane; Prosper, Felipe; Rosenwald, Andreas; Schwaenen, Carsten; Schübeler, Dirk; Seifert, Marc; Stürzenhofecker, Benjamin; Weber, Michael; Wessendorf, Swen; Loeffler, Markus; Trümper, Lorenz; Stein, Harald; Spang, Rainer; Esteller, Manel; Barker, David; Hasenclever, Dirk; Siebert, Reiner

2009-03-12

Lymphomas are assumed to originate at different stages of lymphocyte development through chromosomal aberrations. Thus, different lymphomas resemble lymphocytes at distinct differentiation stages and show characteristic morphologic, genetic, and transcriptional features. Here, we have performed a microarray-based DNA methylation profiling of 83 mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) characterized for their morphologic, genetic, and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchic clustering indicated that methylation patterns in maB-NHLs were not strictly associated with morphologic, genetic, or transcriptional features. By supervised analyses, we identified 56 genes de novo methylated in all lymphoma subtypes studied and 22 methylated in a lymphoma subtype-specific manner. Remarkably, the group of genes de novo methylated in all lymphoma subtypes was significantly enriched for polycomb targets in embryonic stem cells. De novo methylated genes in all maB-NHLs studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in nonhematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHLs with different morphologic, genetic, and transcriptional background share a similar stem cell-like epigenetic pattern. This suggests that maB-NHLs originate from cells with stem cell features or that stemness was acquired during lymphomagenesis by epigenetic remodeling.

Geographical distribution of genetic diversity in Secale landrace and wild accessions.

PubMed

Hagenblad, Jenny; Oliveira, Hugo R; Forsberg, Nils E G; Leino, Matti W

2016-01-19

Rye, Secale cereale L., has historically been a crop of major importance and is still a key cereal in many parts of Europe. Single populations of cultivated rye have been shown to capture a large proportion of the genetic diversity present in the species, but the distribution of genetic diversity in subspecies and across geographical areas is largely unknown. Here we explore the structure of genetic diversity in landrace rye and relate it to that of wild and feral relatives. A total of 567 SNPs were analysed in 434 individuals from 76 accessions of wild, feral and cultivated rye. Genetic diversity was highest in cultivated rye, slightly lower in feral rye taxa and significantly lower in the wild S. strictum Presl. and S. africanum Stapf. Evaluation of effects from ascertainment bias suggests underestimation of diversity primarily in S. strictum and S. africanum. Levels of ascertainment bias, STRUCTURE and principal component analyses all supported the proposed classification of S. africanum and S. strictum as a separate species from S. cereale. S. afghanicum (Vav.) Roshev, S. ancestrale Zhuk., S. dighoricum (Vav.) Roshev, S. segetale (Zhuk.) Roshev and S. vavilovii Grossh. seemed, in contrast, to share the same gene pool as S. cereale and their genetic clustering was more dependent on geographical origin than taxonomic classification. S. vavilovii was found to be the most likely wild ancestor of cultivated rye. Among cultivated rye landraces from Europe, Asia and North Africa five geographically discrete genetic clusters were identified. These had only limited overlap with major agro-climatic zones. Slash-and-burn rye from the Finnmark area in Scandinavia formed a distinct cluster with little similarity to other landrace ryes. Regional studies of Northern and South-West Europe demonstrate different genetic distribution patterns as a result of varying cultivation intensity. With the exception of S. strictum and S. africanum different rye taxa share the majority of the genetic variation. Due to the vast sharing of genetic diversity within the S. cereale clade, ascertainment bias seems to be a lesser problem in rye than in predominantly selfing species. By exploiting within accession diversity geographic structure can be shown on a much finer scale than previously reported.

Genetic characterization of canine parvovirus from dogs in Pakistan.

PubMed

Shabbir, M Z; Sohail, M U; Chaudhary, U N; Yaqub, W; Rashid, I; Saleem, M H; Munir, M

Canine parvoviruses (CPV) exist as antigenic variants with varying frequencies and genetic variabilities across the globe. Given the endemicity and high prevalence in Pakistan, we characterized the CPVs originating from dogs-population to elucidate viral diversity and evolution. Fecal samples from clinically diseased pups (n = 17) of different breeds and age (2-6 months) were processed for hemagglutination assay (HA), and later for partial amplification of VP2 gene sequence and amino acid analysis. A total of 11 samples (64.71%) were found positive both in hemagglutination and PCR assays. Phylogenetic and evolutionary analysis demonstrated higher genetic heterogeneity in studied strains and constituted seven clusters within the CPV-2a group, however, they shared high level of identity with Chinese strains. Further studies are necessary to elucidate genetic analysis and epidemiology of CPV variants across a wide geographical area of the country.

Phylogenetic distinctiveness of Middle Eastern and Southeast Asian village dog Y chromosomes illuminates dog origins.

PubMed

Brown, Sarah K; Pedersen, Niels C; Jafarishorijeh, Sardar; Bannasch, Danika L; Ahrens, Kristen D; Wu, Jui-Te; Okon, Michaella; Sacks, Benjamin N

2011-01-01

Modern genetic samples are commonly used to trace dog origins, which entails untested assumptions that village dogs reflect indigenous ancestry or that breed origins can be reliably traced to particular regions. We used high-resolution Y chromosome markers (SNP and STR) and mitochondrial DNA to analyze 495 village dogs/dingoes from the Middle East and Southeast Asia, along with 138 dogs from >35 modern breeds to 1) assess genetic divergence between Middle Eastern and Southeast Asian village dogs and their phylogenetic affinities to Australian dingoes and gray wolves (Canis lupus) and 2) compare the genetic affinities of modern breeds to regional indigenous village dog populations. The Y chromosome markers indicated that village dogs in the two regions corresponded to reciprocally monophyletic clades, reflecting several to many thousand years divergence, predating the Neolithic ages, and indicating long-indigenous roots to those regions. As expected, breeds of the Middle East and East Asia clustered within the respective regional village dog clade. Australian dingoes also clustered in the Southeast Asian clade. However, the European and American breeds clustered almost entirely within the Southeast Asian clade, even sharing many haplotypes, suggesting a substantial and recent influence of East Asian dogs in the creation of European breeds. Comparison to 818 published breed dog Y STR haplotypes confirmed this conclusion and indicated that some African breeds reflect another distinct patrilineal origin. The lower-resolution mtDNA marker consistently supported Y-chromosome results. Both marker types confirmed previous findings of higher genetic diversity in dogs from Southeast Asia than the Middle East. Our findings demonstrate the importance of village dogs as windows into the past and provide a reference against which ancient DNA can be used to further elucidate origins and spread of the domestic dog.

Phylogenetic Distinctiveness of Middle Eastern and Southeast Asian Village Dog Y Chromosomes Illuminates Dog Origins

PubMed Central

Brown, Sarah K.; Pedersen, Niels C.; Jafarishorijeh, Sardar; Bannasch, Danika L.; Ahrens, Kristen D.; Wu, Jui-Te; Okon, Michaella; Sacks, Benjamin N.

2011-01-01

Modern genetic samples are commonly used to trace dog origins, which entails untested assumptions that village dogs reflect indigenous ancestry or that breed origins can be reliably traced to particular regions. We used high-resolution Y chromosome markers (SNP and STR) and mitochondrial DNA to analyze 495 village dogs/dingoes from the Middle East and Southeast Asia, along with 138 dogs from >35 modern breeds to 1) assess genetic divergence between Middle Eastern and Southeast Asian village dogs and their phylogenetic affinities to Australian dingoes and gray wolves (Canis lupus) and 2) compare the genetic affinities of modern breeds to regional indigenous village dog populations. The Y chromosome markers indicated that village dogs in the two regions corresponded to reciprocally monophyletic clades, reflecting several to many thousand years divergence, predating the Neolithic ages, and indicating long-indigenous roots to those regions. As expected, breeds of the Middle East and East Asia clustered within the respective regional village dog clade. Australian dingoes also clustered in the Southeast Asian clade. However, the European and American breeds clustered almost entirely within the Southeast Asian clade, even sharing many haplotypes, suggesting a substantial and recent influence of East Asian dogs in the creation of European breeds. Comparison to 818 published breed dog Y STR haplotypes confirmed this conclusion and indicated that some African breeds reflect another distinct patrilineal origin. The lower-resolution mtDNA marker consistently supported Y-chromosome results. Both marker types confirmed previous findings of higher genetic diversity in dogs from Southeast Asia than the Middle East. Our findings demonstrate the importance of village dogs as windows into the past and provide a reference against which ancient DNA can be used to further elucidate origins and spread of the domestic dog. PMID:22194840

Attitudes towards Social Networking and Sharing Behaviors among Consumers of Direct-to-Consumer Personal Genomics

PubMed Central

Lee, Sandra Soo-Jin; Vernez, Simone L.; Ormond, K.E.; Granovetter, Mark

2013-01-01

Little is known about how consumers of direct-to-consumer personal genetic services share personal genetic risk information. In an age of ubiquitous online networking and rapid development of social networking tools, understanding how consumers share personal genetic risk assessments is critical in the development of appropriate and effective policies. This exploratory study investigates how consumers share personal genetic information and attitudes towards social networking behaviors. Methods: Adult participants aged 23 to 72 years old who purchased direct-to-consumer genetic testing from a personal genomics company were administered a web-based survey regarding their sharing activities and social networking behaviors related to their personal genetic test results. Results: 80 participants completed the survey; of those, 45% shared results on Facebook and 50.9% reported meeting or reconnecting with more than 10 other individuals through the sharing of their personal genetic information. For help interpreting test results, 70.4% turned to Internet websites and online sources, compared to 22.7% who consulted their healthcare providers. Amongst participants, 51.8% reported that they believe the privacy of their personal genetic information would be breached in the future. Conclusion: Consumers actively utilize online social networking tools to help them share and interpret their personal genetic information. These findings suggest a need for careful consideration of policy recommendations in light of the current ambiguity of regulation and oversight of consumer initiated sharing activities. PMID:25562728

Attitudes towards Social Networking and Sharing Behaviors among Consumers of Direct-to-Consumer Personal Genomics.

PubMed

Lee, Sandra Soo-Jin; Vernez, Simone L; Ormond, K E; Granovetter, Mark

2013-10-14

Little is known about how consumers of direct-to-consumer personal genetic services share personal genetic risk information. In an age of ubiquitous online networking and rapid development of social networking tools, understanding how consumers share personal genetic risk assessments is critical in the development of appropriate and effective policies. This exploratory study investigates how consumers share personal genetic information and attitudes towards social networking behaviors. Adult participants aged 23 to 72 years old who purchased direct-to-consumer genetic testing from a personal genomics company were administered a web-based survey regarding their sharing activities and social networking behaviors related to their personal genetic test results. 80 participants completed the survey; of those, 45% shared results on Facebook and 50.9% reported meeting or reconnecting with more than 10 other individuals through the sharing of their personal genetic information. For help interpreting test results, 70.4% turned to Internet websites and online sources, compared to 22.7% who consulted their healthcare providers. Amongst participants, 51.8% reported that they believe the privacy of their personal genetic information would be breached in the future. Consumers actively utilize online social networking tools to help them share and interpret their personal genetic information. These findings suggest a need for careful consideration of policy recommendations in light of the current ambiguity of regulation and oversight of consumer initiated sharing activities.

Cortical interneuron dysfunction in epilepsy associated with autism spectrum disorders.

PubMed

Jacob, John

2016-02-01

Autism and epilepsy are two associated disorders that are highly prevalent, share common developmental origins, and demonstrate substantial heritability. In this review, cross-disciplinary data in a rapidly evolving field that bridges neurology and psychiatry are synthesized to identify shared biologic mechanisms. The relationship between these debilitating, lifelong conditions is examined at the clinical, genetic, and neurophysiologic levels in humans and in animal models. Scopus and PubMed searches were used to identify relevant literature. Clinical observations have prompted speculation about the interdependence of autism and epilepsy, but causal relationships have proved difficult to determine. Despite their heritability, the genetic basis of autism spectrum disorder (ASD) and epilepsy has remained largely elusive until the advent of next-generation sequencing. This approach has revealed that mutations that are either causal or confer an increased disease risk are found in numerous different genes, any one of which accounts for only a small percentage of cases. Conversely, even cases with identical clinical phenotypes can be genetically heterogeneous. Candidate gene identification has facilitated the development of mouse genetic models, which in parallel with human studies have implicated shared brain regions and circuits that mediate disease expression. Diverse genetic causes of ASD and epilepsy converge on cortical interneuron circuits as one important mediator of both disorders. Cortical interneurons are among the most diverse cell types in the brain and their unique chemical and electrical coupling exert a powerful inhibitory influence on excitatory neurons via the release of the neurotransmitter, γ-aminobutyric acid (GABA). These multifaceted approaches have validated theories derived from the field of developmental neurobiology, which propose that the neurologic and neuropsychiatric manifestations are caused by an altered ratio of excitation to inhibition in the cortex. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Potential key bases of ribosomal RNA to kingdom-specific spectra of antibiotic susceptibility and the possible archaeal origin of eukaryotes.

PubMed

Xie, Qiang; Wang, Yanhui; Lin, Jinzhong; Qin, Yan; Wang, Ying; Bu, Wenjun

2012-01-01

In support of the hypothesis of the endosymbiotic origin of eukaryotes, much evidence has been found to support the idea that some organelles of eukaryotic cells originated from bacterial ancestors. Less attention has been paid to the identity of the host cell, although some biochemical and molecular genetic properties shared by archaea and eukaryotes have been documented. Through comparing 507 taxa of 16S-18S rDNA and 347 taxa of 23S-28S rDNA, we found that archaea and eukaryotes share twenty-six nucleotides signatures in ribosomal DNA. These signatures exist in all living eukaryotic organisms, whether protist, green plant, fungus, or animal. This evidence explicitly supports the archaeal origin of eukaryotes. In the ribosomal RNA, besides A2058 in Escherichia coli vs. G2400 in Saccharomyces cerevisiae, there still exist other twenties of sites, in which the bases are kingdom-specific. Some of these sites concentrate in the peptidyl transferase centre (PTC) of the 23S-28S rRNA. The results suggest potential key sites to explain the kingdom-specific spectra of drug resistance of ribosomes.

The archaebacterial origin of eukaryotes.

PubMed

Cox, Cymon J; Foster, Peter G; Hirt, Robert P; Harris, Simon R; Embley, T Martin

2008-12-23

The origin of the eukaryotic genetic apparatus is thought to be central to understanding the evolution of the eukaryotic cell. Disagreement about the source of the relevant genes has spawned competing hypotheses for the origins of the eukaryote nuclear lineage. The iconic rooted 3-domains tree of life shows eukaryotes and archaebacteria as separate groups that share a common ancestor to the exclusion of eubacteria. By contrast, the eocyte hypothesis has eukaryotes originating within the archaebacteria and sharing a common ancestor with a particular group called the Crenarchaeota or eocytes. Here, we have investigated the relative support for each hypothesis from analysis of 53 genes spanning the 3 domains, including essential components of the eukaryotic nucleic acid replication, transcription, and translation apparatus. As an important component of our analysis, we investigated the fit between model and data with respect to composition. Compositional heterogeneity is a pervasive problem for reconstruction of ancient relationships, which, if ignored, can produce an incorrect tree with strong support. To mitigate its effects, we used phylogenetic models that allow for changing nucleotide or amino acid compositions over the tree and data. Our analyses favor a topology that supports the eocyte hypothesis rather than archaebacterial monophyly and the 3-domains tree of life.

It takes two to tango: information-sharing with offspring among heterosexual parents following identity-release sperm donation.

PubMed

Isaksson, S; Skoog-Svanberg, A; Sydsjö, G; Linell, L; Lampic, C

2016-01-01

How do heterosexual parents reason about and experience information-sharing with offspring following identity-release sperm donation? Sharing information about using donor-conception with offspring is a complex process at several levels, with the parent's personal beliefs and the child's responses serving as driving or impeding forces for the information-sharing process. The overall view of disclosure in gamete donation has shifted from secrecy to openness, but there is still uncertainty among parents concerning how and when to tell the child about his/her genetic origin. Most research on donor-conceived families has focused on donation treatment under anonymous or known circumstances, and there is a lack of studies in settings with identity-release donations. A qualitative interview study among 30 parents following identity-release sperm donation treatment. Interviews were conducted from February 2014 to March 2015. The present study is part of the prospective longitudinal Swedish Study on Gamete Donation (SSGD), including all fertility clinics performing gamete donation in Sweden. A sample of participants in the SSGD, consisting of heterosexual parents with children aged 7-8 years following identity-release sperm donation, participated in individual semi-structured interviews. The analysis revealed one main theme: information-sharing is a process, with three subthemes; (i) the parent as process manager, (ii) the child as force or friction and (iii) being in the process. The first two subthemes were viewed as being linked together and their content served as driving or impeding forces in the information-sharing process. The fact that the study was performed within the context of the Swedish legislation on identity-release donation must be taken into consideration as regards transferability to other populations, as this may affect parents' reasoning concerning their information-sharing with the child. The present findings highlight the role of the donor-conceived child in the information-sharing process and may contribute to develop counselling that increases parents' confidence in handling children's reactions to information about their genetic origin. Financial support from The Swedish Research Council, The Family Planning Fund in Uppsala and Ferring Pharmaceuticals. There are no conflicts of interest to declare. N/A. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.

PubMed

Kim, Hoon; Zheng, Siyuan; Amini, Seyed S; Virk, Selene M; Mikkelsen, Tom; Brat, Daniel J; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E; Cohen, Mark L; Van Meir, Erwin G; Scarpace, Lisa; Laird, Peter W; Weinstein, John N; Lander, Eric S; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S; Verhaak, Roel G W

2015-03-01

Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. © 2015 Kim et al.; Published by Cold Spring Harbor Laboratory Press.

The Origins of Diverse Domains of Mathematics: Generalist Genes but Specialist Environments

PubMed Central

Kovas, Y.; Petrill, S. A.; Plomin, R.

2009-01-01

The authors assessed 2,502 ten-year-old children, members of 1,251 pairs of twins, on a Web-based battery of problems from 5 diverse aspects of mathematics assessed as part of the U.K. national curriculum. This 1st genetic study into the etiology of variation in different domains of mathematics showed that the heritability estimates were moderate and highly similar across domains and that these genetic influences were mostly general. Environmental factors unique to each twin in a family (rather than shared by the 2 twins) explained most of the remaining variance, and these factors were mostly specific to each domain. PMID:19756208

The Origins of Diverse Domains of Mathematics: Generalist Genes but Specialist Environments.

PubMed

Kovas, Y; Petrill, S A; Plomin, R

2007-02-01

The authors assessed 2,502 ten-year-old children, members of 1,251 pairs of twins, on a Web-based battery of problems from 5 diverse aspects of mathematics assessed as part of the U.K. national curriculum. This 1st genetic study into the etiology of variation in different domains of mathematics showed that the heritability estimates were moderate and highly similar across domains and that these genetic influences were mostly general. Environmental factors unique to each twin in a family (rather than shared by the 2 twins) explained most of the remaining variance, and these factors were mostly specific to each domain.

A brief history of autism, the autism/vaccine hypothesis and a review of the genetic basis of autism spectrum disorders.

PubMed

Blake, Jerome; Hoyme, H Eugene; Crotwell, Patricia L

2013-01-01

Autism spectrum disorders (ASD) represent a common spectrum of developmental disabilities, sharing deficits in social interactions, communication and restricted interests or repetitive behaviors with difficult transitions. In this article, we review the history of the identification and classification of autism and the origin of the now widely-debunked autism/vaccine hypothesis. The differences between syndromal (complex) and non-syndromal (essential) autism are described and illustrated with case descriptions where appropriate. Finally, the evidence that autism is fundamentally a genetic disease is discussed, including family studies, the role of DNA copy number variation and known single gene mutations.

Caught you: threats to confidentiality due to the public release of large-scale genetic data sets

PubMed Central

2010-01-01

Background Large-scale genetic data sets are frequently shared with other research groups and even released on the Internet to allow for secondary analysis. Study participants are usually not informed about such data sharing because data sets are assumed to be anonymous after stripping off personal identifiers. Discussion The assumption of anonymity of genetic data sets, however, is tenuous because genetic data are intrinsically self-identifying. Two types of re-identification are possible: the "Netflix" type and the "profiling" type. The "Netflix" type needs another small genetic data set, usually with less than 100 SNPs but including a personal identifier. This second data set might originate from another clinical examination, a study of leftover samples or forensic testing. When merged to the primary, unidentified set it will re-identify all samples of that individual. Even with no second data set at hand, a "profiling" strategy can be developed to extract as much information as possible from a sample collection. Starting with the identification of ethnic subgroups along with predictions of body characteristics and diseases, the asthma kids case as a real-life example is used to illustrate that approach. Summary Depending on the degree of supplemental information, there is a good chance that at least a few individuals can be identified from an anonymized data set. Any re-identification, however, may potentially harm study participants because it will release individual genetic disease risks to the public. PMID:21190545

Caught you: threats to confidentiality due to the public release of large-scale genetic data sets.

PubMed

Wjst, Matthias

2010-12-29

Large-scale genetic data sets are frequently shared with other research groups and even released on the Internet to allow for secondary analysis. Study participants are usually not informed about such data sharing because data sets are assumed to be anonymous after stripping off personal identifiers. The assumption of anonymity of genetic data sets, however, is tenuous because genetic data are intrinsically self-identifying. Two types of re-identification are possible: the "Netflix" type and the "profiling" type. The "Netflix" type needs another small genetic data set, usually with less than 100 SNPs but including a personal identifier. This second data set might originate from another clinical examination, a study of leftover samples or forensic testing. When merged to the primary, unidentified set it will re-identify all samples of that individual. Even with no second data set at hand, a "profiling" strategy can be developed to extract as much information as possible from a sample collection. Starting with the identification of ethnic subgroups along with predictions of body characteristics and diseases, the asthma kids case as a real-life example is used to illustrate that approach. Depending on the degree of supplemental information, there is a good chance that at least a few individuals can be identified from an anonymized data set. Any re-identification, however, may potentially harm study participants because it will release individual genetic disease risks to the public.

The Evolution and Functional Impact of Human Deletion Variants Shared with Archaic Hominin Genomes

PubMed Central

Lin, Yen-Lung; Pavlidis, Pavlos; Karakoc, Emre; Ajay, Jerry; Gokcumen, Omer

2015-01-01

Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins. However, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. We identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the Human–Neandertal divergence (ancient) and only approximately 9% of which have been introgressed from Neandertals (introgressed). Recurrence, incomplete lineage sorting between human and chimp lineages, and hominid-specific insertions constitute the remaining approximately 4% of allele sharing between humans and archaic hominins. We observed that ancient deletions correspond to more than 13% of all common (>5% allele frequency) deletion variation among modern humans. Our analyses indicate that the genomic landscapes of both ancient and introgressed deletion variants were primarily shaped by purifying selection, eliminating large and exonic variants. We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts. The affected genes are involved in metabolism of external and internal compounds, growth and sperm formation, as well as susceptibility to psoriasis and Crohn’s disease. Our analyses suggest that these “exonic” deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection. Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes. PMID:25556237

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.

The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders.

PubMed

Grant, J D; Lynskey, M T; Madden, P A F; Nelson, E C; Few, L R; Bucholz, K K; Statham, D J; Martin, N G; Heath, A C; Agrawal, A

2015-12-01

Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses. Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24-37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder. Additive genetic (a(2) = 0.48-0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a(2) = 0.39) and shared environmental (c(2) = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38-0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40-73% of the genetic variance per substance. Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.

Origin of Japanese White-Eyes and Brown-Eared Bulbuls on the Volcano Islands.

PubMed

Sugita, Norimasa; Kawakami, Kazuto; Nishiumi, Isao

2016-04-01

The Ogasawara Archipelago comprises two groups of oceanic islands: the Bonin Islands, formed in the Paleogene, and the Volcano Islands, formed in the Quaternary. These groups are located within a moderate distance (ca. 160-270 km) of one another; thus, most land bird species are not distinguished as different subspecies. Two land birds, however, show unusual distribution. The Japanese white-eyes Zosterops japonicus originally inhabited only the Volcano Islands, but has been introduced to the Bonin Islands. The brown-eared bulbuls Hypsipetes amaurotis are distributed as a different subspecies. We investigated their genetic differences and divergences in the Ogasawara Archipelago using mitochondria DNA. The Volcano population of white-eyes had four endemic haplotypes that were divergent from one another, except for the Bonin population, which shared three haplotypes with the Volcano, Izu, and Ryukyu Islands and did not have any endemic haplotype. This is the first genetic suggestion that the Bonin population is a hybrid of introduced populations. With respect to bulbuls, the Volcano and Bonin Islands each had a single endemic haplotype. The Volcano haplotype is closest to a haplotype shared with Izu, the Japanese mainland, Daito and Ryukyu, whereas the Bonin haplotype is closest to one endemic to the south Ryukyu Islands. This indicates that the sources of the two bulbul populations can be geologically and temporally distinguished. The populations of the two species in the Ogasawara Archipelago are irreplaceable, owing to their genetic differences and should be regarded as evolutionarily significant units. In order to prevent introgression between the two populations, we must restrict interisland transfers.

Creativity and psychopathology: a shared vulnerability model.

PubMed

Carson, Shelley H

2011-03-01

Creativity is considered a positive personal trait. However, highly creative people have demonstrated elevated risk for certain forms of psychopathology, including mood disorders, schizophrenia spectrum disorders, and alcoholism. A model of shared vulnerability explains the relation between creativity and psychopathology. This model, supported by recent findings from neuroscience and molecular genetics, suggests that the biological determinants conferring risk for psychopathology interact with protective cognitive factors to enhance creative ideation. Elements of shared vulnerability include cognitive disinhibition (which allows more stimuli into conscious awareness), an attentional style driven by novelty salience, and neural hyperconnectivity that may increase associations among disparate stimuli. These vulnerabilities interact with superior meta-cognitive protective factors, such as high IQ, increased working memory capacity, and enhanced cognitive flexibility, to enlarge the range and depth of stimuli available in conscious awareness to be manipulated and combined to form novel and original ideas.

Clonal Outbreak of Plasmodium falciparum Infection in Eastern Panama

PubMed Central

Obaldia, Nicanor; Baro, Nicholas K.; Calzada, Jose E.; Santamaria, Ana M.; Daniels, Rachel; Wong, Wesley; Chang, Hsiao-Han; Hamilton, Elizabeth J.; Arevalo-Herrera, Myriam; Herrera, Socrates; Wirth, Dyann F.; Hartl, Daniel L.; Marti, Matthias; Volkman, Sarah K.

2015-01-01

Identifying the source of resurgent parasites is paramount to a strategic, successful intervention for malaria elimination. Although the malaria incidence in Panama is low, a recent outbreak resulted in a 6-fold increase in reported cases. We hypothesized that parasites sampled from this epidemic might be related and exhibit a clonal population structure. We tested the genetic relatedness of parasites, using informative single-nucleotide polymorphisms and drug resistance loci. We found that parasites were clustered into 3 clonal subpopulations and were related to parasites from Colombia. Two clusters of Panamanian parasites shared identical drug resistance haplotypes, and all clusters shared a chloroquine-resistance genotype matching the pfcrt haplotype of Colombian origin. Our findings suggest these resurgent parasite populations are highly clonal and that the high clonality likely resulted from epidemic expansion of imported or vestigial cases. Malaria outbreak investigations that use genetic tools can illuminate potential sources of epidemic malaria and guide strategies to prevent further resurgence in areas where malaria has been eliminated. PMID:25336725

The evolution of vision.

PubMed

Gehring, Walter J

2014-01-01

In this review, the evolution of vision is retraced from its putative origins in cyanobacteria to humans. Circadian oscillatory clocks, phototropism, and phototaxis require the capability to detect light. Photosensory proteins allow us to reconstruct molecular phylogenetic trees. The evolution of animal eyes leading from an ancestral prototype to highly complex image forming eyes can be deciphered on the basis of evolutionary developmental genetic experiments and comparative genomics. As all bilaterian animals share the same master control gene, Pax6, and the same retinal and pigment cell determination genes, we conclude that the different eye-types originated monophyletically and subsequently diversified by divergent, parallel, or convergent evolution. © 2012 Wiley Periodicals, Inc.

Tracing common origins of Genomic Islands in prokaryotes based on genome signature analyses.

PubMed

van Passel, Mark Wj

2011-09-01

Horizontal gene transfer constitutes a powerful and innovative force in evolution, but often little is known about the actual origins of transferred genes. Sequence alignments are generally of limited use in tracking the original donor, since still only a small fraction of the total genetic diversity is thought to be uncovered. Alternatively, approaches based on similarities in the genome specific relative oligonucleotide frequencies do not require alignments. Even though the exact origins of horizontally transferred genes may still not be established using these compositional analyses, it does suggest that compositionally very similar regions are likely to have had a common origin. These analyses have shown that up to a third of large acquired gene clusters that reside in the same genome are compositionally very similar, indicative of a shared origin. This brings us closer to uncovering the original donors of horizontally transferred genes, and could help in elucidating possible regulatory interactions between previously unlinked sequences.

Reconstructing the Indian Origin and Dispersal of the European Roma: A Maternal Genetic Perspective

PubMed Central

Mendizabal, Isabel; Valente, Cristina; Gusmão, Alfredo; Alves, Cíntia; Gomes, Verónica; Goios, Ana; Parson, Walther; Calafell, Francesc; Alvarez, Luis; Amorim, António; Gusmão, Leonor

2011-01-01

Previous genetic, anthropological and linguistic studies have shown that Roma (Gypsies) constitute a founder population dispersed throughout Europe whose origins might be traced to the Indian subcontinent. Linguistic and anthropological evidence point to Indo-Aryan ethnic groups from North-western India as the ancestral parental population of Roma. Recently, a strong genetic hint supporting this theory came from a study of a private mutation causing primary congenital glaucoma. In the present study, complete mitochondrial control sequences of Iberian Roma and previously published maternal lineages of other European Roma were analyzed in order to establish the genetic affinities among Roma groups, determine the degree of admixture with neighbouring populations, infer the migration routes followed since the first arrival to Europe, and survey the origin of Roma within the Indian subcontinent. Our results show that the maternal lineage composition in the Roma groups follows a pattern of different migration routes, with several founder effects, and low effective population sizes along their dispersal. Our data allowed the confirmation of a North/West migration route shared by Polish, Lithuanian and Iberian Roma. Additionally, eleven Roma founder lineages were identified and degrees of admixture with host populations were estimated. Finally, the comparison with an extensive database of Indian sequences allowed us to identify the Punjab state, in North-western India, as the putative ancestral homeland of the European Roma, in agreement with previous linguistic and anthropological studies. PMID:21264345

All roads lead to weediness: Patterns of genomic divergence reveal extensive recurrent weedy rice origins from South Asian Oryza.

PubMed

Huang, Zhongyun; Young, Nelson D; Reagon, Michael; Hyma, Katie E; Olsen, Kenneth M; Jia, Yulin; Caicedo, Ana L

2017-06-01

Weedy rice (Oryza spp.), a weedy relative of cultivated rice (O. sativa), infests and persists in cultivated rice fields worldwide. Many weedy rice populations have evolved similar adaptive traits, considered part of the 'agricultural weed syndrome', making this an ideal model to study the genetic basis of parallel evolution. Understanding parallel evolution hinges on accurate knowledge of the genetic background and origins of existing weedy rice groups. Using population structure analyses of South Asian and US weedy rice, we show that weeds in South Asia have highly heterogeneous genetic backgrounds, with ancestry contributions both from cultivated varieties (aus and indica) and wild rice. Moreover, the two main groups of weedy rice in the USA, which are also related to aus and indica cultivars, constitute a separate origin from that of Asian weeds. Weedy rice populations in South Asia largely converge on presence of red pericarps and awns and on ease of shattering. Genomewide divergence scans between weed groups from the USA and South Asia, and their crop relatives are enriched for loci involved in metabolic processes. Some candidate genes related to iconic weedy traits and competitiveness are highly divergent between some weed-crop pairs, but are not shared among all weed-crop comparisons. Our results show that weedy rice is an extreme example of recurrent evolution, and suggest that most populations are evolving their weedy traits through different genetic mechanisms. © 2017 John Wiley & Sons Ltd.

Common Psychiatric Disorders and Caffeine Use, Tolerance, and Withdrawal: An Examination of Shared Genetic and Environmental Effects

PubMed Central

Bergin, Jocilyn E.; Kendler, Kenneth S.

2012-01-01

Background Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Method Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. Results GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation = 0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. Conclusions There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes. PMID:22854069

Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects.

PubMed

Bergin, Jocilyn E; Kendler, Kenneth S

2012-08-01

Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation=0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes.

Managing Polyploidy in Ex Situ Conservation Genetics: The Case of the Critically Endangered Adriatic Sturgeon (Acipenser naccarii)

PubMed Central

Congiu, Leonardo; Pujolar, Jose Martin; Forlani, Anna; Cenadelli, Silvia; Dupanloup, Isabelle; Barbisan, Federica; Galli, Andrea; Fontana, Francesco

2011-01-01

While the current expansion of conservation genetics enables to address more efficiently the management of threatened species, alternative methods for genetic relatedness data analysis in polyploid species are necessary. Within this framework, we present a standardized and simple protocol specifically designed for polyploid species that can facilitate management of genetic diversity, as exemplified by the ex situ conservation program for the tetraploid Adriatic sturgeon Acipenser naccarii. A critically endangered endemic species of the Adriatic Sea tributaries, its persistence is strictly linked to the ex situ conservation of a single captive broodstock currently decimated to about 25 individuals, which represents the last remaining population of Adriatic sturgeon of certain wild origin. The genetic variability of three F1 broodstocks available as future breeders was estimated based on mitochondrial and microsatellite information and compared with the variability of the parental generation. Genetic data showed that the F1 stocks have only retained part of the genetic variation present in the original stock due to the few parent pairs used as founders. This prompts for the urgent improvement of the current F1 stocks by incorporating new founders that better represent the genetic diversity available. Following parental allocation based on band sharing values, we set up a user-friendly tool for selection of candidate breeders according to relatedness between all possible parent-pairs that secures the use of non-related individuals. The approach developed here could also be applied to other endangered tetraploid sturgeon species overexploited for caviar production, particularly in regions lacking proper infrastructure and/or expertise. PMID:21483472

Investigating the genetic and environmental bases of biases in threat recognition and avoidance in children with anxiety problems

PubMed Central

2012-01-01

Background Adults with anxiety show biased categorization and avoidance of threats. Such biases may emerge through complex interplay between genetics and environments, occurring early in life. Research on threat biases in children has focuses on a restricted range of biases, with insufficient focus on genetic and environmental origins. Here, we explore differences between children with and without anxiety problems in under-studied areas of threat bias. We focused both on associations with anxious phenotype and the underlying gene-environmental correlates for two specific processes: the categorisation of threat faces and avoidance learning. Method Two-hundred and fifty 10-year old MZ and DZ twin pairs (500 individuals) completed tasks assessing accuracy in the labelling of threatening facial expressions and in the acquisition of avoidant responses to a card associated with a masked threatening face. To assess whether participants met criteria for an anxiety disorder, parents of twins completed a self-guided computerized version of the Development and Well-being Assessment (DAWBA). Comparison of MZ and DZ twin correlations using model-fitting were used to compute estimates of genetic, shared and non-shared environmental effects. Results Of the 500 twins assessed, 25 (5%) met diagnostic criteria for a current anxiety disorder. Children with anxiety disorders were more accurate in their ability to recognize disgust faces than those without anxiety disorders, but were commensurate on identifying other threatening face emotions (angry, fearful, sad). Children with anxiety disorders but also more strongly avoided selecting a conditioned stimulus than non-anxious children. While recognition of socially threatening faces was moderately heritable, avoidant responses were heavily influenced by the non-shared environment. Conclusion These data add to other findings on threat biases in anxious children. Specifically, we found biases in the labelling of some negative-valence faces and in the acquisition of avoidant responses. While non-shared environmental effects explained all of the variance on threat avoidance, some of this may be due to measurement error. PMID:22788754

Genetic characterization of local Criollo pig breeds from the Americas using microsatellite markers.

PubMed

Revidatti, M A; Delgado Bermejo, J V; Gama, L T; Landi Periati, V; Ginja, C; Alvarez, L A; Vega-Pla, J L; Martínez, A M

2014-11-01

Little is known about local Criollo pig genetic resources and relationships among the various populations. In this paper, genetic diversity and relationships among 17 Criollo pig populations from 11 American countries were assessed with 24 microsatellite markers. Heterozygosities, F-statistics, and genetic distances were estimated, and multivariate, genetic structure and admixture analyses were performed. The overall means for genetic variability parameters based on the 24 microsatellite markers were the following: mean number of alleles per locus of 6.25 ± 2.3; effective number of alleles per locus of 3.33 ± 1.56; allelic richness per locus of 4.61 ± 1.37; expected and observed heterozygosity of 0.62 ± 0.04 and 0.57 ± 0.02, respectively; within-population inbreeding coefficient of 0.089; and proportion of genetic variability accounted for by differences among breeds of 0.11 ± 0.01. Genetic differences were not significantly associated with the geographical location to which breeds were assigned or their country of origin. Still, the NeighborNet dendrogram depicted the clustering by geographic origin of several South American breeds (Criollo Boliviano, Criollo of northeastern Argentina wet, and Criollo of northeastern Argentina dry), but some unexpected results were also observed, such as the grouping of breeds from countries as distant as El Salvador, Mexico, Ecuador, and Cuba. The results of genetic structure and admixture analyses indicated that the most likely number of ancestral populations was 11, and most breeds clustered separately when this was the number of predefined populations, with the exception of some closely related breeds that shared the same cluster and others that were admixed. These results indicate that Criollo pigs represent important reservoirs of pig genetic diversity useful for local development as well as for the pig industry.

Origins, genetic structure, and systematics of the narrow endemic peatmosses (Sphagnum): S. guwassanense and S. triseriporum (Sphagnaceae).

PubMed

Shaw, A Jonathan; Shaw, Blanka; Johnson, Matthew G; Higuchi, Masanobu; Arikawa, Tomotsugu; Ueno, Takeshi; Devos, Nicolas

2013-06-01

Sphagnum dominates vast expanses of wetland habitats throughout the northern hemisphere and species delimitation within the genus is important because floristic changes associated with a warming global climate may have measureable impacts on large-scale ecological processes. Most northern hemisphere peatmoss species (Sphagnum) have circumboreal ranges, but the Japanese species generally known as S. calymmatophyllum is endemic to Honshu Island. This prompted a population genetic and phylogenetic analysis to resolve the origin(s), population structure, and phylogenetic relationships of this morphologically variable species. • Sixty plants collected from Mt. Gassan and Mt. Hakkoda were genotyped for 12 microsatellite loci. Two plastid loci and three anonymous nuclear loci were sequenced in a subset of the plants, plus representatives from 10 closely related species. • Gametophytes exhibited fixed or nearly fixed heterozygosity at 9-10 of the 12 microsatellite loci. Two genetic groups were resolved by the microsatellite data, individuals showed no evidence of admixture, and the two groups of plants differ in morphology. They are heterozygous for different sets of alleles. The two taxa share plastid DNA sequences with two species that are common in Alaska. • Two taxa were distinguished: S. guwassanense and S. triseriporum. Both are allopolyploids; they originated independently from different but closely related progenitors. The maternal progenitor was likely either S. orientale or S. inexspectatum. The two allopolyploid taxa are heterozygous for (different) private microsatellite alleles, and one progenitor could be extinct.

HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe.

PubMed

Inotai, D; Szilvasi, A; Benko, S; Boros-Major, A; Illes, Z; Bors, A; Kiss, K P; Rajczy, K; Gelle-Hossó, A; Buhler, S; Nunes, J M; Sanchez-Mazas, A; Tordai, A

2015-08-01

Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

ORIGINS AND GENETIC DIVERSITY OF INTRODUCED POPULATIONS OF THE PUERTO RICAN RED-EYED COQUÍ, ELEUTHERODACTYLUS ANTILLENSIS, IN SAINT CROIX (U.S. VIRGIN ISLANDS) AND PANAMÁ

PubMed Central

Barker, Brittany S.; Rodríguez-Robles, Javier A.

2017-01-01

The Red-eyed Coquí, Eleutherodactylus antillensis, is a terrestrial frog endemic to the Puerto Rican Bank (Puerto Rico and numerous islands and cays off its eastern coast), in the eastern Caribbean Sea. The species was likely introduced in Saint Croix, an island c. 100 km southeast of Puerto Rico, in the late 1930s, and in Panamá City, Panamá, in the late 1950s or early 1960s, but the source(s) of these introductions are unknown. We analyzed sequence data from one mtDNA locus and four nuDNA introns to infer the origin(s) of the Saint Croix and Panamá City populations and quantify their genetic diversity. Saint Croix and Panamanian populations do not share any haplotypes, and they cluster with different native populations, suggesting that they are derived from separate sources in the Puerto Rican Bank. Patterns of population structure trace the probable sources of E. antillensis in Saint Croix to islands off Puerto Rico’s eastern coast, which include Vieques, Culebra, Saint Thomas, Saint John, Tortola, and Virgin Gorda, and possibly to eastern Puerto Rico as well. In contrast, Panamá City E. antillensis probably originated from either western or eastern Puerto Rico. Genetic diversity in the introduced populations is similar to or lower than in populations in the species’ native range, indicating that genetic diversity has not increased in the alien frogs. Our findings may facilitate the development of preventive measures to minimize introductions of non-native amphibians in the Caribbean and Central America. PMID:28649148

Comprehensive view of the population history of Arabia as inferred by mtDNA variation.

PubMed

Černý, Viktor; Čížková, Martina; Poloni, Estella S; Al-Meeri, Ali; Mulligan, Connie J

2016-04-01

Genetic and archaeological research supports the theory that Arabia was the first region traversed by modern humans as they left Africa and dispersed throughout Eurasia. However, the role of Arabia from the initial migration out of Africa until more recent times is still unclear. We have generated 379 new hypervariable segment 1 (HVS-1) sequences from a range of geographic locations throughout Yemen. We compare these data to published HVS-1 sequences representing Arabia and neighboring regions to build a unique dataset of 186 populations and 14,290 sequences. We identify 4,563 haplotypes unevenly distributed across Arabia and neighboring regions. Arabia contains higher proportions of shared haplotypes than the regions with which it shares these haplotypes, suggesting high levels of migration through the region. Populations in Arabia show higher levels of population expansion than those in East Africa, but lower levels than the Near East, Middle East or India. Arabian populations also show very high levels of genetic variation that overlaps with variation from most other regions. We take a population genetics approach to provide a comprehensive view of the relationships of Arabian and neighboring populations. We show that Arabian populations share closest links to the Near East and North Africa, but have a more ancient origin with slower demographic growth and/or lower migration rates. Our conclusions are supported by phylogenetic studies but also suggest that recent migrations have erased signals of earlier events. © 2015 Wiley Periodicals, Inc.

Northward dispersal of sea kraits (Laticauda semifasciata) beyond their typical range

PubMed Central

Park, Jaejin; Kim, Il-Hun; Fong, Jonathan J.; Koo, Kyo-Soung; Choi, Woo-Jin; Tsai, Tein-Shun

2017-01-01

Marine reptiles are declining globally, and recent climate change may be a contributing factor. The study of sea snakes collected beyond their typical distribution range provides valuable insight on how climate change affects marine reptile populations. Recently, we collected 12 Laticauda semifasciata (11 females, 1 male) from the waters around southern South Korea—an area located outside its typical distribution range (Japan, China including Taiwan, Philippines and Indonesia). We investigated the genetic origin of Korean specimens by analyzing mitochondrial cytochrome b gene (Cytb) sequences. Six individuals shared haplotypes with a group found in Taiwan-southern Ryukyu Islands, while the remaining six individuals shared haplotypes with a group encompassing the entire Ryukyu Archipelago. These results suggest L. semifasciata moved into Korean waters from the Taiwan-Ryukyu region via the Taiwan Warm Current and/or the Kuroshio Current, with extended survival facilitated by ocean warming. We highlight several contributing factors that increase the chances that L. semifasciata establishes new northern populations beyond the original distribution range. PMID:28644894

Phylogenetic analysis of two goat-origin PCV2 isolates in China.

PubMed

Wang, Xiaomin; Li, Wenliang; Xu, Xianglan; Wang, Wei; He, Kongwang; Fan, Hongjie

2018-04-20

Complete genome characterization of non-porcine origin Porcine circovirus type 2 (PCV2) was first described in 2014 in China. In the present study, we first identified PCV2 nucleotides in goat samples and the prevalence of PCV2 in goat was 6.15%. However, only two new strains, Goat2014-4 and Goat2014-5, could be completely sequenced. The genome of the strain Goat2014-4, which collected from the goat infected with PPRV, contains 1766 nt; strain Goat2014-5, which originated from a healthy goat, is comprised of 1767 nt. The results showed that they shared the highest nucleotide identity with BDH and the lowest similarity with DK1980PMWSfree strain and they belonged only to genotype PCV2d. Meanwhile, they shared higher homology with porcine-origin PCV2 strains than others. Moreover, a detailed analysis of the capsid amino acid sequences revealed that there were distinct differences for goat2014-4 (708 bp) and goat2014-5 (705 bp); strain Goat2014-4 showed an elongation of two amino acids, and strains Goat2014-5 showed an elongation of one amino acid compared with other reference strains. This is the first report of the genetic analysis of goat-origin PCV2 isolates. It also provides an additional supported evidence for cross-species transmission of PCV2. Copyright © 2018 Elsevier B.V. All rights reserved.

The etiology of social aggression: a nuclear twin family study.

PubMed

Slawinski, Brooke L; Klump, Kelly L; Burt, S Alexandra

2018-04-02

Social aggression is a form of antisocial behavior in which social relationships and social status are used to damage reputations and inflict emotional harm on others. Despite extensive research examining the prevalence and consequences of social aggression, only a few studies have examined its genetic-environmental etiology, with markedly inconsistent results. We estimated the etiology of social aggression using the nuclear twin family (NTF) model. Maternal-report, paternal-report, and teacher-report data were collected for twin social aggression (N = 1030 pairs). We also examined the data using the classical twin (CT) model to evaluate whether its strict assumptions may have biased previous heritability estimates. The best-fitting NTF model for all informants was the ASFE model, indicating that additive genetic, sibling environmental, familial environmental, and non-shared environmental influences significantly contribute to the etiology of social aggression in middle childhood. However, the best-fitting CT model varied across informants, ranging from AE and ACE to CE. Specific heritability estimates for both NTF and CT models also varied across informants such that teacher reports indicated greater genetic influences and father reports indicated greater shared environmental influences. Although the specific NTF parameter estimates varied across informants, social aggression generally emerged as largely additive genetic (A = 0.15-0.77) and sibling environmental (S = 0.42-0.72) in origin. Such findings not only highlight an important role for individual genetic risk in the etiology of social aggression, but also raise important questions regarding the role of the environment.

Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health.

PubMed

Cabello, Felipe C; Godfrey, Henry P; Tomova, Alexandra; Ivanova, Larisa; Dölz, Humberto; Millanao, Ana; Buschmann, Alejandro H

2013-07-01

The worldwide growth of aquaculture has been accompanied by a rapid increase in therapeutic and prophylactic usage of antimicrobials including those important in human therapeutics. Approximately 80% of antimicrobials used in aquaculture enter the environment with their activity intact where they select for bacteria whose resistance arises from mutations or more importantly, from mobile genetic elements containing multiple resistance determinants transmissible to other bacteria. Such selection alters biodiversity in aquatic environments and the normal flora of fish and shellfish. The commonality of the mobilome (the total of all mobile genetic elements in a genome) between aquatic and terrestrial bacteria together with the presence of residual antimicrobials, biofilms, and high concentrations of bacteriophages where the aquatic environment may also be contaminated with pathogens of human and animal origin can stimulate exchange of genetic information between aquatic and terrestrial bacteria. Several recently found genetic elements and resistance determinants for quinolones, tetracyclines, and β-lactamases are shared between aquatic bacteria, fish pathogens, and human pathogens, and appear to have originated in aquatic bacteria. Excessive use of antimicrobials in aquaculture can thus potentially negatively impact animal and human health as well as the aquatic environment and should be better assessed and regulated. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Population Structure of Mountain Pine Beetle Symbiont Leptographium longiclavatum and the Implication on the Multipartite Beetle-Fungi Relationships

PubMed Central

Tsui, Clement Kin-Ming; Farfan, Lina; Roe, Amanda D.; Rice, Adrianne V.; Cooke, Janice E. K.; El-Kassaby, Yousry A.; Hamelin, Richard C.

2014-01-01

Over 18 million ha of forests have been destroyed in the past decade in Canada by the mountain pine beetle (MPB) and its fungal symbionts. Understanding their population dynamics is critical to improving modeling of beetle epidemics and providing potential clues to predict population expansion. Leptographium longiclavatum and Grosmannia clavigera are fungal symbionts of MPB that aid the beetle to colonize and kill their pine hosts. We investigated the genetic structure and demographic expansion of L. longiclavatum in populations established within the historic distribution range and in the newly colonized regions. We identified three genetic clusters/populations that coincide with independent geographic locations. The genetic profiles of the recently established populations in northern British Columbia (BC) and Alberta suggest that they originated from central and southern BC. Approximate Bayesian Computation supports the scenario that this recent expansion represents an admixture of individuals originating from BC and the Rocky Mountains. Highly significant correlations were found among genetic distance matrices of L. longiclavatum, G. clavigera, and MPB. This highlights the concordance of demographic processes in these interacting organisms sharing a highly specialized niche and supports the hypothesis of long-term multipartite beetle-fungus co-evolutionary history and mutualistic relationships. PMID:25153489

Genomic architecture of adaptive color pattern divergence and convergence in Heliconius butterflies

PubMed Central

Supple, Megan A.; Hines, Heather M.; Dasmahapatra, Kanchon K.; Lewis, James J.; Nielsen, Dahlia M.; Lavoie, Christine; Ray, David A.; Salazar, Camilo; McMillan, W. Owen; Counterman, Brian A.

2013-01-01

Identifying the genetic changes driving adaptive variation in natural populations is key to understanding the origins of biodiversity. The mosaic of mimetic wing patterns in Heliconius butterflies makes an excellent system for exploring adaptive variation using next-generation sequencing. In this study, we use a combination of techniques to annotate the genomic interval modulating red color pattern variation, identify a narrow region responsible for adaptive divergence and convergence in Heliconius wing color patterns, and explore the evolutionary history of these adaptive alleles. We use whole genome resequencing from four hybrid zones between divergent color pattern races of Heliconius erato and two hybrid zones of the co-mimic Heliconius melpomene to examine genetic variation across 2.2 Mb of a partial reference sequence. In the intergenic region near optix, the gene previously shown to be responsible for the complex red pattern variation in Heliconius, population genetic analyses identify a shared 65-kb region of divergence that includes several sites perfectly associated with phenotype within each species. This region likely contains multiple cis-regulatory elements that control discrete expression domains of optix. The parallel signatures of genetic differentiation in H. erato and H. melpomene support a shared genetic architecture between the two distantly related co-mimics; however, phylogenetic analysis suggests mimetic patterns in each species evolved independently. Using a combination of next-generation sequencing analyses, we have refined our understanding of the genetic architecture of wing pattern variation in Heliconius and gained important insights into the evolution of novel adaptive phenotypes in natural populations. PMID:23674305

Explaining individual differences in alcohol intake in adults: evidence for genetic and cultural transmission?

PubMed

van Beek, Jenny H D A; de Moor, Marleen H M; Geels, Lot M; Willemsen, Gonneke; Boomsma, Dorret I

2014-03-01

The current study aimed to describe what proportion of variation in adult alcohol intake is attributable to genetic differences among individuals and what proportion to differences in environmental experiences individuals have been exposed to. Effects of age, gender, spousal resemblance, and cultural transmission of alcohol intake from parents to offspring were taken into account. In a twin-family design, the effects of genetic and cultural transmission and shared and nonshared environment on alcohol intake were estimated with genetic structural equation models. Data originated from adult twins, their siblings, parents (n = 12,587), and spouses (n = 429) registered with the population-based Netherlands Twin Register (63.5% female; ages 18-97 years). Alcohol intake (grams per day) was higher among men than women and increased with age. Broad-sense heritability estimates were similar across sex and age (53%). Spousal resemblance was observed (r = .39) but did not significantly affect the heritability estimates. No effects of cultural transmission were detected. In total, 23% of the variation in alcohol intake was explained by additive genetic effects, 30% by dominant (nonadditive) gene action, and 47% by environmental effects that were not shared among family members. Individual differences in adult alcohol intake are explained by genetic and individual-specific environmental effects. The same genes are expressed in males and females and in younger and older participants. A substantial part of the heritability of alcohol intake is attributable to nonadditive gene action. Effects of cultural transmission that have been reported in adolescence are not present in adulthood.

A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility

PubMed Central

Gupta, Aditi; Juyal, Garima; Sood, Ajit; Midha, Vandana; Yamazaki, Keiko; Vich Vila, Arnau; Esaki, Motohiro; Matsui, Toshiyuki; Takahashi, Atsushi; Kubo, Michiaki; Weersma, Rinse K; Thelma, B K

2017-01-01

The first ever genome-wide association study (GWAS) of ulcerative colitis in genetically distinct north Indian population identified two novel genes namely CFB and SLC44A4. Considering their biological relevance, we investigated allelic/genetic heterogeneity in these genes among ulcerative colitis cohorts of north Indian, Japanese and Dutch origin using high-density ImmunoChip case–control genotype data. Comparative linkage disequilibrium profiling and test of association were performed. Of the 28 CFB SNPs, similar strength of association was observed for rs4151657 (novel ulcerative colitis GWAS SNP) in north Indians (P=1.73 × 10−10) and Japanese (P=2.02 × 10−12) but not in the Dutch. Further, a three-marker haplotype was shared between north Indians and Japanese (P<10−8), but a different five-marker haplotype was associated (P=2.07 × 10−6) in the Dutch. Of the 22 SLC44A4 SNPs, rs2736428 (novel ulcerative colitis GWAS SNP) was found significantly associated in north Indians (P=4.94 × 10−10) and Japanese (P=3.37 × 10−9), but not among the Dutch. These results suggest (i) apparent allelic heterogeneity in CFB and genetic heterogeneity in SLC44A4 across different ethnic groups; (ii) shared ulcerative colitis genetic etiological factors among Asians; and finally (iii) re-exploration of GWAS findings together with high-density genotyping/sequencing and trans-ethnic fine mapping approaches may help identify shared and population-specific risk variants and enable to explain missing disease heritability. PMID:27759029

Genomic diversity and evolution of the head crest in the rock pigeon.

PubMed

Shapiro, Michael D; Kronenberg, Zev; Li, Cai; Domyan, Eric T; Pan, Hailin; Campbell, Michael; Tan, Hao; Huff, Chad D; Hu, Haofu; Vickrey, Anna I; Nielsen, Sandra C A; Stringham, Sydney A; Hu, Hao; Willerslev, Eske; Gilbert, M Thomas P; Yandell, Mark; Zhang, Guojie; Wang, Jun

2013-03-01

The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.

The ties that bind: genetic relatedness predicts the fission and fusion of social groups in wild African elephants.

PubMed

Archie, Elizabeth A; Moss, Cynthia J; Alberts, Susan C

2006-03-07

Many social animals live in stable groups. In contrast, African savannah elephants (Loxodonta africana) live in unusually fluid, fission-fusion societies. That is, 'core' social groups are composed of predictable sets of individuals; however, over the course of hours or days, these groups may temporarily divide and reunite, or they may fuse with other social groups to form much larger social units. Here, we test the hypothesis that genetic relatedness predicts patterns of group fission and fusion among wild, female African elephants. Our study of a single Kenyan population spans 236 individuals in 45 core social groups, genotyped at 11 microsatellite and one mitochondrial DNA (mtDNA) locus. We found that genetic relatedness predicted group fission; adult females remained with their first order maternal relatives when core groups fissioned temporarily. Relatedness also predicted temporary fusion between social groups; core groups were more likely to fuse with each other when the oldest females in each group were genetic relatives. Groups that shared mtDNA haplotypes were also significantly more likely to fuse than groups that did not share mtDNA. Our results suggest that associations between core social groups persist for decades after the original maternal kin have died. We discuss these results in the context of kin selection and its possible role in the evolution of elephant sociality.

A Neolithic expansion, but strong genetic structure, in the independent history of New Guinea

PubMed Central

Bergström, Anders; Oppenheimer, Stephen J; Mentzer, Alexander J; Auckland, Kathryn; Robson, Kathryn; Attenborough, Robert; Alpers, Michael P; Koki, George; Pomat, William; Siba, Peter; Xue, Yali; Sandhu, Manjinder S; Tyler-Smith, Chris

2018-01-01

New Guinea shows human occupation since ~50 thousand years ago (kya), independent adoption of plant cultivation ~10 kya, and great cultural and linguistic diversity today. We performed genome-wide SNP genotyping on 381 individuals from 85 language groups in Papua New Guinea (PNG) and find a sharp divide originating 10-20 kya between lowland and highland groups, and a lack of non-New Guinean admixture in the latter. All highlanders share ancestry within the last 10 kya, with major population growth in the same period, suggesting population structure was reshaped following the Neolithic lifestyle transition. However, genetic differentiation between groups in PNG is much stronger than in comparable regions in Eurasia, demonstrating that such a transition does not necessarily limit the genetic and linguistic diversity of human societies. PMID:28912245

Genetic Variability of the Neogregarine Apicystis bombi, an Etiological Agent of an Emergent Bumblebee Disease

PubMed Central

Maebe, Kevin; Arbetman, Marina; Morales, Carolina; Graystock, Peter; Hughes, William O. H.; Plischuk, Santiago; Lange, Carlos E.; de Graaf, Dirk C.; Zapata, Nelson; de la Rosa, Jose Javier Perez; Murray, Tomás E.; Brown, Mark J. F.; Smagghe, Guy

2013-01-01

The worldwide spread of diseases is considered a major threat to biodiversity and a possible driver of the decline of pollinator populations, particularly when novel species or strains of parasites emerge. Previous studies have suggested that populations of introduced European honeybee (Apis mellifera) and bumblebee species (Bombus terrestris and Bombus ruderatus) in Argentina share the neogregarine parasite Apicystis bombi with the native bumblebee (Bombus dahlbomii). In this study we investigated whether A. bombi is acting as an emergent parasite in the non-native populations. Specifically, we asked whether A. bombi, recently identified in Argentina, was introduced by European, non-native bees. Using ITS1 and ITS2 to assess the parasite’s intraspecific genetic variation in bees from Argentina and Europe, we found a largely unstructured parasite population, with only 15% of the genetic variation being explained by geographic location. The most abundant haplotype in Argentina (found in all 9 specimens of non-native species) was identical to the most abundant haplotype in Europe (found in 6 out of 8 specimens). Similarly, there was no evidence of structuring by host species, with this factor explaining only 17% of the genetic variation. Interestingly, parasites in native Bombus ephippiatus from Mexico were genetically distant from the Argentine and European samples, suggesting that sufficient variability does exist in the ITS region to identify continent-level genetic structure in the parasite. Thus, the data suggest that A. bombi from Argentina and Europe share a common, relatively recent origin. Although our data did not provide information on the direction of transfer, the absence of genetic structure across space and host species suggests that A. bombi may be acting as an emergent infectious disease across bee taxa and continents. PMID:24324696

Data sharing and intellectual property in a genomic epidemiology network: policies for large-scale research collaboration.

PubMed Central

Chokshi, Dave A.; Parker, Michael; Kwiatkowski, Dominic P.

2006-01-01

Genomic epidemiology is a field of research that seeks to improve the prevention and management of common diseases through an understanding of their molecular origins. It involves studying thousands of individuals, often from different populations, with exacting techniques. The scale and complexity of such research has required the formation of research consortia. Members of these consortia need to agree on policies for managing shared resources and handling genetic data. Here we consider data-sharing and intellectual property policies for an international research consortium working on the genomic epidemiology of malaria. We outline specific guidelines governing how samples and data are transferred among its members; how results are released into the public domain; when to seek protection for intellectual property; and how intellectual property should be managed. We outline some pragmatic solutions founded on the basic principles of promoting innovation and access. PMID:16710548

Identification of genetic loci shared between schizophrenia and the Big Five personality traits.

PubMed

Smeland, Olav B; Wang, Yunpeng; Lo, Min-Tzu; Li, Wen; Frei, Oleksandr; Witoelar, Aree; Tesli, Martin; Hinds, David A; Tung, Joyce Y; Djurovic, Srdjan; Chen, Chi-Hua; Dale, Anders M; Andreassen, Ole A

2017-05-22

Schizophrenia is associated with differences in personality traits, and recent studies suggest that personality traits and schizophrenia share a genetic basis. Here we aimed to identify specific genetic loci shared between schizophrenia and the Big Five personality traits using a Bayesian statistical framework. Using summary statistics from genome-wide association studies (GWAS) on personality traits in the 23andMe cohort (n = 59,225) and schizophrenia in the Psychiatric Genomics Consortium cohort (n = 82,315), we evaluated overlap in common genetic variants. The Big Five personality traits neuroticism, extraversion, openness, agreeableness and conscientiousness were measured using a web implementation of the Big Five Inventory. Applying the conditional false discovery rate approach, we increased discovery of genetic loci and identified two loci shared between neuroticism and schizophrenia and six loci shared between openness and schizophrenia. The study provides new insights into the relationship between personality traits and schizophrenia by highlighting genetic loci involved in their common genetic etiology.

The “Genetic Program”: Behind the Genesis of an Influential Metaphor

PubMed Central

Peluffo, Alexandre E.

2015-01-01

The metaphor of the “genetic program,” indicating the genome as a set of instructions required to build a phenotype, has been very influential in biology despite various criticisms over the years. This metaphor, first published in 1961, is thought to have been invented independently in two different articles, one by Ernst Mayr and the other by François Jacob and Jacques Monod. Here, after a detailed analysis of what both parties meant by “genetic program,” I show, using unpublished archives, the strong resemblance between the ideas of Mayr and Monod and suggest that their idea of genetic program probably shares a common origin. I explore the possibility that the two men met before 1961 and also exchanged their ideas through common friends and colleagues in the field of molecular biology. Based on unpublished correspondence of Jacob and Monod, I highlight the important events that influenced the preparation of their influential paper, which introduced the concept of the genetic program. Finally, I suggest that the genetic program metaphor may have preceded both papers and that it was probably used informally before 1961. PMID:26170444

It takes two to tango: information-sharing with offspring among heterosexual parents following identity-release sperm donation

PubMed Central

Isaksson, S.; Skoog-Svanberg, A.; Sydsjö, G.; Linell, L.; Lampic, C.

2016-01-01

STUDY QUESTION How do heterosexual parents reason about and experience information-sharing with offspring following identity-release sperm donation? SUMMARY ANSWER Sharing information about using donor-conception with offspring is a complex process at several levels, with the parent's personal beliefs and the child's responses serving as driving or impeding forces for the information-sharing process. WHAT IS KNOWN ALREADY The overall view of disclosure in gamete donation has shifted from secrecy to openness, but there is still uncertainty among parents concerning how and when to tell the child about his/her genetic origin. Most research on donor-conceived families has focused on donation treatment under anonymous or known circumstances, and there is a lack of studies in settings with identity-release donations. STUDY DESIGN, SIZE, DURATION A qualitative interview study among 30 parents following identity-release sperm donation treatment. Interviews were conducted from February 2014 to March 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS The present study is part of the prospective longitudinal Swedish Study on Gamete Donation (SSGD), including all fertility clinics performing gamete donation in Sweden. A sample of participants in the SSGD, consisting of heterosexual parents with children aged 7–8 years following identity-release sperm donation, participated in individual semi-structured interviews. MAIN RESULTS AND THE ROLE OF CHANCE The analysis revealed one main theme: information-sharing is a process, with three subthemes; (i) the parent as process manager, (ii) the child as force or friction and (iii) being in the process. The first two subthemes were viewed as being linked together and their content served as driving or impeding forces in the information-sharing process. LIMITATIONS, REASONS FOR CAUTION The fact that the study was performed within the context of the Swedish legislation on identity-release donation must be taken into consideration as regards transferability to other populations, as this may affect parents' reasoning concerning their information-sharing with the child. WIDER IMPLICATIONS OF THE FINDINGS The present findings highlight the role of the donor-conceived child in the information-sharing process and may contribute to develop counselling that increases parents' confidence in handling children's reactions to information about their genetic origin. STUDY FUNDING/COMPETING INTEREST(S) Financial support from The Swedish Research Council, The Family Planning Fund in Uppsala and Ferring Pharmaceuticals. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. PMID:26637490

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

Genesis of the novel human-infecting influenza A(H10N8) virus and potential genetic diversity of the virus in poultry, China.

PubMed

Qi, W; Zhou, X; Shi, W; Huang, L; Xia, W; Liu, D; Li, H; Chen, S; Lei, F; Cao, L; Wu, J; He, F; Song, W; Li, Q; Li, H; Liao, M; Liu, M

2014-06-26

Human infection with a novel influenza A(H10N8) virus was first described in China in December 2013. However, the origin and genetic diversity of this virus is still poorly understood. We performed a phylogenetic analysis and coalescent analysis of two viruses from the first case of influenza A(H10N8) (A/Jiangxi-Donghu/346-1/2013 and A/Jiangxi-Donghu/346-2/2013 and a novel A(H10N8) virus (A/chicken/Jiangxi/102/2013) isolated from a live poultry market that the patient had visited. The haemagglutinin (HA), neuraminidase (NA), PA subunit of the virus polymerase complex, nucleoprotein (NP), M and nonstructural protein (NS) genes of the three virus strains shared the same genetic origins. The origins of their HA and NA genes were similar: originally from wild birds to ducks, and then to chickens. The PA, NP, M, and NS genes were similar to those of chicken influenza A(H9N2) viruses. Coalescent analyses showed that the reassortment of these genes from A(H9N2) to A(H10N8) might have occurred at least twice. However, the PB1 and PB2 genes of the chicken A(H10N8) virus most likely originated from H7-like viruses of ducks, while those of the viruses from the case most likely stemmed from A(H9N2) viruses circulating in chickens. The oseltamivir-resistance mutation, R292K (R291K in A(H10N8) numbering) in the NA protein, occurred after four days of oseltamivir treatment. It seems that A(H10N8) viruses might have become established among poultry and their genetic diversity might be much higher than what we have observed.

Why did eukaryotes evolve only once? Genetic and energetic aspects of conflict and conflict mediation

PubMed Central

Blackstone, Neil W.

2013-01-01

According to multi-level theory, evolutionary transitions require mediating conflicts between lower-level units in favour of the higher-level unit. By this view, the origin of eukaryotes and the origin of multicellularity would seem largely equivalent. Yet, eukaryotes evolved only once in the history of life, whereas multicellular eukaryotes have evolved many times. Examining conflicts between evolutionary units and mechanisms that mediate these conflicts can illuminate these differences. Energy-converting endosymbionts that allow eukaryotes to transcend surface-to-volume constraints also can allocate energy into their own selfish replication. This principal conflict in the origin of eukaryotes can be mediated by genetic or energetic mechanisms. Genome transfer diminishes the heritable variation of the symbiont, but requires the de novo evolution of the protein-import apparatus and was opposed by selection for selfish symbionts. By contrast, metabolic signalling is a shared primitive feature of all cells. Redox state of the cytosol is an emergent feature that cannot be subverted by an individual symbiont. Hypothetical scenarios illustrate how metabolic regulation may have mediated the conflicts inherent at different stages in the origin of eukaryotes. Aspects of metabolic regulation may have subsequently been coopted from within-cell to between-cell pathways, allowing multicellularity to emerge repeatedly. PMID:23754817

Why did eukaryotes evolve only once? Genetic and energetic aspects of conflict and conflict mediation.

PubMed

Blackstone, Neil W

2013-07-19

According to multi-level theory, evolutionary transitions require mediating conflicts between lower-level units in favour of the higher-level unit. By this view, the origin of eukaryotes and the origin of multicellularity would seem largely equivalent. Yet, eukaryotes evolved only once in the history of life, whereas multicellular eukaryotes have evolved many times. Examining conflicts between evolutionary units and mechanisms that mediate these conflicts can illuminate these differences. Energy-converting endosymbionts that allow eukaryotes to transcend surface-to-volume constraints also can allocate energy into their own selfish replication. This principal conflict in the origin of eukaryotes can be mediated by genetic or energetic mechanisms. Genome transfer diminishes the heritable variation of the symbiont, but requires the de novo evolution of the protein-import apparatus and was opposed by selection for selfish symbionts. By contrast, metabolic signalling is a shared primitive feature of all cells. Redox state of the cytosol is an emergent feature that cannot be subverted by an individual symbiont. Hypothetical scenarios illustrate how metabolic regulation may have mediated the conflicts inherent at different stages in the origin of eukaryotes. Aspects of metabolic regulation may have subsequently been coopted from within-cell to between-cell pathways, allowing multicellularity to emerge repeatedly.

The double life of DNA

PubMed Central

McMurray, Cynthia T.; Vijg, Jan

2015-01-01

This issue of Current Opinions focuses on the dual role of DNA in life and death. In ancient Roman religion and myth, Janus is the god who looks both to the past and to the future. He guides the beginnings of life, its progression from one condition to another, and he foresees distant events. The analogy to DNA could not be stronger. Closely interacting with the environment, our basic genetics provides the origin of life, guides the quality of health with age, predicts disease, and ultimately foresees our end. A shared and deep interest in the origin of life has long prompted our desire to define aging, and, ultimately, to understand whether it can be reversed. In this special issue, the authors collectively review concepts of normative aging, DNA instability, DNA repair, the genetic contribution of age and diet to disease, and how the basic molecular transactions of DNA give it a double life that guides health and survival, as well as the transitions to death. PMID:25282314

Is Mania the Hypertension of the Mood? Discussion of A Hypothesis

PubMed Central

Rihmer, Zoltán; Gonda, Xénia; Döme, Péter

2017-01-01

Abstract: Beyond both being biphasic/bidirectional disorders (hypo)mania and essential hypertension share a surprising number of similarities and an overlap between their genetics, biological background, underlying personality and temperamental factors, precipitating factors, comorbidity and response to treatment, indicating a possibly partially shared biological background. Based on theoretical knowledge, similarities related to characteristics, manifestation and course, and the results of pharmacological studies related to the effects and side effects of pharmacotherapies used in the treatment of these two distinct disorders, the authors outline a hypothesis discussing the similar origins of these two phenomena and thus mania being the hypertension of mood in memory of Athanasios Koukopoulos, one of the greatest researchers and theoreticists of mania of all time. PMID:28503115

A Predominant Variable-Number Tandem-Repeat Cluster of Mycobacterium tuberculosis Isolates among Asylum Seekers in the Netherlands and Denmark, Deciphered by Whole-Genome Sequencing

PubMed Central

de Neeling, Albert; Rasmussen, Erik Michael; Norman, Anders; Mulder, Arnout; van Hunen, Rianne; de Vries, Gerard; Haddad, Walid; Anthony, Richard; Lillebaek, Troels; van der Hoek, Wim; van Soolingen, Dick

2017-01-01

ABSTRACT In many countries, Mycobacterium tuberculosis isolates are routinely subjected to variable-number tandem-repeat (VNTR) typing to investigate M. tuberculosis transmission. Unexpectedly, cross-border clusters were identified among African refugees in the Netherlands and Denmark, although transmission in those countries was unlikely. Whole-genome sequencing (WGS) was applied to analyze transmission in depth and to assess the precision of VNTR typing. WGS was applied to 40 M. tuberculosis isolates from refugees in the Netherlands and Denmark (most of whom were from the Horn of Africa) that shared the exact same VNTR profile. Cluster investigations were undertaken to identify in-country epidemiological links. Combining WGS results for the isolates (all members of the central Asian strain [CAS]/Delhi genotype), from both European countries, an average genetic distance of 80 single-nucleotide polymorphisms (SNPs) (maximum, 153 SNPs) was observed. The few pairs of isolates with confirmed epidemiological links, except for one pair, had a maximum distance of 12 SNPs. WGS divided this refugee cluster into several subclusters of patients from the same country of origin. Although the M. tuberculosis cases, mainly originating from African countries, shared the exact same VNTR profile, most were clearly distinguished by WGS. The average genetic distance in this specific VNTR cluster was 2 times greater than that in other VNTR clusters. Thus, identical VNTR profiles did not represent recent direct M. tuberculosis transmission for this group of patients. It appears that either these strains from Africa are extremely conserved genetically or there is ongoing transmission of this genotype among refugees on their long migration routes from Africa to Europe. PMID:29167288

A Predominant Variable-Number Tandem-Repeat Cluster of Mycobacterium tuberculosis Isolates among Asylum Seekers in the Netherlands and Denmark, Deciphered by Whole-Genome Sequencing.

PubMed

Jajou, Rana; de Neeling, Albert; Rasmussen, Erik Michael; Norman, Anders; Mulder, Arnout; van Hunen, Rianne; de Vries, Gerard; Haddad, Walid; Anthony, Richard; Lillebaek, Troels; van der Hoek, Wim; van Soolingen, Dick

2018-02-01

In many countries, Mycobacterium tuberculosis isolates are routinely subjected to variable-number tandem-repeat (VNTR) typing to investigate M. tuberculosis transmission. Unexpectedly, cross-border clusters were identified among African refugees in the Netherlands and Denmark, although transmission in those countries was unlikely. Whole-genome sequencing (WGS) was applied to analyze transmission in depth and to assess the precision of VNTR typing. WGS was applied to 40 M. tuberculosis isolates from refugees in the Netherlands and Denmark (most of whom were from the Horn of Africa) that shared the exact same VNTR profile. Cluster investigations were undertaken to identify in-country epidemiological links. Combining WGS results for the isolates (all members of the central Asian strain [CAS]/Delhi genotype), from both European countries, an average genetic distance of 80 single-nucleotide polymorphisms (SNPs) (maximum, 153 SNPs) was observed. The few pairs of isolates with confirmed epidemiological links, except for one pair, had a maximum distance of 12 SNPs. WGS divided this refugee cluster into several subclusters of patients from the same country of origin. Although the M. tuberculosis cases, mainly originating from African countries, shared the exact same VNTR profile, most were clearly distinguished by WGS. The average genetic distance in this specific VNTR cluster was 2 times greater than that in other VNTR clusters. Thus, identical VNTR profiles did not represent recent direct M. tuberculosis transmission for this group of patients. It appears that either these strains from Africa are extremely conserved genetically or there is ongoing transmission of this genotype among refugees on their long migration routes from Africa to Europe. Copyright © 2018 Jajou et al.

Binary and microsatellite polymorphisms of the Y-chromosome in the Mbenzele pygmies from the Central African Republic.

PubMed

Coia, Valentina; Caglià, Alessandra; Arredi, Barbara; Donati, Francesco; Santos, Fabrício R; Pandya, Arpita; Taglioli, Luca; Paoli, Giorgio; Pascali, Vincenzo; Spedini, Gabriella; Destro-Bisol, Giovanni; Tyler-Smith, Chris

2004-01-01

This study analyzes the variation of six binary polymorphisms and six microsatellites in the Mbenzele Pygmies from the Central African Republic. Five different haplogroups (B2b, E(xE3a), E3a, P and BR(xB2b,DE,P)) were observed, with frequencies ranging from 0.022 (haplogroup P) to 0.609 (haplogroup E3a). A comparison of haplogroup frequencies indicates a close genetic affinity between the Mbenzele and the Biaka Pygmies, a finding consistent with the common origin and the geographical proximity of the two populations. The haplogroups P, BR(xB2b,DE,P) and E(xE3a), which are rare in sub-Saharan Africa but common in western Eurasia, were observed with frequencies ranging from 0.022 (haplogroup P) to 0.087 (haplogroup E(xE3a)). Thirty different microsatellite haplotypes were detected, with frequencies ranging from 0.022 to 0.152. The Mbenzele share the highest percent of microsatellite haplotypes with the Biaka Pygmies. Five out seven haplotypes which are shared by the Mbenzele and Biaka Pygmies belong to haplogroup E3a, which suggests that they are of Bantu origin. The plot based on F(st) genetic distances calculated using microsatellite data provides a picture of population relationships which is in part congruent and in part complementary to that obtained using haplogroup frequencies. Finally, the Mbenzele and Biaka Pygmies were found to be markedly more genetically similar using Y-chromosomal than autosomal microsatellites. We suggest that this could be due to the higher phylogenetic stability of Y-chromosome and to the effect of the male-biased gene flow during the Bantu expansion. Copyright 2003 Wiley-Liss, Inc.

Molecular characterization and phylogenetic relationship of wild type 1 poliovirus strains circulating across Pakistan and Afghanistan bordering areas during 2010-2012.

PubMed

Shaukat, Shahzad; Angez, Mehar; Alam, Muhammad Masroor; Sharif, Salmaan; Khurshid, Adnan; Malik, Farzana; Rehman, Lubna; Zaidi, Syed Sohail Zahoor

2014-01-01

Pakistan and Afghanistan share a long uncontrolled border with extensive population movement on both sides. Wild poliovirus transmission has never been interrupted in this block due to war against terrorism, poor public health infrastructure, misconceptions about polio vaccines and inadequate immunization activities. All these issues complicate the eradication operations and reinforce the complexity of wiping out poliomyelitis from this region. This study illustrates the origins and routes of cross-border wild poliovirus type 1 (WPV1) transmission during 2010-2012 between Pakistan and Afghanistan. Sequence analyses were conducted based on complete VP1 capsid protein sequences for WPV1 study strains to determine the origin of poliovirus genetic lineages and their evolutionary relationships. Phylogenetic tree was constructed from VP1 gene sequences applying Maximum Likelihood method using Kimura 2- parameter model in MEGA program v 5.0. A total of 72 (14.3%) out of 502 wild-type 1 polioviruses were found circulating in border areas of both countries during 2010-2012. Molecular phylogenetic analysis classified these strains in to two sub-genotypes with four clusters and 18 lineages. Genetic data confirmed that the most of WPV1 lineages (12; 66.6%) were transmitted from Pakistan to Afghanistan. However, the genetic diversity was significantly reduced during 2012 as most of the lineages were completely eliminated. In conclusion, Pakistan-Afghanistan block has emerged as a single poliovirus reservoir sharing the multiple poliovirus lineages due to uncontrolled movement of people across the borders between two countries. If it is neglected, it can jeopardize the extensive global efforts done so-far to eradicate the poliovirus infection. Our data will be helpful to devise the preventive strategies for effective control of wild poliovirus transmission in this region.

Original Mycobacterial Sin, a consequence of highly homologous antigens?

PubMed

Jenkins, A O; Michel, A; Rutten, V

2017-05-01

The role of antigens shared between Mycobacteria in in-vivo cross-reactive immune responses in host animals, have been reported to be responsible for reduced BCG vaccination efficacy as well reduced specificity of routine immunological diagnostic tests. This presents with significant disease control challenges in humans and animals. The present review highlights the results of previous studies on the effect of pre-sensitization to environmental mycobacteria on either pathogenic mycobacteria and/or M. bovis BCG, in experimental animals. It also takes an in-depth view into assessing the genetic similarities and relationships between atypical mycobacteria and Mycobacterium tuberculosis complex (MTBC) and how they might explain the immunological imprint of environmental mycobacteria in directing the hosts' immune response upon subsequent exposure to other classes of mycobacteria. The outcome of this review suggests that genetic closeness between particular atypical mycobacteria and MTBC usually indicate a higher level of homology for certain shared protective antigens. This ultimately results in a higher level of cross reactive immune responses as compared with other atypical mycobacteria that are further away genetically. This would explain the different effects of environmental mycobacteria on MTBC that have been reported in the different studies. In other words the direction of the host immune system in response to exposure to MTBC would depend on the type of environmental mycobacteria that was encountered in the initial exposure. We also explain these mycobacterial interactions in the context of the phenomenon of "Original Mycobacterial Sin". The effects of these inevitable mycobacterial interactions on field diagnosis and control by vaccination and how to circumvent them are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Comparative analysis of barophily-related amino acid content in protein domains of Pyrococcus abyssi and Pyrococcus furiosus.

PubMed

Yafremava, Liudmila S; Di Giulio, Massimo; Caetano-Anollés, Gustavo

2013-01-01

Amino acid substitution patterns between the nonbarophilic Pyrococcus furiosus and its barophilic relative P. abyssi confirm that hydrostatic pressure asymmetry indices reflect the extent to which amino acids are preferred by barophilic archaeal organisms. Substitution patterns in entire protein sequences, shared protein domains defined at fold superfamily level, domains in homologous sequence pairs, and domains of very ancient and very recent origin now provide further clues about the environment that led to the genetic code and diversified life. The pyrococcal proteomes are very similar and share a very early ancestor. Relative amino acid abundance analyses showed that biases in the use of amino acids are due to their shared fold superfamilies. Within these repertoires, only two of the five amino acids that are preferentially barophilic, aspartic acid and arginine, displayed this preference significantly and consistently across structure and in domains appearing in the ancestor. The more primordial asparagine, lysine and threonine displayed a consistent preference for nonbarophily across structure and in the ancestor. Since barophilic preferences are already evident in ancient domains that are at least ~3 billion year old, we conclude that barophily is a very ancient trait that unfolded concurrently with genetic idiosyncrasies in convergence towards a universal code.

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

PubMed

Rommelse, Nanda N J; Franke, Barbara; Geurts, Hilde M; Hartman, Catharina A; Buitelaar, Jan K

2010-03-01

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD. This review will provide an overview on all available studies [family based, twin, candidate gene, linkage, and genome wide association (GWA) studies] shedding light on the role of shared genetic underpinnings of ADHD and ASD. It is concluded that family and twin studies do provide support for the hypothesis that ADHD and ASD originate from partly similar familial/genetic factors. Only a few candidate gene studies, linkage studies and GWA studies have specifically addressed this co-occurrence, pinpointing to some promising pleiotropic genes, loci and single nucleotide polymorphisms (SNPs), but the research field is in urgent need for better designed and powered studies to tackle this complex issue. We propose that future studies examining shared familial etiological factors for ADHD and ASD use a family-based design in which the same phenotypic (ADHD and ASD), candidate endophenotypic, and environmental measurements are obtained from all family members. Multivariate multi-level models are probably best suited for the statistical analysis.

Genetic Diversity and Phylogenetic Analysis of South-East Asian Duck Populations Based on the mtDNA D-loop Sequences

PubMed Central

Sultana, H.; Seo, D. W.; Bhuiyan, M. S. A.; Choi, N. R.; Hoque, M. R.; Heo, K. N.; Lee, J. H.

2016-01-01

The maternally inherited mitochondrial DNA (mtDNA) D–loop region is widely used for exploring genetic relationships and for investigating the origin of various animal species. Currently, domestic ducks play an important role in animal protein supply. In this study, partial mtDNA D–loop sequences were obtained from 145 samples belonging to six South-East Asian duck populations and commercial duck population. All these populations were closely related to the mallard duck (Anas platyrhynchos), as indicated by their mean overall genetic distance. Sixteen nucleotide substitutions were identified in sequence analyses allowing the distinction of 28 haplotypes. Around 42.76% of the duck sequences were classified as Hap_02, which completely matched with Anas platyrhynchos duck species. The neighbor-joining phylogenetic tree also revealed that South-East Asian duck populations were closely related to Anas platyrhynchos. Network profiles were also traced using the 28 haplotypes. Overall, results showed that those duck populations D-loop haplotypes were shared between several duck breeds from Korea and Bangladesh sub continental regions. Therefore, these results confirmed that South-East Asian domestic duck populations have been domesticated from Anas platyrhynchos duck as the maternal origins. PMID:27004808

Nuclear, chloroplast, and mitochondrial data of a US cannabis DNA database.

PubMed

Houston, Rachel; Birck, Matthew; LaRue, Bobby; Hughes-Stamm, Sheree; Gangitano, David

2018-05-01

As Cannabis sativa (marijuana) is a controlled substance in many parts of the world, the ability to track biogeographical origin of cannabis could provide law enforcement with investigative leads regarding its trade and distribution. Population substructure and inbreeding may cause cannabis plants to become more genetically related. This genetic relatedness can be helpful for intelligence purposes. Analysis of autosomal, chloroplast, and mitochondrial DNA allows for not only prediction of biogeographical origin of a plant but also discrimination between individual plants. A previously validated, 13-autosomal STR multiplex was used to genotype 510 samples. Samples were analyzed from four different sites: 21 seizures at the US-Mexico border, Northeastern Brazil, hemp seeds purchased in the US, and the Araucania area of Chile. In addition, a previously reported multi-loci system was modified and optimized to genotype five chloroplast and two mitochondrial markers. For this purpose, two methods were designed: a homopolymeric STR pentaplex and a SNP triplex with one chloroplast (Cscp001) marker shared by both methods for quality control. For successful mitochondrial and chloroplast typing, a novel real-time PCR quantitation method was developed and validated to accurately estimate the quantity of the chloroplast DNA (cpDNA) using a synthetic DNA standard. Moreover, a sequenced allelic ladder was also designed for accurate genotyping of the homopolymeric STR pentaplex. For autosomal typing, 356 unique profiles were generated from the 425 samples that yielded full STR profiles and 25 identical genotypes within seizures were observed. Phylogenetic analysis and case-to-case pairwise comparisons of 21 seizures at the US-Mexico border, using the Fixation Index (F ST ) as genetic distance, revealed the genetic association of nine seizures that formed a reference population. For mitochondrial and chloroplast typing, subsampling was performed, and 134 samples were genotyped. Complete haplotypes (STRs and SNPs) were observed for 127 samples. As expected, extensive haplotype sharing was observed; five distinguishable haplotypes were detected. In the reference population, the same haplotype was observed 39 times and two unique haplotypes were also detected. Haplotype sharing was observed between the US border seizures, Brazil, and Chile, while the hemp samples generated a distinct haplotype. Phylogenetic analysis of the four populations was performed, and results revealed that both autosomal and lineage markers could discern population substructure.

Evidence for Shared Predisposition in the Relationship between Cannabis Use and Subcortical Brain Structure

PubMed Central

Pagliaccio, David; Barch, Deanna M.; Bogdan, Ryan; Wood, Phillip K.; Lynskey, Michael T.; Heath, Andrew C.; Agrawal, Arpana

2015-01-01

Importance Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use. Objective To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations. Design Cross-sectional diagnostic interview, behavioral, and neuroimaging data. Setting Community sampling and established family registries. Participants Data from 483 participants (22-35 years old), enrolled in the on-going Human Connectome Project; 262 participants reported cannabis exposure, i.e. ever using cannabis in their lifetime. Main Outcome Measures Whole brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever use, age of onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed-models were used to examine volume differences in sex-matched, concordant unexposed (Npairs=71), exposed (Npairs=81), or exposure discordant (Npairs=89) sibling pairs. Results Cannabis exposure was related to smaller left amygdala (~2.3%) and right ventral striatum volumes (~3.5%). These volumetric differences were within the range of normal variation. The relationship between left amygdala volume and cannabis use was largely due to shared genetic factors (ρg=−0.43, p=0.004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use. Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs. Conclusions and Relevance Differences in amygdala volume in cannabis users are attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (e.g. ventral striatum) or at more severe levels of cannabis involvement and deserve further study. PMID:26308883

The role of the Vlax Roma in shaping the European Romani maternal genetic history.

PubMed

Salihović, Marijana Peričić; Barešić, Ana; Klarić, Irena Martinović; Cukrov, Slavena; Lauc, Lovorka Barać; Janićijević, Branka

2011-10-01

The Roma are comprised of many founder groups of common Indian origins but different socio-cultural characteristics. The Vlax Roma are one of the founder Roma populations characterized by a period of bondage in the historic Romanian principalities, and by the archaic Romanian language. Demographic history suggests different migration routes of Roma populations, especially after their arrival in Mesopotamia and the eastern boundary of the Byzantine Empire. Although various genetic studies of uniparental genetic markers showed a connection between Roma genetic legacy and their migration routes, precise sampling of Roma populations elucidates this relationship in more detail. In this study, we analyzed mitochondrial DNA of 384 Croatian Vlax Roma from two geographic locations in the context of 734 European Roma samples. Our results show that Roma migration routes are marked with two Near-Eastern haplogroups, X2 and U3, whose inverse proportional incidence clearly separates the Balkan and the Vlax Roma from other Roma populations that reached Europe as part of the first migration wave. Spatial and temporal characteristics of these haplogroups indicate a possibility of their admixture with Roma populations before arrival in Europe. Distribution of haplogroup M35 indicates that all Vlax Roma populations descend from one single founder population that might even reach back to the original ancestral Indian population. Founder effects followed by strict endogamy rules can be traced from India to contemporary small, local communities, as in the case of two Croatian Vlax Roma populations that show clear population differentiation despite similar origins and shared demographic history. Copyright © 2011 Wiley-Liss, Inc.

The Image and Data Archive at the Laboratory of Neuro Imaging.

PubMed

Crawford, Karen L; Neu, Scott C; Toga, Arthur W

2016-01-01

The LONI Image and Data Archive (IDA)(1) is a repository for sharing and long-term preservation of neuroimaging and biomedical research data. Originally designed to archive strictly medical image files, the IDA has evolved over the last ten years and now encompasses the storage and dissemination of neuroimaging, clinical, biospecimen, and genetic data. In this article, we report upon the genesis of the IDA and how it currently securely manages data and protects data ownership. Copyright © 2015 Elsevier Inc. All rights reserved.

Shared genetic contributions of fruit and vegetable consumption with BMI in families 20 y after sharing a household.

PubMed

Martin, Lisa J; Lee, Seung-Yeon; Couch, Sarah C; Morrison, John; Woo, Jessica G

2011-10-01

Obesity has a strong genetic basis, but the identification of genetic variants has not resulted in improved clinical care. However, phenotypes that influence weight, such as diet, may have shared underpinnings with obesity. Interestingly, diet also has a genetic basis. Thus, we hypothesized that the genetic underpinnings of diet may partially overlap with the genetics of obesity. Our objective was to determine whether dietary intake and BMI share heritable components in adulthood. We used a cross-sectional cohort of parents and adult offspring (n = 1410) from the Princeton Follow-up Study. Participants completed Block food-frequency questionnaires 15-27 y after sharing a household. Heritability of dietary intakes was estimated by using variance components analysis. Bivariate genetic analyses were used to estimate the shared effects between BMI and heritable dietary intakes. Fruit, vegetable, and protein consumption exhibited moderate heritability [(mean ± SE) 0.26 ± 0.06, 0.32 ± 0.06, and 0.21 ± 0.06, respectively; P < 0.001], but other dietary intakes were modest (h(2) < 0.2). Only fruit and vegetable consumption exhibited genetic correlations with BMI (ρ(g) = -0.28 ± 0.13 and -0.30 ± 0.13, respectively; P < 0.05). Phenotypic correlations with BMI were not significant. We showed that fruit, vegetable, and protein intakes are moderately heritable and that fruit and vegetable consumption shares underlying genetic effects with BMI in adulthood, which suggests that individuals genetically predisposed to low fruit and vegetable consumption may be predisposed to higher BMI. Thus, obese individuals who have low fruit and vegetable consumption may require targeted interventions that go beyond low-calorie, plant-based programs for weight management.

The origin and evolution of Homo sapiens

PubMed Central

Stringer, Chris

2016-01-01

If we restrict the use of Homo sapiens in the fossil record to specimens which share a significant number of derived features in the skeleton with extant H. sapiens, the origin of our species would be placed in the African late middle Pleistocene, based on fossils such as Omo Kibish 1, Herto 1 and 2, and the Levantine material from Skhul and Qafzeh. However, genetic data suggest that we and our sister species Homo neanderthalensis shared a last common ancestor in the middle Pleistocene approximately 400–700 ka, which is at least 200 000 years earlier than the species origin indicated from the fossils already mentioned. Thus, it is likely that the African fossil record will document early members of the sapiens lineage showing only some of the derived features of late members of the lineage. On that basis, I argue that human fossils such as those from Jebel Irhoud, Florisbad, Eliye Springs and Omo Kibish 2 do represent early members of the species, but variation across the African later middle Pleistocene/early Middle Stone Age fossils shows that there was not a simple linear progression towards later sapiens morphology, and there was chronological overlap between different ‘archaic’ and ‘modern’ morphs. Even in the late Pleistocene within and outside Africa, we find H. sapiens specimens which are clearly outside the range of Holocene members of the species, showing the complexity of recent human evolution. The impact on species recognition of late Pleistocene gene flow between the lineages of modern humans, Neanderthals and Denisovans is also discussed, and finally, I reconsider the nature of the middle Pleistocene ancestor of these lineages, based on recent morphological and genetic data. This article is part of the themed issue ‘Major transitions in human evolution’. PMID:27298468

The origin and evolution of Homo sapiens.

PubMed

Stringer, Chris

2016-07-05

If we restrict the use of Homo sapiens in the fossil record to specimens which share a significant number of derived features in the skeleton with extant H. sapiens, the origin of our species would be placed in the African late middle Pleistocene, based on fossils such as Omo Kibish 1, Herto 1 and 2, and the Levantine material from Skhul and Qafzeh. However, genetic data suggest that we and our sister species Homo neanderthalensis shared a last common ancestor in the middle Pleistocene approximately 400-700 ka, which is at least 200 000 years earlier than the species origin indicated from the fossils already mentioned. Thus, it is likely that the African fossil record will document early members of the sapiens lineage showing only some of the derived features of late members of the lineage. On that basis, I argue that human fossils such as those from Jebel Irhoud, Florisbad, Eliye Springs and Omo Kibish 2 do represent early members of the species, but variation across the African later middle Pleistocene/early Middle Stone Age fossils shows that there was not a simple linear progression towards later sapiens morphology, and there was chronological overlap between different 'archaic' and 'modern' morphs. Even in the late Pleistocene within and outside Africa, we find H. sapiens specimens which are clearly outside the range of Holocene members of the species, showing the complexity of recent human evolution. The impact on species recognition of late Pleistocene gene flow between the lineages of modern humans, Neanderthals and Denisovans is also discussed, and finally, I reconsider the nature of the middle Pleistocene ancestor of these lineages, based on recent morphological and genetic data.This article is part of the themed issue 'Major transitions in human evolution'. © 2016 The Author(s).

Integrating paleoecology and genetics of bird populations in two sky island archipelagos.

PubMed

McCormack, John E; Bowen, Bonnie S; Smith, Thomas B

2008-06-27

Genetic tests of paleoecological hypotheses have been rare, partly because recent genetic divergence is difficult to detect and time. According to fossil plant data, continuous woodland in the southwestern USA and northern Mexico became fragmented during the last 10,000 years, as warming caused cool-adapted species to retreat to high elevations. Most genetic studies of resulting 'sky islands' have either failed to detect recent divergence or have found discordant evidence for ancient divergence. We test this paleoecological hypothesis for the region with intraspecific mitochondrial DNA and microsatellite data from sky-island populations of a sedentary bird, the Mexican jay (Aphelocoma ultramarina). We predicted that populations on different sky islands would share common, ancestral alleles that existed during the last glaciation, but that populations on each sky island, owing to their isolation, would contain unique variants of postglacial origin. We also predicted that divergence times estimated from corrected genetic distance and a coalescence model would post-date the last glacial maximum. Our results provide multiple independent lines of support for postglacial divergence, with the predicted pattern of shared and unique mitochondrial DNA haplotypes appearing in two independent sky-island archipelagos, and most estimates of divergence time based on corrected genetic distance post-dating the last glacial maximum. Likewise, an isolation model based on multilocus gene coalescence indicated postglacial divergence of five pairs of sky islands. In contrast to their similar recent histories, the two archipelagos had dissimilar historical patterns in that sky islands in Arizona showed evidence for older divergence, suggesting different responses to the last glaciation. This study is one of the first to provide explicit support from genetic data for a postglacial divergence scenario predicted by one of the best paleoecological records in the world. Our results demonstrate that sky islands act as generators of genetic diversity at both recent and historical timescales and underscore the importance of thorough sampling and the use of loci with fast mutation rates to studies that test hypotheses concerning recent genetic divergence.

CMCpy: Genetic Code-Message Coevolution Models in Python

PubMed Central

Becich, Peter J.; Stark, Brian P.; Bhat, Harish S.; Ardell, David H.

2013-01-01

Code-message coevolution (CMC) models represent coevolution of a genetic code and a population of protein-coding genes (“messages”). Formally, CMC models are sets of quasispecies coupled together for fitness through a shared genetic code. Although CMC models display plausible explanations for the origin of multiple genetic code traits by natural selection, useful modern implementations of CMC models are not currently available. To meet this need we present CMCpy, an object-oriented Python API and command-line executable front-end that can reproduce all published results of CMC models. CMCpy implements multiple solvers for leading eigenpairs of quasispecies models. We also present novel analytical results that extend and generalize applications of perturbation theory to quasispecies models and pioneer the application of a homotopy method for quasispecies with non-unique maximally fit genotypes. Our results therefore facilitate the computational and analytical study of a variety of evolutionary systems. CMCpy is free open-source software available from http://pypi.python.org/pypi/CMCpy/. PMID:23532367

Recent Advances in the Genetics of Vocal Learning

PubMed Central

Condro, Michael C.; White, Stephanie A.

2015-01-01

Language is a complex communicative behavior unique to humans, and its genetic basis is poorly understood. Genes associated with human speech and language disorders provide some insights, originating with the FOXP2 transcription factor, a mutation in which is the source of an inherited form of developmental verbal dyspraxia. Subsequently, targets of FOXP2 regulation have been associated with speech and language disorders, along with other genes. Here, we review these recent findings that implicate genetic factors in human speech. Due to the exclusivity of language to humans, no single animal model is sufficient to study the complete behavioral effects of these genes. Fortunately, some animals possess subcomponents of language. One such subcomponent is vocal learning, which though rare in the animal kingdom, is shared with songbirds. We therefore discuss how songbird studies have contributed to the current understanding of genetic factors that impact human speech, and support the continued use of this animal model for such studies in the future. PMID:26052371

Genetic pleiotropy explains associations between musical auditory discrimination and intelligence.

PubMed

Mosing, Miriam A; Pedersen, Nancy L; Madison, Guy; Ullén, Fredrik

2014-01-01

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions.

Genetic Pleiotropy Explains Associations between Musical Auditory Discrimination and Intelligence

PubMed Central

Mosing, Miriam A.; Pedersen, Nancy L.; Madison, Guy; Ullén, Fredrik

2014-01-01

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions. PMID:25419664

Genetic and environmental factors affecting birth size variation: a pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts.

PubMed

Yokoyama, Yoshie; Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo; Fagnani, Corrado; Stazi, Maria A; Brescianini, Sonia; Ji, Fuling; Ning, Feng; Pang, Zengchang; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Rebato, Esther; Hopper, John L; Cutler, Tessa L; Saudino, Kimberly J; Nelson, Tracy L; Whitfield, Keith E; Corley, Robin P; Huibregtse, Brooke M; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Llewellyn, Clare H; Fisher, Abigail; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Bartels, Meike; van Beijsterveldt, Catharina E M; Willemsen, Gonneke; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas S; Craig, Jeffrey M; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Haworth, Claire M A; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Rasmussen, Finn; Tynelius, Per; Tarnoki, Adam D; Tarnoki, David L; Ooki, Syuichi; Rose, Richard J; Pietiläinen, Kirsi H; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko; Silventoinen, Karri

2018-05-19

The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

PubMed Central

Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

2014-01-01

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. PMID:24128326

HapZipper: sharing HapMap populations just got easier.

PubMed

Chanda, Pritam; Elhaik, Eran; Bader, Joel S

2012-11-01

The rapidly growing amount of genomic sequence data being generated and made publicly available necessitate the development of new data storage and archiving methods. The vast amount of data being shared and manipulated also create new challenges for network resources. Thus, developing advanced data compression techniques is becoming an integral part of data production and analysis. The HapMap project is one of the largest public resources of human single-nucleotide polymorphisms (SNPs), characterizing over 3 million SNPs genotyped in over 1000 individuals. The standard format and biological properties of HapMap data suggest that a dedicated genetic compression method can outperform generic compression tools. We propose a compression methodology for genetic data by introducing HapZipper, a lossless compression tool tailored to compress HapMap data beyond benchmarks defined by generic tools such as gzip, bzip2 and lzma. We demonstrate the usefulness of HapZipper by compressing HapMap 3 populations to <5% of their original sizes. HapZipper is freely downloadable from https://bitbucket.org/pchanda/hapzipper/downloads/HapZipper.tar.bz2.

The relationship between parent-child conflict and adolescent antisocial behavior: confirming shared environmental mediation.

PubMed

Klahr, Ashlea M; Rueter, Martha A; McGue, Matt; Iacono, William G; Burt, S Alexandra

2011-07-01

Prior studies have indicated that the relationship between parent-child conflict and adolescent antisocial behavior is at least partially shared environmental in origin. However, all available research on this topic (to our knowledge) relies exclusively on parent and/or adolescent informant-reports, both of which are subject to various forms of rater bias. As the presence of significant shared environmental effects has often been attributed to rater bias in the past (Baker et al. Journal of Abnormal Psychology 16:219-235, 2007; Bartels et al. Journal of the American Academy of Child and Adolescent Psychiatry 42:1351-1359, 2003, Twin Research 7:162-175, 2004; Hewitt et al. Behavior Genetics 22:293-317, 1992), it would be important to confirm that findings of shared environmental mediation persist when even examining (presumably more objective) observer-ratings of these constructs. The current study thus examined the origins of the relationship between parent-child conflict and adolescent acting-out behavior, as measured using both observer-ratings and various informant-reports. Participants included 1,199 adopted and non-adopted adolescents in 610 families from the Sibling Interaction and Behavior Study (SIBS). Results indicated that parent-child conflict consistently predicts acting-out behavior in adopted adolescents, and moreover, that this association is equivalent to that in biologically-related adolescents. Most importantly, these findings did not vary across parent- and adolescent-reported or observer-ratings of parent-child conflict and acting-out behavior. Such findings argue strongly against rater bias as a primary explanation of shared environmental mediation of the association between parent-child conflict and adolescent antisocial behavior.

Transmission Genetics of Allorecognition in Hydractinia Symbiolongicarpus (Cnidaria: Hydrozoa)

PubMed Central

Mokady, O.; Buss, L. W.

1996-01-01

Allorecognition is ubiquitous, or nearly so, amongst colonial invertebrates. Despite the prominent role that such phenomena have played both in evolutionary theory and in speculations on the origin of the vertebrate immune system, unambiguous data on the transmission genetics of fusibility (i.e., the ability of two individuals to fuse upon tissue contact) is lacking for any metazoan outside of the phylum Chordata. We have developed lines of the hydroid Hydractinia symbiolongicarpus (Phylum Cnidaria) inbred for fusibility and here report results of breeding experiments establishing that fusibility segregates as expected for a single locus with codominantly expressed alleles, with one shared allele producing a fusible phenotype. Surveys of fusibility in field populations and additional breeding experiments indicate the presence of an extensive allele series. PMID:8725230

Examining the etiological associations among higher-order temperament dimensions

PubMed Central

Allan, Nicholas P.; Mikolajewski, Amy J.; Lonigan, Christopher J.; Hart, Sara A.; Taylor, Jeanette

2014-01-01

A multivariate independent pathway model was used to examine the shared and unique genetic and environmental influences of Positive Affect (PA), Negative Affect (NA), and effortful control (EC) in a sample of 686 twin pairs (M age = 10.07, SD = 1.74). There were common genetic influences and nonshared environmental influences shared across all three temperament dimensions and shared environmental influences in common to NA and EC. There were also significant independent genetic influences unique to PA and NA and significant independent shared environmental influences unique to PA. This study demonstrates that there are genetic and environmental influences that affect the covariance among temperament dimensions as well as unique genetic and environmental influences that influence the dimensions independently. PMID:24729641

A Neolithic expansion, but strong genetic structure, in the independent history of New Guinea.

PubMed

Bergström, Anders; Oppenheimer, Stephen J; Mentzer, Alexander J; Auckland, Kathryn; Robson, Kathryn; Attenborough, Robert; Alpers, Michael P; Koki, George; Pomat, William; Siba, Peter; Xue, Yali; Sandhu, Manjinder S; Tyler-Smith, Chris

2017-09-15

New Guinea shows human occupation since ~50 thousand years ago (ka), independent adoption of plant cultivation ~10 ka, and great cultural and linguistic diversity today. We performed genome-wide single-nucleotide polymorphism genotyping on 381 individuals from 85 language groups in Papua New Guinea and find a sharp divide originating 10 to 20 ka between lowland and highland groups and a lack of non-New Guinean admixture in the latter. All highlanders share ancestry within the last 10 thousand years, with major population growth in the same period, suggesting population structure was reshaped following the Neolithic lifestyle transition. However, genetic differentiation between groups in Papua New Guinea is much stronger than in comparable regions in Eurasia, demonstrating that such a transition does not necessarily limit the genetic and linguistic diversity of human societies. Copyright © 2017, American Association for the Advancement of Science.

Genetic evidence supports song learning in the three-wattled bellbird Procnias tricarunculata (Cotingidae).

PubMed

Saranathan, Vinodkumar; Hamilton, Deborah; Powell, George V N; Kroodsma, Donald E; Prum, Richard O

2007-09-01

Vocal learning is thought to have evolved in three clades of birds (parrots, hummingbirds, and oscine passerines), and three clades of mammals (whales, bats, and primates). Behavioural data indicate that, unlike other suboscine passerines, the three-wattled bellbird Procnias tricarunculata (Cotingidae) is capable of vocal learning. Procnias tricarunculata shows conspicuous vocal ontogeny, striking geographical variation in song, and rapid temporal change in song within a population. Deprivation studies of vocal development in P. tricarunculata are impractical. Here, we report evidence from mitochondrial DNA sequences and nuclear microsatellite loci that genetic variation within and among the four allopatric breeding populations of P. tricarunculata is not congruent with variation in vocal behaviour. Sequences of the mitochondrial DNA control region document extensive haplotype sharing among localities and song types, and no phylogenetic resolution of geographical populations or behavioural groups. The vocally differentiated, allopatric breeding populations of P. tricarunculata are only weakly genetically differentiated populations, and are not distinct taxa. Mitochondrial DNA and microsatellite variation show small (2.9% and 13.5%, respectively) but significant correlation with geographical distance, but no significant residual variation by song type. Estimates of the strength of selection that would be needed to maintain the observed geographical pattern in vocal differentiation if songs were genetically based are unreasonably high, further discrediting the hypothesis of a genetic origin of vocal variation. These data support a fourth, phylogenetically independent origin of avian vocal learning in Procnias. Geographical variations in P. tricarunculata vocal behaviour are likely culturally evolved dialects.

Population genetic structure in Sabatieria (Nematoda) reveals intermediary gene flow and admixture between distant cold seeps from the Mediterranean Sea.

PubMed

De Groote, Annelies; Hauquier, Freija; Vanreusel, Ann; Derycke, Sofie

2017-07-01

There is a general lack of information on the dispersal and genetic structuring for populations of small-sized deep-water taxa, including free-living nematodes which inhabit and dominate the seafloor sediments. This is also true for unique and scattered deep-sea habitats such as cold seeps. Given the limited dispersal capacity of marine nematodes, genetic differentiation between such geographically isolated habitat patches is expected to be high. Against this background, we examined genetic variation in both mitochondrial (COI) and nuclear (18S and 28S ribosomal) DNA markers of 333 individuals of the genus Sabatieria, abundantly present in reduced cold-seep sediments. Samples originated from four Eastern Mediterranean cold seeps, separated by hundreds of kilometers, and one seep in the Southeast Atlantic. Individuals from the Mediterranean and Atlantic were divided into two separate but closely-related species clades. Within the Eastern Mediterranean, all specimens belonged to a single species, but with a strong population genetic structure (Φ ST  = 0.149). The haplotype network of COI contained 19 haplotypes with the most abundant haplotype (52% of the specimens) shared between all four seeps. The number of private haplotypes was high (15), but the number of mutations between haplotypes was low (1-8). These results indicate intermediary gene flow among the Mediterranean Sabatieria populations with no evidence of long-term barriers to gene flow. The presence of shared haplotypes and multiple admixture events indicate that Sabatieria populations from disjunct cold seeps are not completely isolated, with gene flow most likely facilitated through water current transportation of individuals and/or eggs. Genetic structure and molecular diversity indices are comparable to those of epiphytic shallow-water marine nematodes, while no evidence of sympatric cryptic species was found for the cold-seep Sabatieria.

The contribution of genetics and environment to obesity.

PubMed

Albuquerque, David; Nóbrega, Clévio; Manco, Licínio; Padez, Cristina

2017-09-01

Obesity is a global health problem mainly attributed to lifestyle changes such as diet, low physical activity or socioeconomics factors. However, several evidences consistently showed that genetics contributes significantly to the weight-gain susceptibility. A systematic literature search of most relevant original, review and meta-analysis, restricted to English was conducted in PubMed, Web of Science and Google scholar up to May 2017 concerning the contribution of genetics and environmental factors to obesity. Several evidences suggest that obesogenic environments contribute to the development of an obese phenotype. However, not every individual from the same population, despite sharing the same obesogenic environment, develop obesity. After more than 10 years of investigation on the genetics of obesity, the variants found associated with obesity represent only 3% of the estimated BMI-heritability, which is around 47-80%. Moreover, genetic factors per se were unable to explain the rapid spread of obesity prevalence. The integration of multi-omics data enables scientists having a better picture and to elucidate unknown pathways contributing to obesity. New studies based on case-control or gene candidate approach will be important to identify new variants associated with obesity susceptibility and consequently unveiling its genetic architecture. This will lead to an improvement of our understanding about underlying mechanisms involved in development and origin of the actual obesity epidemic. The integration of several omics will also provide insights about the interplay between genes and environments contributing to the obese phenotype. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study

PubMed Central

Alemany, Silvia; Rijsdijk, Frühling V.; Haworth, Claire Margaret Alison; Fañanás, Lourdes; Plomin, Robert

2013-01-01

Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added asa covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors. PMID:23627958

Genetic diversity based on SSR analysis of the cultured snakehead fish, Channa argus, (Channidae) in China.

PubMed

Zhu, S-R; Li, J-L; Xie, N; Zhu, L-M; Wang, Q; Yue, G-H

2014-02-13

The snakehead fish Channa argus is an important food fish in China. We identified six microsatellite loci for C. argus. These six microsatellite loci and four other microsatellite markers were used to analyze genetic diversity in four cultured populations of C. argus (SD, JX, HN, and ZJ) and determine their relationships. A total of 154 alleles were detected at the 10 microsatellite loci. The average expected and observed heterozygosities varied from 0.70-0.84 and 0.69-0.83, respectively, and polymorphism information content ranged between 0.66 and 0.82 in the four populations, indicating high genetic diversity. Population JX deviated from mutation-drift equilibrium and may have experienced a recent bottleneck. Analysis of pairwise genetic differentiation revealed FST values that ranged from 0.028 to 0.100, which indicates a moderate level of genetic differentiation. The largest distances were observed between populations HN and SD, whereas the smallest distances were obtained between populations HN and JX. Genetic clustering analysis demonstrated that the ZJ and HN populations probably share the same origin. This information about the genetic diversity within each of the four populations, and their genetic relationships will be useful for future genetic improvement of C. argus through selective breeding.

Y chromosomal evidence on the origin of northern Thai people.

PubMed

Brunelli, Andrea; Kampuansai, Jatupol; Seielstad, Mark; Lomthaisong, Khemika; Kangwanpong, Daoroong; Ghirotto, Silvia; Kutanan, Wibhu

2017-01-01

The Khon Mueang represent the major group of people present in today's northern Thailand. While linguistic and genetic data seem to support a shared ancestry between Khon Mueang and other Tai-Kadai speaking people, the possibility of an admixed origin with contribution from local Mon-Khmer population could not be ruled out. Previous studies conducted on northern Thai people did not provide a definitive answer and, in addition, have largely overlooked the distribution of paternal lineages in the area. In this work we aim to provide a comprehensive analysis of Y paternal lineages in northern Thailand and to explicitly model the origin of the Khon Mueang population. We obtained and analysed new Y chromosomal haplogroup data from more than 500 northern Thai individuals including Khon Mueang, Mon-Khmer and Tai-Kadai. We also explicitly simulated different demographic scenarios, developed to explain the Khon Mueang origin, employing an ABC simulation framework on both mitochondrial and Y microsatellites data. Our results highlighted a similar haplogroup composition of Khon Mueang and Tai-Kadai populations in northern Thailand, with shared high frequencies of haplogroups O-PK4, O-M117 and O-M111. Our ABC simulations also favoured a model in which the ancestors of modern Khon Mueang originated recently after a split from the other Tai-Kadai populations. Our different analyses concluded that the ancestors of Khon Mueang are likely to have originated from the same source of the other Tai-Kadai groups in southern China, with subsequent admixture events involving native Mon-Khmer speakers restricted to some specific populations.

Chaotic homes and school achievement: a twin study

PubMed Central

Hanscombe, Ken B; Haworth, Claire MA; Davis, Oliver SP; Jaffee, Sara R; Plomin, Robert

2011-01-01

Background Chaotic homes predict poor school performance. Given that it is known that genes affect both children's experience of household chaos and their school achievement, to what extent is the relationship between high levels of noise and environmental confusion in the home, and children's school performance, mediated by heritable child effects? This is the first study to explore the genetic and environmental pathways between household chaos and academic performance. Method Children's perceptions of family chaos at ages 9 and 12 and their school performance at age 12 were assessed in more than 2,300 twin pairs. The use of child-specific measures in a multivariate genetic analysis made it possible to investigate the genetic and environmental origins of the covariation between children's experience of chaos in the home and their school achievement. Results Children's experience of family chaos and their school achievement were significantly correlated in the expected negative direction (r = −.26). As expected, shared environmental factors explained a large proportion (63%) of the association. However, genetic factors accounted for a significant proportion (37%) of the association between children's experience of household chaos and their school performance. Conclusions The association between chaotic homes and poor performance in school, previously assumed to be entirely environmental in origin, is in fact partly genetic. How children's home environment affects their academic achievement is not simply in the direction environment → child → outcome. Instead, genetic factors that influence children's experience of the disordered home environment also affect how well they do at school. The relationship between the child, their environment and their performance at school is complex: both genetic and environmental factors play a role. PMID:21675992

Origins of neurogenesis, a cnidarian view.

PubMed

Galliot, Brigitte; Quiquand, Manon; Ghila, Luiza; de Rosa, Renaud; Miljkovic-Licina, Marijana; Chera, Simona

2009-08-01

New perspectives on the origin of neurogenesis emerged with the identification of genes encoding post-synaptic proteins as well as many "neurogenic" regulators as the NK, Six, Pax, bHLH proteins in the Demosponge genome, a species that might differentiate sensory cells but no neurons. However, poriferans seem to miss some key regulators of the neurogenic circuitry as the Hox/paraHox and Otx-like gene families. Moreover as a general feature, many gene families encoding evolutionarily-conserved signaling proteins and transcription factors were submitted to a wave of gene duplication in the last common eumetazoan ancestor, after Porifera divergence. In contrast gene duplications in the last common bilaterian ancestor, Urbilateria, are limited, except for the bHLH Atonal-class. Hence Cnidaria share with Bilateria a large number of genetic tools. The expression and functional analyses currently available suggest a neurogenic function for numerous orthologs in developing or adult cnidarians where neurogenesis takes place continuously. As an example, in the Hydra polyp, the Clytia medusa and the Acropora coral, the Gsx/cnox2/Anthox-2 ParaHox gene likely supports neurogenesis. Also neurons and nematocytes (mechanosensory cells) share in hydrozoans a common stem cell and several regulatory genes indicating that they can be considered as sister cells. Performed in anthozoan and medusozoan species, these studies should tell us more about the way(s) evolution hazards achieved the transition from epithelial to neuronal cell fate, and about the robustness of the genetic circuitry that allowed neuromuscular transmission to arise and be maintained across evolution.

Why do we differ in number sense? Evidence from a genetically sensitive investigation☆

PubMed Central

Tosto, M.G.; Petrill, S.A.; Halberda, J.; Trzaskowski, M.; Tikhomirova, T.N.; Bogdanova, O.Y.; Ly, R.; Wilmer, J.B.; Naiman, D.Q.; Germine, L.; Plomin, R.; Kovas, Y.

2014-01-01

Basic intellectual abilities of quantity and numerosity estimation have been detected across animal species. Such abilities are referred to as ‘number sense’. For human species, individual differences in number sense are detectable early in life, persist in later development, and relate to general intelligence. The origins of these individual differences are unknown. To address this question, we conducted the first large-scale genetically sensitive investigation of number sense, assessing numerosity discrimination abilities in 837 pairs of monozygotic and 1422 pairs of dizygotic 16-year-old twin pairs. Univariate genetic analysis of the twin data revealed that number sense is modestly heritable (32%), with individual differences being largely explained by non-shared environmental influences (68%) and no contribution from shared environmental factors. Sex-Limitation model fitting revealed no differences between males and females in the etiology of individual differences in number sense abilities. We also carried out Genome-wide Complex Trait Analysis (GCTA) that estimates the population variance explained by additive effects of DNA differences among unrelated individuals. For 1118 unrelated individuals in our sample with genotyping information on 1.7 million DNA markers, GCTA estimated zero heritability for number sense, unlike other cognitive abilities in the same twin study where the GCTA heritability estimates were about 25%. The low heritability of number sense, observed in this study, is consistent with the directional selection explanation whereby additive genetic variance for evolutionary important traits is reduced. PMID:24696527

Weak sharing of genetic association signals in three lung cancer subtypes: evidence at the SNP, gene, regulation, and pathway levels.

PubMed

O'Brien, Timothy D; Jia, Peilin; Caporaso, Neil E; Landi, Maria Teresa; Zhao, Zhongming

2018-02-27

There are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC has many subtypes, but the two most common are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). These subtypes are mainly classified by physiological and pathological characteristics, although there is increasing evidence of genetic and molecular differences as well. Although some work has been done at the somatic level to explore the genetic and biological differences among subtypes, little work has been done that interrogates these differences at the germline level to characterize the unique and shared susceptibility genes for each subtype. We used single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) of European samples to interrogate the similarity of the subtypes at the SNP, gene, pathway, and regulatory levels. We expanded these genotyped SNPs to include all SNPs in linkage disequilibrium (LD) using data from the 1000 Genomes Project. We mapped these SNPs to several lung tissue expression quantitative trait loci (eQTL) and enhancer datasets to identify regulatory SNPs and their target genes. We used these genes to perform a biological pathway analysis for each subtype. We identified 8295, 8734, and 8361 SNPs with moderate association signals for LUAD, LUSC, and SCLC, respectively. Those SNPs had p < 1 × 10 - 3 in the original GWAS or were within LD (r 2 > 0.8, Europeans) to the genotyped SNPs. We identified 215, 320, and 172 disease-associated genes for LUAD, LUSC, and SCLC, respectively. Only five genes (CHRNA5, IDH3A, PSMA4, RP11-650 L12.2, and TBC1D2B) overlapped all subtypes. Furthermore, we observed only two pathways from the Kyoto Encyclopedia of Genes and Genomes shared by all subtypes. At the regulatory level, only three eQTL target genes and two enhancer target genes overlapped between all subtypes. Our results suggest that the three lung cancer subtypes do not share much genetic signal at the SNP, gene, pathway, or regulatory level, which differs from the common subtype classification based upon histology. However, three (CHRNA5, IDH3A, and PSMA4) of the five genes shared between the subtypes are well-known lung cancer genes that may act as general lung cancer genes regardless of subtype.

Allele Sharing and Evidence for Sexuality in a Mitochondrial Clade of Bdelloid Rotifers

PubMed Central

Signorovitch, Ana; Hur, Jae; Gladyshev, Eugene; Meselson, Matthew

2015-01-01

Rotifers of Class Bdelloidea are common freshwater invertebrates of ancient origin whose apparent asexuality has posed a challenge to the view that sexual reproduction is essential for long-term evolutionary success in eukaryotes and to hypotheses for the advantage of sex. The possibility nevertheless exists that bdelloids reproduce sexually under unknown or inadequately investigated conditions. Although certain methods of population genetics offer definitive means for detecting infrequent or atypical sex, they have not previously been applied to bdelloid rotifers. We conducted such a test with bdelloids belonging to a mitochondrial clade of Macrotrachela quadricornifera. This revealed a striking pattern of allele sharing consistent with sexual reproduction and with meiosis of an atypical sort, in which segregation occurs without requiring homologous chromosome pairs. PMID:25977472

The Population Genetics of Cultivation: Domestication of a Traditional Chinese Medicine, Scrophularia ningpoensis Hemsl. (Scrophulariaceae)

PubMed Central

Chen, Chuan; Li, Pan; Wang, Rui-Hong; Schaal, Barbara A.; Fu, Cheng-Xin

2014-01-01

Background Domestic cultivation of medicinal plants is an important strategy for protecting these species from over harvesting. Some species of medicinal plants have been brought into cultivation for more than hundreds years. Concerns about severe loss of genetic diversity and sustainable cultivation can potentially limit future use of these valuable plants. Genetic studies with comprehensive sampling of multiple medicinal species by molecular markers will allow for assessment and management of these species. Here we examine the population genetic consequences of cultivation and domestication in Scrophularia ningpoensis Hemsl. We used chloroplast DNA and genomic AFLP markers to clarify not only the effects of domestication on genetic diversity, but also determine the geographic origins of cultivars and their genetic divergence from native populations. These results will allow both better management of cultivated populations, but also provide insights for crop improvement. Results Twenty-one cpDNA haplotypes of S. ningpoensis were identified. Wild populations contain all haplotypes, whereas only three haplotypes were found in cultivated populations with wild populations having twice the haplotype diversity of cultivated populations. Genetic differentiation between cultivated populations and wild populations was significant. Genomic AFLP markers revealed similar genetic diversity patterns. Furthermore, Structure analysis grouped all wild populations into two gene pools; two of which shared the same gene pool with cultivated S. ningpoensis. The result of Neighbor-Joining analysis was consistent with the structure analysis. In principal coordinate analysis, three cultivated populations from Zhejiang Province grouped together and were separated from other cultivated populations. Conclusions These results suggest that cultivated S. ningpoensis has experienced dramatic loss of genetic diversity under anthropogenic influence. We postulate that strong artificial selection for medicinal quality has resulted in genetic differentiation between cultivated and wild populations. Furthermore, it appears that wild populations in Jiangxi-Hunan area were involved in the origin of cultivated S. ningpoensis. PMID:25157628

Genetic diversity and population structure in the threatened Oregon silverspot butterfly (Speyeria zerene hippolyta) in western Oregon and northwestern California— Implications for future translocations and the establishment of new populations

USGS Publications Warehouse

Miller, Mark P.; Mullins, Thomas D.; Haig, Susan M.

2016-09-20

Executive SummaryWe present results of population genetic analyses performed on Oregon silverspot butterflies (OSB; Speyeria zerene hippolyta) in western Oregon and northwestern California. We used DNA sequences from a 561-base pair region of the mitochondrial cytochrome oxidase subunit I (COI) gene for a dataset comprised of 112 S. z. hippolyta and 32 S. z. gloriosa individuals collected at 9 locations in western Oregon and northwestern California. The most pertinent findings thus far are summarized as follows:Among OSB populations, genetic diversity is lowest at Mount Hebo and highest at Rock Creek and Bray Point. Of the 32 haplotypes detected in OSB, only 2 were shared among populations (1 shared by Mount Hebo, Cascade Head, Bray Point, and Rock Creek, and 1 shared by Rock Creek and Lake Earl). The remaining 30 haplotypes were identified in individual populations, highlighting the strong differentiation among sites. It is unclear if the shared haplotypes represent widespread, naturally occurring genetic variation or if allele sharing among populations is due to translocation history.Using full siblings of individuals that were released at Rock Creek and Bray Point in 2012 as comparison standards, the analyses suggest that 54 percent of the sampled individuals from Bray Point were naturally recruited into the population and were not originating from the 2012 release of captive reared individuals. Likewise, 33 percent of the analyzed individuals from Rock Creek were naturally recruited. Both of these estimates may be underestimates if the shared alleles that we identified among populations are naturally occurring and not a product of the 2012 translocations.The results suggest that there are about 12–13 COI haplotypes in the Mount Hebo population. The U.S. Fish and Wildlife Service anticipates using Mount Hebo as the source of individuals when establishing new populations in the future. Nonlinear regression models based on a series of rarefaction analyses suggest that progeny from 12, 37, 109, and 326 female individuals would be required to respectively capture 25, 50, 75, and 90 percent of the allelic diversity from Mount Hebo.Phylogenetic analyses identified two different haplotype groups, but the two groups did not correspond to the different subspecies used in the analysis. One group included 22 S. z. hippolyta haplotypes and 7 haplotypes identified in S. z. gloriosa. The second group included eight haplotypes from S. z. hippolyta, three haplotypes from S. z. gloriosa, and one haplotype that was detected in both subspecies.

Nurture Net of Nature: Re-Evaluating the Role of Shared Environments in Academic Achievement and Verbal Intelligence

PubMed Central

Daw, Jonathan; Guo, Guang; Harris, Kathie Mullan

2016-01-01

Prominent authors in the behavioral genetics tradition have long argued that shared environments do not meaningfully shape intelligence and academic achievement. However, we argue that these conclusions are erroneous due to large violations of the additivity assumption underlying behavioral genetics methods – that sources of genetic and shared and nonshared environmental variance are independent and non-interactive. This is compounded in some cases by the theoretical equation of the effective and objective environments, where the former is defined by whether siblings are made more or less similar, and the latter by whether siblings are equally subject to the environmental characteristic in question. Using monozygotic twin fixed effects models, which compare outcomes among genetically identical pairs, we show that many characteristics of objectively shared environments significantly moderate the effects of nonshared environments on adolescent academic achievement and verbal intelligence, violating the additivity assumption of behavioral genetic methods. Importantly, these effects would be categorized as nonshared environmental influences in standard twin models despite their roots in shared environments. These findings should encourage caution among those who claim that the frequently trivial variance attributed to shared environments in behavioral genetic models means that families, schools, and neighborhoods do not meaningfully influence these outcomes. PMID:26004471

Nurture net of nature: Re-evaluating the role of shared environments in academic achievement and verbal intelligence.

PubMed

Daw, Jonathan; Guo, Guang; Harris, Kathie Mullan

2015-07-01

Prominent authors in the behavioral genetics tradition have long argued that shared environments do not meaningfully shape intelligence and academic achievement. However, we argue that these conclusions are erroneous due to large violations of the additivity assumption underlying behavioral genetics methods - that sources of genetic and shared and nonshared environmental variance are independent and non-interactive. This is compounded in some cases by the theoretical equation of the effective and objective environments, where the former is defined by whether siblings are made more or less similar, and the latter by whether siblings are equally subject to the environmental characteristic in question. Using monozygotic twin fixed effects models, which compare outcomes among genetically identical pairs, we show that many characteristics of objectively shared environments significantly moderate the effects of nonshared environments on adolescent academic achievement and verbal intelligence, violating the additivity assumption of behavioral genetic methods. Importantly, these effects would be categorized as nonshared environmental influences in standard twin models despite their roots in shared environments. These findings should encourage caution among those who claim that the frequently trivial variance attributed to shared environments in behavioral genetic models means that families, schools, and neighborhoods do not meaningfully influence these outcomes. Copyright © 2015. Published by Elsevier Inc.

Assessing the evidence for shared genetic risks across psychiatric disorders and traits.

PubMed

Martin, Joanna; Taylor, Mark J; Lichtenstein, Paul

2017-12-04

Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.

Comparative oncology: what dogs and other species can teach us about humans with cancer

PubMed Central

Schiffman, Joshua D.; Breen, Matthew

2015-01-01

Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us. PMID:26056372

Mutational profiles of breast cancer metastases from a rapid autopsy series reveal multiple evolutionary trajectories.

PubMed

Avigdor, Bracha Erlanger; Cimino-Mathews, Ashley; DeMarzo, Angelo M; Hicks, Jessica L; Shin, James; Sukumar, Saraswati; Fetting, John; Argani, Pedram; Park, Ben H; Wheelan, Sarah J

2017-12-21

Heterogeneity within and among tumors in a metastatic cancer patient is a well-established phenomenon that may confound treatment and accurate prognosis. Here, we used whole-exome sequencing to survey metastatic breast cancer tumors from 5 patients in a rapid autopsy program to construct the origin and genetic development of metastases. Metastases were obtained from 5 breast cancer patients using a rapid autopsy protocol and subjected to whole-exome sequencing. Metastases were evaluated for sharing of somatic mutations, correlation of copy number variation and loss of heterozygosity, and genetic similarity scores. Pathological features of the patients' disease were assessed by immunohistochemical analyses. Our data support a monoclonal origin of metastasis in 3 cases, but in 2 cases, metastases arose from at least 2 distinct subclones in the primary tumor. In the latter 2 cases, the primary tumor presented with mixed histologic and pathologic features, suggesting early divergent evolution within the primary tumor with maintenance of metastatic capability in multiple lineages. We used genetic and histopathological evidence to demonstrate that metastases can be derived from a single or multiple independent clones within a primary tumor. This underscores the complexity of breast cancer clonal evolution and has implications for how best to determine and implement therapies for early- and late-stage disease.

Mutational profiles of breast cancer metastases from a rapid autopsy series reveal multiple evolutionary trajectories

PubMed Central

Avigdor, Bracha Erlanger; Cimino-Mathews, Ashley; DeMarzo, Angelo M.; Hicks, Jessica L.; Shin, James; Sukumar, Saraswati; Fetting, John; Argani, Pedram; Park, Ben H.; Wheelan, Sarah J.

2017-01-01

Heterogeneity within and among tumors in a metastatic cancer patient is a well-established phenomenon that may confound treatment and accurate prognosis. Here, we used whole-exome sequencing to survey metastatic breast cancer tumors from 5 patients in a rapid autopsy program to construct the origin and genetic development of metastases. Metastases were obtained from 5 breast cancer patients using a rapid autopsy protocol and subjected to whole-exome sequencing. Metastases were evaluated for sharing of somatic mutations, correlation of copy number variation and loss of heterozygosity, and genetic similarity scores. Pathological features of the patients’ disease were assessed by immunohistochemical analyses. Our data support a monoclonal origin of metastasis in 3 cases, but in 2 cases, metastases arose from at least 2 distinct subclones in the primary tumor. In the latter 2 cases, the primary tumor presented with mixed histologic and pathologic features, suggesting early divergent evolution within the primary tumor with maintenance of metastatic capability in multiple lineages. We used genetic and histopathological evidence to demonstrate that metastases can be derived from a single or multiple independent clones within a primary tumor. This underscores the complexity of breast cancer clonal evolution and has implications for how best to determine and implement therapies for early- and late-stage disease. PMID:29263308

Heterogeneity in the Segmental Development of the Aortic Tree: Impact on Management of Genetically Triggered Aortic Aneurysms

PubMed Central

Sherif, Hisham M.F.

2014-01-01

An extensive search of the medical literature examining the development of the thoracic aortic tree reveals that the thoracic aorta does not develop as one unit or in one stage: the oldest part of the thoracic aorta is the descending aorta with the aortic arch being the second oldest, developing under influence from the neural crest cell. Following in chronological order are the proximal ascending aorta and aortic root, which develop from a conotruncal origin. Different areas of the thoracic aorta develop under the influence of different gene sets. These parts develop from different cell lineages: the aortic root (the conotruncus), developing from the mesoderm; the ascending aorta and aortic arch, developing from the neural crest cells; and the descending aorta from the mesoderm. Findings illustrate that the thoracic aorta is not a single entity, in developmental terms. It develops from three or four distinct areas, at different stages of embryonic life, and under different sets of genes and signaling pathways. Genetically triggered thoracic aortic aneurysms are not a monolithic group but rather share a multi-genetic origin. Identification of therapeutic targets should be based on the predilection of certain genes to cause aneurysmal disease in specific aortic segments. PMID:26798739

Recent origin and semi-permeable species boundaries in the scleractinian coral genus Stylophora from the Red Sea.

PubMed

Arrigoni, Roberto; Benzoni, Francesca; Terraneo, Tullia I; Caragnano, Annalisa; Berumen, Michael L

2016-10-07

Reticulate evolution, introgressive hybridisation, and phenotypic plasticity have been documented in scleractinian corals and have challenged our ability to interpret speciation processes. Stylophora is a key model system in coral biology and physiology, but genetic analyses have revealed that cryptic lineages concealed by morphological stasis exist in the Stylophora pistillata species complex. The Red Sea represents a hotspot for Stylophora biodiversity with six morphospecies described, two of which are regionally endemic. We investigated Stylophora species boundaries from the Red Sea and the associated Symbiodinium by sequencing seven DNA loci. Stylophora morphospecies from the Red Sea were not resolved based on mitochondrial phylogenies and showed nuclear allele sharing. Low genetic differentiation, weak isolation, and strong gene flow were found among morphospecies although no signals of genetic recombination were evident among them. Stylophora mamillata harboured Symbiodinium clade C whereas the other two Stylophora morphospecies hosted either Symbiodinium clade A or C. These evolutionary patterns suggest that either gene exchange occurs through reticulate evolution or that multiple ecomorphs of a phenotypically plastic species occur in the Red Sea. The recent origin of the lineage leading to the Red Sea Stylophora may indicate an ongoing speciation driven by environmental changes and incomplete lineage sorting.

Recent origin and semi-permeable species boundaries in the scleractinian coral genus Stylophora from the Red Sea

PubMed Central

Arrigoni, Roberto; Benzoni, Francesca; Terraneo, Tullia I.; Caragnano, Annalisa; Berumen, Michael L.

2016-01-01

Reticulate evolution, introgressive hybridisation, and phenotypic plasticity have been documented in scleractinian corals and have challenged our ability to interpret speciation processes. Stylophora is a key model system in coral biology and physiology, but genetic analyses have revealed that cryptic lineages concealed by morphological stasis exist in the Stylophora pistillata species complex. The Red Sea represents a hotspot for Stylophora biodiversity with six morphospecies described, two of which are regionally endemic. We investigated Stylophora species boundaries from the Red Sea and the associated Symbiodinium by sequencing seven DNA loci. Stylophora morphospecies from the Red Sea were not resolved based on mitochondrial phylogenies and showed nuclear allele sharing. Low genetic differentiation, weak isolation, and strong gene flow were found among morphospecies although no signals of genetic recombination were evident among them. Stylophora mamillata harboured Symbiodinium clade C whereas the other two Stylophora morphospecies hosted either Symbiodinium clade A or C. These evolutionary patterns suggest that either gene exchange occurs through reticulate evolution or that multiple ecomorphs of a phenotypically plastic species occur in the Red Sea. The recent origin of the lineage leading to the Red Sea Stylophora may indicate an ongoing speciation driven by environmental changes and incomplete lineage sorting. PMID:27713475

Quantitative analysis of population-scale family trees with millions of relatives.

PubMed

Kaplanis, Joanna; Gordon, Assaf; Shor, Tal; Weissbrod, Omer; Geiger, Dan; Wahl, Mary; Gershovits, Michael; Markus, Barak; Sheikh, Mona; Gymrek, Melissa; Bhatia, Gaurav; MacArthur, Daniel G; Price, Alkes L; Erlich, Yaniv

2018-04-13

Family trees have vast applications in fields as diverse as genetics, anthropology, and economics. However, the collection of extended family trees is tedious and usually relies on resources with limited geographical scope and complex data usage restrictions. We collected 86 million profiles from publicly available online data shared by genealogy enthusiasts. After extensive cleaning and validation, we obtained population-scale family trees, including a single pedigree of 13 million individuals. We leveraged the data to partition the genetic architecture of human longevity and to provide insights into the geographical dispersion of families. We also report a simple digital procedure to overlay other data sets with our resource. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Over Six Thousand Trypanosoma cruzi Strains Classified into Discrete Typing Units (DTUs): Attempt at an Inventory.

PubMed

Brenière, Simone Frédérique; Waleckx, Etienne; Barnabé, Christian

2016-08-01

Trypanosoma cruzi, the causative agent of Chagas disease, presents wide genetic diversity. Currently, six discrete typing units (DTUs), named TcI to TcVI, and a seventh one called TcBat are used for strain typing. Beyond the debate concerning this classification, this systematic review has attempted to provide an inventory by compiling the results of 137 articles that have used it. A total of 6,343 DTU identifications were analyzed according to the geographical and host origins. Ninety-one percent of the data available is linked to South America. This sample, although not free of potential bias, nevertheless provides today's picture of T. cruzi genetic diversity that is closest to reality. DTUs were genotyped from 158 species, including 42 vector species. Remarkably, TcI predominated in the overall sample (around 60%), in both sylvatic and domestic cycles. This DTU known to present a high genetic diversity, is very widely distributed geographically, compatible with a long-term evolution. The marsupial is thought to be its most ancestral host and the Gran Chaco region the place of its putative origin. TcII was rarely sampled (9.6%), absent, or extremely rare in North and Central America, and more frequently identified in domestic cycles than in sylvatic cycles. It has a low genetic diversity and has probably found refuge in some mammal species. It is thought to originate in the south-Amazon area. TcIII and TcIV were also rarely sampled. They showed substantial genetic diversity and are thought to be composed of possible polyphyletic subgroups. Even if they are mostly associated with sylvatic transmission cycles, a total of 150 human infections with these DTUs have been reported. TcV and TcVI are clearly associated with domestic transmission cycles. Less than 10% of these DTUs were identified together in sylvatic hosts. They are thought to originate in the Gran Chaco region, where they are predominant and where putative parents exist (TcII and TcIII). Trends in host-DTU specificities exist, but generally it seems that the complexity of the cycles and the participation of numerous vectors and mammal hosts in a shared area, maintains DTU diversity.

Formamide and the origin of life

NASA Astrophysics Data System (ADS)

Saladino, Raffaele; Crestini, Claudia; Pino, Samanta; Costanzo, Giovanna; Di Mauro, Ernesto

2012-03-01

The complexity of life boils down to the definition: “self-sustained chemical system capable of undergoing Darwinian evolution” (Joyce, 1994) [1]. The term “self-sustained” implies a set of chemical reactions capable of harnessing energy from the environment, using it to carry out programmed anabolic and catabolic functions. We briefly present our opinion on the general validity of this definition. Running anabolic and catabolic functions entails complex chemical information whose stability, reproducibility and evolution constitute the core of what is dubbed genetics. Life as-we-know-it is made of the intimate interaction of metabolism and genetics, both built around the chemistry of the most common elements of the Universe (hydrogen, oxygen, nitrogen, carbon). Other elements like phosphorus and sulphur play important but ancillary and potentially replaceable roles. The reproducible interaction of metabolic and genetic cycles results in the hypercycles of organization and de-organization of chemical information that we consider living entities. In order to approach the problem of the origin of life it is therefore reasonable to start from the assumption that both metabolism and genetics had a common origin, shared a common chemical frame, were embedded in physical-chemical conditions favourable for the onset of both. The most abundant three-atoms organic compound in interstellar environment is hydrogen cyanide HCN, the most abundant three-atoms inorganic compound is water H2O. The combination of the two results in the formation of formamide H2NCOH. We have explored the chemistry of formamide in conditions compatible with the synthesis and the stability of compounds of potential pre-genetic and pre-metabolic interest. We discuss evidence showing (i) that all the compounds necessary for the build-up of nucleic acids are easily obtained abiotically, (ii) that essentially all the steps leading to the spontaneous generation of RNA are abiotically possible, (iii) that the key compounds of extant metabolic cycles are obtained in the same chemical frame, often in the same test tube. How close are these observations to a plausible scenario for the origin of life?

Shared genetic variance between obesity and white matter integrity in Mexican Americans.

PubMed

Spieker, Elena A; Kochunov, Peter; Rowland, Laura M; Sprooten, Emma; Winkler, Anderson M; Olvera, Rene L; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John; Glahn, David C; Curran, Joanne E

2015-01-01

Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18-81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m(2)) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h (2) = 0.58), WC (h (2) = 0.57), and FA (h (2) = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = -0.25), body (ρG = -0.30), and splenium (ρG = -0.26) of the corpus callosum, internal capsule (ρG = -0.29), and thalamic radiation (ρG = -0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = -0.39, p = 0.020; ρG = -0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors.

Blood pressure and cerebral white matter share common genetic factors in Mexican Americans.

PubMed

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2011-02-01

Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7 × 1.7 × 3 mm; 55 directions) diffusion tensor imaging data were analyzed for 332 (202 females; mean age 47.9 ± 13.3 years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements (pulse pressure, systolic BP, and diastolic BP) and fractional anisotropy (whole-brain and regional values). Intersubject variance in pulse pressure and systolic BP exhibited a significant genetic overlap with variance in whole-brain fractional anisotropy values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=-0.75; P=0.01). The pattern of genetic overlap between BP and WM integrity was generally in agreement with the pulse-wave encephalopathy theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development, suggesting a possible role for genotype-by-age interactions.

Blood Pressure and Cerebral White Matter Share Common Genetic Factors in Mexican-Americans

PubMed Central

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2010-01-01

Elevated arterial pulse pressure (PP) and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially due to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy (FA) of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican-Americans. The patterns of whole-brain and regional genetic overlap between BP and FA were interpreted in the context the pulse-wave encephalopathy (PWE) theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7×1.7×3mm, 55 directions) diffusion tensor imaging (DTI) data were analyzed for 332 (202 females; mean age=47.9±13.3years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements [PP, systolic (SBP) and diastolic (DBP)] and FA (whole-brain and regional values). Intersubject variance in PP and SBP exhibited a significant genetic overlap with variance in whole-brain FA values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=−.75, p=0.01). The pattern of genetic overlap between BP and WM integrity was generally in-agreement with the PWE theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development suggesting a possible role for genotype-by-age interactions. PMID:21135356

Shared genetic basis for migraine and ischemic stroke

PubMed Central

Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S.; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G.; Terwindt, Gisela M.; Sturm, Jonathan; Bis, Joshua C.; Hopewell, Jemma C.; Ferrari, Michel D.; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F.; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I.; Mitchell, Braxton D.; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T.; Kurth, Tobias; Ikram, M. Arfan; Reiner, Alex P.; Longstreth, W.T.; Rothwell, Peter M.; Strachan, David P.; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B.; Davey Smith, George; van Duijn, Cornelia M.; Stefansson, Kari; Worrall, Bradford B.; Nyholt, Dale R.; Markus, Hugh S.; van den Maagdenberg, Arn M.J.M.; Cotsapas, Chris; Zwart, John A.; Palotie, Aarno

2015-01-01

Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10−28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10−20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. PMID:25934857

Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins

PubMed Central

Silberg, Judy L.; Gillespie, Nathan; Moore, Ashlee A.; Eaves, Lindon J.; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

2015-01-01

Objective Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. Method We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Results Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. Conclusions There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children. PMID:25728588

Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins.

PubMed

Silberg, Judy L; Gillespie, Nathan; Moore, Ashlee A; Eaves, Lindon J; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

2015-04-01

Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.

From Wolves to Dogs, and Back: Genetic Composition of the Czechoslovakian Wolfdog.

PubMed

Smetanová, Milena; Černá Bolfíková, Barbora; Randi, Ettore; Caniglia, Romolo; Fabbri, Elena; Galaverni, Marco; Kutal, Miroslav; Hulva, Pavel

2015-01-01

The Czechoslovakian Wolfdog is a unique dog breed that originated from hybridization between German Shepherds and wild Carpathian wolves in the 1950s as a military experiment. This breed was used for guarding the Czechoslovakian borders during the cold war and is currently kept by civilian breeders all round the world. The aim of our study was to characterize, for the first time, the genetic composition of this breed in relation to its known source populations. We sequenced the hypervariable part of the mtDNA control region and genotyped the Amelogenin gene, four sex-linked microsatellites and 39 autosomal microsatellites in 79 Czechoslovakian Wolfdogs, 20 German Shepherds and 28 Carpathian wolves. We performed a range of population genetic analyses based on both empirical and simulated data. Only two mtDNA and two Y-linked haplotypes were found in Czechoslovakian Wolfdogs. Both mtDNA haplotypes were of domestic origin, while only one of the Y-haplotypes was shared with German Shepherds and the other was unique to Czechoslovakian Wolfdogs. The observed inbreeding coefficient was low despite the small effective population size of the breed, possibly due to heterozygote advantages determined by introgression of wolf alleles. Moreover, Czechoslovakian Wolfdog genotypes were distinct from both parental populations, indicating the role of founder effect, drift and/or genetic hitchhiking. The results revealed the peculiar genetic composition of the Czechoslovakian Wolfdog, showing a limited introgression of wolf alleles within a higher proportion of the dog genome, consistent with the reiterated backcrossing used in the pedigree. Artificial selection aiming to keep wolf-like phenotypes but dog-like behavior resulted in a distinctive genetic composition of Czechoslovakian Wolfdogs, which provides a unique example to study the interactions between dog and wolf genomes.

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

Phylogeography of the endangered Otago skink, Oligosoma otagense: population structure, hybridisation and genetic diversity in captive populations.

PubMed

Chapple, David G; Birkett, Alisha; Miller, Kimberly A; Daugherty, Charles H; Gleeson, Dianne M

2012-01-01

Climatic cooling and substantial tectonic activity since the late Miocene have had a pronounced influence on the evolutionary history of the fauna of New Zealand's South Island. However, many species have recently experienced dramatic range reductions due to habitat fragmentation and the introduction of mammalian predators and competitors. These anthropogenic impacts have been particularly severe in the tussock grasslands of the Otago region. The Otago skink (Oligosoma otagense), endemic to the region, is one of the most critically endangered vertebrates in New Zealand. We use mitochondrial DNA sequence data to investigate the evolutionary history of the Otago skink, examine its population genetic structure, and assess the level of genetic diversity in the individuals in the captive breeding program. Our data indicate that the Otago skink diverged from its closest relatives in the Miocene, consistent with the commencement of tectonic uplift of the Southern Alps. However, there is evidence for past introgression with the scree skink (O. waimatense) in the northern Otago-southern Canterbury region. The remnant populations in eastern Otago and western Otago are estimated to have diverged in the mid-Pliocene, with no haplotypes shared between these two regions. This divergence accounts for 95% of the genetic diversity in the species. Within both regions there is strong genetic structure among populations, although shared haplotypes are generally evident between adjacent localities. Although substantial genetic diversity is present in the captive population, all individuals originate from the eastern region and the majority had haplotypes that were not evident in the intensively managed populations at Macraes Flat. Our data indicate that eastern and western populations should continue to be regarded as separate management units. Knowledge of the genetic diversity of the breeding stock will act to inform the captive management of the Otago skink and contribute to a key recovery action for the species.

Investigating genetic and environmental contributions to adolescent externalizing behavior in a collectivistic culture: a multi-informant twin study.

PubMed

Chen, J; Yu, J; Zhang, J; Li, X; McGue, M

2015-07-01

Little is known about the etiology of adolescents' externalizing behavior (Ext) in collectivistic cultures. We aimed to fill this gap by investigating the genetic and environmental influences on Ext in Chinese adolescents. The etiological heterogeneity of aggression (AGG) and rule breaking (RB) was also examined. The study sample included 908 pairs of same-sex twins aged from 10 to 18 years (mean = 13.53 years, s.d. = 2.26). Adolescents' Ext were assessed with the Achenbach System of Empirically Based Assessment including Child Behavior Checklist, Teacher Report Form, and Youth Self-Report. Univariate genetic analyses showed that genetic influences on all measures were moderate ranging from 34% to 50%, non-shared environmental effects ranged from 23% to 52%, and shared environmental effects were significant in parent- and teacher-reported measures ranging from 29% to 43%. Bivariate genetic analyses indicated that AGG and RB shared large genetic influences (r g = 0.64-0.79) but moderate non-shared environmental factors (r e = 0.34-0.52). Chinese adolescents' Ext was moderately influenced by genetic factors. AGG and RB had moderate independent genetic and non-shared environmental influences, and thus constitute etiologically distinct dimensions within Ext in Chinese adolescents. The heritability of AGG, in particular, was smaller in Chinese adolescents than suggested by previous data obtained on Western peers. This study suggests that the collectivistic cultural values and Confucianism philosophy may attenuate genetic potential in Ext, especially AGG.

β-globin gene cluster haplotypes in ethnic minority populations of southwest China

PubMed Central

Sun, Hao; Liu, Hongxian; Huang, Kai; Lin, Keqin; Huang, Xiaoqin; Chu, Jiayou; Ma, Shaohui; Yang, Zhaoqing

2017-01-01

The genetic diversity and relationships among ethnic minority populations of southwest China were investigated using seven polymorphic restriction enzyme sites in the β-globin gene cluster. The haplotypes of 1392 chromosomes from ten ethnic populations living in southwest China were determined. Linkage equilibrium and recombination hotspot were found between the 5′ sites and 3′ sites of the β-globin gene cluster. 5′ haplotypes 2 (+−−−), 6 (−++−+), 9 (−++++) and 3′ haplotype FW3 (−+) were the predominant haplotypes. Notably, haplotype 9 frequency was significantly high in the southwest populations, indicating their difference with other Chinese. The interpopulation differentiation of southwest Chinese minority populations is less than those in populations of northern China and other continents. Phylogenetic analysis shows that populations sharing same ethnic origin or language clustered to each other, indicating current β-globin cluster diversity in the Chinese populations reflects their ethnic origin and linguistic affiliations to a great extent. This study characterizes β-globin gene cluster haplotypes in southwest Chinese minorities for the first time, and reveals the genetic variability and affinity of these populations using β-globin cluster haplotype frequencies. The results suggest that ethnic origin plays an important role in shaping variations of the β-globin gene cluster in the southwestern ethnic populations of China. PMID:28205625

Shared Predisposition in the Association Between Cannabis Use and Subcortical Brain Structure.

PubMed

Pagliaccio, David; Barch, Deanna M; Bogdan, Ryan; Wood, Phillip K; Lynskey, Michael T; Heath, Andrew C; Agrawal, Arpana

2015-10-01

Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use. To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations. Cross-sectional diagnostic interview, behavioral, and neuroimaging data were collected from community sampling and established family registries from August 2012 to September 2014. This study included data from 483 participants (22-35 years old) enrolled in the ongoing Human Connectome Project, with 262 participants reporting cannabis exposure (ie, ever used cannabis in their lifetime). Cannabis exposure was measured with the Semi-Structured Assessment for the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever used, age at onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed models were used to examine volume differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81 pairs), or exposure discordant (n = 89 pairs) sibling pairs. Among 483 study participants, cannabis exposure was related to smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P < .005) volumes. These volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (ρg = -0.43; P = .004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use (fixed effect = -7.43; t = -0.93, P = .35). Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs (fixed effect = 12.56; t = 2.97; P = .003). In this study, differences in amygdala volume in cannabis users were attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (eg, ventral striatum) or at more severe levels of cannabis involvement and deserve further study.

Digging up the roots of an insular hotspot of genetic diversity: decoupled mito-nuclear histories in the evolution of the Corsican-Sardinian endemic lizard Podarcis tiliguerta.

PubMed

Salvi, Daniele; Pinho, Catarina; Harris, D James

2017-03-02

Mediterranean islands host a disproportionately high level of biodiversity and endemisms. Growing phylogeographic evidence on island endemics has unveiled unexpectedly complex patterns of intra-island diversification, which originated at diverse spatial and temporal scales. We investigated multilocus genetic variation of the Corsican-Sardinian endemic lizard Podarcis tiliguerta with the aim of shedding more light on the evolutionary processes underlying the origin of Mediterranean island biodiversity. We analysed DNA sequences of mitochondrial (12S and nd4) and nuclear (acm4 and mc1r) gene fragments in 174 individuals of P. tiliguerta from 81 localities across the full range of the species in a geographic and genealogical framework. We found surprisingly high genetic diversity both at mitochondrial and nuclear loci. Seventeen reciprocally monophyletic allopatric mitochondrial haplogroups were sharply divided into four main mitochondrial lineages (two in Corsica and two in Sardinia) of Miocene origin. In contrast, shallow divergence and shared diversity within and between islands was observed at the nuclear loci. We evaluated alternative biogeographic and evolutionary scenarios to explain such profound discordance in spatial and phylogenetic patterning between mitochondrial and nuclear genomes. While neutral models provided unparsimonious explanations for the observed pattern, the hypothesis of environmental selection driving mitochondrial divergence in the presence of nuclear gene flow is favoured. Our study on the genetic variation of P. tiliguerta reveals surprising levels of diversity underlining a complex phylogeographic pattern with a striking example of mito-nuclear discordance. These findings have profound implications, not only for the taxonomy and conservation of P. tiliguerta. Growing evidence on deep mitochondrial breaks in absence of geographic barriers and of climatic factors associated to genetic variation of Corsican-Sardinian endemics warrants additional investigation on the potential role of environmental selection driving the evolution of diversity hotspots within Mediterranean islands.

A multivariate twin study of early literacy in Japanese Kana

PubMed Central

Fujisawa, Keiko K.; Wadsworth, Sally J.; Kakihana, Shinichiro; Olson, Richard K.; DeFries, John C.; Byrne, Brian; Ando, Juko

2013-01-01

This first Japanese twin study of early literacy development investigated the extent to which genetic and environmental factors influence individual differences in prereading skills in 238 pairs of twins at 42 months of age. Twin pairs were individually tested on measures of phonological awareness, kana letter name/sound knowledge, receptive vocabulary, visual perception, nonword repetition, and digit span. Results obtained from univariate behavioral-genetic analyses yielded little evidence for genetic influences, but substantial shared-environmental influences, for all measures. Phenotypic confirmatory factor analysis suggested three correlated factors: phonological awareness, letter name/sound knowledge, and general prereading skills. Multivariate behavioral genetic analyses confirmed relatively small genetic and substantial shared environmental influences on the factors. The correlations among the three factors were mostly attributable to shared environment. Thus, shared environmental influences play an important role in the early reading development of Japanese children. PMID:23997545

A phylogenomic data-driven exploration of viral origins and evolution

PubMed Central

Nasir, Arshan; Caetano-Anollés, Gustavo

2015-01-01

The origin of viruses remains mysterious because of their diverse and patchy molecular and functional makeup. Although numerous hypotheses have attempted to explain viral origins, none is backed by substantive data. We take full advantage of the wealth of available protein structural and functional data to explore the evolution of the proteomic makeup of thousands of cells and viruses. Despite the extremely reduced nature of viral proteomes, we established an ancient origin of the “viral supergroup” and the existence of widespread episodes of horizontal transfer of genetic information. Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Phylogenomic analysis uncovered a universal tree of life and revealed that modern viruses reduced from multiple ancient cells that harbored segmented RNA genomes and coexisted with the ancestors of modern cells. The model for the origin and evolution of viruses and cells is backed by strong genomic and structural evidence and can be reconciled with existing models of viral evolution if one considers viruses to have originated from ancient cells and not from modern counterparts. PMID:26601271

Genome-wide genetic diversity, population structure and admixture analysis in African and Asian cattle breeds.

PubMed

Edea, Z; Bhuiyan, M S A; Dessie, T; Rothschild, M F; Dadi, H; Kim, K S

2015-02-01

Knowledge about genetic diversity and population structure is useful for designing effective strategies to improve the production, management and conservation of farm animal genetic resources. Here, we present a comprehensive genome-wide analysis of genetic diversity, population structure and admixture based on 244 animals sampled from 10 cattle populations in Asia and Africa and genotyped for 69,903 autosomal single-nucleotide polymorphisms (SNPs) mainly derived from the indicine breed. Principal component analysis, STRUCTURE and distance analysis from high-density SNP data clearly revealed that the largest genetic difference occurred between the two domestic lineages (taurine and indicine), whereas Ethiopian cattle populations represent a mosaic of the humped zebu and taurine. Estimation of the genetic influence of zebu and taurine revealed that Ethiopian cattle were characterized by considerable levels of introgression from South Asian zebu, whereas Bangladeshi populations shared very low taurine ancestry. The relationships among Ethiopian cattle populations reflect their history of origin and admixture rather than phenotype-based distinctions. The high within-individual genetic variability observed in Ethiopian cattle represents an untapped opportunity for adaptation to changing environments and for implementation of within-breed genetic improvement schemes. Our results provide a basis for future applications of genome-wide SNP data to exploit the unique genetic makeup of indigenous cattle breeds and to facilitate their improvement and conservation.

Origins of individual differences in imitation: links with language, pretend play, and socially insightful behavior in two-year-old twins.

PubMed

McEwen, Fiona; Happé, Francesca; Bolton, Patrick; Rijsdijk, Fruhling; Ronald, Angelica; Dworzynski, Katharina; Plomin, Robert

2007-01-01

Imitation, vocabulary, pretend play, and socially insightful behavior were investigated in 5,206 same- and opposite-sex 2-year-old twin pairs in the United Kingdom. Individual differences in imitative ability were due to modest heritability (30%), while environmental factors shared between twins (42%) and unique to each twin (28%) also made significant contributions to the variance. Imitation correlated significantly, although modestly, with vocabulary, pretend play, and socially insightful behavior, and the strongest relationship was with vocabulary. A model that represented the covariance between the variables as being due to correlated latent genetic and environmental factors fitted the data well, with shared environmental factors influencing most of the covariance. Parents who encourage imitation may also tend to foster the development of language, pretence, and socially insightful behavior.

Genetic approaches refine ex situ lowland tapir (Tapirus terrestris) conservation.

PubMed

Gonçalves da Silva, Anders; Lalonde, Danielle R; Quse, Viviana; Shoemaker, Alan; Russello, Michael A

2010-01-01

Ex situ conservation management remains an important tool in the face of continued habitat loss and global environmental change. Here, we use microsatellite marker variation to evaluate conventional assumptions of pedigree-based ex situ population management and directly inform a captive lowland tapir breeding program within a range country. We found relatively high levels of genetic variation (N(total) = 41; mean H(E) = 0.67 across 10 variable loci) and little evidence for relatedness among founder individuals (N(founders) = 10; mean relatedness = -0.05). Seven of 29 putative parent-offspring relationships were excluded by parentage analysis based on allele sharing, and we identified 2 individuals of high genetic value to the population (mk

Open sharing of genomic data: Who does it and why?

PubMed

Haeusermann, Tobias; Greshake, Bastian; Blasimme, Alessandro; Irdam, Darja; Richards, Martin; Vayena, Effy

2017-01-01

We explored the characteristics and motivations of people who, having obtained their genetic or genomic data from Direct-To-Consumer genetic testing (DTC-GT) companies, voluntarily decide to share them on the publicly accessible web platform openSNP. The study is the first attempt to describe open data sharing activities undertaken by individuals without institutional oversight. In the paper we provide a detailed overview of the distribution of the demographic characteristics and motivations of people engaged in genetic or genomic open data sharing. The geographical distribution of the respondents showed the USA as dominant. There was no significant gender divide, the age distribution was broad, educational background varied and respondents with and without children were equally represented. Health, even though prominent, was not the respondents' primary or only motivation to be tested. As to their motivations to openly share their data, 86.05% indicated wanting to learn about themselves as relevant, followed by contributing to the advancement of medical research (80.30%), improving the predictability of genetic testing (76.02%) and considering it fun to explore genotype and phenotype data (75.51%). Whereas most respondents were well aware of the privacy risks of their involvement in open genetic data sharing and considered the possibility of direct, personal repercussions troubling, they estimated the risk of this happening to be negligible. Our findings highlight the diversity of DTC-GT consumers who decide to openly share their data. Instead of focusing exclusively on health-related aspects of genetic testing and data sharing, our study emphasizes the importance of taking into account benefits and risks that stretch beyond the health spectrum. Our results thus lend further support to the call for a broader and multi-faceted conceptualization of genomic utility.

Dramatic genotypic difference in, and effect of genetic crossing on, tissue culture-induced mobility of retrotransposon Tos17 in rice.

PubMed

Lin, Chunjing; Lin, Xiuyun; Hu, Lanjuan; Yang, Jingjing; Zhou, Tianqi; Long, Likun; Xu, Chunming; Xing, Shaochen; Qi, Bao; Dong, Yingshan; Liu, Bao

2012-11-01

KEY MESSAGE : We show for the first time that intraspecific crossing may impact mobility of the prominent endogenous retrotransposon Tos17 under tissue culture conditions in rice. Tos17, an endogenous copia retrotransposon of rice, is transpositionally active in tissue culture. To study whether there exists fundamental genotypic difference in the tissue culture-induced mobility of Tos17, and if so, whether the difference is under genetic and/or epigenetic control, we conducted this investigation. We show that dramatic difference in tissue culture-induced Tos17 mobility exists among different rice pure-line cultivars sharing the same maternal parent: of the three lines studied that harbor Tos17, two showed mobilization of Tos17, which accrued in proportion to subculture duration, while the third line showed total quiescence (immobility) of the element and the fourth line did not contain the element. In reciprocal F1 hybrids between Tos17-mobile and -immobile (or absence) parental lines, immobility was dominant over mobility. In reciprocal F1 hybrids between both Tos17-mobile parental lines, an additive or synergistic effect on mobility of the element was noticed. In both types of reciprocal F1 hybrids, clear difference in the extent of Tos17 mobility was noted between crossing directions. Given that all lines share the same maternal parent, this observation indicates the existence of epigenetic parent-of-origin effect. We conclude that the tissue culture-induced mobility of Tos17 in rice is under complex genetic and epigenetic control, which can be either enhanced or repressed by intraspecific genetic crossing.

Genetic variability of Taenia solium cysticerci recovered from experimentally infected pigs and from naturally infected pigs using microsatellite markers

PubMed Central

Eguiluz, María; Roncal, Elisa; Quiñones-García, Stefany; Clipman, Steven J.; Calcina, Juan; Gavidia, Cesar M.; Sheen, Patricia; Garcia, Hector H.; Gilman, Robert H.; Gonzalez, Armando E.; Zimic, Mirko

2017-01-01

The adult Taenia solium, the pork tapeworm, usually lives as a single worm in the small intestine of humans, its only known definitive host. Mechanisms of genetic variation in T. solium are poorly understood. Using three microsatellite markers previously reported [1], this study explored the genetic variability of T. solium from cysts recovered from experimentally infected pigs. It then explored the genetic epidemiology and transmission in naturally infected pigs and adult tapeworms recovered from human carriers from an endemic rural community in Peru. In an initial study on experimental infection, two groups of three piglets were each infected with proglottids from one of two genetically different tapeworms for each of the microsatellites. After 7 weeks, pigs were slaughtered and necropsy performed. Thirty-six (92.3%) out of 39 cysts originated from one tapeworm, and 27 (100%) out of 27 cysts from the other had exactly the same genotype as the parental tapeworm. This suggests that the microsatellite markers may be a useful tool for studying the transmission of T. solium. In the second study, we analyzed the genetic variation of T. solium in cysts recovered from eight naturally infected pigs, and from adult tapeworms recovered from four human carriers; they showed genetic variability. Four pigs had cysts with only one genotype, and four pigs had cysts with two different genotypes, suggesting that multiple infections of genetically distinct parental tapeworms are possible. Six pigs harbored cysts with a genotype corresponding to one of the identified tapeworms from the human carriers. In the dendrogram, cysts appeared to cluster within the corresponding pigs as well as with the geographical origin, but this association was not statistically significant. We conclude that genotyping of microsatellite size polymorphisms is a potentially important tool to trace the spread of infection and pinpoint sources of infection as pigs spread cysts with a shared parental genotype. PMID:29284011

Genetic variability of Taenia solium cysticerci recovered from experimentally infected pigs and from naturally infected pigs using microsatellite markers.

PubMed

Pajuelo, Mónica J; Eguiluz, María; Roncal, Elisa; Quiñones-García, Stefany; Clipman, Steven J; Calcina, Juan; Gavidia, Cesar M; Sheen, Patricia; Garcia, Hector H; Gilman, Robert H; Gonzalez, Armando E; Zimic, Mirko

2017-12-01

The adult Taenia solium, the pork tapeworm, usually lives as a single worm in the small intestine of humans, its only known definitive host. Mechanisms of genetic variation in T. solium are poorly understood. Using three microsatellite markers previously reported [1], this study explored the genetic variability of T. solium from cysts recovered from experimentally infected pigs. It then explored the genetic epidemiology and transmission in naturally infected pigs and adult tapeworms recovered from human carriers from an endemic rural community in Peru. In an initial study on experimental infection, two groups of three piglets were each infected with proglottids from one of two genetically different tapeworms for each of the microsatellites. After 7 weeks, pigs were slaughtered and necropsy performed. Thirty-six (92.3%) out of 39 cysts originated from one tapeworm, and 27 (100%) out of 27 cysts from the other had exactly the same genotype as the parental tapeworm. This suggests that the microsatellite markers may be a useful tool for studying the transmission of T. solium. In the second study, we analyzed the genetic variation of T. solium in cysts recovered from eight naturally infected pigs, and from adult tapeworms recovered from four human carriers; they showed genetic variability. Four pigs had cysts with only one genotype, and four pigs had cysts with two different genotypes, suggesting that multiple infections of genetically distinct parental tapeworms are possible. Six pigs harbored cysts with a genotype corresponding to one of the identified tapeworms from the human carriers. In the dendrogram, cysts appeared to cluster within the corresponding pigs as well as with the geographical origin, but this association was not statistically significant. We conclude that genotyping of microsatellite size polymorphisms is a potentially important tool to trace the spread of infection and pinpoint sources of infection as pigs spread cysts with a shared parental genotype.

SEARCHBreast: a new resource to locate and share surplus archival material from breast cancer animal models to help address the 3Rs.

PubMed

Blyth, Karen; Carter, Phil; Morrissey, Bethny; Chelala, Claude; Jones, Louise; Holen, Ingunn; Speirs, Valerie

2016-04-01

Animal models have contributed to our understanding of breast cancer, with publication of results in high-impact journals almost invariably requiring extensive in vivo experimentation. As such, many laboratories hold large collections of surplus animal material, with only a fraction being used in publications relating to the original projects. Despite being developed at considerable cost, this material is an invisible and hence an underutilised resource, which often ends up being discarded. Within the breast cancer research community there is both a need and desire to make this valuable material available for researchers. Lack of a coordinated system for visualisation and localisation of this has prevented progress. To fulfil this unmet need, we have developed a novel initiative called Sharing Experimental Animal Resources: Coordinating Holdings-Breast (SEARCHBreast) which facilitates sharing of archival tissue between researchers on a collaborative basis and, de facto will reduce overall usage of animal models in breast cancer research. A secure searchable database has been developed where researchers can find, share, or upload materials related to animal models of breast cancer, including genetic and transplant models. SEARCHBreast is a virtual compendium where the physical material remains with the original laboratory. A bioanalysis pipeline is being developed for the analysis of transcriptomics data associated with mouse models, allowing comparative study with human and cell line data. Additionally, SEARCHBreast is committed to promoting the use of humanised breast tissue models as replacement alternatives to animals. Access to this unique resource is freely available to all academic researchers following registration at https://searchbreast.org.

A Primer on the Genetics of Comorbid Eating Disorders and Substance Use Disorders.

PubMed

Munn-Chernoff, Melissa A; Baker, Jessica H

2016-03-01

Eating disorders (EDs) and substance use disorders (SUDs) frequently co-occur; however, the reasons for this are unclear. We review the current literature on genetic risk for EDs and SUDs, as well as preliminary findings exploring whether these classes of disorders have overlapping genetic risk. Overall, genetic factors contribute to individual differences in liability to multiple EDs and SUDs. Although initial family studies concluded that no shared familial (which includes genetic) risk between EDs and SUDs exists, twin studies suggest a moderate proportion of shared variance is attributable to overlapping genetic factors, particularly for those EDs characterized by binge eating and/or inappropriate compensatory behaviours. No adoption or molecular genetic studies have examined shared genetic risk between these classes of disorders. Research investigating binge eating and inappropriate compensatory behaviours using emerging statistical genetic methods, as well as examining gene-environment interplay, will provide important clues into the aetiology of comorbid EDs and SUDs. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Comparative genetics of hybrid incompatibility: sterility in two Solanum species crosses.

PubMed

Moyle, Leonie C; Nakazato, Takuya

2008-07-01

The genetic basis of hybrid sterility can provide insight into the genetic and evolutionary origins of species barriers. We examine the genetics of hybrid incompatibility between two diploid plant species in the plant clade Solanum sect. Lycopersicon. Using a set of near-isogenic lines (NILs) representing the wild species Solanum pennellii (formerly Lycopersicon pennellii) in the genetic background of the cultivated tomato S. lycopersicum (formerly L. esculentum), we found that hybrid pollen and seed infertility are each based on a modest number of loci, male (pollen) and other (seed) incompatibility factors are roughly comparable in number, and seed-infertility QTL act additively or recessively. These findings are remarkably consistent with our previous analysis in a different species pair, S. lycopersicum x S. habrochaites. Data from both studies contrast strongly with data from Drosophila. Finally, QTL for pollen and seed sterility from the two Solanum studies were chromosomally colocalized, indicating a shared evolutionary history for these QTL, a nonrandom genomic distribution of loci causing sterility, and/or a proclivity of certain genes to be involved in hybrid sterility. We show that comparative mapping data can delimit the probable timing of evolution of detected QTL and discern which sterility loci likely evolved earliest among species.

Shared genetic variance between obesity and white matter integrity in Mexican Americans

PubMed Central

Spieker, Elena A.; Kochunov, Peter; Rowland, Laura M.; Sprooten, Emma; Winkler, Anderson M.; Olvera, Rene L.; Almasy, Laura; Duggirala, Ravi; Fox, Peter T.; Blangero, John; Glahn, David C.; Curran, Joanne E.

2015-01-01

Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18–81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h2 = 0.58), WC (h2 = 0.57), and FA (h2 = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = −0.25), body (ρG = −0.30), and splenium (ρG = −0.26) of the corpus callosum, internal capsule (ρG = −0.29), and thalamic radiation (ρG = −0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = −0.39, p = 0.020; ρG = −0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors. PMID:25763009

Integrating paleoecology and genetics of bird populations in two sky island archipelagos

PubMed Central

McCormack, John E; Bowen, Bonnie S; Smith, Thomas B

2008-01-01

Background Genetic tests of paleoecological hypotheses have been rare, partly because recent genetic divergence is difficult to detect and time. According to fossil plant data, continuous woodland in the southwestern USA and northern Mexico became fragmented during the last 10,000 years, as warming caused cool-adapted species to retreat to high elevations. Most genetic studies of resulting 'sky islands' have either failed to detect recent divergence or have found discordant evidence for ancient divergence. We test this paleoecological hypothesis for the region with intraspecific mitochondrial DNA and microsatellite data from sky-island populations of a sedentary bird, the Mexican jay (Aphelocoma ultramarina). We predicted that populations on different sky islands would share common, ancestral alleles that existed during the last glaciation, but that populations on each sky island, owing to their isolation, would contain unique variants of postglacial origin. We also predicted that divergence times estimated from corrected genetic distance and a coalescence model would post-date the last glacial maximum. Results Our results provide multiple independent lines of support for postglacial divergence, with the predicted pattern of shared and unique mitochondrial DNA haplotypes appearing in two independent sky-island archipelagos, and most estimates of divergence time based on corrected genetic distance post-dating the last glacial maximum. Likewise, an isolation model based on multilocus gene coalescence indicated postglacial divergence of five pairs of sky islands. In contrast to their similar recent histories, the two archipelagos had dissimilar historical patterns in that sky islands in Arizona showed evidence for older divergence, suggesting different responses to the last glaciation. Conclusion This study is one of the first to provide explicit support from genetic data for a postglacial divergence scenario predicted by one of the best paleoecological records in the world. Our results demonstrate that sky islands act as generators of genetic diversity at both recent and historical timescales and underscore the importance of thorough sampling and the use of loci with fast mutation rates to studies that test hypotheses concerning recent genetic divergence. PMID:18588695

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

PubMed

Zeng, Yanni; Navarro, Pau; Xia, Charley; Amador, Carmen; Fernandez-Pujals, Ana M; Thomson, Pippa A; Campbell, Archie; Nagy, Reka; Clarke, Toni-Kim; Hafferty, Jonathan D; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2016-12-01

Both genetic and environmental factors contribute to risk of depression, but estimates of their relative contributions are limited. Commonalities between clinically-assessed major depressive disorder (MDD) and self-declared depression (SDD) are also unclear. Using data from a large Scottish family-based cohort (GS:SFHS, N=19,994), we estimated the genetic and environmental variance components for MDD and SDD. The components representing the genetic effect associated with genome-wide common genetic variants (SNP heritability), the additional pedigree-associated genetic effect and non-genetic effects associated with common environments were estimated in a linear mixed model (LMM). Both MDD and SDD had significant contributions from components representing the effect from common genetic variants, the additional genetic effect associated with the pedigree and the common environmental effect shared by couples. The estimate of correlation between SDD and MDD was high (r=1.00, se=0.20) for common-variant-associated genetic effect and lower for the additional genetic effect from the pedigree (r=0.57, se=0.08) and the couple-shared environmental effect (r=0.53, se=0.22). Both genetics and couple-shared environmental effects were major factors influencing liability to depression. SDD may provide a scalable alternative to MDD in studies seeking to identify common risk variants. Rarer variants and environmental effects may however differ substantially according to different definitions of depression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Family Aggregation and Heritability of ESRD in Taiwan: A Population-Based Study.

PubMed

Wu, Hsin Hsu; Kuo, Chang Fu; Li, I Jung; Weng, Cheng Hao; Lee, Cheng Chia; Tu, Kun Hua; Liu, Shou Hsuan; Chen, Yung Chang; Yang, Chih Wei; Luo, Shue Fen; See, Lai Chu; Yu, Kuang Hui; Huang, Lu Hsiang; Zhang, Weiya; Doherty, Michael; Tian, Ya Chung

2017-11-01

Aggregation of end-stage renal disease (ESRD) has been observed in families of European origin, as well as those of African origin. However, it is not well documented if this disease aggregates in Asian families. Furthermore, the contribution of genetic factors and shared environmental factors to family aggregation remains unclear. Population-based cross-sectional cohort study. All 23,422,955 individuals registered in the Taiwan National Health Insurance Research Database in 2013. Among these, 47.45%, 57.45%, 47.29%, and 1.51% had a known parent, child, sibling, or twin, respectively. We identified 87,849 patients who had a diagnosis of ESRD. Family history of ESRD. ESRD and heritability defined as the proportion of phenotypic variance attributable to genetic factors. Having an affected first-degree relative with ESRD was associated with an adjusted relative risk of 2.46 (95% CI, 2.32-2.62). Relative risks were 96.38 (95% CI, 48.3-192.34) for twins of patients with ESRD, 2.15 (95% CI, 2.02-2.29) for parents, 2.78 (95% CI, 2.53-3.05) for offspring, 4.96 (95% CI, 4.19-5.88) for siblings, and 1.66 (95% CI, 1.54-1.78) for spouses without genetic similarities. Heritability in this study was 31.1% to 11.4% for shared environmental factors and 57.5% for nonshared environmental factors. This was a registry database study and we did not have detailed information about clinical findings or the definite causes of ESRD. This whole population-based family study in Asia confirmed, in a Taiwanese population, that a family history of ESRD is a strong risk factor for this disease. Moderate heritability was noted and environmental factors were related to disease. Family history of ESRD is an important piece of clinical information. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.

PubMed

Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G; Terwindt, Gisela M; Sturm, Jonathan; Bis, Joshua C; Hopewell, Jemma C; Ferrari, Michel D; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I; Mitchell, Braxton D; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T; Kurth, Tobias; Ikram, M Arfan; Reiner, Alex P; Longstreth, W T; Rothwell, Peter M; Strachan, David P; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B; Davey Smith, George; van Duijn, Cornelia M; Stefansson, Kari; Worrall, Bradford B; Nyholt, Dale R; Markus, Hugh S; van den Maagdenberg, Arn M J M; Cotsapas, Chris; Zwart, John A; Palotie, Aarno; Dichgans, Martin

2015-05-26

To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10(-20) for the CE score in MO). Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. © 2015 American Academy of Neurology.

Public and Biobank Participant Attitudes toward Genetic Research Participation and Data Sharing

PubMed Central

Lemke, A.A.; Wolf, W.A.; Hebert-Beirne, J.; Smith, M.E.

2010-01-01

Research assessing attitudes toward consent processes for high-throughput genomic-wide technologies and widespread sharing of data is limited. In order to develop a better understanding of stakeholder views toward these issues, this cross-sectional study assessed public and biorepository participant attitudes toward research participation and sharing of genetic research data. Forty-nine individuals participated in 6 focus groups; 28 in 3 public focus groups and 21 in 3 NUgene biorepository participant focus groups. In the public focus groups, 75% of participants were women, 75% had some college education or more, 46% were African-American and 29% were Hispanic. In the NUgene focus groups, 67% of participants were women, 95% had some college education or more, and the majority (76%) of participants was Caucasian. Five major themes were identified in the focus group data: (a) a wide spectrum of understanding of genetic research; (b) pros and cons of participation in genetic research; (c) influence of credibility and trust of the research institution; (d) concerns about sharing genetic research data and need for transparency in the Policy for Sharing of Data in National Institutes of Health-Supported or Conducted Genome-Wide Association Studies; (e) a need for more information and education about genetic research. In order to increase public understanding and address potential concerns about genetic research, future efforts should be aimed at involving the public in genetic research policy development and in identifying or developing appropriate educational strategies to meet the public's needs. PMID:20805700

The growth and gaps of genetic data sharing policies in the United States

PubMed Central

Arias, Jalayne J.; Pham-Kanter, Genevieve; Campbell, Eric G.

2014-01-01

The 1996 Bermuda Principles launched a new era in data sharing, reflecting a growing belief that the rapid public dissemination of research data was crucial to scientific progress in genetics. A historical review of data sharing policies in the field of genetics and genomics reflects changing scientific norms and evolving views of genomic data, particularly related to human subjects’ protections and privacy concerns. The 2013 NIH Draft Genomic Data Sharing (GDS) Policy incorporates the most significant protections and guidelines to date. The GDS Policy, however, will face difficult challenges ahead as geneticists seek to balance the very real concerns of research participants and the scientific norms that propel research forward. This article provides a novel evaluation of genetic and GDS policies’ treatment of human subjects’ protections. The article examines not only the policies, but also some of the most pertinent scientific, legal, and regulatory developments that occurred alongside data sharing policies. This historical perspective highlights the challenges that future data sharing policies, including the recently disseminated NIH GDS Draft Policy, will encounter. PMID:27774180

Muju Virus, Harbored by Myodes regulus in Korea, Might Represent a Genetic Variant of Puumala Virus, the Prototype Arvicolid Rodent-Borne Hantavirus

PubMed Central

Lee, Jin Goo; Gu, Se Hun; Baek, Luck Ju; Shin, Ok Sarah; Park, Kwang Sook; Kim, Heung-Chul; Klein, Terry A.; Yanagihara, Richard; Song, Jin-Won

2014-01-01

The genome of Muju virus (MUJV), identified originally in the royal vole (Myodes regulus) in Korea, was fully sequenced to ascertain its genetic and phylogenetic relationship with Puumala virus (PUUV), harbored by the bank vole (My. glareolus), and a PUUV-like virus, named Hokkaido virus (HOKV), in the grey red-backed vole (My. rufocanus) in Japan. Whole genome sequence analysis of the 6544-nucleotide large (L), 3652-nucleotide medium (M) and 1831-nucleotide small (S) segments of MUJV, as well as the amino acid sequences of their gene products, indicated that MUJV strains from different capture sites might represent genetic variants of PUUV, the prototype arvicolid rodent-borne hantavirus in Europe. Distinct geographic-specific clustering of MUJV was found in different provinces in Korea, and phylogenetic analyses revealed that MUJV and HOKV share a common ancestry with PUUV. A better understanding of the taxonomic classification and pathogenic potential of MUJV must await its isolation in cell culture. PMID:24736214

Genetic and phylogenetic analysis of a novel parvovirus isolated from chickens in Guangxi, China.

PubMed

Feng, Bin; Xie, Zhixun; Deng, Xianwen; Xie, Liji; Xie, Zhiqin; Huang, Li; Fan, Qin; Luo, Sisi; Huang, Jiaoling; Zhang, Yanfang; Zeng, Tingting; Wang, Sheng; Wang, Leyi

2016-11-01

A previously unidentified chicken parvovirus (ChPV) strain, associated with runting-stunting syndrome (RSS), is now endemic among chickens in China. To explore the genetic diversity of ChPV strains, we determined the first complete genome sequence of a novel ChPV isolate (GX-CH-PV-7) identified in chickens in Guang Xi, China, and showed moderate genome sequence similarity to reference strains. Analysis showed that the viral genome sequence is 86.4 %-93.9 % identical to those of other ChPVs. Genetic and phylogenetic analyses showed that this newly emergent GX-CH-PV-7 is closely related to Gallus gallus enteric parvovirus isolate ChPV 798 from the USA, indicating that they may share a common ancestor. The complete DNA sequence is 4612 bp long with an A+T content of 56.66 %. We determined the first complete genome sequence of a previously unidentified ChPV strain to elucidate its origin and evolutionary status.

The heritability of aptitude and exceptional talent across different domains in adolescents and young adults.

PubMed

Vinkhuyzen, Anna A E; van der Sluis, Sophie; Posthuma, Danielle; Boomsma, Dorret I

2009-07-01

The origin of individual differences in aptitude, defined as a domain-specific skill within the normal ability range, and talent, defined as a domain specific skill of exceptional quality, is under debate. The nature of the variation in aptitudes and exceptional talents across different domains was investigated in a population based twin sample. Self-report data from 1,685 twin pairs (12-24 years) were analyzed for Music, Arts, Writing, Language, Chess, Mathematics, Sports, Memory, and Knowledge. The influence of shared environment was small for both aptitude and talent. Additive and non-additive genetic effects explained the major part of the substantial familial clustering in the aptitude measures with heritability estimates ranging between .32 and .71. Heritability estimates for talents were higher and ranged between .50 and .92. In general, the genetic architecture for aptitude and talent was similar in men and women. Genetic factors contribute to a large extent to variation in aptitude and talent across different domains of intellectual, creative, and sports abilities.

Inherited behavioral susceptibility to adiposity in infancy: a multivariate genetic analysis of appetite and weight in the Gemini birth cohort.

PubMed

Llewellyn, Clare H; van Jaarsveld, Cornelia H M; Plomin, Robert; Fisher, Abigail; Wardle, Jane

2012-03-01

The behavioral susceptibility model proposes that inherited differences in traits such as appetite confer differential risk of weight gain and contribute to the heritability of weight. Evidence that the FTO gene may influence weight partly through its effects on appetite supports this model, but testing the behavioral pathways for multiple genes with very small effects is not feasible. Twin analyses make it possible to get a broad-based estimate of the extent of shared genetic influence between appetite and weight. The objective was to use multivariate twin analyses to test the hypothesis that associations between appetite and weight are underpinned by shared genetic effects. Data were from Gemini, a population-based birth cohort of twins (n = 4804) born in 2007. Infant weights at 3 mo were taken from the records of health professionals. Appetite was assessed at 3 mo for the milk-feeding period by using the Baby Eating Behaviour Questionnaire (BEBQ), a parent-reported measure of appetite [enjoyment of food, food responsiveness, slowness in eating (SE), satiety responsiveness (SR), and appetite size (AS)]. Multivariate quantitative genetic modeling was used to test for shared genetic influences. Significant correlations were found between all BEBQ traits and weight. Significant shared genetic influence was identified for weight with SE, SR, and AS; genetic correlations were between 0.22 and 0.37. Shared genetic effects explained 41-45% of these phenotypic associations. Differences in weight in infancy may be due partly to genetically determined differences in appetitive traits that confer differential susceptibility to obesogenic environments.

Shared genetic influences on negative emotionality and major depression/conduct disorder comorbidity.

PubMed

Tackett, Jennifer L; Waldman, Irwin D; Van Hulle, Carol A; Lahey, Benjamin B

2011-08-01

To investigate whether genetic contributions to major depressive disorder and conduct disorder comorbidity are shared with genetic influences on negative emotionality. Primary caregivers of 2,022 same- and opposite-sex twin pairs 6 to 18 years of age comprised a population-based sample. Participants were randomly selected across five regions in Tennessee, with stratification by age and geographic location. Face-to-face structured interviews were conducted with the primary caregiver of a representative sample of twins. After accounting for genetic influences on negative emotionality, genetic influences on major depressive disorder/conduct disorder comorbidity were nonsignficant, but only in male twins. Specifically, 19% of the variance in the two disorders was accounted for by genetic factors shared with negative emotionality in male twins. Although the full hypothesis could not be tested in female twins, 10% to 11% of the variance in the two disorders was also accounted for by genetic factors shared with negative emotionality. Common shared environmental and nonshared environmental influences were found for major depressive disorder/conduct disorder comorbidity in male and female twins. Negative emotionality represents an important dispositional trait that may explain genetic influences on major depressive disorder/conduct disorder comorbidity, at least for boys. Models of major depressive disorder/conduct disorder comorbidity must simultaneously measure common and specific genetic and environmental factors for a full understanding of this phenomenon. Gender differences require specific research attention in dispositional factors and developmental progression. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

MHC class II genes in European wolves: a comparison with dogs.

PubMed

Seddon, Jennifer M; Ellegren, Hans

2002-10-01

The genome of the grey wolf, one of the most widely distributed land mammal species, has been subjected to both stochastic factors, including biogeographical subdivision and population fragmentation, and strong selection during the domestication of the dog. To explore the effects of drift and selection on the partitioning of MHC variation in the diversification of species, we present nine DQA, 10 DQB, and 17 DRB1 sequences of the second exon for European wolves and compare them with sequences of North American wolves and dogs. The relatively large number of class II alleles present in both European and North American wolves attests to their large historical population sizes, yet there are few alleles shared between these regions at DQB and DRB1. Similarly, the dog has an extensive array of class II MHC alleles, a consequence of a genetically diverse origin, but allelic overlap with wolves only at DQA. Although we might expect a progression from shared alleles to shared allelic lineages during differentiation, the partitioning of diversity between wolves and dogs at DQB and DRB1 differs from that at DQA. Furthermore, an extensive region of nucleotide sequence shared between DRB1 and DQB alleles and a shared motif suggests intergenic recombination may have contributed to MHC diversity in the Canidae.

The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals.

PubMed

Shaw, Liam; Ribeiro, Andre L R; Levine, Adam P; Pontikos, Nikolas; Balloux, Francois; Segal, Anthony W; Roberts, Adam P; Smith, Andrew M

2017-09-12

The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed the salivary microbiomes of an extended family of Ashkenazi Jewish individuals living in several cities and investigated associations with both shared household and host genetic similarities. We found that environmental effects dominated over genetic effects. While there was weak evidence of geographical structuring at the level of cities, we observed a large and significant effect of shared household on microbiome composition, supporting the role of the immediate shared environment in dictating the presence or absence of taxa. This effect was also seen when including adults who had grown up in the same household but moved out prior to the time of sampling, suggesting that the establishment of the salivary microbiome earlier in life may affect its long-term composition. We found weak associations between host genetic relatedness and microbiome dissimilarity when using family pedigrees as proxies for genetic similarity. However, this association disappeared when using more-accurate measures of kinship based on genome-wide genetic markers, indicating that the environment rather than host genetics is the dominant factor affecting the composition of the salivary microbiome in closely related individuals. Our results support the concept that there is a consistent core microbiome conserved across global scales but that small-scale effects due to a shared living environment significantly affect microbial community composition. IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years. Copyright © 2017 Shaw et al.

Genetic structure of Tibetan populations in Gansu revealed by forensic STR loci.

PubMed

Yao, Hong-Bing; Wang, Chuan-Chao; Wang, Jiang; Tao, Xiaolan; Shang, Lei; Wen, Shao-Qing; Du, Qiajun; Deng, Qiongying; Xu, Bingying; Huang, Ying; Wang, Hong-Dan; Li, Shujin; Bin Cong; Ma, Liying; Jin, Li; Krause, Johannes; Li, Hui

2017-01-23

The origin and diversification of Sino-Tibetan speaking populations have been long-standing hot debates. However, the limited genetic information of Tibetan populations keeps this topic far from clear. In the present study, we genotyped 15 forensic autosomal short tandem repeats (STRs) from 803 unrelated Tibetan individuals from Gansu Province (635 from Gannan and 168 from Tianzhu) in northwest China. We combined these data with published dataset to infer a detailed population affinities and genetic substructure of Sino-Tibetan populations. Our results revealed Tibetan populations in Gannan and Tianzhu are genetically very similar with Tibetans from other regions. The Tibetans in Tianzhu have received more genetic influence from surrounding lowland populations. The genetic structure of Sino-Tibetan populations was strongly correlated with linguistic affiliations. Although the among-population variances are relatively small, the genetic components for Tibetan, Lolo-Burmese, and Han Chinese were quite distinctive, especially for the Deng, Nu, and Derung of Lolo-Burmese. Han Chinese but not Tibetans are suggested to share substantial genetic component with southern natives, such as Tai-Kadai and Hmong-Mien speaking populations, and with other lowland East Asian populations, which implies there might be extensive gene flow between those lowland groups and Han Chinese after Han Chinese were separated from Tibetans. The dataset generated in present study is also valuable for forensic identification and paternity tests in China.

Genetic structure of Tibetan populations in Gansu revealed by forensic STR loci

PubMed Central

Yao, Hong-Bing; Wang, Chuan-Chao; Wang, Jiang; Tao, Xiaolan; Shang, Lei; Wen, Shao-Qing; Du, Qiajun; Deng, Qiongying; Xu, Bingying; Huang, Ying; Wang, Hong-Dan; Li, Shujin; Bin Cong; Ma, Liying; Jin, Li; Krause, Johannes; Li, Hui

2017-01-01

The origin and diversification of Sino-Tibetan speaking populations have been long-standing hot debates. However, the limited genetic information of Tibetan populations keeps this topic far from clear. In the present study, we genotyped 15 forensic autosomal short tandem repeats (STRs) from 803 unrelated Tibetan individuals from Gansu Province (635 from Gannan and 168 from Tianzhu) in northwest China. We combined these data with published dataset to infer a detailed population affinities and genetic substructure of Sino-Tibetan populations. Our results revealed Tibetan populations in Gannan and Tianzhu are genetically very similar with Tibetans from other regions. The Tibetans in Tianzhu have received more genetic influence from surrounding lowland populations. The genetic structure of Sino-Tibetan populations was strongly correlated with linguistic affiliations. Although the among-population variances are relatively small, the genetic components for Tibetan, Lolo-Burmese, and Han Chinese were quite distinctive, especially for the Deng, Nu, and Derung of Lolo-Burmese. Han Chinese but not Tibetans are suggested to share substantial genetic component with southern natives, such as Tai-Kadai and Hmong-Mien speaking populations, and with other lowland East Asian populations, which implies there might be extensive gene flow between those lowland groups and Han Chinese after Han Chinese were separated from Tibetans. The dataset generated in present study is also valuable for forensic identification and paternity tests in China. PMID:28112227

Shared Genetic Influences on Negative Emotionality and Major Depression/Conduct Disorder Comorbidity

ERIC Educational Resources Information Center

Tackett, Jennifer L.; Waldman, Irwin D.; Van Hulle, Carol A.; Lahey, Benjamin B.

2011-01-01

Objective: To investigate whether genetic contributions to major depressive disorder and conduct disorder comorbidity are shared with genetic influences on negative emotionality. Method: Primary caregivers of 2,022 same- and opposite-sex twin pairs 6 to 18 years of age comprised a population-based sample. Participants were randomly selected across…

Genomic patterns of nucleotide diversity in divergent populations of U.S. weedy rice

PubMed Central

2010-01-01

Background Weedy rice (red rice), a conspecific weed of cultivated rice (Oryza sativa L.), is a significant problem throughout the world and an emerging threat in regions where it was previously absent. Despite belonging to the same species complex as domesticated rice and its wild relatives, the evolutionary origins of weedy rice remain unclear. We use genome-wide patterns of single nucleotide polymorphism (SNP) variation in a broad geographic sample of weedy, domesticated, and wild Oryza samples to infer the origin and demographic processes influencing U.S. weedy rice evolution. Results We find greater population structure than has been previously reported for U.S. weedy rice, and that the multiple, genetically divergent populations have separate origins. The two main U.S. weedy rice populations share genetic backgrounds with cultivated O. sativa varietal groups not grown commercially in the U.S., suggesting weed origins from domesticated ancestors. Hybridization between weedy groups and between weedy rice and local crops has also led to the evolution of distinct U.S. weedy rice populations. Demographic simulations indicate differences among the main weedy groups in the impact of bottlenecks on their establishment in the U.S., and in the timing of divergence from their cultivated relatives. Conclusions Unlike prior research, we did not find unambiguous evidence for U.S. weedy rice originating via hybridization between cultivated and wild Oryza species. Our results demonstrate the potential for weedy life-histories to evolve directly from within domesticated lineages. The diverse origins of U.S. weedy rice populations demonstrate the multiplicity of evolutionary forces that can influence the emergence of weeds from a single species complex. PMID:20550656

Evolution and Structural Organization of the C Proteins of Paramyxovirinae

PubMed Central

Karlin, David G.

2014-01-01

The phosphoprotein (P) gene of most Paramyxovirinae encodes several proteins in overlapping frames: P and V, which share a common N-terminus (PNT), and C, which overlaps PNT. Overlapping genes are of particular interest because they encode proteins originated de novo, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space. The C proteins cluster in three groups, comprising measles, Nipah, and Sendai virus. We predicted that all C proteins have a similar organization: a variable, disordered N-terminus and a conserved, α-helical C-terminus. We confirmed this predicted organization by biophysically characterizing recombinant C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza virus 1 (Sendai group). We also found that the C of the measles and Nipah groups have statistically significant sequence similarity, indicating a common origin. Although the C of the Sendai group lack sequence similarity with them, we speculate that they also have a common origin, given their similar genomic location and structural organization. Since C is dispensable for viral replication, unlike PNT, we hypothesize that C may have originated de novo by overprinting PNT in the ancestor of Paramyxovirinae. Intriguingly, in measles virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different regions of the C-terminus of C, indicating they have probably originated independently. This arrangement, in which the same genetic region encodes simultaneously a crucial functional motif (a STAT1-binding site) and a highly constrained region (the C-terminus of C), seems paradoxical, since it should severely reduce the ability of the virus to adapt. The fact that it originated twice suggests that it must be balanced by an evolutionary advantage, perhaps from reducing the size of the genetic region vulnerable to mutations. PMID:24587180

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

Genetic and environmental origins of gambling behaviors from ages 18 to 25: A longitudinal twin family study.

PubMed

King, Serena M; Keyes, Margaret; Winters, Ken C; McGue, Matt; Iacono, William G

2017-05-01

Gambling behaviors tend to increase in prevalence from late adolescence to young adulthood, and the underlying genetic and environmental influences during this period remain largely understudied. We examined the genetic and environmental influences on gambling behaviors contributing to stability and change from ages 18 to 25 in a longitudinal, behavioral genetic mixed-sex twin study design. Participants were enrolled in the Minnesota Twin Family Study. A range of gambling behaviors (maximum frequency, average frequency, money lost, and gambling problems) were assessed at ages 18 and 25. The results of our study support the following conclusions: (a) the genetic and environmental factors impacting a range of gambling behaviors are largely similar in men and women, (b) genetic factors increase in influence from 18 to 25 (21% at age 18 to 57% at age 25), (c) shared environmental factors are influential at age 18, but tend to decrease from ages 18 to 25 (55% at age 18 to 10% at age 25), and (d) nonshared environmental influences are similarly significant and are small to moderate in magnitude at both ages. The findings add to a small yet important research area regarding determinants of youth gambling behaviors and have the potential to inform prevention and intervention efforts. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A Multimethodological Study of Preschoolers' Preferences for Aggressive Television and Video Games.

PubMed

Jamnik, Matthew R; DiLalla, Lisabeth F

2018-01-01

The association between aggressive media and related behavior is complicated, and the role of underlying genetics has not been adequately explored. A better understanding of the role of genetics on the relationship between aggressive media and behavior, especially in young children, is critical. Using a twin/triplets sample (N = 184 children), the authors investigated the association between preschoolers' preferred media choices and their aggressive behaviors. A multimeasure methodology was utilized, examining children's reports of their preferred media games and shows, observed child negativity and aggression in the lab, and parent reports of their own and their children's aggressive behaviors. The results demonstrated a significant relationship between maternal aggression and parent-reported child aggression, especially for boys. Genetic analyses demonstrated significant heritability for children's parent-reported aggressive behaviors, supporting the biological basis of aggression, but not for media aggression preferences. Controlling for genetics, the authors found that the association between media preferences and aggressive behavior may be genetic in origin. These results emphasize the importance of considering shared genetics underlying the relationship between children's aggressive behaviors and their media preferences, as well as environmental influences. By examining preschoolers, the present study provides insight into the importance of media influences in children younger than those previously studied.

Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs

PubMed Central

Fradin, Delphine; Cheslack-Postava, Keely; Ladd-Acosta, Christine; Newschaffer, Craig; Chakravarti, Aravinda; Arking, Dan E.; Feinberg, Andrew; Fallin, M. Daniele

2010-01-01

Background Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association. Methods and Findings We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE) and the National Institute of Mental Health (NIMH) autism repository. We report parametric (GH, Genehunter) and allele-sharing linkage (Aspex) results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LODGH = 3.79, empirical p<0.005 and LODAspex = 2.96, p = 0.008), 15 (LODGH = 3.09, empirical p<0.005 and LODAspex = 3.62, empirical p = 0.003) and 20 (LODGH = 3.36, empirical p<0.005 and LODAspex = 3.38, empirical p = 0.006). Conclusions These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism. PMID:20824079

Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia

PubMed Central

Klütsch, C F C; Seppälä, E H; Fall, T; Uhlén, M; Hedhammar, Å; Lohi, H; Savolainen, P

2011-01-01

The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60–100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480–3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage. PMID:20497152

Neurofibromatosis: part 2--clinical management.

PubMed

Batista, Pollyanna Barros; Bertollo, Eny Maria Goloni; Costa, Danielle de Souza; Eliam, Lucas; Cunha, Karin Soares Gonçalves; Cunha-Melo, José Renan; Darrigo Junior, Luiz Guilherme; Geller, Mauro; Gianordoli-Nascimento, Ingrid Faria; Madeira, Luciana Gonçalves; Mendes, Hérika Martins; Miranda, Débora Marques de; Mata-Machado, Nikolas Andre; Morato, Eric Grossi; Pavarino, Érika Cristina; Pereira, Luciana Baptista; Rezende, Nilton Alves de; Rodrigues, Luíza de Oliveira; Sette, Jorge Bezerra Cavalcanti

2015-06-01

Part 1 of this guideline addressed the differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH). NF shares some features such as the genetic origin of the neural tumors and cutaneous manifestations, and affects nearly 80 thousand Brazilians. Increasing scientific knowledge on NF has allowed better clinical management and reduced rate of complications and morbidity, resulting in higher quality of life for NF patients. Most medical doctors are able to perform NF diagnosis, but the wide range of clinical manifestations and the inability to predict the onset or severity of new features, consequences, or complications make NF management a real clinical challenge, requiring the support of different specialists for proper treatment and genetic counseling, especially in NF2 and SCH. The present text suggests guidelines for the clinical management of NF, with emphasis on NF1.

The etiology of mathematical self-evaluation and mathematics achievement: understanding the relationship using a cross-lagged twin study from age 9 to 12

PubMed Central

Luo, Yu L.L.; Kovas, Yulia; Haworth, Claire M.A.; Plomin, Robert

2011-01-01

The genetic and environmental origins of individual differences in mathematical self-evaluation over time and its association with later mathematics achievement were investigated in a UK sample of 2138 twin pairs at ages 9 and 12. Self-evaluation indexed how good children think they are at mathematical activities and how much they like those activities. Mathematics achievement was assessed by teachers based on UK National Curriculum standards. At both ages self-evaluation was approximately 40% heritable, with the rest of the variance explained by non-shared environment. The results also suggested moderate reciprocal associations between self-evaluation and mathematics achievement across time, with earlier self-evaluation predicting later performance and earlier performance predicting later self-evaluation. These cross-lagged relationships were genetically rather than environmentally mediated. PMID:22102781

Haplotype Sharing Provides Insights into Fine-Scale Population History and Disease in Finland.

PubMed

Martin, Alicia R; Karczewski, Konrad J; Kerminen, Sini; Kurki, Mitja I; Sarin, Antti-Pekka; Artomov, Mykyta; Eriksson, Johan G; Esko, Tõnu; Genovese, Giulio; Havulinna, Aki S; Kaprio, Jaakko; Konradi, Alexandra; Korányi, László; Kostareva, Anna; Männikkö, Minna; Metspalu, Andres; Perola, Markus; Prasad, Rashmi B; Raitakari, Olli; Rotar, Oxana; Salomaa, Veikko; Groop, Leif; Palotie, Aarno; Neale, Benjamin M; Ripatti, Samuli; Pirinen, Matti; Daly, Mark J

2018-05-03

Finland provides unique opportunities to investigate population and medical genomics because of its adoption of unified national electronic health records, detailed historical and birth records, and serial population bottlenecks. We assembled a comprehensive view of recent population history (≤100 generations), the timespan during which most rare-disease-causing alleles arose, by comparing pairwise haplotype sharing from 43,254 Finns to that of 16,060 Swedes, Estonians, Russians, and Hungarians from geographically and linguistically adjacent countries with different population histories. We find much more extensive sharing in Finns, with at least one ≥ 5 cM tract on average between pairs of unrelated individuals. By coupling haplotype sharing with fine-scale birth records from more than 25,000 individuals, we find that although haplotype sharing broadly decays with geographical distance, there are pockets of excess haplotype sharing; individuals from northeast Finland typically share several-fold more of their genome in identity-by-descent segments than individuals from southwest regions. We estimate recent effective population-size changes through time across regions of Finland, and we find that there was more continuous gene flow as Finns migrated from southwest to northeast between the early- and late-settlement regions than was dichotomously described previously. Lastly, we show that haplotype sharing is locally enriched by an order of magnitude among pairs of individuals sharing rare alleles and especially among pairs sharing rare disease-causing variants. Our work provides a general framework for using haplotype sharing to reconstruct an integrative view of recent population history and gain insight into the evolutionary origins of rare variants contributing to disease. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Research review: the shared environment as a key source of variability in child and adolescent psychopathology.

PubMed

Burt, S Alexandra

2014-04-01

Behavioral genetic research has historically concluded that the more important environmental influences were nonshared or result in differences between siblings, whereas environmental influences that create similarities between siblings (referred to as shared environmental influences) were indistinguishable from zero. Recent theoretical and meta-analytic work {Burt. Psychological Bulletin [135 (2009) 608]} has challenged this conclusion as it relates to child and adolescent psychopathology, however, arguing that the shared environment is a moderate, persistent, and identifiable source of individual differences in such outcomes prior to adulthood. The current review seeks to bolster research on the shared environment by highlighting both the logistic advantages inherent in studies of the shared environment, as well as the use of nontraditional but still genetically informed research designs to study shared environmental influences. Although often moderate in magnitude prior to adulthood and free of unsystematic measurement error, shared environmental influences are nevertheless likely to have been underestimated in prior research. Moreover, the shared environment is likely to include proximal effects of the family, as well as the effects of more distal environmental contexts such as neighborhood and school. These risk and protective factors could influence the child either as main effects or as moderators of genetic influence (i.e. gene-environment interactions). Finally, because the absence of genetic relatedness in an otherwise nonindependent dataset also qualifies as 'genetically informed', studies of the shared environment are amenable to the use of novel and non-traditional designs (with appropriate controls for selection). The shared environment makes important contributions to most forms of child and adolescent psychopathology. Empirical examinations of the shared environment would thus be of real and critical value for understanding the development and persistence of common mental health issues prior to adulthood. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Genetic and environmental influences on separation anxiety disorder symptoms and their moderation by age and sex.

PubMed

Feigon, S A; Waldman, I D; Levy, F; Hay, D A

2001-09-01

We estimated genetic and environmental influences on mother-rated DSM-III-R separation anxiety disorder (SAD) symptoms in 2043 3 to 18-year-old male and female twin pairs and their siblings (348 pairs) recruited from the Australian NH&MRC Twin Registry. Using DeFries and Fulker's (1985) multiple regression analysis, we found that genetic and shared environmental influences both contributed appreciably to variation in SAD symptoms (h2 = .47, SE = .07; c2 = .21, SE = .05) and were significantly moderated by both sex and age. Genetic influences were greater for girls than boys (h2 = .50 and .14, respectively), whereas shared environmental influences were greater for boys than girls (c2 = .51 and .21, respectively). Genetic influences increased with age. whereas shared environmental influences decreased with age. Shared environmental influences were greater in magnitude for twins than for nontwin siblings (c2 = .28 versus .13, respectively). Implications of these findings for theories of the cause of separation anxiety are discussed.

Can Chimpanzee Biology Highlight Human Origin and Evolution?

PubMed Central

Roffman, Itai; Nevo, Eviatar

2010-01-01

The closest living relatives of humans are their chimpanzee/bonobo (Pan) sister species, members of the same subfamily “Homininae”. This classification is supported by over 50 years of research in the fields of chimpanzee cultural diversity, language competency, genomics, anatomy, high cognition, psychology, society, self-consciousness and relation to others, tool use/production, as well as Homo level emotions, symbolic competency, memory recollection, complex multifaceted problem-solving capabilities, and interspecies communication. Language competence and symbolism can be continuously bridged from chimpanzee to man. Emotions, intercommunity aggression, body language, gestures, facial expressions, and vocalization of intonations seem to parallel between the sister taxa Homo and Pan. The shared suite of traits between Pan and Homo genus demonstrated in this article integrates old and new information on human–chimpanzee evolution, bilateral informational and cross-cultural exchange, promoting the urgent need for Pan cultures in the wild to be protected, as they are part of the cultural heritage of mankind. Also, we suggest that bonobos, Pan paniscus, based on shared traits with Australopithecus, need to be included in Australopithecine’s subgenus, and may even represent living-fossil Australopithecines. Unfolding bonobo and chimpanzee biology highlights our common genetic and cultural evolutionary origins. PMID:23908781

A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

PubMed Central

Boucher, Gabrielle; Beauchamp, Claudine; Trynka, Gosia; Dubois, Patrick C.; Lagacé, Caroline; Stokkers, Pieter C. F.; Hommes, Daan W.; Barisani, Donatella; Palmieri, Orazio; Annese, Vito; van Heel, David A.; Weersma, Rinse K.; Daly, Mark J.; Wijmenga, Cisca; Rioux, John D.

2011-01-01

Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0×10−5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1×10−2 in CelD and <1×10−3 in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37×10−8 and 6.39×10−9, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55×10−10 and 1.38×10−11 respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect. PMID:21298027

Hybridogenesis through thelytokous parthenogenesis in two Cataglyphis desert ants.

PubMed

Eyer, P A; Leniaud, L; Darras, H; Aron, S

2013-02-01

Hybridogenesis is a sexual reproductive system, whereby parents from different genetic origin hybridize. Both the maternal and paternal genomes are expressed in somatic tissues, but the paternal genome is systematically excluded from the germ line, which is therefore purely maternal. Recently, a unique case of hybridogenesis at a social level was reported in the desert ant Cataglyphis hispanica. All workers are sexually produced hybridogens, whereas sexual forms (new queens and males) are produced by queens through parthenogenesis. Thus, only maternal genes are perpetuated across generations. Here, we show that such an unusual reproductive strategy also evolved in two other species of Cataglyphis belonging to the same phylogenetic group, Cataglyphis velox and Cataglyphis mauritanica. In both species, queens mate exclusively with males originating from a different genetic lineage than their own to produce hybrid workers, while they use parthenogenesis to produce the male and female reproductive castes. In contrast to single-queen colonies of C. hispanica, colonies of C. velox and C. mauritanica are headed by several queens. Most queens within colonies share the same multilocus genotype and never transmit their mates' alleles to the reproductive castes. Social hybridogenesis in the desert ants has direct consequences on the genetic variability of populations and on caste determination. We also discuss the maintenance of this reproductive strategy within the genus Cataglyphis. © 2012 Blackwell Publishing Ltd.

The origin of the p.E180 growth hormone receptor gene mutation.

PubMed

Ostrer, Harry

2016-06-01

Laron syndrome, an autosomal recessive condition of extreme short stature, is caused by the absence or dysfunction of the growth hormone receptor. A recurrent mutation in the GHR gene, p.E180, did not alter the encoded amino acid, but activated a cryptic splice acceptor resulting in a receptor protein with an 8-amino acid deletion in the extracellular domain. This mutation has been observed among Sephardic Jews and among individuals in Ecuador, Brazil and Chile, most notably in a large genetic isolate in Loja, Ecuador. A common origin has been postulated based on a shared genetic background of markers flanking this mutation, suggesting that the Lojanos (and others) may have Sephardic (Converso) Jewish ancestry. Analysis of the population structure of Lojanos based on genome-wide analysis demonstrated European, Sephardic Jewish and Native American ancestry in this group. X-autosomal comparison and monoallelic Y chromosomal and mitochondrial genetic analysis demonstrated gender-biased admixture between Native American women and European and Sephardic Jewish men. These findings are compatible with the co-occurrence of the Inquisition and the colonization of the Americas, including Converso Jews escaping the Inquisition in the Iberian Peninsula. Although not found among Lojanos, Converso Jews also brought founder mutations to contemporary Hispanic and Latino populations in the BRCA1 (c.68_69delAG) and BLM (c.2207_2212delATCTGAinsTAGATTC) genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Do Viruses Exchange Genes across Superkingdoms of Life?

PubMed

Malik, Shahana S; Azem-E-Zahra, Syeda; Kim, Kyung Mo; Caetano-Anollés, Gustavo; Nasir, Arshan

2017-01-01

Viruses can be classified into archaeoviruses, bacterioviruses, and eukaryoviruses according to the taxonomy of the infected host. The host-constrained perception of viruses implies preference of genetic exchange between viruses and cellular organisms of their host superkingdoms and viral origins from host cells either via escape or reduction. However, viruses frequently establish non-lytic interactions with organisms and endogenize into the genomes of bacterial endosymbionts that reside in eukaryotic cells. Such interactions create opportunities for genetic exchange between viruses and organisms of non-host superkingdoms. Here, we take an atypical approach to revisit virus-cell interactions by first identifying protein fold structures in the proteomes of archaeoviruses, bacterioviruses, and eukaryoviruses and second by tracing their spread in the proteomes of superkingdoms Archaea, Bacteria, and Eukarya. The exercise quantified protein structural homologies between viruses and organisms of their host and non-host superkingdoms and revealed likely candidates for virus-to-cell and cell-to-virus gene transfers. Unexpected lifestyle-driven genetic affiliations between bacterioviruses and Eukarya and eukaryoviruses and Bacteria were also predicted in addition to a large cohort of protein folds that were universally shared by viral and cellular proteomes and virus-specific protein folds not detected in cellular proteomes. These protein folds provide unique insights into viral origins and evolution that are generally difficult to recover with traditional sequence alignment-dependent evolutionary analyses owing to the fast mutation rates of viral gene sequences.

The genetic-environmental etiology of cognitive school readiness and later academic achievement in early childhood.

PubMed

Lemelin, Jean-Pascal; Boivin, Michel; Forget-Dubois, Nadine; Dionne, Ginette; Séguin, Jean R; Brendgen, Mara; Vitaro, Frank; Tremblay, Richard E; Pérusse, Daniel

2007-01-01

Using a genetic design of 840 60-month-old twins, this study investigated the genetic and environmental contributions to (a) individual differences in four components of cognitive school readiness, (b) the general ability underlying these four components, and (c) the predictive association between school readiness and school achievement. Results revealed that the contribution of the shared environment for cognitive school readiness was substantial. Genetic effects were more important for the core abilities underlying school readiness than for each specific skill, although shared environment remained the largest factor overall. Genetic, shared, and nonshared environmental factors all accounted for the predictive association between school readiness and early school achievement. These results contribute to a better understanding of the early determinants of school readiness.

Childhood separation anxiety disorder and adult onset panic attacks share a common genetic diathesis.

PubMed

Roberson-Nay, Roxann; Eaves, Lindon J; Hettema, John M; Kendler, Kenneth S; Silberg, Judy L

2012-04-01

Childhood separation anxiety disorder (SAD) is hypothesized to share etiologic roots with panic disorder. The aim of this study was to estimate the genetic and environmental sources of covariance between childhood SAD and adult onset panic attacks (AOPA), with the primary goal to determine whether these two phenotypes share a common genetic diathesis. Participants included parents and their monozygotic or dizygotic twins (n = 1,437 twin pairs) participating in the Virginia Twin Study of Adolescent Behavioral Development and those twins who later completed the Young Adult Follow-Up (YAFU). The Child and Adolescent Psychiatric Assessment was completed at three waves during childhood/adolescence followed by the Structured Clinical Interview for DSM-III-R at the YAFU. Two separate, bivariate Cholesky models were fit to childhood diagnoses of SAD and overanxious disorder (OAD), respectively, and their relation with AOPA; a trivariate Cholesky model also examined the collective influence of childhood SAD and OAD on AOPA. In the best-fitting bivariate model, the covariation between SAD and AOPA was accounted for by genetic and unique environmental factors only, with the genetic factor associated with childhood SAD explaining significant variance in AOPA. Environmental risk factors were not significantly shared between SAD and AOPA. By contrast, the genetic factor associated with childhood OAD did not contribute significantly to AOPA. Results of the trivariate Cholesky reaffirmed outcomes of bivariate models. These data indicate that childhood SAD and AOPA share a common genetic diathesis that is not observed for childhood OAD, strongly supporting the hypothesis of a specific genetic etiologic link between the two phenotypes. © 2012 Wiley Periodicals, Inc.

Choice of Reading Comprehension Test Influences the Outcomes of Genetic Analyses

PubMed Central

Betjemann, Rebecca S.; Keenan, Janice M.; Olson, Richard K.; DeFries, John C.

2010-01-01

Does the choice of test for assessing reading comprehension influence the outcome of genetic analyses? A twin design compared two types of reading comprehension tests classified as primarily associated with word decoding (RC-D) or listening comprehension (RC-LC). For both types of tests, the overall genetic influence is high and nearly identical. However, the tests differed significantly in how they covary with the genes associated with decoding and listening comprehension. Although Cholesky decomposition showed that both types of comprehension tests shared significant genetic influence with both decoding and listening comprehension, RC-D tests shared most genetic variance with decoding, and RC-LC tests shared most with listening comprehension. Thus, different tests used to measure the same construct may manifest very different patterns of genetic covariation. These results suggest that the apparent discrepancies among the findings of previous twin studies of reading comprehension could be due at least in part to test differences. PMID:21804757

Pathogenicity and genetic characterization of a duck Tembusu virus associated with egg-dropping in Muscovy ducks.

PubMed

Shen, Han-Qin; Lin, Wen-Cheng; Wang, Zhan-Xin; Zhang, Kai; Yan, Zhuan-Qiang; Zhou, Qing-Feng; Qin, Jian-Ping; Xie, Qing-Mei; Bi, Ying-Zuo; Chen, Feng

2016-09-02

Duck Tembusu virus (DTMUV) has spread to the major duck-farming region in China, causing acute egg-production drop in Chinese duck population. In this study, we characterized a DTMUV strain (named GD2014) isolated from an egg-production drop duck farm in Guangdong province, South China. The virus was pathogenic to Muscovy duck embryos and caused severe egg production drop for laying Muscovy ducks. The genome sequence of GD2014 shared 97-99% homologies with other waterfowl-origin Tembusu viruses, and shared 89% identities with MM1775 strain isolated from mosquito. Phylogenetic analysis of entire open reading frame (ORF), E gene and NS5 gene indicated that GD2014 belonged to Ntaya group. These results have implications for understanding the orgin, emergence and pathogenicity of DTMUV as well as for the development of vaccines and diagnostics based on epidemiological data. Copyright © 2016 Elsevier B.V. All rights reserved.

Exome-Wide Association Analysis of Coronary Artery Disease in the Kingdom of Saudi Arabia Population

PubMed Central

de Kovel, Carolien G.; Mulder, Flip; van Setten, Jessica; van ‘t Slot, Ruben; Al-Rubaish, Abdullah; Alshehri, Abdullah M.; Al Faraidy, Khalid; Al-Ali, Abdullah; Al-Madan, Mohammed; Al Aqaili, Issa; Larbi, Emmanuel; Al-Ali, Rudaynah; Alzahrani, Alhusain; Asselbergs, Folkert W.; Koeleman, Bobby P. C.; Al-Ali, Amein

2016-01-01

Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h2 = 0.53, S.E. = 0.1, p = 4e-12) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations. PMID:26849363

Resistance patterns, ESBL genes, and genetic relatedness of Escherichia coli from dogs and owners

PubMed Central

Carvalho, A.C.; Barbosa, A.V.; Arais, L.R.; Ribeiro, P.F.; Carneiro, V.C.; Cerqueira, A.M.F.

2016-01-01

Antimicrobial resistance in Escherichia coli isolated from pet dogs can be considered a potential threat of infection for the human population. Our objective was to characterize the resistance pattern, extended spectrum beta-lactamase production and genetic relatedness of multiresistant E. coli strains isolated from dogs (n = 134), their owners (n = 134), and humans who claim to have no contact with dogs (n = 44, control), searching for sharing of strains. The strains were assessed for their genetic relatedness by phylogenetic grouping and pulsed-field gel electrophoresis. Multiresistant E. coli strains were isolated from 42 (31.3%) fecal samples from pairs of dogs and owners, totaling 84 isolates, and from 19 (43.1%) control group subjects. The strains showed high levels of resistance to ampicillin, streptomycin, tetracycline, trimethoprim and sulfamethoxazole regardless of host species or group of origin. The blaTEM, blaCTX-M, and blaSHV genes were detected in similar proportions in all groups. All isolates positive for bla genes were ESBL producers. The phylogenetic group A was the most prevalent, irrespective of the host species. None of the strains belonging to the B2 group contained bla genes. Similar resistance patterns were found for strains from dogs, owners and controls; furthermore, identical PFGE profiles were detected in four (9.5%) isolate pairs from dogs and owners, denoting the sharing of strains. Pet dogs were shown to be a potential household source of multiresistant E. coli strains. PMID:26887238

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

Genetic influences on heart rate variability

PubMed Central

Golosheykin, Simon; Grant, Julia D.; Novak, Olga V.; Heath, Andrew C.; Anokhin, Andrey P.

2016-01-01

Heart rate variability (HRV) is the variation of cardiac inter-beat intervals over time resulting largely from the interplay between the sympathetic and parasympathetic branches of the autonomic nervous system. Individual differences in HRV are associated with emotion regulation, personality, psychopathology, cardiovascular health, and mortality. Previous studies have shown significant heritability of HRV measures. Here we extend genetic research on HRV by investigating sex differences in genetic underpinnings of HRV, the degree of genetic overlap among different measurement domains of HRV, and phenotypic and genetic relationships between HRV and the resting heart rate (HR). We performed electrocardiogram (ECG) recordings in a large population-representative sample of young adult twins (n = 1060 individuals) and computed HRV measures from three domains: time, frequency, and nonlinear dynamics. Genetic and environmental influences on HRV measures were estimated using linear structural equation modeling of twin data. The results showed that variability of HRV and HR measures can be accounted for by additive genetic and non-shared environmental influences (AE model), with no evidence for significant shared environmental effects. Heritability estimates ranged from 47 to 64%, with little difference across HRV measurement domains. Genetic influences did not differ between genders for most variables except the square root of the mean squared differences between successive R-R intervals (RMSSD, higher heritability in males) and the ratio of low to high frequency power (LF/HF, distinct genetic factors operating in males and females). The results indicate high phenotypic and especially genetic correlations between HRV measures from different domains, suggesting that >90% of genetic influences are shared across measures. Finally, about 40% of genetic variance in HRV was shared with HR. In conclusion, both HR and HRV measures are highly heritable traits in the general population of young adults, with high degree of genetic overlap across different measurement domains. PMID:27114045

Psychopathic personality traits in 5 year old twins: the importance of genetic and shared environmental influences.

PubMed

Tuvblad, Catherine; Fanti, Kostas A; Andershed, Henrik; Colins, Olivier F; Larsson, Henrik

2017-04-01

There is limited research on the genetic and environmental bases of psychopathic personality traits in children. In this study, psychopathic personality traits were assessed in a total of 1189 5-year-old boys and girls drawn from the Preschool Twin Study in Sweden. Psychopathic personality traits were assessed with the Child Problematic Traits Inventory, a teacher-report measure of psychopathic personality traits in children ranging from 3 to 12 years old. Univariate results showed that genetic influences accounted for 57, 25, and 74 % of the variance in the grandiose-deceitful, callous-unemotional, and impulsive-need for stimulation dimensions, while the shared environment accounted for 17, 48 and 9 % (n.s.) in grandiose-deceitful and callous-unemotional, impulsive-need for stimulation dimensions, respectively. No sex differences were found in the genetic and environmental variance components. The non-shared environment accounted for the remaining 26, 27 and 17 % of the variance, respectively. The three dimensions of psychopathic personality were moderately correlated (0.54-0.66) and these correlations were primarily mediated by genetic and shared environmental factors. In contrast to research conducted with adolescent and adult twins, we found that both genetic and shared environmental factors influenced psychopathic personality traits in early childhood. These findings indicate that etiological models of psychopathic personality traits would benefit by taking developmental stages and processes into consideration.

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics

PubMed Central

Evans, Barbara J

2014-01-01

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved—but still imperfect—framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics. Genet Med 16 7, 504–509. PMID:24357850

Viruses and mobile elements as drivers of evolutionary transitions

PubMed Central

2016-01-01

The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses. I present evidence that, at least up to and including the origin of multicellularity, evolutionary transitions are driven by the coevolution of hosts with these genetic parasites along with sharing of ‘public goods’. Selfish elements drive evolutionary transitions at two distinct levels. First, mathematical modelling of evolutionary processes, such as evolution of primitive replicator populations or unicellular organisms, indicates that only increasing organizational complexity, e.g. emergence of multicellular aggregates, can prevent the collapse of the host–parasite system under the pressure of parasites. Second, comparative genomic analysis reveals numerous cases of recruitment of genes with essential functions in cellular life forms, including those that enable evolutionary transitions. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431520

The last sea nomads of the Indonesian archipelago: genomic origins and dispersal

PubMed Central

Kusuma, Pradiptajati; Brucato, Nicolas; Cox, Murray P; Letellier, Thierry; Manan, Abdul; Nuraini, Chandra; Grangé, Philippe; Sudoyo, Herawati; Ricaut, François-Xavier

2017-01-01

The Bajo, the world’s largest remaining sea nomad group, are scattered across hundreds of recently settled communities in Island Southeast Asia, along the coasts of Indonesia, Malaysia and the Philippines. With a significant role in historical trading, the Bajo lived until recently as nomads, spending their entire lives on houseboats while moving long distances to fish and trade. Along the routes they traveled, the Bajo settled and intermarried with local land-based groups, leading to ‘maritime creolization’, a process whereby Bajo communities retained their culture, but assimilated – and frequently married into – local groups. The origins of the Bajo have remained unclear despite several hypotheses from oral tradition, culture and language, all currently without supporting genetic evidence. Here, we report genome-wide SNP analyses on 73 Bajo individuals from three communities across Indonesia – the Derawan of Northeast Borneo, the Kotabaru of Southeast Borneo and the Kendari of Southeast Sulawesi, with 87 new samples from three populations surrounding the area where these Bajo peoples live. The Bajo likely share a common connection with Southern Sulawesi, but crucially, each Bajo community also exhibits unique genetic contributions from neighboring populations. PMID:28513608

A molecular epidemiological study of rabies epizootics in kudu (Tragelaphus strepsiceros) in Namibia

PubMed Central

Mansfield, Karen; McElhinney, Lorraine; Hübschle, Otto; Mettler, Felix; Sabeta, Claude; Nel, Louis H; Fooks, Anthony R

2006-01-01

Background A panel of 37 rabies virus isolates were collected and studied, originating mainly from the northern and central regions of Namibia, between 1980 and 2003. Results These virus isolates demonstrated a high degree of genetic similarity with respect to a 400 bp region of the nucleoprotein gene, with the virus isolates originating from kudu antelope (n = 10) sharing 97.2–100% similarity with jackal isolates, and 97–100% similarity with those isolated from domestic dogs. Phylogenetic analysis suggested that these viruses were all of the canid rabies biotype of southern Africa. The viruses from kudu were closely associated with jackal isolates (n = 6), bat-eared fox isolates (n = 2) and domestic dog isolates (n = 2) at the genetic level and identical at the amino acid level, irrespective of the year of isolation. Conclusion These data suggest that jackal and kudu may form part of the same epidemiological cycle of rabies in Namibian wildlife, and might demonstrate the close-relationship between rabies virus strains that circulate within Namibia and those that circulate between Namibia and its neighbouring countries such as Botswana and South Africa. PMID:16412222

Viruses and mobile elements as drivers of evolutionary transitions.

PubMed

Koonin, Eugene V

2016-08-19

The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses. I present evidence that, at least up to and including the origin of multicellularity, evolutionary transitions are driven by the coevolution of hosts with these genetic parasites along with sharing of 'public goods'. Selfish elements drive evolutionary transitions at two distinct levels. First, mathematical modelling of evolutionary processes, such as evolution of primitive replicator populations or unicellular organisms, indicates that only increasing organizational complexity, e.g. emergence of multicellular aggregates, can prevent the collapse of the host-parasite system under the pressure of parasites. Second, comparative genomic analysis reveals numerous cases of recruitment of genes with essential functions in cellular life forms, including those that enable evolutionary transitions.This article is part of the themed issue 'The major synthetic evolutionary transitions'. © 2016 The Authors.

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

Ancient DNA reveals that the genetic structure of the northern Han Chinese was shaped prior to 3,000 years ago.

PubMed

Zhao, Yong-Bin; Zhang, Ye; Zhang, Quan-Chao; Li, Hong-Jie; Cui, Ying-Qiu; Xu, Zhi; Jin, Li; Zhou, Hui; Zhu, Hong

2015-01-01

The Han Chinese are the largest ethnic group in the world, and their origins, development, and expansion are complex. Many genetic studies have shown that Han Chinese can be divided into two distinct groups: northern Han Chinese and southern Han Chinese. The genetic history of the southern Han Chinese has been well studied. However, the genetic history of the northern Han Chinese is still obscure. In order to gain insight into the genetic history of the northern Han Chinese, 89 human remains were sampled from the Hengbei site which is located in the Central Plain and dates back to a key transitional period during the rise of the Han Chinese (approximately 3,000 years ago). We used 64 authentic mtDNA data obtained in this study, 27 Y chromosome SNP data profiles from previously studied Hengbei samples, and genetic datasets of the current Chinese populations and two ancient northern Chinese populations to analyze the relationship between the ancient people of Hengbei and present-day northern Han Chinese. We used a wide range of population genetic analyses, including principal component analyses, shared mtDNA haplotype analyses, and geographic mapping of maternal genetic distances. The results show that the ancient people of Hengbei bore a strong genetic resemblance to present-day northern Han Chinese and were genetically distinct from other present-day Chinese populations and two ancient populations. These findings suggest that the genetic structure of northern Han Chinese was already shaped 3,000 years ago in the Central Plain area.

Ancient DNA Reveals That the Genetic Structure of the Northern Han Chinese Was Shaped Prior to 3,000 Years Ago

PubMed Central

Zhang, Quan-Chao; Li, Hong-Jie; Cui, Ying-Qiu; Xu, Zhi; Jin, Li; Zhou, Hui; Zhu, Hong

2015-01-01

The Han Chinese are the largest ethnic group in the world, and their origins, development, and expansion are complex. Many genetic studies have shown that Han Chinese can be divided into two distinct groups: northern Han Chinese and southern Han Chinese. The genetic history of the southern Han Chinese has been well studied. However, the genetic history of the northern Han Chinese is still obscure. In order to gain insight into the genetic history of the northern Han Chinese, 89 human remains were sampled from the Hengbei site which is located in the Central Plain and dates back to a key transitional period during the rise of the Han Chinese (approximately 3,000 years ago). We used 64 authentic mtDNA data obtained in this study, 27 Y chromosome SNP data profiles from previously studied Hengbei samples, and genetic datasets of the current Chinese populations and two ancient northern Chinese populations to analyze the relationship between the ancient people of Hengbei and present-day northern Han Chinese. We used a wide range of population genetic analyses, including principal component analyses, shared mtDNA haplotype analyses, and geographic mapping of maternal genetic distances. The results show that the ancient people of Hengbei bore a strong genetic resemblance to present-day northern Han Chinese and were genetically distinct from other present-day Chinese populations and two ancient populations. These findings suggest that the genetic structure of northern Han Chinese was already shaped 3,000 years ago in the Central Plain area. PMID:25938511

The Genetic Legacy of Religious Diversity and Intolerance: Paternal Lineages of Christians, Jews, and Muslims in the Iberian Peninsula

PubMed Central

Adams, Susan M.; Bosch, Elena; Balaresque, Patricia L.; Ballereau, Stéphane J.; Lee, Andrew C.; Arroyo, Eduardo; López-Parra, Ana M.; Aler, Mercedes; Grifo, Marina S. Gisbert; Brion, Maria; Carracedo, Angel; Lavinha, João; Martínez-Jarreta, Begoña; Quintana-Murci, Lluis; Picornell, Antònia; Ramon, Misericordia; Skorecki, Karl; Behar, Doron M.; Calafell, Francesc; Jobling, Mark A.

2008-01-01

Most studies of European genetic diversity have focused on large-scale variation and interpretations based on events in prehistory, but migrations and invasions in historical times could also have had profound effects on the genetic landscape. The Iberian Peninsula provides a suitable region for examination of the demographic impact of such recent events, because its complex recent history has involved the long-term residence of two very different populations with distinct geographical origins and their own particular cultural and religious characteristics—North African Muslims and Sephardic Jews. To address this issue, we analyzed Y chromosome haplotypes, which provide the necessary phylogeographic resolution, in 1140 males from the Iberian Peninsula and Balearic Islands. Admixture analysis based on binary and Y-STR haplotypes indicates a high mean proportion of ancestry from North African (10.6%) and Sephardic Jewish (19.8%) sources. Despite alternative possible sources for lineages ascribed a Sephardic Jewish origin, these proportions attest to a high level of religious conversion (whether voluntary or enforced), driven by historical episodes of social and religious intolerance, that ultimately led to the integration of descendants. In agreement with the historical record, analysis of haplotype sharing and diversity within specific haplogroups suggests that the Sephardic Jewish component is the more ancient. The geographical distribution of North African ancestry in the peninsula does not reflect the initial colonization and subsequent withdrawal and is likely to result from later enforced population movement—more marked in some regions than in others—plus the effects of genetic drift. PMID:19061982

Population genetic structure of the people of Qatar.

PubMed

Hunter-Zinck, Haley; Musharoff, Shaila; Salit, Jacqueline; Al-Ali, Khalid A; Chouchane, Lotfi; Gohar, Abeer; Matthews, Rebecca; Butler, Marcus W; Fuller, Jennifer; Hackett, Neil R; Crystal, Ronald G; Clark, Andrew G

2010-07-09

People of the Qatar peninsula represent a relatively recent founding by a small number of families from three tribes of the Arabian Peninsula, Persia, and Oman, with indications of African admixture. To assess the roles of both this founding effect and the customary first-cousin marriages among the ancestral Islamic populations in Qatar's population genetic structure, we obtained and genotyped with Affymetrix 500k SNP arrays DNA samples from 168 self-reported Qatari nationals sampled from Doha, Qatar. Principal components analysis was performed along with samples from the Human Genetic Diversity Project data set, revealing three clear clusters of genotypes whose proximity to other human population samples is consistent with Arabian origin, a more eastern or Persian origin, and individuals with African admixture. The extent of linkage disequilibrium (LD) is greater than that of African populations, and runs of homozygosity in some individuals reflect substantial consanguinity. However, the variance in runs of homozygosity is exceptionally high, and the degree of identity-by-descent sharing generally appears to be lower than expected for a population in which nearly half of marriages are between first cousins. Despite the fact that the SNPs of the Affymetrix 500k chip were ascertained with a bias toward SNPs common in Europeans, the data strongly support the notion that the Qatari population could provide a valuable resource for the mapping of genes associated with complex disorders and that tests of pairwise interactions are particularly empowered by populations with elevated LD like the Qatari. Copyright 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The Genetic and Environmental Sources of Resemblance Between Normative Personality and Personality Disorder Traits.

PubMed

Kendler, K S; Aggen, S H; Gillespie, Nathan; Neale, M C; Knudsen, G P; Krueger, R F; Czajkowski, Nikolai; Ystrom, Eivind; Reichborn-Kjennerud, T

2017-04-01

Recent work has suggested a high level of congruence between normative personality, most typically represented by the "big five" factors, and abnormal personality traits. In 2,293 Norwegian adult twins ascertained from a population-based registry, the authors evaluated the degree of sharing of genetic and environmental influences on normative personality, assessed by the Big Five Inventory (BFI), and personality disorder traits (PDTs), assessed by the Personality Inventory for DSM-5-Norwegian Brief Form (PID-5-NBF). For four of the five BFI dimensions, the strongest genetic correlation was observed with the expected PID-5-NBF dimension (e.g., neuroticism with negative affectivity [+], conscientiousness with disinhibition [-]). However, neuroticism, conscientiousness, and agreeableness had substantial genetic correlations with other PID-5-NBF dimensions (e.g., neuroticism with compulsivity [+], agreeableness with detachment [-]). Openness had no substantial genetic correlations with any PID-5-NBF dimension. The proportion of genetic risk factors shared in aggregate between the BFI traits and the PID-5-NBF dimensions was quite high for conscientiousness and neuroticism, relatively robust for extraversion and agreeableness, but quite low for openness. Of the six PID-5-NBF dimensions, three (negative affectivity, detachment, and disinhibition) shared, in aggregate, most of their genetic risk factors with normative personality traits. Genetic factors underlying psychoticism, antagonism, and compulsivity were shared to a lesser extent, suggesting that they are influenced by etiological factors not well indexed by the BFI.

Tracing the origin of the east-west population admixture in the Altai region (Central Asia).

PubMed

González-Ruiz, Mercedes; Santos, Cristina; Jordana, Xavier; Simón, Marc; Lalueza-Fox, Carles; Gigli, Elena; Aluja, Maria Pilar; Malgosa, Assumpció

2012-01-01

A recent discovery of Iron Age burials (Pazyryk culture) in the Altai Mountains of Mongolia may shed light on the mode and tempo of the generation of the current genetic east-west population admixture in Central Asia. Studies on ancient mitochondrial DNA of this region suggest that the Altai Mountains played the role of a geographical barrier between West and East Eurasian lineages until the beginning of the Iron Age. After the 7th century BC, coinciding with Scythian expansion across the Eurasian steppes, a gradual influx of East Eurasian sequences in Western steppes is detected. However, the underlying events behind the genetic admixture in Altai during the Iron Age are still unresolved: 1) whether it was a result of migratory events (eastward firstly, westward secondly), or 2) whether it was a result of a local demographic expansion in a 'contact zone' between European and East Asian people. In the present work, we analyzed the mitochondrial DNA lineages in human remains from Bronze and Iron Age burials of Mongolian Altai. Here we present support to the hypothesis that the gene pool of Iron Age inhabitants of Mongolian Altai was similar to that of western Iron Age Altaians (Russia and Kazakhstan). Thus, this people not only shared the same culture (Pazyryk), but also shared the same genetic east-west population admixture. In turn, Pazyryks appear to have a similar gene pool that current Altaians. Our results further show that Iron Age Altaians displayed mitochondrial lineages already present around Altai region before the Iron Age. This would provide support for a demographic expansion of local people of Altai instead of westward or eastward migratory events, as the demographic event behind the high population genetic admixture and diversity in Central Asia.

Tracing the Origin of the East-West Population Admixture in the Altai Region (Central Asia)

PubMed Central

González-Ruiz, Mercedes; Santos, Cristina; Jordana, Xavier; Simón, Marc; Lalueza-Fox, Carles; Gigli, Elena; Aluja, Maria Pilar; Malgosa, Assumpció

2012-01-01

A recent discovery of Iron Age burials (Pazyryk culture) in the Altai Mountains of Mongolia may shed light on the mode and tempo of the generation of the current genetic east-west population admixture in Central Asia. Studies on ancient mitochondrial DNA of this region suggest that the Altai Mountains played the role of a geographical barrier between West and East Eurasian lineages until the beginning of the Iron Age. After the 7th century BC, coinciding with Scythian expansion across the Eurasian steppes, a gradual influx of East Eurasian sequences in Western steppes is detected. However, the underlying events behind the genetic admixture in Altai during the Iron Age are still unresolved: 1) whether it was a result of migratory events (eastward firstly, westward secondly), or 2) whether it was a result of a local demographic expansion in a ‘contact zone’ between European and East Asian people. In the present work, we analyzed the mitochondrial DNA lineages in human remains from Bronze and Iron Age burials of Mongolian Altai. Here we present support to the hypothesis that the gene pool of Iron Age inhabitants of Mongolian Altai was similar to that of western Iron Age Altaians (Russia and Kazakhstan). Thus, this people not only shared the same culture (Pazyryk), but also shared the same genetic east-west population admixture. In turn, Pazyryks appear to have a similar gene pool that current Altaians. Our results further show that Iron Age Altaians displayed mitochondrial lineages already present around Altai region before the Iron Age. This would provide support for a demographic expansion of local people of Altai instead of westward or eastward migratory events, as the demographic event behind the high population genetic admixture and diversity in Central Asia. PMID:23152818

Over Six Thousand Trypanosoma cruzi Strains Classified into Discrete Typing Units (DTUs): Attempt at an Inventory

PubMed Central

Brenière, Simone Frédérique; Waleckx, Etienne; Barnabé, Christian

2016-01-01

Trypanosoma cruzi, the causative agent of Chagas disease, presents wide genetic diversity. Currently, six discrete typing units (DTUs), named TcI to TcVI, and a seventh one called TcBat are used for strain typing. Beyond the debate concerning this classification, this systematic review has attempted to provide an inventory by compiling the results of 137 articles that have used it. A total of 6,343 DTU identifications were analyzed according to the geographical and host origins. Ninety-one percent of the data available is linked to South America. This sample, although not free of potential bias, nevertheless provides today’s picture of T. cruzi genetic diversity that is closest to reality. DTUs were genotyped from 158 species, including 42 vector species. Remarkably, TcI predominated in the overall sample (around 60%), in both sylvatic and domestic cycles. This DTU known to present a high genetic diversity, is very widely distributed geographically, compatible with a long-term evolution. The marsupial is thought to be its most ancestral host and the Gran Chaco region the place of its putative origin. TcII was rarely sampled (9.6%), absent, or extremely rare in North and Central America, and more frequently identified in domestic cycles than in sylvatic cycles. It has a low genetic diversity and has probably found refuge in some mammal species. It is thought to originate in the south-Amazon area. TcIII and TcIV were also rarely sampled. They showed substantial genetic diversity and are thought to be composed of possible polyphyletic subgroups. Even if they are mostly associated with sylvatic transmission cycles, a total of 150 human infections with these DTUs have been reported. TcV and TcVI are clearly associated with domestic transmission cycles. Less than 10% of these DTUs were identified together in sylvatic hosts. They are thought to originate in the Gran Chaco region, where they are predominant and where putative parents exist (TcII and TcIII). Trends in host-DTU specificities exist, but generally it seems that the complexity of the cycles and the participation of numerous vectors and mammal hosts in a shared area, maintains DTU diversity. PMID:27571035

Intraspecific Polymorphism, Interspecific Divergence, and the Origins of Function-Altering Mutations in Deer Mouse Hemoglobin

PubMed Central

Natarajan, Chandrasekhar; Hoffmann, Federico G.; Lanier, Hayley C.; Wolf, Cole J.; Cheviron, Zachary A.; Spangler, Matthew L.; Weber, Roy E.; Fago, Angela; Storz, Jay F.

2015-01-01

Major challenges for illuminating the genetic basis of phenotypic evolution are to identify causative mutations, to quantify their functional effects, to trace their origins as new or preexisting variants, and to assess the manner in which segregating variation is transduced into species differences. Here, we report an experimental analysis of genetic variation in hemoglobin (Hb) function within and among species of Peromyscus mice that are native to different elevations. A multilocus survey of sequence variation in the duplicated HBA and HBB genes in Peromyscus maniculatus revealed that function-altering amino acid variants are widely shared among geographically disparate populations from different elevations, and numerous amino acid polymorphisms are also shared with closely related species. Variation in Hb-O2 affinity within and among populations of P. maniculatus is attributable to numerous amino acid mutations that have individually small effects. One especially surprising feature of the Hb polymorphism in P. maniculatus is that an appreciable fraction of functional standing variation in the two transcriptionally active HBA paralogs is attributable to recurrent gene conversion from a tandemly linked HBA pseudogene. Moreover, transpecific polymorphism in the duplicated HBA genes is not solely attributable to incomplete lineage sorting or introgressive hybridization; instead, it is mainly attributable to recurrent interparalog gene conversion that has occurred independently in different species. Partly as a result of concerted evolution between tandemly duplicated globin genes, the same amino acid changes that contribute to variation in Hb function within P. maniculatus also contribute to divergence in Hb function among different species of Peromyscus. In the case of function-altering Hb mutations in Peromyscus, there is no qualitative or quantitative distinction between segregating variants within species and fixed differences between species. PMID:25556236

Genetic diversity and differentiation among insular honey bee populations in the southwest Indian Ocean likely reflect old geographical isolation and modern introductions.

PubMed

Techer, Maéva Angélique; Clémencet, Johanna; Simiand, Christophe; Turpin, Patrick; Garnery, Lionel; Reynaud, Bernard; Delatte, Hélène

2017-01-01

With globalization the Western honey bee has become a nearly cosmopolitan species, but it was originally restricted to the Old World. This renowned model of biodiversity has diverged into five evolutionary lineages and several geographic "subspecies." If Apis mellifera unicolor is indubitably an African subspecies endemic to Madagascar, its relationship with honey bees from three archipelagos in the southwest Indian Ocean (SWIO) hotspot of biodiversity is misunderstood. We compared recent mtDNA diversity data to an original characterization of the nuclear diversity from honey bees in the Mascarenes and Comoros archipelagos, using 14 microsatellites, but also additional mtDNA tRNALeu-cox2 analysis. Our sampling offers the most comprehensive dataset for the SWIO populations with a total of 3,270 colonies from 10 islands compared with 855 samples from Madagascar, 113 from Africa, and 138 from Europe. Comprehensive mitochondrial screening confirmed that honey bees from La Réunion, Mauritius, and Comoros archipelagos are mainly of African origin (88.1% out of 2,746 colonies) and that coexistence with European lineages occurs only in the Mascarenes. PCA, Bayesian, and genetic differentiation analysis showed that African colonies are not significantly distinct on each island, but have diversified among islands and archipelagos. FST levels progressively decreased in significance from European and African continental populations, to SWIO insular and continental populations, and finally among islands from the same archipelago. Among African populations, Madagascar shared a nuclear background with and was most closely related to SWIO island populations (except Rodrigues). Only Mauritius Island presented clear cytoplasmic disequilibrium and genetic structure characteristic of an admixed population undergoing hybridization, in this case, between A. m. unicolor and A. m. ligustica, A. m. carnica and A. m. mellifera-like individuals. Finally, global genetic clustering analysis helped to better depict the colonization and introduction pattern of honey bee populations in these archipelagos.

Genetic diversity and differentiation among insular honey bee populations in the southwest Indian Ocean likely reflect old geographical isolation and modern introductions

PubMed Central

Clémencet, Johanna; Simiand, Christophe; Turpin, Patrick; Garnery, Lionel; Reynaud, Bernard; Delatte, Hélène

2017-01-01

With globalization the Western honey bee has become a nearly cosmopolitan species, but it was originally restricted to the Old World. This renowned model of biodiversity has diverged into five evolutionary lineages and several geographic “subspecies.” If Apis mellifera unicolor is indubitably an African subspecies endemic to Madagascar, its relationship with honey bees from three archipelagos in the southwest Indian Ocean (SWIO) hotspot of biodiversity is misunderstood. We compared recent mtDNA diversity data to an original characterization of the nuclear diversity from honey bees in the Mascarenes and Comoros archipelagos, using 14 microsatellites, but also additional mtDNA tRNALeu-cox2 analysis. Our sampling offers the most comprehensive dataset for the SWIO populations with a total of 3,270 colonies from 10 islands compared with 855 samples from Madagascar, 113 from Africa, and 138 from Europe. Comprehensive mitochondrial screening confirmed that honey bees from La Réunion, Mauritius, and Comoros archipelagos are mainly of African origin (88.1% out of 2,746 colonies) and that coexistence with European lineages occurs only in the Mascarenes. PCA, Bayesian, and genetic differentiation analysis showed that African colonies are not significantly distinct on each island, but have diversified among islands and archipelagos. FST levels progressively decreased in significance from European and African continental populations, to SWIO insular and continental populations, and finally among islands from the same archipelago. Among African populations, Madagascar shared a nuclear background with and was most closely related to SWIO island populations (except Rodrigues). Only Mauritius Island presented clear cytoplasmic disequilibrium and genetic structure characteristic of an admixed population undergoing hybridization, in this case, between A. m. unicolor and A. m. ligustica, A. m. carnica and A. m. mellifera-like individuals. Finally, global genetic clustering analysis helped to better depict the colonization and introduction pattern of honey bee populations in these archipelagos. PMID:29281653

Quasi-causal associations of physical activity and neighborhood walkability with body mass index: a twin study.

PubMed

Duncan, Glen E; Cash, Stephanie Whisnant; Horn, Erin E; Turkheimer, Eric

2015-01-01

Physical activity, neighborhood walkability, and body mass index (BMI, kg/m(2)) associations were tested using quasi-experimental twin methods. We hypothesized that physical activity and walkability were independently associated with BMI within twin pairs, controlling for genetic and environmental background shared between them. Data were from 6376 (64% female; 58% identical) same-sex pairs, University of Washington Twin Registry, 2008-2013. Neighborhood walking, moderate-to-vigorous physical activity (MVPA), and BMI were self-reported. Residential address was used to calculate walkability. Phenotypic (non-genetically informed) and biometric (genetically informed) regression was employed, controlling for age, sex, and race. Walking and MVPA were associated with BMI in phenotypic analyses; associations were attenuated but significant in biometric analyses (Ps<0.05). Walkability was not associated with BMI, however, was associated with walking (but not MVPA) in both phenotypic and biometric analyses (Ps<0.05), with no attenuation accounting for shared genetic and environmental background. The association between activity and BMI is largely due to shared genetic and environmental factors, but a significant causal relationship remains accounting for shared background. Although walkability is not associated with BMI, it is associated with neighborhood walking (but not MVPA) accounting for shared background, suggesting a causal relationship between them. Copyright © 2014 Elsevier Inc. All rights reserved.

Shared Environment Estimates for Educational Attainment: A Puzzle and Possible Solutions.

PubMed

Freese, Jeremy; Jao, Yu-Han

2017-02-01

Classical behavioral genetics models for twin and other family designs decompose traits into heritability, shared environment, and nonshared environment components. Estimates of heritability of adult traits are pervasively observed to be far higher than those of shared environment, which has been used to make broad claims about the impotence of upbringing. However, the most commonly studied nondemographic variable in many areas of social science, educational attainment, exhibits robustly high estimates both for heritability and for shared environment. When previously noticed, the usual explanation has emphasized family resources, but evidence suggests this is unlikely to explain the anomalous high estimates for shared environment of educational attainment. We articulate eight potential complementary explanations and discuss evidence of their prospective contributions to resolving the puzzle. In so doing, we hope to further consideration of how behavioral genetics findings may advance studies of social stratification beyond the effort to articulate specific genetic influences. © 2015 Wiley Periodicals, Inc.

High-throughput multiplex cpDNA resequencing clarifies the genetic diversity and genetic relationships among Brassica napus, Brassica rapa and Brassica oleracea.

PubMed

Qiao, Jiangwei; Cai, Mengxian; Yan, Guixin; Wang, Nian; Li, Feng; Chen, Binyun; Gao, Guizhen; Xu, Kun; Li, Jun; Wu, Xiaoming

2016-01-01

Brassica napus (rapeseed) is a recent allotetraploid plant and the second most important oilseed crop worldwide. The origin of B. napus and the genetic relationships with its diploid ancestor species remain largely unresolved. Here, chloroplast DNA (cpDNA) from 488 B. napus accessions of global origin, 139 B. rapa accessions and 49 B. oleracea accessions were populationally resequenced using Illumina Solexa sequencing technologies. The intraspecific cpDNA variants and their allelic frequencies were called genomewide and further validated via EcoTILLING analyses of the rpo region. The cpDNA of the current global B. napus population comprises more than 400 variants (SNPs and short InDels) and maintains one predominant haplotype (Bncp1). Whole-genome resequencing of the cpDNA of Bncp1 haplotype eliminated its direct inheritance from any accession of the B. rapa or B. oleracea species. The distribution of the polymorphism information content (PIC) values for each variant demonstrated that B. napus has much lower cpDNA diversity than B. rapa; however, a vast majority of the wild and cultivated B. oleracea specimens appeared to share one same distinct cpDNA haplotype, in contrast to its wild C-genome relatives. This finding suggests that the cpDNA of the three Brassica species is well differentiated. The predominant B. napus cpDNA haplotype may have originated from uninvestigated relatives or from interactions between cpDNA mutations and natural/artificial selection during speciation and evolution. These exhaustive data on variation in cpDNA would provide fundamental data for research on cpDNA and chloroplasts. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Frequency of cystathionine beta-synthase 844INS68 polymorphism in Southern Iran.

PubMed

Senemar, Sara; Doroudchi, Mehrnoosh; Pezeshki, Abdul Mohammad; Bazrgar, Masood; Torab-Jahromi, Ardeshir; Ghaderi, Abbas

2009-02-01

Iranian population with an Indo-European origin is one of the oldest populations in the world. Historical evidence suggests the close similarity in the origin of Iranian, European and north Indian population. However, there are few anthropological and genetic evidences on this subject. This study, which is the first report from Iran, was performed to investigate the genetic origin of Iranian population using a polymorphism in Cystathionine beta synthase (CBS) gene known as 844INS68bp in this respect, genomic DNA was extracted from the whole blood of 480 healthy normal blood donors referred to Fars Blood Transfusion Center, using a salting out method. The fragment containing 844INS68bp was amplified, the normal fragment was 174 bp and the fragment containing the insertion was 242 bp in length. Results indicated that 418 (87.08%) out of 480 individuals had a normal (N/N) genotype, 59 (12.29%) individuals were heterozygote (N/I) and 3 (0.63%) had homozygote a mutated genotype (I/I). The total frequency of 844INS68bp allele was found 6.8% which is similar to with the reported in White Caucasians. Comparison of the genotype of this study with the polymorphism in other populations revealed that Southern Iranian population has a great similarity with other Caucasians populations' especially South Italy and North America while differed from East Asian and African populations. These results are in agreement with the result of other studied polymorphisms. Therefore, despite the great admixture of Iranian population with the neighboring non-Caucasian populations during the time, Iranian population still share a genetic background with other Caucasian populations.

[Identification of Y-chromosomal Genetic Types for the Soldier's Remains from Huaihai Campaign].

PubMed

Wang, C Z; Wen, S Q; Shi, M S; Yu, X E; Wang, X J; Pan, Y L; Zhang, Y F; Li, H; Tan, J Z

2017-08-01

To identify the Y-chromosomal genetic types for the soldier's remains from Huaihai Campaign, and to offer a clue for search of their paternal relatives. DNA of the remains were extracted by the ancient DNA extraction method. Yfiler kit was used for the multiplex amplification of 17 Y-STR loci. The haplogroups of the samples were speculated. Detailed genotyping of the selected Y-SNP was performed based on the latest Y-chromosome phylogenetic tree. Haplotype-sharing analysis was done based on the data of Y-SNP and Y-STR, the closest modern individual information to the genetic relationship of remains was gained. A total of 8 Y-STR haplotypes were observed on 17 Y-STR loci of 8 male individuals. Furthermore, 6 Y-SNP haplogroups were identified, which were O2a1-M95+, O1a1-P203+, O3*-M122+/M234-, D1-M15+, C3*-ST and R1a1-M17+. Identification of Y-chromosomal genetic types for the soldier's remains from Huaihai Campaign shows a reference value on inferring the geographical origins of old materials. Copyright© by the Editorial Department of Journal of Forensic Medicine

Genetic diversity of clinical Mycobacterium avium subsp. hominissuis and Mycobacterium intracellulare isolates causing pulmonary diseases recovered from different geographical regions.

PubMed

Ichikawa, Kazuya; van Ingen, Jakko; Koh, Won-Jung; Wagner, Dirk; Salfinger, Max; Inagaki, Takayuki; Uchiya, Kei-Ichi; Nakagawa, Taku; Ogawa, Kenji; Yamada, Kiyofumi; Yagi, Tetsuya

2015-12-01

Mycobacterium avium complex (MAC) infections are increasing annually in many countries. MAC strains are the most common nontuberculous mycobacterial pathogens isolated from respiratory samples and predominantly consist of two species, Mycobacterium avium and Mycobacterium intracellulare. The aim of this study was to analyze the molecular epidemiology and genetic backgrounds of clinical MAC isolates collected from The Netherlands, Germany, United States, Korea and Japan. Variable numbers of tandem repeats (VNTR) analysis was used to examine the genetic relatedness of clinical isolates of M. avium subsp. hominissuis (n=261) and M. intracellulare (n=116). Minimum spanning tree and unweighted pair group method using arithmetic averages analyses based on the VNTR data indicated that M. avium subsp. hominissuis isolates from Japan shared a high degree of genetic relatedness with Korean isolates, but not with isolates from Europe or the United States, whereas M. intracellulare isolates did not show any specific clustering by geographic origin. The findings from the present study indicate that strains of M. avium subsp. hominissuis, but not M. intracellulare, exhibit geographical differences in genetic diversity and imply that MAC strains may have different sources, routes of transmission and perhaps clinical manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

Heritability of Thoracic Spine Curvature and Genetic Correlations With Other Spine Traits: The Framingham Study

PubMed Central

Yau, Michelle S; Demissie, Serkalem; Zhou, Yanhua; Anderson, Dennis E; Lorbergs, Amanda L; Kiel, Douglas P; Allaire, Brett T; Yang, Laiji; Cupples, L Adrienne; Travison, Thomas G; Bouxsein, Mary L; Karasik, David; Samelson, Elizabeth J

2017-01-01

Hyperkyphosis is a common spinal disorder in older adults, characterized by excessive forward curvature of the thoracic spine and adverse health outcomes. The etiology of hyperkyphosis has not been firmly established, but may be related to changes that occur with aging in the vertebrae, discs, joints, and muscles, which function as a unit to support the spine. Determining the contribution of genetics to thoracic spine curvature and the degree of genetic sharing among co-occurring measures of spine health may provide insight into the etiology of hyperkyphosis. The purpose of our study was to estimate heritability of thoracic spine curvature using T4–T12 kyphosis (Cobb) angle and genetic correlations between thoracic spine curvature and vertebral fracture, intervertebral disc height narrowing, facet joint osteoarthritis (OA), lumbar spine volumetric bone mineral density (vBMD), and paraspinal muscle area and density, which were all assessed from computed tomography (CT) images. Participants included 2063 women and men in the second and third generation offspring of the original cohort of the Framingham Study. Heritability of kyphosis angle, adjusted for age, sex, and weight, was 54% (95% confidence interval [CI], 43% to 64%). We found moderate genetic correlations between kyphosis angle and paraspinal muscle area ( ρ^G, −0.46; 95% CI, −0.67 to −0.26), vertebral fracture ( ρ^G, 0.39; 95% CI, 0.18 to 0.61), vBMD ( ρ^G,−0.23; 95% CI, −0.41 to −0.04), and paraspinal muscle density ( ρ^G,−0.22; 95% CI, −0.48 to 0.03). Genetic correlations between kyphosis angle and disc height narrowing ( ρ^G, 0.17; 95% CI, −0.05 to 0.38) and facet joint OA ( ρ^G, 0.05; 95% CI, −0.15 to 0.24) were low. Thoracic spine curvature may be heritable and share genetic factors with other age-related spine traits including trunk muscle size, vertebral fracture, and bone mineral density. PMID:27455046

Introduction to 'Homology and convergence in nervous system evolution'.

PubMed

Strausfeld, Nicholas J; Hirth, Frank

2016-01-05

The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso-ventral and anterior-posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the 'Cambrian explosion' arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss homology and convergence in nervous system evolution. By integrating knowledge ranging from evolutionary theory and palaeontology to comparative developmental genetics and phylogenomics, the meeting covered disparities in nervous system origins as well as correspondences of neural circuit organization and behaviours, all of which allow evidence-based debates for and against the proposition that the nervous systems and brains of animals might derive from a common ancestor. © 2015 The Author(s).

Presence of a Shared 5'-Leader Sequence in Ancestral Human and Mammalian Retroviruses and Its Transduction into Feline Leukemia Virus.

PubMed

Kawasaki, Junna; Kawamura, Maki; Ohsato, Yoshiharu; Ito, Jumpei; Nishigaki, Kazuo

2017-10-15

Recombination events induce significant genetic changes, and this process can result in virus genetic diversity or in the generation of novel pathogenicity. We discovered a new recombinant feline leukemia virus (FeLV) gag gene harboring an unrelated insertion, termed the X region, which was derived from Felis catus endogenous gammaretrovirus 4 (FcERV-gamma4). The identified FcERV-gamma4 proviruses have lost their coding capabilities, but some can express their viral RNA in feline tissues. Although the X-region-carrying recombinant FeLVs appeared to be replication-defective viruses, they were detected in 6.4% of tested FeLV-infected cats. All isolated recombinant FeLV clones commonly incorporated a middle part of the FcERV-gamma4 5'-leader region as an X region. Surprisingly, a sequence corresponding to the portion contained in all X regions is also present in at least 13 endogenous retroviruses (ERVs) observed in the cat, human, primate, and pig genomes. We termed this shared genetic feature the commonly shared (CS) sequence. Despite our phylogenetic analysis indicating that all CS-sequence-carrying ERVs are classified as gammaretroviruses, no obvious closeness was revealed among these ERVs. However, the Shannon entropy in the CS sequence was lower than that in other parts of the provirus genome. Notably, the CS sequence of human endogenous retrovirus T had 73.8% similarity with that of FcERV-gamma4, and specific signals were detected in the human genome by Southern blot analysis using a probe for the FcERV-gamma4 CS sequence. Our results provide an interesting evolutionary history for CS-sequence circulation among several distinct ancestral viruses and a novel recombined virus over a prolonged period. IMPORTANCE Recombination among ERVs or modern viral genomes causes a rapid evolution of retroviruses, and this phenomenon can result in the serious situation of viral disease reemergence. We identified a novel recombinant FeLV gag gene that contains an unrelated sequence, termed the X region. This region originated from the 5' leader of FcERV-gamma4, a replication-incompetent feline ERV. Surprisingly, a sequence corresponding to the X region is also present in the 5' portion of other ERVs, including human endogenous retroviruses. Scattered copies of the ERVs carrying the unique genetic feature, here named the commonly shared (CS) sequence, were found in each host genome, suggesting that ancestral viruses may have captured and maintained the CS sequence. More recently, a novel recombinant FeLV hijacked the CS sequence from inactivated FcERV-gamma4 as the X region. Therefore, tracing the CS sequences can provide unique models for not only the modern reservoir of new recombinant viruses but also the genetic features shared among ancient retroviruses. Copyright © 2017 American Society for Microbiology.

Shared Genetic Architecture in the Relationship between Adult Stature and Subclinical Coronary Artery Atherosclerosis

PubMed Central

Cassidy-Bushrow, Andrea E.; Bielak, Lawrence F.; Sheedy, Patrick F.; Turner, Stephen T.; Chu, Julia S.; Peyser, Patricia A.

2011-01-01

Background Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. Methods 877 asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Results Adult height was significantly and inversely associated with CAC score (P=0.01). After adjusting for age, sex, and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P=0.001) and -1 (P<0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P=0.024). Conclusions Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. PMID:21937044

Shared genetic architecture in the relationship between adult stature and subclinical coronary artery atherosclerosis.

PubMed

Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Sheedy, Patrick F; Turner, Stephen T; Chu, Julia S; Peyser, Patricia A

2011-12-01

Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. 877 Asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Adult height was significantly and inversely associated with CAC score (P = 0.01). After adjusting for age, sex and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P = 0.001) and -1 (P < 0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P = 0.024). Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Canadian Open Genetics Repository (COGR): a unified clinical genomics database as a community resource for standardising and sharing genetic interpretations.

PubMed

Lerner-Ellis, Jordan; Wang, Marina; White, Shana; Lebo, Matthew S

2015-07-01

The Canadian Open Genetics Repository is a collaborative effort for the collection, storage, sharing and robust analysis of variants reported by medical diagnostics laboratories across Canada. As clinical laboratories adopt modern genomics technologies, the need for this type of collaborative framework is increasingly important. A survey to assess existing protocols for variant classification and reporting was delivered to clinical genetics laboratories across Canada. Based on feedback from this survey, a variant assessment tool was made available to all laboratories. Each participating laboratory was provided with an instance of GeneInsight, a software featuring versioning and approval processes for variant assessments and interpretations and allowing for variant data to be shared between instances. Guidelines were established for sharing data among clinical laboratories and in the final outreach phase, data will be made readily available to patient advocacy groups for general use. The survey demonstrated the need for improved standardisation and data sharing across the country. A variant assessment template was made available to the community to aid with standardisation. Instances of the GeneInsight tool were provided to clinical diagnostic laboratories across Canada for the purpose of uploading, transferring, accessing and sharing variant data. As an ongoing endeavour and a permanent resource, the Canadian Open Genetics Repository aims to serve as a focal point for the collaboration of Canadian laboratories with other countries in the development of tools that take full advantage of laboratory data in diagnosing, managing and treating genetic diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genetic and environmental contributions to the associations between intraindividual variability in reaction time and cognitive function.

PubMed

Finkel, Deborah; Pedersen, Nancy L

2014-01-01

Intraindividual variability (IIV) in reaction time has been related to cognitive decline, but questions remain about the nature of this relationship. Mean and range in movement and decision time for simple reaction time were available from 241 individuals aged 51-86 years at the fifth testing wave of the Swedish Adoption/Twin Study of Aging. Cognitive performance on four factors was also available: verbal, spatial, memory, and speed. Analyses indicated that range in reaction time could be used as an indicator of IIV. Heritability estimates were 35% for mean reaction and 20% for range in reaction. Multivariate analysis indicated that the genetic variance on the memory, speed, and spatial factors is shared with genetic variance for mean or range in reaction time. IIV shares significant genetic variance with fluid ability in late adulthood, over and above and genetic variance shared with mean reaction time.

Experiences of college-age youths in families with a recessive genetic condition.

PubMed

Hern, Marcia J; Beery, Theresa A; Barry, Detrice G

2006-05-01

Growing up in a family with a recessive genetic condition can trigger questions about progeny effect. This study explored perceptions of family hardiness and information sharing by 18- to 21-year-olds about genetic risk. Semistructured interviews, the Family Hardiness Index (FHI), and a Family Information Sharing Analog Scale (FISAS) were used. Participants included 11 youths who had relatives with hemophilia and 4 with sickle cell anemia. Findings revealed seven themes: assimilating premature knowledge; caring for others, denying self; cautioning during development; experiencing continual sickness; feeling less than; magnifying transition experiences; and sustaining by faith. There was no significant correlation between total FHI and FISAS. However, there was a statistically significant difference in FISAS between genetic condition variance. Specifically, higher hardiness was found and information sharing correlated among college youths in families with hemophilia. Additional research can lead to nursing interventions to provide genetic information to youths in families for illness variance.

The legacy of Columbus in American horse populations assessed by microsatellite markers.

PubMed

Cortés, O; Dunner, S; Gama, L T; Martínez, A M; Delgado, J V; Ginja, C; Jiménez, L M; Jordana, J; Luis, C; Oom, M M; Sponenberg, D P; Zaragoza, P; Vega-Pla, J L

2017-08-01

Criollo horse populations descend from horses brought from the Iberian Peninsula over the period of colonization (15th to 17th century). They are spread throughout the Americas and have potentially undergone genetic hybridization with other breeds in the recent past. In this study, 25 autosomal microsatellites were genotyped in 50 horse breeds representing Criollo populations from 12 American countries (27 breeds), breeds from the Iberian Peninsula (19), one breed each from France and Morocco and two cosmopolitan horse breeds (Thoroughbred and Arabian). The genetic relationships among breeds identified five clusters: Celtic; Iberian; North American with Thoroughbred influence; most Colombian breeds; and nearly all other Criollo breeds. The group of "all other Criollo breeds" had the closest genetic relationship with breeds originating from the Iberian Peninsula, specifically with the Celtic group. For the whole set of Criollo breeds analysed, the estimated genetic contribution from other breeds was approximately 50%, 30% and 20% for the Celtic, Iberian and Arab-Thoroughbred groups, respectively. The spatial distribution of genetic diversity indicates that hotspots of genetic diversity are observed in populations from Colombia, Ecuador, Brazil, Paraguay and western United States, possibly indicating points of arrival and dispersion of Criollo horses in the American continent. These results indicate that Criollo breeds share a common ancestry, but that each breed has its own identity. © 2017 Blackwell Verlag GmbH.

Genetic Diversity among Clostridium botulinum Strains Harboring bont/A2 and bont/A3 Genes

PubMed Central

Raphael, Brian H.; Joseph, Lavin A.; Meno, Sarah R.; Fernández, Rafael A.; Maslanka, Susan E.

2012-01-01

Clostridium botulinum type A strains are known to be genetically diverse and widespread throughout the world. Genetic diversity studies have focused mainly on strains harboring one type A botulinum toxin gene, bont/A1, although all reported bont/A gene variants have been associated with botulism cases. Our study provides insight into the genetic diversity of C. botulinum type A strains, which contain bont/A2 (n = 42) and bont/A3 (n = 4) genes, isolated from diverse samples and geographic origins. Genetic diversity was assessed by using bont nucleotide sequencing, content analysis of the bont gene clusters, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Sequences of bont genes obtained in this study showed 99.9 to 100% identity with other bont/A2 or bont/A3 gene sequences available in public databases. The neurotoxin gene clusters of the subtype A2 and A3 strains analyzed in this study were similar in gene content. C. botulinum strains harboring bont/A2 and bont/A3 genes were divided into six and two MLST profiles, respectively. Four groups of strains shared a similarity of at least 95% by PFGE; the largest group included 21 out of 46 strains. The strains analyzed in this study showed relatively limited genetic diversity using either MLST or PFGE. PMID:23042179

Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population

PubMed Central

Yin, Xianyong; Wineinger, Nathan E.; Wang, Kai; Yue, Weihua; Norgren, Nina; Wang, Ling; Yao, Weiyi; Jiang, Xiaoyun; Wu, Bo; Cui, Yong; Shen, Changbing; Cheng, Hui; Zhou, Fusheng; Chen, Gang; Zuo, Xianbo; Zheng, Xiaodong; Fan, Xing; Wang, Hongyan; Wang, Lifang; Lee, Jimmy; Lam, Max; Tai, E. Shyong; Zhang, Zheng; Huang, Qiong; Sun, Liangdan; Xu, Jinhua; Yang, Sen; Wilhelmsen, Kirk C.; Liu, Jianjun; Schork, Nicholas J.; Zhang, Xuejun

2016-01-01

Background Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. Methods We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. Results We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10−8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10−16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. Limitations Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. Conclusion We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways. PMID:27091718

Temperament and Character in the Child and Adolescent Twin Study in Sweden (CATSS): Comparison to the General Population, and Genetic Structure Analysis

PubMed Central

Garcia, Danilo; Lundström, Sebastian; Brändström, Sven; Råstam, Maria; Cloninger, C. Robert; Kerekes, Nóra; Nilsson, Thomas; Anckarsäter, Henrik

2013-01-01

Background The Child and Adolescent Twin Study in Sweden (CATSS) is an on-going, large population-based longitudinal twin study. We aimed (1) to investigate the reliability of two different versions (125-items and 238-items) of Cloninger's Temperament and Character Inventory (TCI) used in the CATSS and the validity of extracting the short version from the long version, (2) to compare these personality dimensions between twins and adolescents from the general population, and (3) to investigate the genetic structure of Cloninger's model. Method Reliability and correlation analyses were conducted for both TCI versions, 2,714 CATSS-twins were compared to 631 adolescents from the general population, and the genetic structure was investigated through univariate genetic analyses, using a model-fitting approach with structural equation-modeling techniques based on same-sex twin pairs from the CATSS (423 monozygotic and 408 dizygotic pairs). Results The TCI scores from the short and long versions showed comparable reliability coefficients and were strongly correlated. Twins scored about half a standard deviation higher in the character scales. Three of the four temperament dimensions (Novelty Seeking, Harm Avoidance, and Persistence) had strong genetic and non-shared environmental effects, while Reward Dependence and the three character dimensions had moderate genetic effects, and both shared and non-shared environmental effects. Conclusions Twins showed higher scores in character dimensions compared to adolescents from the general population. At least among adolescents there is a shared environmental influence for all of the character dimensions, but only for one of the temperament dimensions (i.e., Reward Dependence). This specific finding regarding the existence of shared environmental factors behind the character dimensions in adolescence, together with earlier findings showing a small shared environmental effects on character among young adults and no shared environmental effects on character among adults, suggest that there is a shift in type of environmental influence from adolescence to adulthood regarding character. PMID:23940581

Autosomal STRs provide genetic evidence for the hypothesis that Tai people originate from southern China.

PubMed

Sun, Hao; Zhou, Chi; Huang, Xiaoqin; Lin, Keqin; Shi, Lei; Yu, Liang; Liu, Shuyuan; Chu, Jiayou; Yang, Zhaoqing

2013-01-01

Tai people are widely distributed in Thailand, Laos and southwestern China and are a large population of Southeast Asia. Although most anthropologists and historians agree that modern Tai people are from southwestern China and northern Thailand, the place from which they historically migrated remains controversial. Three popular hypotheses have been proposed: northern origin hypothesis, southern origin hypothesis or an indigenous origin. We compared the genetic relationships between the Tai in China and their "siblings" to test different hypotheses by analyzing 10 autosomal microsatellites. The genetic data of 916 samples from 19 populations were analyzed in this survey. The autosomal STR data from 15 of the 19 populations came from our previous study (Lin et al., 2010). 194 samples from four additional populations were genotyped in this study: Han (Yunnan), Dai (Dehong), Dai (Yuxi) and Mongolian. The results of genetic distance comparisons, genetic structure analyses and admixture analyses all indicate that populations from northern origin hypothesis have large genetic distances and are clearly differentiated from the Tai. The simulation-based ABC analysis also indicates this. The posterior probability of the northern origin hypothesis is just 0.04 [95%CI: (0.01-0.06)]. Conversely, genetic relationships were very close between the Tai and populations from southern origin or an indigenous origin hypothesis. Simulation-based ABC analyses were also used to distinguish the southern origin hypothesis from the indigenous origin hypothesis. The results indicate that the posterior probability of the southern origin hypothesis [0.640, 95%CI: (0.524-0.757)] is greater than that of the indigenous origin hypothesis [0.324, 95%CI: (0.211-0.438)]. Therefore, we propose that the genetic evidence does not support the hypothesis of northern origin. Our genetic data indicate that the southern origin hypothesis has higher probability than the other two hypotheses statistically, suggesting that the Tai people most likely originated from southern China.

A search for imprinted quantitative trait loci (QTLs) for birth weight

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

Pandya, A.; Llewellyn, B.; Schieken, R.

1994-09-01

Previous studies have generally provided strong evidence that maternal effects are a much more important determinant of birth weight than the genes of the fetus. In the past, these findings have been interpreted as reflecting a genetically determined maternal constraint on fetal growth. However, the recognition that the expression of a gene can be influenced by its parental origin has provided an alternative explanation for apparent maternal effects. In the mouse, a growing number of imprinted genes have been identified which can profoundly influence birth weight or body size including IGF-1, IGF-2, and their respective receptor loci. To determine whethermore » any of the loci are QTLs for body size in man, we have used parental typing data to classify dizygotic twins according to their identity by descent (IBD) for polymorphic markers at or near the candidate loci. The contrast between the correlations of DZ pairs sharing both alleles IBD and no alleles IBD can provide evidence for a candidate gene effect while the contrast between twins sharing one maternal or one paternal allele IBD can provide evidence for any effect of imprinting that may exist at the locus. Finally, the inclusion of data on MZ twins in an overall analysis permits the resolution of the imprinting and marker gene effects from other sources of genetic and environmental variation. We have applied this model to birth weight data on 181 pairs of twins who were classified according to their allele sharing at the IGF-1 locus. In keeping with other observations, the data show no evidence that the IGF-1 locus is imprinted in man. Although our results are consistent with the possibility that this locus may account for 15-20% of the genetic variation, the apparent effect is not statistically significant. Partitioned twin analysis appears to be a useful method for detecting the effects of specific candidate gene on continuously distributed traits.« less

The ABCs of Math: A Genetic Analysis of Mathematics and Its Links With Reading Ability and General Cognitive Ability

PubMed Central

Hart, Sara A.; Petrill, Stephen A.; Thompson, Lee A.; Plomin, Robert

2009-01-01

The goal of this first major report from the Western Reserve Reading Project Math component is to explore the etiology of the relationship among tester-administered measures of mathematics ability, reading ability, and general cognitive ability. Data are available on 314 pairs of monozygotic and same-sex dizygotic twins analyzed across 5 waves of assessment. Univariate analyses provide a range of estimates of genetic (h2 = .00 –.63) and shared (c2 = .15–.52) environmental influences across math calculation, fluency, and problem solving measures. Multivariate analyses indicate genetic overlap between math problem solving with general cognitive ability and reading decoding, whereas math fluency shares significant genetic overlap with reading fluency and general cognitive ability. Further, math fluency has unique genetic influences. In general, math ability has shared environmental overlap with general cognitive ability and decoding. These results indicate that aspects of math that include problem solving have different genetic and environmental influences than math calculation. Moreover, math fluency, a timed measure of calculation, is the only measured math ability with unique genetic influences. PMID:20157630

Cryptic within cryptic: genetics, morphometrics, and bioacoustics delimitate a new species of Eleutherodactylus (Anura: Eleutherodactylidae) from Eastern Cuba.

PubMed

Rodríguez, Ariel; Dugo-Cota, Álvaro; Montero-Mendieta, Santiago; Gonzalez-Voyer, Alejandro; Bosch, Roberto Alonso; Vences, Miguel; Vilà, Carles

2017-01-20

We studied the variation in genetics, bioacustics, and morphology in Eleutherodactylus glamyrus, a regionally endemic frog species restricted to high elevations in the Sierra Maestra Massif, Western Cuba that was originally described as a cryptic species hidden under the name E. auriculatus. Genetic analysis of mtDNA sequences of the 16S and cob genes identify two allopatric and strongly supported mitochondrial clades (phylogroups) which also showed no haplotype sharing in the nuclear Rag-1 gene. Bioacustic, and morphological comparisons concordantly identify these two phylogroups as independent evolutionary lineages. Therefore, we herein restrict the name Eleutherodactylus glamyrus Estrada and Hedges to populations represented in our analyses as the western phylogroup (Cordillera del Turquino to Pico La Bayamesa) and consider specimens from the eastern phylogroup (Sierra del Cobre) to represent a new species described and named as Eleutherodactylus cattus. Our results add to the growing list of Eleutherodactylus species endemic to Cuba and highlight the importance of combining different sources of evidence for obtaining robust assessments of species limits in amphibians.

Origins of tmRNA: the missing link in the birth of protein synthesis?

PubMed

Macé, Kevin; Gillet, Reynald

2016-09-30

The RNA world hypothesis refers to the early period on earth in which RNA was central in assuring both genetic continuity and catalysis. The end of this era coincided with the development of the genetic code and protein synthesis, symbolized by the apparition of the first non-random messenger RNA (mRNA). Modern transfer-messenger RNA (tmRNA) is a unique hybrid molecule which has the properties of both mRNA and transfer RNA (tRNA). It acts as a key molecule during trans-translation, a major quality control pathway of modern bacterial protein synthesis. tmRNA shares many common characteristics with ancestral RNA. Here, we present a model in which proto-tmRNAs were the first molecules on earth to support non-random protein synthesis, explaining the emergence of early genetic code. In this way, proto-tmRNA could be the missing link between the first mRNA and tRNA molecules and modern ribosome-mediated protein synthesis. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

PubMed

Evans, Barbara J

2014-07-01

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

Causes of individual differences in adolescent optimism: a study in Dutch twins and their siblings.

PubMed

Mavioğlu, Rezan Nehir; Boomsma, Dorret I; Bartels, Meike

2015-11-01

The aim of this study was to investigate the degree to which genetic and environmental influences affect variation in adolescent optimism. Optimism (3 items and 6 items approach) and pessimism were assessed by the Life Orientation Test-Revised (LOT-R) in 5,187 adolescent twins and 999 of their non-twin siblings from the Netherlands Twin Register (NTR). Males reported significantly higher optimism scores than females, while females score higher on pessimism. Genetic structural equation modeling revealed that about one-third of the variance in optimism and pessimism was due to additive genetic effects, with the remaining variance being explained by non-shared environmental effects. A bivariate correlated factor model revealed two dimensions with a genetic correlation of -.57 (CI -.67, -.47), while the non-shared environmental correlation was estimated to be -.21 (CI -.25, -.16). Neither an effect of shared environment, non-additive genetic influences, nor quantitative sex differences was found for both dimensions. This result indicates that individual differences in adolescent optimism are mainly accounted for by non-shared environmental factors. These environmental factors do not contribute to the similarity of family members, but to differences between them. Familial resemblance in optimism and pessimism assessed in adolescents is fully accounted for by genetic overlap between family members.

Pervasive sharing of genetic effects in autoimmune disease.

PubMed

Cotsapas, Chris; Voight, Benjamin F; Rossin, Elizabeth; Lage, Kasper; Neale, Benjamin M; Wallace, Chris; Abecasis, Gonçalo R; Barrett, Jeffrey C; Behrens, Timothy; Cho, Judy; De Jager, Philip L; Elder, James T; Graham, Robert R; Gregersen, Peter; Klareskog, Lars; Siminovitch, Katherine A; van Heel, David A; Wijmenga, Cisca; Worthington, Jane; Todd, John A; Hafler, David A; Rich, Stephen S; Daly, Mark J

2011-08-01

Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA)<0.01). We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

Cannabis controversies: how genetics can inform the study of comorbidity.

PubMed

Agrawal, Arpana; Lynskey, Michael T

2014-03-01

To review three key and controversial comorbidities of cannabis use-other illicit drug use, psychosis and depression, as well as suicide, from a genetically informed perspective. Selective review. Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression, as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. © 2014 Society for the Study of Addiction.

Cannabis Controversies: How genetics can inform the study of comorbidity

PubMed Central

Agrawal, Arpana; Lynskey, Michael T.

2014-01-01

Aims To review three key and controversial comorbidities of cannabis use – other illicit drug use, psychosis and depression as well as suicide, from a genetically informed perspective. Design Selective review. Results Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Conclusions Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. PMID:24438181

Pedigree- and SNP-Associated Genetics and Recent Environment are the Major Contributors to Anthropometric and Cardiometabolic Trait Variation.

PubMed

Xia, Charley; Amador, Carmen; Huffman, Jennifer; Trochet, Holly; Campbell, Archie; Porteous, David; Hastie, Nicholas D; Hayward, Caroline; Vitart, Veronique; Navarro, Pau; Haley, Chris S

2016-02-01

Genome-wide association studies have successfully identified thousands of loci for a range of human complex traits and diseases. The proportion of phenotypic variance explained by significant associations is, however, limited. Given the same dense SNP panels, mixed model analyses capture a greater proportion of phenotypic variance than single SNP analyses but the total is generally still less than the genetic variance estimated from pedigree studies. Combining information from pedigree relationships and SNPs, we examined 16 complex anthropometric and cardiometabolic traits in a Scottish family-based cohort comprising up to 20,000 individuals genotyped for ~520,000 common autosomal SNPs. The inclusion of related individuals provides the opportunity to also estimate the genetic variance associated with pedigree as well as the effects of common family environment. Trait variation was partitioned into SNP-associated and pedigree-associated genetic variation, shared nuclear family environment, shared couple (partner) environment and shared full-sibling environment. Results demonstrate that trait heritabilities vary widely but, on average across traits, SNP-associated and pedigree-associated genetic effects each explain around half the genetic variance. For most traits the recently-shared environment of couples is also significant, accounting for ~11% of the phenotypic variance on average. On the other hand, the environment shared largely in the past by members of a nuclear family or by full-siblings, has a more limited impact. Our findings point to appropriate models to use in future studies as pedigree-associated genetic effects and couple environmental effects have seldom been taken into account in genotype-based analyses. Appropriate description of the trait variation could help understand causes of intra-individual variation and in the detection of contributing loci and environmental factors.

Genetic variation in Mediterranean Helichrysum italicum (Asteraceae; Gnaphalieae): do disjunct populations of subsp. microphyllum have a common origin?

PubMed

Galbany-Casals, M; Blanco-Moreno, J M; Garcia-Jacas, N; Breitwieser, I; Smissen, R D

2011-07-01

The yellow-flowered everlasting daisy Helichrysum italicum (Asteraceae, Gnaphalieae) is widely distributed in the Mediterranean basin, where it grows in continuous and widespread populations in diverse open habitats. Helichrysum italicum subsp. microphyllum has a disjunct distribution in the Balearic Islands (Majorca and Dragonera), Corsica, Sardinia, Crete and Cyprus. Numerous morphological intermediates between subsp. italicum and subsp. microphyllum are known from Corsica, where the two subspecies co-occur. The aims of the study were to investigate if subsp. microphyllum has a common origin, constituting an independent gene pool from subsp. italicum, or if the morphological differences between subsp. microphyllum and subsp. italicum have arisen independently in different locations from a common wider gene pool. Our analyses of AFLP, cpDNA sequences and morphological characters show that there is geographic structure to the genetic variation within H. italicum, with eastern and western Mediterranean groups, which do not correspond with the division into subsp. microphyllum and subsp. italicum as currently circumscribed. Local selection on quantitative trait loci provides sufficient explanation for the morphological divergence observed and is consistent with genetic data. Within the western Mediterranean group of the species we found considerable polymorphism in chloroplast DNA sequences among and within some populations. Comparison with chloroplast DNA sequences from other Helichrysum species showed that some chloroplast haplotypes are shared across species. © 2010 German Botanical Society and The Royal Botanical Society of the Netherlands.

Population Genetic Structure of the People of Qatar

PubMed Central

Hunter-Zinck, Haley; Musharoff, Shaila; Salit, Jacqueline; Al-Ali, Khalid A.; Chouchane, Lotfi; Gohar, Abeer; Matthews, Rebecca; Butler, Marcus W.; Fuller, Jennifer; Hackett, Neil R.; Crystal, Ronald G.; Clark, Andrew G.

2010-01-01

People of the Qatar peninsula represent a relatively recent founding by a small number of families from three tribes of the Arabian Peninsula, Persia, and Oman, with indications of African admixture. To assess the roles of both this founding effect and the customary first-cousin marriages among the ancestral Islamic populations in Qatar's population genetic structure, we obtained and genotyped with Affymetrix 500k SNP arrays DNA samples from 168 self-reported Qatari nationals sampled from Doha, Qatar. Principal components analysis was performed along with samples from the Human Genetic Diversity Project data set, revealing three clear clusters of genotypes whose proximity to other human population samples is consistent with Arabian origin, a more eastern or Persian origin, and individuals with African admixture. The extent of linkage disequilibrium (LD) is greater than that of African populations, and runs of homozygosity in some individuals reflect substantial consanguinity. However, the variance in runs of homozygosity is exceptionally high, and the degree of identity-by-descent sharing generally appears to be lower than expected for a population in which nearly half of marriages are between first cousins. Despite the fact that the SNPs of the Affymetrix 500k chip were ascertained with a bias toward SNPs common in Europeans, the data strongly support the notion that the Qatari population could provide a valuable resource for the mapping of genes associated with complex disorders and that tests of pairwise interactions are particularly empowered by populations with elevated LD like the Qatari. PMID:20579625

Dopamine and serotonin genetic risk scores predicting substance and nicotine use in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Groenman, Annabeth P.; Greven, Corina U.; van Donkelaar, Marjolein M.J.; Schellekens, Arnt; van Hulzen, Kimm J.E.; Rommelse, Nanda; Hartman, Catharina A.; Hoekstra, Pieter J.; Luman, Marjolein; Franke, Barbara; Faraone, Stephen V.; Oosterlaan, Jaap; Buitelaar, Jan K.

2015-01-01

Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence. The co-occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared genetic liability. Several neurobiological pathways have been implicated in both ADHD and SUDs, including dopamine and serotonin pathways. We hypothesized that variations in dopamine and serotonin neurotransmission genes were involved in the genetic liability to develop SUDs/nicotine dependence in ADHD. The current study included participants with ADHD (n=280) who were originally part of the Dutch International Multicenter ADHD Genetics study. Participants were aged 5–15 years and attending outpatient clinics at enrollment in the study. Diagnoses of ADHD, SUDs, nicotine dependence, age of first nicotine and substance use, and alcohol use severity were based on semi-structured interviews and questionnaires. Genetic risk scores were created for both serotonergic and dopaminergic risk genes previously shown to be associated with ADHD and SUDs and/or nicotine dependence. The serotonin genetic risk score significantly predicted alcohol use severity. No significant serotonin*dopamine risk score or effect of stimulant medication was found. The current study adds to literature by providing insight into genetic underpinnings of the comorbidity of ADHD and SUDs. While the focus of the literature so far has been mostly on dopamine, our study suggests that serotonin may also play a role in the relationship between these disorders. PMID:25752199

Intensive Management and Natural Genetic Variation in Red Deer (Cervus elaphus).

PubMed

Galarza, Juan A; Sánchez-Fernández, Beatriz; Fandos, Paulino; Soriguer, Ramón

2017-07-01

The current magnitude of big-game hunting has outpaced the natural growth of populations, making artificial breeding necessary to rapidly boost hunted populations. In this study, we evaluated if the rapid increase of red deer (Cervus elaphus) abundance, caused by the growing popularity of big-game hunting, has impacted the natural genetic diversity of the species. We compared several genetic diversity metrics between 37 fenced populations subject to intensive management and 21 wild free-ranging populations. We also included a historically protected population from a national park as a baseline for comparisons. Contrary to expectations, our results showed no significant differences in genetic diversity between wild and fenced populations. Relatively lower genetic diversity was observed in the protected population, although differences were not significant in most cases. Bottlenecks were detected in both wild and fenced populations, as well as in the protected population. Assignment tests identified individuals that did not belong to their population of origin, indicating anthropogenic movement. We discuss the most likely processes, which could have led to the observed high levels of genetic variability and lack of differentiation between wild and fenced populations and suggest cautionary points for future conservation. We illustrate our comparative approach in red deer. However, our results and interpretations can be largely applicable to most ungulates subject to big-game hunting as most of them share a common exploitation-recovery history as well as many ecological traits. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

PubMed

Schmitz, Roland; Wright, George W; Huang, Da Wei; Johnson, Calvin A; Phelan, James D; Wang, James Q; Roulland, Sandrine; Kasbekar, Monica; Young, Ryan M; Shaffer, Arthur L; Hodson, Daniel J; Xiao, Wenming; Yu, Xin; Yang, Yandan; Zhao, Hong; Xu, Weihong; Liu, Xuelu; Zhou, Bin; Du, Wei; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Connors, Joseph M; Campo, Elias; Lopez-Guillermo, Armando; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa M; Tay Kuang Wei, Kevin; Zelenetz, Andrew D; Leonard, John P; Bartlett, Nancy L; Tran, Bao; Shetty, Jyoti; Zhao, Yongmei; Soppet, Dan R; Pittaluga, Stefania; Wilson, Wyndham H; Staudt, Louis M

2018-04-12

Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88 L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).

Resistance patterns, ESBL genes, and genetic relatedness of Escherichia coli from dogs and owners.

PubMed

Carvalho, A C; Barbosa, A V; Arais, L R; Ribeiro, P F; Carneiro, V C; Cerqueira, A M F

2016-01-01

Antimicrobial resistance in Escherichia coli isolated from pet dogs can be considered a potential threat of infection for the human population. Our objective was to characterize the resistance pattern, extended spectrum beta-lactamase production and genetic relatedness of multiresistant E. coli strains isolated from dogs (n=134), their owners (n=134), and humans who claim to have no contact with dogs (n=44, control), searching for sharing of strains. The strains were assessed for their genetic relatedness by phylogenetic grouping and pulsed-field gel electrophoresis. Multiresistant E. coli strains were isolated from 42 (31.3%) fecal samples from pairs of dogs and owners, totaling 84 isolates, and from 19 (43.1%) control group subjects. The strains showed high levels of resistance to ampicillin, streptomycin, tetracycline, trimethoprim and sulfamethoxazole regardless of host species or group of origin. The blaTEM, blaCTX-M, and blaSHV genes were detected in similar proportions in all groups. All isolates positive for bla genes were ESBL producers. The phylogenetic group A was the most prevalent, irrespective of the host species. None of the strains belonging to the B2 group contained bla genes. Similar resistance patterns were found for strains from dogs, owners and controls; furthermore, identical PFGE profiles were detected in four (9.5%) isolate pairs from dogs and owners, denoting the sharing of strains. Pet dogs were shown to be a potential household source of multiresistant E. coli strains. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Sources of individual differences in depressive symptoms: analysis of two samples of twins and their families.

PubMed

Kendler, K S; Walters, E E; Truett, K R; Heath, A C; Neale, M C; Martin, N G; Eaves, L J

1994-11-01

Self-reported symptoms of depression are commonly used in mental health research to assess current psychiatric state, yet wide variation in these symptoms among individuals has been found in both clinical and epidemiologic populations. The authors sought to understand, from a genetic-epidemiologic perspective, the sources of individual differences in depressive symptoms. Self-reported symptoms of depression were assessed in two samples of twins and their spouses, parents, siblings, and offspring: one sample contained volunteer twins recruited through the American Association of Retired Persons and their relatives (N = 19,203 individuals) and the other contained twins from a population-based twin registry in Virginia and their relatives (N = 11,242 individuals). Model fitting by an iterative, diagonal, weighted least squares method was applied to the 80 different family relationships in the extended twin-family design. Independent analyses of the two samples revealed that the level of depressive symptoms was modestly familial, and familial resemblance could be explained solely by genetic factors and spousal resemblance. The estimated heritability of depressive symptoms was between 30% and 37%. There was no evidence that the liability to depressive symptoms was environmentally transmitted from parents to offspring or was influenced by environmental factors shared either generally among siblings or specifically between twins. With correction for unreliability of measurement, genetic factors accounted for half of the stable variance in depressive symptoms. Depressive symptoms in adulthood partly reflect enduring characteristics of temperament that are substantially influenced by hereditary factors but little, or not at all, by shared environmental experiences in the family of origin.

Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors

PubMed Central

Thornton, Laura M.; Welch, Elisabeth; Munn-Chernoff, Melissa A.; Lichtenstein, Paul; Bulik, Cynthia M.

2015-01-01

We evaluated the extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA). Participants were 6,899 women from the Swedish Twin study of Adults Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the co-expression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN. PMID:26916469

Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors.

PubMed

Thornton, Laura M; Welch, Elisabeth; Munn-Chernoff, Melissa A; Lichtenstein, Paul; Bulik, Cynthia M

2016-10-01

The extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA) were evaluated. Participants were 6,899 women from the Swedish Twin Study of Adults: Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the coexpression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN. © 2016 The American Association of Suicidology.

Sharing the benefits of genetic resources: from biodiversity to human genetics.

PubMed

Schroeder, Doris; Lasén-Díaz, Carolina

2006-12-01

Benefit sharing aims to achieve an equitable exchange between the granting of access to a genetic resource and the provision of compensation. The Convention on Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro, is the only international legal instrument setting out obligations for sharing the benefits derived from the use of biodiversity. The CBD excludes human genetic resources from its scope, however, this article considers whether it should be expanded to include those resources, so as to enable research subjects to claim a share of the benefits to be negotiated on a case-by-case basis. Our conclusion on this question is: 'No, the CBD should not be expanded to include human genetic resources.' There are essential differences between human and non-human genetic resources, and, in the context of research on humans, an essentially fair exchange model is already available between the health care industry and research subjects. Those who contribute to research should receive benefits in the form of accessible new health care products and services, suitable for local health needs and linked to economic prosperity (e.g. jobs). When this exchange model does not apply, as is often the case in developing countries, individually negotiated benefit sharing agreements between researchers and research subjects should not be used as 'window dressing'. Instead, national governments should focus their finances on the best economic investment they could make; the investment in population health and health research as outlined by the World Health Organization's Commission on Macroeconomics and Health; whilst international barriers to such spending need to be removed.

The Geographic Origins of Ethnic Groups in the Indian Subcontinent: Exploring Ancient Footprints with Y-DNA Haplogroups.

PubMed

Mahal, David G; Matsoukas, Ianis G

2018-01-01

Several studies have evaluated the movements of large populations to the Indian subcontinent; however, the ancient geographic origins of smaller ethnic communities are not clear. Although historians have attempted to identify the origins of some ethnic groups, the evidence is typically anecdotal and based upon what others have written before. In this study, recent developments in DNA science were assessed to provide a contemporary perspective by analyzing the Y chromosome haplogroups of some key ethnic groups and tracing their ancient geographical origins from genetic markers on the Y-DNA haplogroup tree. A total of 2,504 Y-DNA haplotypes, representing 50 different ethnic groups in the Indian subcontinent, were analyzed. The results identified 14 different haplogroups with 14 geographic origins for these people. Moreover, every ethnic group had representation in more than one haplogroup, indicating multiple geographic origins for these communities. The results also showed that despite their varied languages and cultural differences, most ethnic groups shared some common ancestors because of admixture in the past. These findings provide new insights into the ancient geographic origins of ethnic groups in the Indian subcontinent. With about 2,000 other ethnic groups and tribes in the region, it is expected that more scientific discoveries will follow, providing insights into how, from where, and when the ancestors of these people arrived in the subcontinent to create so many different communities.

The Geographic Origins of Ethnic Groups in the Indian Subcontinent: Exploring Ancient Footprints with Y-DNA Haplogroups

PubMed Central

Mahal, David G.; Matsoukas, Ianis G.

2018-01-01

Several studies have evaluated the movements of large populations to the Indian subcontinent; however, the ancient geographic origins of smaller ethnic communities are not clear. Although historians have attempted to identify the origins of some ethnic groups, the evidence is typically anecdotal and based upon what others have written before. In this study, recent developments in DNA science were assessed to provide a contemporary perspective by analyzing the Y chromosome haplogroups of some key ethnic groups and tracing their ancient geographical origins from genetic markers on the Y-DNA haplogroup tree. A total of 2,504 Y-DNA haplotypes, representing 50 different ethnic groups in the Indian subcontinent, were analyzed. The results identified 14 different haplogroups with 14 geographic origins for these people. Moreover, every ethnic group had representation in more than one haplogroup, indicating multiple geographic origins for these communities. The results also showed that despite their varied languages and cultural differences, most ethnic groups shared some common ancestors because of admixture in the past. These findings provide new insights into the ancient geographic origins of ethnic groups in the Indian subcontinent. With about 2,000 other ethnic groups and tribes in the region, it is expected that more scientific discoveries will follow, providing insights into how, from where, and when the ancestors of these people arrived in the subcontinent to create so many different communities. PMID:29410676

Population-specific genetic modification of Huntington's disease in Venezuela.

PubMed

Chao, Michael J; Kim, Kyung-Hee; Shin, Jun Wan; Lucente, Diane; Wheeler, Vanessa C; Li, Hong; Roach, Jared C; Hood, Leroy; Wexler, Nancy S; Jardim, Laura B; Holmans, Peter; Jones, Lesley; Orth, Michael; Kwak, Seung; MacDonald, Marcy E; Gusella, James F; Lee, Jong-Min

2018-05-01

Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a different ancestral origin but not explaining the earlier age at onset in these Venezuelans. GWA analysis of the Venezuelan HD cluster suggests both population-specific and population-shared genetic modifiers. Genome-wide significant signals at 7p21.2-21.1 and suggestive association signals at 4p14 and 17q21.2 are evident only in Venezuelan HD, but genome-wide significant association signals at the established European chromosome 15 modifier locus are improved when Venezuelan HD data are included in the meta-analysis. Venezuelan-specific association signals on chromosome 7 center on SOSTDC1, which encodes a bone morphogenetic protein antagonist. The corresponding SNPs are associated with reduced expression of SOSTDC1 in non-Venezuelan tissue samples, suggesting that interaction of reduced SOSTDC1 expression with a population-specific genetic or environmental factor may be responsible for modification of HD onset in Venezuela. Detection of population-specific modification in Venezuelan HD supports the value of distinct disease populations in revealing novel aspects of a disease and population-relevant therapeutic strategies.

A wild origin of the loss-of-function lycopene beta cyclase (CYC-b) allele in cultivated, red-fleshed papaya (Carica papaya).

PubMed

Wu, Meng; Lewis, Jamicia; Moore, Richard C

2017-01-01

The red flesh of some papaya cultivars is caused by a recessive loss-of-function mutation in the coding region of the chromoplast-specific lycopene beta cyclase gene (CYC-b). We performed an evolutionary genetic analysis of the CYC-b locus in wild and cultivated papaya to uncover the origin of this loss-of-function allele in cultivated papaya. We analyzed the levels and patterns of genetic diversity at the CYC-b locus and six loci in a 100-kb region flanking CYC-b and compared these to genetic diversity levels at neutral autosomal loci. The evolutionary relationships of CYC-b haplotypes were assessed using haplotype network analysis of the CYC-b locus and the 100-kb CYC-b region. Genetic diversity at the recessive CYC-b allele (y) was much lower relative to the dominant Y allele found in yellow-fleshed wild and cultivated papaya due to a strong selective sweep. Haplotype network analyses suggest the y allele most likely arose in the wild and was introduced into domesticated varieties after the first papaya domestication event. The shared haplotype structure between some wild, feral, and cultivated haplotypes around the y allele supports subsequent escape of this allele from red cultivars back into wild populations through feral intermediates. Our study supports a protracted domestication process of papaya through the introgression of wild-derived traits and gene flow from cultivars to wild populations. Evidence of gene flow from cultivars to wild populations through feral intermediates has implications for the introduction of transgenic papaya into Central American countries. © 2017 Botanical Society of America.

Population-specific genetic modification of Huntington's disease in Venezuela

PubMed Central

Chao, Michael J.; Kim, Kyung-Hee; Shin, Jun Wan; Lucente, Diane; Wheeler, Vanessa C.; Li, Hong; Roach, Jared C.; Hood, Leroy; Jardim, Laura B.; Jones, Lesley; Orth, Michael; Kwak, Seung; MacDonald, Marcy E.; Gusella, James F.

2018-01-01

Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a different ancestral origin but not explaining the earlier age at onset in these Venezuelans. GWA analysis of the Venezuelan HD cluster suggests both population-specific and population-shared genetic modifiers. Genome-wide significant signals at 7p21.2–21.1 and suggestive association signals at 4p14 and 17q21.2 are evident only in Venezuelan HD, but genome-wide significant association signals at the established European chromosome 15 modifier locus are improved when Venezuelan HD data are included in the meta-analysis. Venezuelan-specific association signals on chromosome 7 center on SOSTDC1, which encodes a bone morphogenetic protein antagonist. The corresponding SNPs are associated with reduced expression of SOSTDC1 in non-Venezuelan tissue samples, suggesting that interaction of reduced SOSTDC1 expression with a population-specific genetic or environmental factor may be responsible for modification of HD onset in Venezuela. Detection of population-specific modification in Venezuelan HD supports the value of distinct disease populations in revealing novel aspects of a disease and population-relevant therapeutic strategies. PMID:29750799

The complete genome sequence of Yersinia pseudotuberculosis IP31758, the causative agent of Far East scarlet-like fever.

PubMed

Eppinger, Mark; Rosovitz, M J; Fricke, Wolfgang Florian; Rasko, David A; Kokorina, Galina; Fayolle, Corinne; Lindler, Luther E; Carniel, Elisabeth; Ravel, Jacques

2007-08-01

The first reported Far East scarlet-like fever (FESLF) epidemic swept the Pacific coastal region of Russia in the late 1950s. Symptoms of the severe infection included erythematous skin rash and desquamation, exanthema, hyperhemic tongue, and a toxic shock syndrome. The term FESLF was coined for the infection because it shares clinical presentations with scarlet fever caused by group A streptococci. The causative agent was later identified as Yersinia pseudotuberculosis, although the range of morbidities was vastly different from classical pseudotuberculosis symptoms. To understand the origin and emergence of the peculiar clinical features of FESLF, we have sequenced the genome of the FESLF-causing strain Y. pseudotuberculosis IP31758 and compared it with that of another Y. pseudotuberculosis strain, IP32953, which causes classical gastrointestinal symptoms. The unique gene pool of Y pseudotuberculosis IP31758 accounts for more than 260 strain-specific genes and introduces individual physiological capabilities and virulence determinants, with a significant proportion horizontally acquired that likely originated from Enterobacteriaceae and other soil-dwelling bacteria that persist in the same ecological niche. The mobile genome pool includes two novel plasmids phylogenetically unrelated to all currently reported Yersinia plasmids. An icm/dot type IVB secretion system, shared only with the intracellular persisting pathogens of the order Legionellales, was found on the larger plasmid and could contribute to scarlatinoid fever symptoms in patients due to the introduction of immunomodulatory and immunosuppressive capabilities. We determined the common and unique traits resulting from genome evolution and speciation within the genus Yersinia and drew a more accurate species border between Y. pseudotuberculosis and Y. pestis. In contrast to the lack of genetic diversity observed in the evolutionary young descending Y. pestis lineage, the population genetics of Y. pseudotuberculosis is more heterogenous. Both Y. pseudotuberculosis strains IP31758 and the previously sequenced Y. pseudotuberculosis strain IP32953 have evolved by the acquisition of specific plasmids and by the horizontal acquisition and incorporation of different genetic information into the chromosome, which all together or independently seems to potentially impact the phenotypic adaptation of these two strains.

The Complete Genome Sequence of Yersinia pseudotuberculosis IP31758, the Causative Agent of Far East Scarlet-Like Fever

PubMed Central

Eppinger, Mark; Rosovitz, M. J; Fricke, Wolfgang Florian; Rasko, David A; Kokorina, Galina; Fayolle, Corinne; Lindler, Luther E; Carniel, Elisabeth; Ravel, Jacques

2007-01-01

The first reported Far East scarlet-like fever (FESLF) epidemic swept the Pacific coastal region of Russia in the late 1950s. Symptoms of the severe infection included erythematous skin rash and desquamation, exanthema, hyperhemic tongue, and a toxic shock syndrome. The term FESLF was coined for the infection because it shares clinical presentations with scarlet fever caused by group A streptococci. The causative agent was later identified as Yersinia pseudotuberculosis, although the range of morbidities was vastly different from classical pseudotuberculosis symptoms. To understand the origin and emergence of the peculiar clinical features of FESLF, we have sequenced the genome of the FESLF-causing strain Y. pseudotuberculosis IP31758 and compared it with that of another Y. pseudotuberculosis strain, IP32953, which causes classical gastrointestinal symptoms. The unique gene pool of Y pseudotuberculosis IP31758 accounts for more than 260 strain-specific genes and introduces individual physiological capabilities and virulence determinants, with a significant proportion horizontally acquired that likely originated from Enterobacteriaceae and other soil-dwelling bacteria that persist in the same ecological niche. The mobile genome pool includes two novel plasmids phylogenetically unrelated to all currently reported Yersinia plasmids. An icm/dot type IVB secretion system, shared only with the intracellular persisting pathogens of the order Legionellales, was found on the larger plasmid and could contribute to scarlatinoid fever symptoms in patients due to the introduction of immunomodulatory and immunosuppressive capabilities. We determined the common and unique traits resulting from genome evolution and speciation within the genus Yersinia and drew a more accurate species border between Y. pseudotuberculosis and Y. pestis. In contrast to the lack of genetic diversity observed in the evolutionary young descending Y. pestis lineage, the population genetics of Y. pseudotuberculosis is more heterogenous. Both Y. pseudotuberculosis strains IP31758 and the previously sequenced Y. pseudotuberculosis strain IP32953 have evolved by the acquisition of specific plasmids and by the horizontal acquisition and incorporation of different genetic information into the chromosome, which all together or independently seems to potentially impact the phenotypic adaptation of these two strains. PMID:17784789

Adults' perceptions of genetic counseling and genetic testing.

PubMed

Houfek, Julia Fisco; Soltis-Vaughan, Brigette S; Atwood, Jan R; Reiser, Gwendolyn M; Schaefer, G Bradley

2015-02-01

This study described the perceptions of genetic counseling and testing of adults (N = 116) attending a genetic education program. Understanding perceptions of genetic counseling, including the importance of counseling topics, will contribute to patient-focused care as clinical genetic applications for common, complex disorders evolve. Participants completed a survey addressing: the importance of genetic counseling topics, benefits and negative effects of genetic testing, and sharing test results. Topics addressing practical information about genetic conditions were rated most important; topics involving conceptual genetic/genomic principles were rated least important. The most frequently identified benefit and negative effect of testing were prevention/early detection/treatment and psychological distress. Participants perceived that they were more likely to share test results with first-degree than other relatives. Findings suggest providing patients with practical information about genetic testing and genetic contributions to disease, while also determining whether their self-care abilities would be enhanced by teaching genetic/genomic principles. Copyright © 2014 Elsevier Inc. All rights reserved.

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents

PubMed Central

Prom-Wormley, Elizabeth; Eaves, Lindon J.; Rhee, Soo Hyun; Hewitt, John K.; Young, Susan; Corley, Robin; McGue, Matt; Iacono, William G.; Legrand, Lisa; Samek, Diana R.; Murrelle, E. Lenn; Silberg, Judy L.; Miles, Donna R.; Schieken, Richard M.; Beunen, Gaston P.; Thomis, Martine; Rose, Richard J.; Dick, Danielle M.; Boomsma, Dorret I.; Bartels, Meike; Vink, Jacqueline M.; Lichtenstein, Paul; White, Victoria; Kaprio, Jaakko; Neale, Michael C.

2017-01-01

Abstract Introduction: Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation (SI) across adolescence. Methods: Mega-analysis of pooled genetically informative data on SI was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N = 19 313 pairs) between ages 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the United States, Europe, and Australia. Results: Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of SI across developed countries. The estimate of additive genetic contributions to liability of SI increased from approximately 15% to 45% from ages 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to SI at age 13 (70%) and gradually less by age 19 (40%). Conclusions: Both additive genetic and shared environmental factors significantly contribute to variance in SI throughout adolescence. The present study, the largest genetic epidemiological study on SI to date, found consistent results across 11 studies for the etiology of SI. Environmental factors, especially those shared by siblings in a family, primarily influence SI variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. Implications: This is the first study to find evidence of genetic factors in liability to SI at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment. PMID:27807125

Long-term genetic stability and a high-altitude East Asian origin for the peoples of the high valleys of the Himalayan arc

PubMed Central

Jeong, Choongwon; Ozga, Andrew T.; Witonsky, David B.; Malmström, Helena; Edlund, Hanna; Hofman, Courtney A.; Hagan, Richard W.; Jakobsson, Mattias; Lewis, Cecil M.; Aldenderfer, Mark S.; Di Rienzo, Anna

2016-01-01

The high-altitude transverse valleys [>3,000 m above sea level (masl)] of the Himalayan arc from Arunachal Pradesh to Ladahk were among the last habitable places permanently colonized by prehistoric humans due to the challenges of resource scarcity, cold stress, and hypoxia. The modern populations of these valleys, who share cultural and linguistic affinities with peoples found today on the Tibetan plateau, are commonly assumed to be the descendants of the earliest inhabitants of the Himalayan arc. However, this assumption has been challenged by archaeological and osteological evidence suggesting that these valleys may have been originally populated from areas other than the Tibetan plateau, including those at low elevation. To investigate the peopling and early population history of this dynamic high-altitude contact zone, we sequenced the genomes (0.04×–7.25×, mean 2.16×) and mitochondrial genomes (20.8×–1,311.0×, mean 482.1×) of eight individuals dating to three periods with distinct material culture in the Annapurna Conservation Area (ACA) of Nepal, spanning 3,150–1,250 y before present (yBP). We demonstrate that the region is characterized by long-term stability of the population genetic make-up despite marked changes in material culture. The ancient genomes, uniparental haplotypes, and high-altitude adaptive alleles suggest a high-altitude East Asian origin for prehistoric Himalayan populations. PMID:27325755

Genes, Culture and Conservatism-A Psychometric-Genetic Approach.

PubMed

Schwabe, Inga; Jonker, Wilfried; van den Berg, Stéphanie M

2016-07-01

The Wilson-Patterson conservatism scale was psychometrically evaluated using homogeneity analysis and item response theory models. Results showed that this scale actually measures two different aspects in people: on the one hand people vary in their agreement with either conservative or liberal catch-phrases and on the other hand people vary in their use of the "?" response category of the scale. A 9-item subscale was constructed, consisting of items that seemed to measure liberalism, and this subscale was subsequently used in a biometric analysis including genotype-environment interaction, correcting for non-homogeneous measurement error. Biometric results showed significant genetic and shared environmental influences, and significant genotype-environment interaction effects, suggesting that individuals with a genetic predisposition for conservatism show more non-shared variance but less shared variance than individuals with a genetic predisposition for liberalism.

Shared Genetic Contributions to Anxiety Disorders and Pathological Gambling in a Male Population

PubMed Central

Giddens, Justine L.; Xian, Hong; Scherrer, Jeffrey F.; Eisen, Seth A.; Potenza, Marc N.

2013-01-01

Background Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Method Data from the Vietnam Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). Results While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (ra =0.53). In contrast, substantial correlations were observed between both the genetic (ra=0.34) and unique environmental (re =0.31) contributions to PG and PD. Limitations Results may be limited to middle aged males. Conclusions The existence of shared genetic contributions between PG and both GAD and PD suggest that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women, adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences. PMID:21481943

Shared genetic contributions to anxiety disorders and pathological gambling in a male population.

PubMed

Giddens, Justine L; Xian, Hong; Scherrer, Jeffrey F; Eisen, Seth A; Potenza, Marc N

2011-08-01

Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Data from the Vietnam Era Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r(A)=0.53). In contrast, substantial correlations were observed between both the genetic (r(A)=0.34) and unique environmental (r(E)=0.31) contributions to PG and PD. Results may be limited to middle aged males. The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences. Copyright © 2011. Published by Elsevier B.V.

Genetic and environmental influences on affiliation with deviant peers during adolescence and early adulthood.

PubMed

Tarantino, Nicholas; Tully, Erin C; Garcia, Sarah E; South, Susan; Iacono, William G; McGue, Matt

2014-03-01

Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youths exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence has suggested that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at 3 discrete ages: 15, 18, and 21 years of age. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping, whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Genetic and Environmental Influences on Affiliation with Deviant Peers during Adolescence and Early Adulthood

PubMed Central

Tarantino, Nicholas; Tully, Erin C.; Garcia, Sarah E.; South, Susan; Iacono, William G.; McGue, Matt

2014-01-01

Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youth exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence suggests that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at three discrete ages-15-, 18-, and 21-years-old. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PMID:24015689

Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.

PubMed

Nudel, R; Simpson, N H; Baird, G; O'Hare, A; Conti-Ramsden, G; Bolton, P F; Hennessy, E R; Ring, S M; Davey Smith, G; Francks, C; Paracchini, S; Monaco, A P; Fisher, S E; Newbury, D F

2014-04-01

Specific language impairment (SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome-wide association study of SLI which included parent-of-origin effects and child genotype effects and used 278 families of language-impaired children. The child genotype effects analysis did not identify significant associations. We found genome-wide significant paternal parent-of-origin effects on chromosome 14q12 (P = 3.74 × 10(-8)) and suggestive maternal parent-of-origin effects on chromosome 5p13 (P = 1.16 × 10(-7)). A subsequent targeted association of six single-nucleotide-polymorphisms (SNPs) on chromosome 5 in 313 language-impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction (P = 0.001); as fathers' genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent-of-origin effects. The paternally-associated SNP on chromosome 14 yields a non-synonymous coding change within the NOP9 gene. This gene encodes an RNA-binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent-of-origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders. © 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Genetic and Environmental Contributions to Behavioral Stability and Change in Children 6-36 months of Age Using Louisville Twin Study Data.

PubMed

Davis, Deborah Winders; Finkel, Deborah; Turkheimer, Eric; Dickens, William

2015-11-01

The Infant Behavior Record (IBR) from the Bayley Scales of Infant Development has been used to study behavioral development since the 1960s. Matheny (1983) examined behavioral development at 6, 12, 18, and 24 months from the Louisville Twin Study (LTS). The extracted temperament scales included Task Orientation, Affect-Extraversion, and Activity. He concluded that monozygotic twins were more similar than same-sex dizygotic twins on these dimensions. Since this seminal work was published, a larger LTS sample and more advanced analytical methods are available. In the current analyses, Choleksy decomposition was applied to behavioral data (n = 1231) from twins 6-36 months. Different patterns of genetic continuity vs genetic innovations were identified for each IBR scale. Single common genetic and shared environmental factors explained cross-age twin similarity in the Activity scale. Multiple shared environmental factors and a single genetic factor coming on line at age 18 months contributed to Affect-Extraversion. A single shared environmental factor and multiple genetic factors explained cross-age twin similarity in Task Orientation.

Analysis of genetic diversity of Chinese dairy goats via microsatellite markers.

PubMed

Wang, G Z; Chen, S S; Chao, T L; Ji, Z B; Hou, L; Qin, Z J; Wang, J M

2017-05-01

In this study, 15 polymorphic microsatellite markers were used to analyze the genetic structure and phylogenetic relationships of 6 dairy goat breeds in China, including 4 native developed breeds and 2 introduced breeds. The results showed that a total of 172 alleles were detected in 347 samples of the dairy goat breeds included in this study. The mean number of effective alleles per locus was 4.92. Except for BMS0812, all of the remaining microsatellite loci were highly polymorphic (polymorphism information content [PIC] > 0.5). The analysis of genetic diversity parameters, including the number of effective alleles, PIC, and heterozygosity, revealed that the native developed dairy goat breeds in China harbored a rich genetic diversity. However, these breeds showed a low breeding degree and a high population intermix degree, with a certain degree of inbreeding and within-subpopulation inbreeding coefficient ( > 0). The analysis of population genetic differentiation and phylogenetic tree topologies showed a moderate state of genetic differentiation among subpopulations of native developed breed dairy goats in China (0.05 < gene fixation coefficient [] < 0.15). The native developed breeds shared a common ancestor, namely, the Saanen dairy goat, originating from Europe. The results showed that there was a close genetic relationship between Wendeng and Laoshan dairy goats while the Guanzhong dairy goat and the Xinong Saanen dairy goat were also found to have a close genetic relationship, which were both in agreement with the formation history and geographical distribution of the breeds. This study revealed that adopting genetic management strategies, such as expanding pedigree source and strengthening multi-trait selection, is useful in maintaining the genetic diversity of native developed breeds and improving the population uniformity of dairy goats.

Molecular markers reveal no genetic differentiation between Myrica rivas-martinezii and M. faya (Myricaceae)

PubMed Central

González-Pérez, Miguel A.; Sosa, Pedro A.; Rivero, Elisabeth; González-González, Edna A.; Naranjo, Agustín

2009-01-01

Background and Aims Myrica rivas-martinezii is a critically endangered endemic of the laurel forest of the Canary Islands and co-occurs very close to M. faya. Some authors suggest that M. rivas-martinezii and M. faya are two morphs of the same species, so molecular markers were used to estimate the levels and structuring of genetic variation within and among natural populations in order to evaluate genetic relationships between these two congeners. Methods Six polymorphic microsatellite (simple sequence repeat, SSR) markers were used to determine the genetic diversity and the genetic relationship between both Myrica species. Key Results Most of the natural populations analysed were in Hardy–Weinberg equilibrium for both taxa. Analysis of molecular variance (AMOVA) for both species revealed that most of the genetic variability detected was contained within populations (92·48 and 85·91 % for M. faya and M. rivas-martinezii, respectively), which it is consistent with outcrossing and dioecious plants. Estimates of interpopulation genetic variation, calculated from FST and G′ST, were quite low in the two taxa, and these values did not increase substantially when M. rivas-martinezii and M. faya populations were compared. The UPGMA dendrogram based on Nei's genetic distance clustered the populations by their island origin, independently of taxon. In fact, the mixture of individuals of both taxa did not appreciably disrupt the intrapopulational genetic cohesion, and only 3·76 % variation existed between species. Conclusions All the results obtained using molecular markers indicate clearly that both taxa share the same genetic pool, and they are probably the same taxa. Considering that M. rivas-martinezii is classified as at risk of extinction, there should be a change of focus of the current management actions for the conservation of this putatively endangered Canarian endemic. PMID:19008254

Molecular evolution of shattering loci in U.S. weedy rice.

PubMed

Thurber, Carrie S; Reagon, Michael; Gross, Briana L; Olsen, Kenneth M; Jia, Yulin; Caicedo, Ana L

2010-08-01

Cultivated rice fields worldwide are plagued with weedy rice, a conspecific weed of cultivated rice (Oryza sativa L.). The persistence of weedy rice has been attributed, in part, to its ability to shatter (disperse) seed prior to crop harvesting. In the United States, separately evolved weedy rice groups have been shown to share genomic identity with exotic domesticated cultivars. Here, we investigate the shattering phenotype in a collection of U.S. weedy rice accessions, as well as wild and cultivated relatives. We find that all U.S. weedy rice groups shatter seeds easily, despite multiple origins, and in contrast to a decrease in shattering ability seen in cultivated groups. We assessed allelic identity and diversity at the major shattering locus, sh4, in weedy rice; we find that all cultivated and weedy rice, regardless of population, share similar haplotypes at sh4, and all contain a single derived mutation associated with decreased seed shattering. Our data constitute the strongest evidence to date of an evolution of weeds from domesticated backgrounds. The combination of a shared cultivar sh4 allele and a highly shattering phenotype, suggests that U.S. weedy rice have re-acquired the shattering trait after divergence from their progenitors through alternative genetic mechanisms.

Education Modifies Genetic and Environmental Influences on BMI

PubMed Central

Johnson, Wendy; Kyvik, Kirsten Ohm; Skytthe, Axel; Deary, Ian J.; Sørensen, Thorkild I. A.

2011-01-01

Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height2) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were −.13 in women, −.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity. PMID:21283825

Harmonizing the interpretation of genetic variants across the world: the Malaysian experience.

PubMed

Hassan, Nik Norliza Nik; Plazzer, John-Paul; Smith, Timothy D; Halim-Fikri, Hashim; Macrae, Finlay; Zubaidi, A A L; Zilfalil, Bin Alwi

2016-02-26

Databases for gene variants are very useful for sharing genetic data and to facilitate the understanding of the genetic basis of diseases. This report summarises the issues surrounding the development of the Malaysian Human Variome Project Country Node. The focus is on human germline variants. Somatic variants, mitochondrial variants and other types of genetic variation have corresponding databases which are not covered here, as they have specific issues that do not necessarily apply to germline variations. The ethical, legal, social issues, intellectual property, ownership of the data, information technology implementation, and efforts to improve the standards and systems used in data sharing are discussed. An overarching framework such as provided by the Human Variome Project to co-ordinate activities is invaluable. Country Nodes, such as MyHVP, enable human gene variation associated with human diseases to be collected, stored and shared by all disciplines (clinicians, molecular biologists, pathologists, bioinformaticians) for a consistent interpretation of genetic variants locally and across the world.

The gene-environmental architecture of the development of adolescent substance use.

PubMed

Vitaro, Frank; Dickson, Daniel J; Brendgen, Mara; Laursen, Brett; Dionne, Ginette; Boivin, Michel

2018-02-19

Using a longitudinal twin design and a latent growth curve/autoregressive approach, this study examined the genetic-environmental architecture of substance use across adolescence. Self-reports of substance use (i.e. alcohol, marijuana) were collected at ages 13, 14, 15, and 17 years from 476 twin pairs (475 boys, 477 girls) living in the Province of Quebec, Canada. Substance use increased linearly across the adolescent years. ACE modeling revealed that genetic, as well as shared and non-shared environmental factors explained the overall level of substance use and that these same factors also partly accounted for growth in substance use from age 13 to 17. Additional genetic factors predicted the growth in substance use. Finally, autoregressive effects revealed age-specific non-shared environmental influences and, to a lesser degree, age-specific genetic influences, which together accounted for the stability of substance use across adolescence. The results support and expand the notion that genetic and environmental influences on substance use during adolescence are both developmentally stable and developmentally dynamic.

Genetic and Environmental Influences on Depressive Symptoms in Chinese Adolescents

PubMed Central

Chen, Jie; Li, Xinying; Natsuaki, Misaki N.; Leve, Leslie D.; Harold, Gordon T.

2016-01-01

Adolescent depression is common and has become a major public health concern in China, yet little research has examined the etiology of depression in Chinese adolescents. In the present study, genetic and environmental influences on Chinese adolescent depressive symptoms were investigated in 1181 twin pairs residing in Beijing, China (ages 11 to 19 years). Child- and parent-versions of the Children’s Depression Inventory (CDI) were used to measure adolescents’ depressive symptoms. For self-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 50%, 5%, and 45% of the variation in depressive symptoms, respectively; for parent-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 51%, 18%, and 31% of the variation, respectively. These estimates are generally consistent with previous findings in Western adolescents, supporting the cross-cultural generalizability of etiological model of adolescent depression. Neither qualitative nor quantitative sex differences were found in the etiological model. Future studies are needed to investigate how genes and environments work together (gene-environment interaction, gene-environment correlation) to influence depression in Chinese adolescents. PMID:24311200

Genetic and environmental influences on depressive symptoms in Chinese adolescents.

PubMed

Chen, Jie; Li, Xinying; Natsuaki, Misaki N; Leve, Leslie D; Harold, Gordon T

2014-01-01

Adolescent depression is common and has become a major public health concern in China, yet little research has examined the etiology of depression in Chinese adolescents. In the present study, genetic and environmental influences on Chinese adolescent depressive symptoms were investigated in 1,181 twin pairs residing in Beijing, China (ages 11-19 years). Child- and parent-versions of the children's depression inventory were used to measure adolescents' depressive symptoms. For self-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 50, 5, and 45 % of the variation in depressive symptoms, respectively; for parent-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 51, 18, and 31 % of the variation, respectively. These estimates are generally consistent with previous findings in Western adolescents, supporting the cross-cultural generalizability of etiological model of adolescent depression. Neither qualitative nor quantitative sex differences were found in the etiological model. Future studies are needed to investigate how genes and environments work together (gene-environment interaction, gene-environment correlation) to influence depression in Chinese adolescents.

The lod score method.

PubMed

Rice, J P; Saccone, N L; Corbett, J

2001-01-01

The lod score method originated in a seminal article by Newton Morton in 1955. The method is broadly concerned with issues of power and the posterior probability of linkage, ensuring that a reported linkage has a high probability of being a true linkage. In addition, the method is sequential, so that pedigrees or lod curves may be combined from published reports to pool data for analysis. This approach has been remarkably successful for 50 years in identifying disease genes for Mendelian disorders. After discussing these issues, we consider the situation for complex disorders, where the maximum lod score (MLS) statistic shares some of the advantages of the traditional lod score approach but is limited by unknown power and the lack of sharing of the primary data needed to optimally combine analytic results. We may still learn from the lod score method as we explore new methods in molecular biology and genetic analysis to utilize the complete human DNA sequence and the cataloging of all human genes.

Sex pheromone biosynthetic pathways are conserved between moths and the butterfly Bicyclus anynana

PubMed Central

Liénard, Marjorie A; Wang, Hong-Lei; Lassance, Jean-Marc; Löfstedt, Christer

2014-01-01

Although phylogenetically nested within the moths, butterflies have diverged extensively in a number of life history traits. Whereas moths rely greatly on chemical signals, visual advertisement is the hallmark of mate finding in butterflies. In the context of courtship, however, male chemical signals are widespread in both groups although they likely have multiple evolutionary origins. Here, we report that in males of the butterfly Bicyclus anynana, courtship scents are produced de novo via biosynthetic pathways shared with females of many moth species. We show that two of the pheromone components that play a major role in mate choice, namely the (Z)-9-tetradecenol and hexadecanal, are produced through the activity of a fatty acyl Δ11-desaturase and two specialized alcohol-forming fatty acyl reductases. Our study provides the first evidence of conservation and sharing of ancestral genetic modules for the production of FA-derived pheromones over a long evolutionary timeframe thereby reconciling mate communication in moths and butterflies. PMID:24862548

Structure of some East African Glossina fuscipes fuscipes populations

PubMed Central

Krafsur, E. S.; Marquez, J. G.; Ouma, J. O.

2008-01-01

Glossina fuscipes fuscipes Newstead 1910 (Diptera: Glossinidae) is the primary vector of human sleeping sickness in Kenya and Uganda. This is the first report on its population structure. A total of 688 nucleotides of mitochondrial ribosomal 16S2 and cytochrome oxidase I genes were sequenced. Twenty-one variants were scored in 79 flies from three geographically diverse natural populations. Four haplotypes were shared among populations, eight were private and nine were singletons. The mean haplotype and nucleotide diversities were 0.84 and 0.009, respectively. All populations were genetically differentiated and were at demographic equilibrium. In addition, a longstanding laboratory culture originating from the Central African Republic (CAR-lab) in 1986 (or before) was examined. Haplotype and nucleotide diversities in this culture were 0.95 and 0.012, respectively. None of its 27 haplotypes were shared with the East African populations. A first approximation of relative effective population sizes was Uganda > CAR-lab > Kenya. It was concluded that the structure of G. f. fuscipes populations in East Africa is localized. PMID:18816270

Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome.

PubMed

Goldstein, Jill M; Holsen, Laura; Huang, Grace; Hammond, Bradley D; James-Todd, Tamarra; Cherkerzian, Sara; Hale, Taben M; Handa, Robert J

2016-12-01

Major depressive disorder (MDD) is the number one cause of disability worldwide and is comorbid with many chronic diseases, including obesity/metabolic syndrome (MetS). Women have twice as much risk for MDD and comorbidity with obesity/MetS as men, although pathways for understanding this association remain unclear. On the basis of clinical and preclinical studies, we argue that prenatal maternal stress (ie, excess glucocorticoid expression and associated immune responses) that occurs during the sexual differentiation of the fetal brain has sex-dependent effects on brain development within highly sexually dimorphic regions that regulate mood, stress, metabolic function, the autonomic nervous system, and the vasculature. Furthermore, these effects have lifelong consequences for shared sex-dependent risk of MDD and obesity/MetS. Thus, we propose that there are shared biologic substrates at the anatomical, molecular, and/or genetic levels that produce the comorbid risk for MDD-MetS through sex-dependent fetal origins.

Admixture into and within sub-Saharan Africa.

PubMed

Busby, George Bj; Band, Gavin; Si Le, Quang; Jallow, Muminatou; Bougama, Edith; Mangano, Valentina D; Amenga-Etego, Lucas N; Enimil, Anthony; Apinjoh, Tobias; Ndila, Carolyne M; Manjurano, Alphaxard; Nyirongo, Vysaul; Doumba, Ogobara; Rockett, Kirk A; Kwiatkowski, Dominic P; Spencer, Chris Ca

2016-06-21

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology.

Somitic origin of the medial border of the mammalian scapula and its homology to the avian scapula blade.

PubMed

Valasek, Petr; Theis, Susanne; Krejci, Eliska; Grim, Milos; Maina, Flavio; Shwartz, Yulia; Otto, Anthony; Huang, Ruijin; Patel, Ketan

2010-04-01

The scapula is the main skeletal element of the pectoral girdle allowing muscular fixation of the forelimb to the axial skeleton. The vertebrate limb skeleton has traditionally been considered to develop from the lateral plate mesoderm, whereas the musculature originates from the axial somites. However, in birds, the scapular blade has been shown to develop from the somites. We investigated whether a somitic contribution was also present in the mammalian scapula. Using genetic lineage-tracing techniques, we show that the medial border of the mammalian scapula develops from somitic cells. The medial scapula border serves as the attachment site of girdle muscles (serratus anterior, rhomboidei and levator scapulae). We show that the development of these muscles is independent of the mechanism that controls the formation of all other limb muscles. We suggest that these muscles be specifically referred to as medial girdle muscles. Our results establish the avian scapular blade and medial border of the mammalian scapula as homologous structures as they share the same developmental origin.

Somitic origin of the medial border of the mammalian scapula and its homology to the avian scapula blade

PubMed Central

Valasek, Petr; Theis, Susanne; Krejci, Eliska; Grim, Milos; Maina, Flavio; Shwartz, Yulia; Otto, Anthony; Huang, Ruijin; Patel, Ketan

2010-01-01

The scapula is the main skeletal element of the pectoral girdle allowing muscular fixation of the forelimb to the axial skeleton. The vertebrate limb skeleton has traditionally been considered to develop from the lateral plate mesoderm, whereas the musculature originates from the axial somites. However, in birds, the scapular blade has been shown to develop from the somites. We investigated whether a somitic contribution was also present in the mammalian scapula. Using genetic lineage-tracing techniques, we show that the medial border of the mammalian scapula develops from somitic cells. The medial scapula border serves as the attachment site of girdle muscles (serratus anterior, rhomboidei and levator scapulae). We show that the development of these muscles is independent of the mechanism that controls the formation of all other limb muscles. We suggest that these muscles be specifically referred to as medial girdle muscles. Our results establish the avian scapular blade and medial border of the mammalian scapula as homologous structures as they share the same developmental origin. PMID:20136669

Differential heritability of adult and juvenile antisocial traits.

PubMed

Lyons, M J; True, W R; Eisen, S A; Goldberg, J; Meyer, J M; Faraone, S V; Eaves, L J; Tsuang, M T

1995-11-01

Studies of adult antisocial behavior or criminality usually find genetic factors to be more important than the family environment, whereas studies of delinquency find the family environment to be more important. We compared DSM-III-R antisocial personality disorder symptoms before vs after the age of 15 years within a sample of twins, rather than comparing across studies. We administered the Diagnostic Interview Schedule Version III-revised by telephone to 3226 pairs of male twins from the Vietnam Era Twin Registry. Biometrical modeling was applied to each symptom of antisocial personality disorder and summary measures of juvenile and adult symptoms. Five juvenile symptoms were significantly heritable, and five were significantly influenced by the shared environment. Eight adult symptoms were significantly heritable, and one was significantly influenced by the shared environment. The shared environment explained about six times more variance in juvenile anti-social traits than in adult traits. Shared environmental influences on adult antisocial traits overlapped entirely with those on juvenile traits. Additive genetic factors explained about six times more variance in adult vs juvenile traits. The juvenile genetic determinants overlapped completely with genetic influences on adult traits. The unique environment (plus measurement error) explained the largest proportion of variance in both juvenile and adult antisocial traits. Characteristics of the shared or family environment that promote antisocial behavior during childhood and early adolescence also promote later antisocial behavior, but to a much lesser extent. Genetic causal factors are much more prominent for adult than for juvenile antisocial traits.

Shared versus distinct genetic contributions of mental wellbeing with depression and anxiety symptoms in healthy twins.

PubMed

Routledge, Kylie M; Burton, Karen L O; Williams, Leanne M; Harris, Anthony; Schofield, Peter R; Clark, C Richard; Gatt, Justine M

2016-10-30

Mental wellbeing and mental illness symptoms are typically conceptualized as opposite ends of a continuum, despite only sharing about a quarter in common variance. We investigated the normative variation in measures of wellbeing and of depression and anxiety in 1486 twins who did not meet clinical criteria for an overt diagnosis. We quantified the shared versus distinct genetic and environmental variance between wellbeing and depression and anxiety symptoms. The majority of participants (93%) reported levels of depression and anxiety symptoms within the healthy range, yet only 23% reported a wellbeing score within the "flourishing" range: the remainder were within the ranges of "moderate" (67%) or "languishing" (10%). In twin models, measures of wellbeing and of depression and anxiety shared 50.09% of variance due to genetic factors and 18.27% due to environmental factors; the rest of the variance was due to unique variation impacting wellbeing or depression and anxiety symptoms. These findings suggest that an absence of clinically-significant symptoms of depression and anxiety does not necessarily indicate that an individual is flourishing. Both unique and shared genetic and environmental factors may determine why some individuals flourish in the absence of symptoms while others do not. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genetic Overlap Between Schizophrenia and Volumes of Hippocampus, Putamen, and Intracranial Volume Indicates Shared Molecular Genetic Mechanisms.

PubMed

Smeland, Olav B; Wang, Yunpeng; Frei, Oleksandr; Li, Wen; Hibar, Derrek P; Franke, Barbara; Bettella, Francesco; Witoelar, Aree; Djurovic, Srdjan; Chen, Chi-Hua; Thompson, Paul M; Dale, Anders M; Andreassen, Ole A

2018-06-06

Schizophrenia (SCZ) is associated with differences in subcortical brain volumes and intracranial volume (ICV). However, little is known about the underlying etiology of these brain alterations. Here, we explored whether brain structure volumes and SCZ share genetic risk factors. Using conditional false discovery rate (FDR) analysis, we integrated genome-wide association study (GWAS) data on SCZ (n = 82315) and GWAS data on 7 subcortical brain volumes and ICV (n = 11840). By conditioning the FDR on overlapping associations, this statistical approach increases power to discover genetic loci. To assess the credibility of our approach, we studied the identified loci in larger GWAS samples on ICV (n = 26577) and hippocampal volume (n = 26814). We observed polygenic overlap between SCZ and volumes of hippocampus, putamen, and ICV. Based on conjunctional FDR < 0.05, we identified 2 loci shared between SCZ and ICV implicating genes FOXO3 (rs10457180) and ITIH4 (rs4687658), 2 loci shared between SCZ and hippocampal volume implicating SLC4A10 (rs4664442) and SPATS2L (rs1653290), and 2 loci shared between SCZ and volume of putamen implicating DCC (rs4632195) and DLG2 (rs11233632). The loci shared between SCZ and hippocampal volume or ICV had not reached significance in the primary GWAS on brain phenotypes. Proving our point of increased power, 2 loci did reach genome-wide significance with ICV (rs10457180) and hippocampal volume (rs4664442) in the larger GWAS. Three of the 6 identified loci are novel for SCZ. Altogether, the findings provide new insights into the relationship between SCZ and brain structure volumes, suggesting that their genetic architectures are not independent.

Breast Cancer

MedlinePlus

... a genetic counselor, who can review your family health history. A genetic counselor can also discuss the benefits, risks and limitations of genetic testing to assist you with shared decision-making. Risk ...

Ancestral European roots of Helicobacter pylori in India

PubMed Central

Devi, S Manjulata; Ahmed, Irshad; Francalacci, Paolo; Hussain, M Abid; Akhter, Yusuf; Alvi, Ayesha; Sechi, Leonardo A; Mégraud, Francis; Ahmed, Niyaz

2007-01-01

Background The human gastric pathogen Helicobacter pylori is co-evolved with its host and therefore, origins and expansion of multiple populations and sub populations of H. pylori mirror ancient human migrations. Ancestral origins of H. pylori in the vast Indian subcontinent are debatable. It is not clear how different waves of human migrations in South Asia shaped the population structure of H. pylori. We tried to address these issues through mapping genetic origins of present day H. pylori in India and their genomic comparison with hundreds of isolates from different geographic regions. Results We attempted to dissect genetic identity of strains by multilocus sequence typing (MLST) of the 7 housekeeping genes (atpA, efp, ureI, ppa, mutY, trpC, yphC) and phylogeographic analysis of haplotypes using MEGA and NETWORK software while incorporating DNA sequences and genotyping data of whole cag pathogenicity-islands (cagPAI). The distribution of cagPAI genes within these strains was analyzed by using PCR and the geographic type of cagA phosphorylation motif EPIYA was determined by gene sequencing. All the isolates analyzed revealed European ancestry and belonged to H. pylori sub-population, hpEurope. The cagPAI harbored by Indian strains revealed European features upon PCR based analysis and whole PAI sequencing. Conclusion These observations suggest that H. pylori strains in India share ancestral origins with their European counterparts. Further, non-existence of other sub-populations such as hpAfrica and hpEastAsia, at least in our collection of isolates, suggest that the hpEurope strains enjoyed a special fitness advantage in Indian stomachs to out-compete any endogenous strains. These results also might support hypotheses related to gene flow in India through Indo-Aryans and arrival of Neolithic practices and languages from the Fertile Crescent. PMID:17584914

The CRISPR conundrum: evolve and maybe die, or survive and risk stagnation

PubMed Central

García-Martínez, Jesús; Maldonado, Rafael D.; Guzmán, Noemí M.; Mojica, Francisco J. M.

2018-01-01

CRISPR-Cas represents a prokaryotic defense mechanism against invading genetic elements. Although there is a diversity of CRISPR-Cas systems, they all share similar, essential traits. In general, a CRISPR-Cas system consists of one or more groups of DNA repeats named CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), regularly separated by unique sequences referred to as spacers, and a set of functionally associated cas (CRISPR associated) genes typically located next to one of the repeat arrays. The origin of spacers is in many cases unknown but, when ascertained, they usually match foreign genetic molecules. The proteins encoded by some of the cas genes are in charge of the incorporation of new spacers upon entry of a genetic element. Other Cas proteins participate in generating CRISPR-spacer RNAs and perform the task of destroying nucleic acid molecules carrying sequences similar to the spacer. In this way, CRISPR-Cas provides protection against genetic intruders that could substantially affect the cell viability, thus acting as an adaptive immune system. However, this defensive action also hampers the acquisition of potentially beneficial, horizontally transferred genes, undermining evolution. Here we cover how the model bacterium Escherichia coli deals with CRISPR-Cas to tackle this major dilemma, evolution versus survival. PMID:29850463

Genetic differences among Haplorchis taichui populations in Indochina revealed by mitochondrial COX1 sequences.

PubMed

Thaenkham, U; Phuphisut, O; Nuamtanong, S; Yoonuan, T; Sa-Nguankiat, S; Vonghachack, Y; Belizario, V Y; Dung, D T; Dekumyoy, P; Waikagul, J

2017-09-01

Haplorchis taichui is an intestinal heterophyid fluke that is pathogenic to humans. It is widely distributed in Asia, with a particularly high prevalence in Indochina. Previous work revealed that the lack of gene flow between three distinct populations of Vietnamese H. taichui can be attributed to their geographic isolation with no interconnected river basins. To test the hypothesis that interconnected river basins allow gene flow between otherwise isolated populations of H. taichui, as previously demonstrated for another trematode, Opisthorchis viverrini, we compared the genetic structures of seven populations of H. taichui from various localities in the lower Mekong Basin, in Thailand and Laos, with those in Vietnam, using the mitochondrial cytochrome c oxidase subunit 1 (COX1) gene. To determine the gene flow between these H. taichui populations, we calculated their phylogenetic relationships, genetic distances and haplotype diversity. Each population showed very low nucleotide diversity at this locus. However, high levels of genetic differentiation between the populations indicated very little gene flow. A phylogenetic analysis divided the populations into four clusters that correlated with the country of origin. The negligible gene flow between the Thai and Laos populations, despite sharing the Mekong Basin, caused us to reject our hypothesis. Our data suggest that the distribution of H. taichui populations was incidentally associated with national borders.

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

The genetic and environmental etiology of antisocial behavior from childhood to emerging adulthood.

PubMed

Tuvblad, Catherine; Narusyte, Jurgita; Grann, Martin; Sarnecki, Jerzy; Lichtenstein, Paul

2011-09-01

Previous research suggests that both genetic and environmental influences are important for antisocial behavior across the life span, even though the prevalence and incidence of antisocial behavior varies considerably across ages. However, little is known of how genetic and environmental effects influence the development of antisocial behavior. A total of 2,600 male and female twins from the population-based Swedish Twin Registry were included in the present study. Antisocial behavior was measured on four occasions, when twins were 8-9, 13-14, 16-17, and 19-20 years old. Longitudinal analyses of the data were conducted using structural equation modeling. The stability of antisocial behavior over time was explained by a common latent persistent antisocial behavior factor. A common genetic influence accounted for 67% of the total variance in this latent factor, the shared environment explained 26%, and the remaining 7% was due to the non-shared environment. Significant age-specific shared environmental factors were found at ages 13-14 years, suggesting that common experiences (e.g., peers) are important for antisocial behavior at this age. Results from this study show that genetic as well as shared environmental influences are important in antisocial behavior that persists from childhood to emerging adulthood.

Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection.

PubMed

Tarnoki, David Laszlo; Tarnoki, Adam Domonkos; Medda, Emanuela; Littvay, Levente; Lazar, Zsofia; Toccaceli, Virgilia; Fagnani, Corrado; Stazi, Maria Antonietta; Nisticó, Lorenza; Brescianini, Sonia; Penna, Luana; Lucatelli, Pierleone; Boatta, Emanuele; Zini, Chiara; Fanelli, Fabrizio; Baracchini, Claudio; Meneghetti, Giorgio; Koller, Akos; Osztovits, Janos; Jermendy, Gyorgy; Preda, Istvan; Kiss, Robert Gabor; Karlinger, Kinga; Lannert, Agnes; Horvath, Tamas; Schillaci, Giuseppe; Molnar, Andrea Agnes; Garami, Zsolt; Berczi, Viktor; Horvath, Ildiko

2013-06-01

Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FE(NO)) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FE(NO) levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FE(NO) was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aix(ao)) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FE(NO) and Aix(ao) were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FE(NO) with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FE(NO) and Aix(ao) (r = -0.17; 95%CI:-0.32,-0.02). FE(NO) showed a significant negative genetic correlation with Aix(ao) (r(g) = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FE(NO) are explained both by genetic and non-shared environmental effects. Covariance between FE(NO) and Aix(ao) is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.

1A.09: DISTINCT GENETIC ARCHITECTURE OF RENAL IMPAIRMENT COMPONENTS IN TYPE 2 DIABETES WITHIN CAUCASIAN POPULATIONS OF CELTO-GERMANIC AND SLAVIC ORIGINS.

PubMed

Harvey, F; Blanchet, F Marois; Phillips, M S; Haloui, M; Chalmers, J P; Woodward, M; Marre, M; Harrap, S B; Tremblay, J; Hamet, P

2015-06-01

The genetic architecture of type 2 diabetes (T2D) has been reported to be different between Asian and Caucasian populations (BBRC 2014;452:213-220). It is also well recognized that renal complications of T2D start earlier and are more severe in Asian subjects. Our objective was to determine whether such heterogeneity exists within the Caucasian population with respect to phenotypic and genomic determinants of renal complications in T2D. We analyzed two major aspects of renal impairment: increase of albuminuria as UACR and decline of estimated glomerular filtration rate as log(eGFR) in Caucasian patients during the 5 year period of the ADVANCE trial (NEJM 2014;371:1392-406). Celto-Germanic and Slavic origins of 3449 genotyped subjects were determined by principal component analysis with Eigenstrat software. The first principal component separated the 3449 individuals along a geographical gradient from East/West Europe: 1133 T2D patients were Slavic and 2316 were Celto-Germanic. Phenotypic analyses and Genome Wide Association Studies (GWAS) were performed in the two groups separately. The prevalence of hypertension was significantly higher (p = 1.7x10-32) in ADVANCE Slavic subjects. The prevalence of albuminuria and UACR levels were significantly higher (p = 10-4 and 9.5x10-5, respectively) at baseline and its progression over the 5-year period was steeper (p = 6.2x10-4) in patients of Slavic origin, contrasting with a more significant decline of eGFR in Celto-Germanic subjects (p = 4.9x10-21). Other T2D outcomes (myocardial infarction and stroke) did not exhibit such a difference between East and West Europe. GWAS analyses of eGFR decline did not reveal any associated SNPs (threshold p-value of < 10-3) in common between the two geo-ethnic groups and only 6% of associated genes were shared. Similarly, GWAS of UACR progression showed that only 0.1% of SNPs were common and 7% of genes were shared between the two groups. This was very different for stroke: 25% of SNPs and more than 50% of genes were common. Genetic analyses have to consider geo-ethnic characteristics even within Caucasians, demonstrated here for cardinal features of renal impairment in T2D. Our data suggest that distinct understanding of genomic architectures is important to ascertain clinical utility.

Shared genetic determinants of axial length and height in children: the Guangzhou twin eye study.

PubMed

Zhang, Jian; Hur, Yoon-Mi; Huang, Wenyong; Ding, Xiaohu; Feng, Ke; He, Mingguang

2011-01-01

To describe the association between axial length (AL) and height and to estimate the extent to which shared genetic or environmental factors influence this covariance. Study participants were recruited from the Guangzhou Twin Registry. Axial length was measured using partial coherence laser interferometry. Height was measured with the participants standing without shoes. We computed twin pairwise correlations and cross-twin cross-trait correlations between AL and height for monozygotic and dizygotic twins and performed model-fitting analyses using a multivariate Cholesky model. The right eye was arbitrarily selected to represent AL of participants. Five hundred sixty-five twin pairs (359 monozygotic and 206 dizygotic) aged 7 to 15 years were available for analysis. Phenotypic correlation between AL and height was 0.46 but decreased to 0.19 after adjusting for age, sex, and age × sex interaction. Bivariate Cholesky model-fitting analyses revealed that 89% of phenotypic correlation was due to shared genetic factors and 11% was due to shared random environmental factors, which includes measurement error. Covariance of AL and height is largely attributable to shared genes. Given that AL is a key determinant of myopia, further work is needed to confirm gene sharing between myopia and stature.

Assessment of genome origins and genetic diversity in the genus Eleusine with DNA markers.

PubMed

Salimath, S S; de Oliveira, A C; Godwin, I D; Bennetzen, J L

1995-08-01

Finger millet (Eleusine coracana), an allotetraploid cereal, is widely cultivated in the arid and semiarid regions of the world. Three DNA marker techniques, restriction fragment length polymorphism (RFLP), randomly amplified polymorphic DNA (RAPD), and inter simple sequence repeat amplification (ISSR), were employed to analyze 22 accessions belonging to 5 species of Eleusine. An 8 probe--3 enzyme RFLP combination, 18 RAPD primers, and 6 ISSR primers, respectively, revealed 14, 10, and 26% polymorphism in 17 accessions of E. coracana from Africa and Asia. These results indicated a very low level of DNA sequence variability in the finger millets but did allow each line to be distinguished. The different Eleusine species could be easily identified by DNA marker technology and the 16% intraspecific polymorphism exhibited by the two analyzed accessions of E. floccifolia suggested a much higher level of diversity in this species than in E. coracana. Between species, E. coracana and E. indica shared the most markers, while E. indica and E. tristachya shared a considerable number of markers, indicating that these three species form a close genetic assemblage within the Eleusine. Eleusine floccifolia and E. compressa were found to be the most divergent among the species examined. Comparison of RFLP, RAPD, and ISSR technologies, in terms of the quantity and quality of data output, indicated that ISSRs are particularly promising for the analysis of plant genome diversity.

Genes involved in convergent evolution of eusociality in bees

PubMed Central

Woodard, S. Hollis; Fischman, Brielle J.; Venkat, Aarti; Hudson, Matt E.; Varala, Kranthi; Cameron, Sydney A.; Clark, Andrew G.; Robinson, Gene E.

2011-01-01

Eusociality has arisen independently at least 11 times in insects. Despite this convergence, there are striking differences among eusocial lifestyles, ranging from species living in small colonies with overt conflict over reproduction to species in which colonies contain hundreds of thousands of highly specialized sterile workers produced by one or a few queens. Although the evolution of eusociality has been intensively studied, the genetic changes involved in the evolution of eusociality are relatively unknown. We examined patterns of molecular evolution across three independent origins of eusociality by sequencing transcriptomes of nine socially diverse bee species and combining these data with genome sequence from the honey bee Apis mellifera to generate orthologous sequence alignments for 3,647 genes. We found a shared set of 212 genes with a molecular signature of accelerated evolution across all eusocial lineages studied, as well as unique sets of 173 and 218 genes with a signature of accelerated evolution specific to either highly or primitively eusocial lineages, respectively. These results demonstrate that convergent evolution can involve a mosaic pattern of molecular changes in both shared and lineage-specific sets of genes. Genes involved in signal transduction, gland development, and carbohydrate metabolism are among the most prominent rapidly evolving genes in eusocial lineages. These findings provide a starting point for linking specific genetic changes to the evolution of eusociality. PMID:21482769

Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity.

PubMed

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates--childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation.

Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development.

PubMed

Stergiakouli, Evie; Davey Smith, George; Martin, Joanna; Skuse, David H; Viechtbauer, Wolfgang; Ring, Susan M; Ronald, Angelica; Evans, David E; Fisher, Simon E; Thapar, Anita; St Pourcain, Beate

2017-01-01

Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) symptoms and autism spectrum disorder (ASD) symptoms have been reported. Cross-trait genetic relationships are, however, subject to dynamic changes during development. We investigated the continuity of genetic overlap between ASD and ADHD symptoms in a general population sample during childhood and adolescence. We also studied uni- and cross-dimensional trait-disorder links with respect to genetic ADHD and ASD risk. Social-communication difficulties ( N  ≤ 5551, Social and Communication Disorders Checklist, SCDC) and combined hyperactive-impulsive/inattentive ADHD symptoms ( N  ≤ 5678, Strengths and Difficulties Questionnaire, SDQ-ADHD) were repeatedly measured in a UK birth cohort (ALSPAC, age 7 to 17 years). Genome-wide summary statistics on clinical ASD (5305 cases; 5305 pseudo-controls) and ADHD (4163 cases; 12,040 controls/pseudo-controls) were available from the Psychiatric Genomics Consortium. Genetic trait variances and genetic overlap between phenotypes were estimated using genome-wide data. In the general population, genetic influences for SCDC and SDQ-ADHD scores were shared throughout development. Genetic correlations across traits reached a similar strength and magnitude (cross-trait r g  ≤ 1, p min   =  3 × 10 -4 ) as those between repeated measures of the same trait (within-trait r g  ≤ 0.94, p min   =  7 × 10 -4 ). Shared genetic influences between traits, especially during later adolescence, may implicate variants in K-RAS signalling upregulated genes ( p -meta = 6.4 × 10 -4 ). Uni-dimensionally, each population-based trait mapped to the expected behavioural continuum: risk-increasing alleles for clinical ADHD were persistently associated with SDQ-ADHD scores throughout development (marginal regression R 2  = 0.084%). An age-specific genetic overlap between clinical ASD and social-communication difficulties during childhood was also shown, as per previous reports. Cross-dimensionally, however, neither SCDC nor SDQ-ADHD scores were linked to genetic risk for disorder. In the general population, genetic aetiologies between social-communication difficulties and ADHD symptoms are shared throughout child and adolescent development and may implicate similar biological pathways that co-vary during development. Within both the ASD and the ADHD dimension, population-based traits are also linked to clinical disorder, although much larger clinical discovery samples are required to reliably detect cross-dimensional trait-disorder relationships.

Genetic diversity in Oryza glumaepatula wild rice populations in Costa Rica and possible gene flow from O. sativa.

PubMed

Fuchs, Eric J; Meneses Martínez, Allan; Calvo, Amanda; Muñoz, Melania; Arrieta-Espinoza, Griselda

2016-01-01

Wild crop relatives are an important source of genetic diversity for crop improvement. Diversity estimates are generally lacking for many wild crop relatives. The objective of the present study was to analyze how genetic diversity is distributed within and among populations of the wild rice species Oryza glumaepatula in Costa Rica. We also evaluated the likelihood of gene flow between wild and commercial rice species because the latter is commonly sympatric with wild rice populations. Introgression may change wild species by incorporating alleles from domesticated species, increasing the risk of losing original variation. Specimens from all known O. glumaepatula populations in Costa Rica were analyzed with 444 AFLP markers to characterize genetic diversity and structure. We also compared genetic diversity estimates between O. glumaepatula specimens and O. sativa commercial rice. Our results showed that O. glumaepatula populations in Costa Rica have moderately high levels of genetic diversity, comparable to those found in South American populations. Despite the restricted distribution of this species in Costa Rica, populations are fairly large, reducing the effects of drift on genetic diversity. We found a dismissible but significant structure (θ = 0.02 ± 0.001) among populations. A Bayesian structure analysis suggested that some individuals share a significant proportion of their genomes with O. sativa. These results suggest that gene flow from cultivated O. sativa populations may have occurred in the recent past. These results expose an important biohazard: recurrent hybridization may reduce the genetic diversity of this wild rice species. Introgression may transfer commercial traits into O. glumaepatula, which in turn could alter genetic diversity and increase the likelihood of local extinction. These results have important implications for in situ conservation strategies of the only wild populations of O. glumaepatula in Costa Rica.

New insights into the genetic composition and phylogenetic relationship of wolves and dogs in the Iberian Peninsula.

PubMed

Pires, Ana Elisabete; Amorim, Isabel R; Borges, Carla; Simões, Fernanda; Teixeira, Tatiana; Quaresma, Andreia; Petrucci-Fonseca, Francisco; Matos, José

2017-06-01

This study investigates the gene pool of Portuguese autochthonous dog breeds and their wild counterpart, the Iberian wolf subspecies ( Canis lupus signatus ), using standard molecular markers. A combination of paternal and maternal molecular markers was used to investigate the genetic composition, genetic differentiation and genetic relationship of native Portuguese dogs and the Iberian wolf. A total of 196 unrelated dogs, including breed and village dogs from Portugal, and other dogs from Spain and North Africa, and 56 Iberian wolves (wild and captive) were analyzed for nuclear markers, namely Y chromosome SNPs, Y chromosome STR loci, autosomal STR loci, and a mitochondrial fragment of the control region I. Our data reveal new variants for the molecular markers and confirm significant genetic differentiation between Iberian wolf and native domestic dogs from Portugal. Based on our sampling, no signs of recent introgression between the two subspecies were detected. Y chromosome data do not reveal genetic differentiation among the analyzed dog breeds, suggesting they share the same patrilineal origin. Moreover, the genetic distinctiveness of the Iberian wolf from other wolf populations is further confirmed with the description of new mtDNA variants for this endemism. Our research also discloses new molecular markers for wolf and dog subspecies assignment, which might become particularly relevant in the case of forensic or noninvasive genetic studies. The Iberian wolf represents a relic of the once widespread wolf population in Europe and our study reveals that it is a reservoir of unique genetic diversity of the grey wolf, Canis lupus . These results stress the need for conservation plans that will guarantee the sustainability of this threatened top predator in Iberia.

Genetic diversity in Oryza glumaepatula wild rice populations in Costa Rica and possible gene flow from O. sativa

PubMed Central

Meneses Martínez, Allan; Calvo, Amanda; Muñoz, Melania

2016-01-01

Wild crop relatives are an important source of genetic diversity for crop improvement. Diversity estimates are generally lacking for many wild crop relatives. The objective of the present study was to analyze how genetic diversity is distributed within and among populations of the wild rice species Oryza glumaepatula in Costa Rica. We also evaluated the likelihood of gene flow between wild and commercial rice species because the latter is commonly sympatric with wild rice populations. Introgression may change wild species by incorporating alleles from domesticated species, increasing the risk of losing original variation. Specimens from all known O. glumaepatula populations in Costa Rica were analyzed with 444 AFLP markers to characterize genetic diversity and structure. We also compared genetic diversity estimates between O. glumaepatula specimens and O. sativa commercial rice. Our results showed that O. glumaepatula populations in Costa Rica have moderately high levels of genetic diversity, comparable to those found in South American populations. Despite the restricted distribution of this species in Costa Rica, populations are fairly large, reducing the effects of drift on genetic diversity. We found a dismissible but significant structure (θ = 0.02 ± 0.001) among populations. A Bayesian structure analysis suggested that some individuals share a significant proportion of their genomes with O. sativa. These results suggest that gene flow from cultivated O. sativa populations may have occurred in the recent past. These results expose an important biohazard: recurrent hybridization may reduce the genetic diversity of this wild rice species. Introgression may transfer commercial traits into O. glumaepatula, which in turn could alter genetic diversity and increase the likelihood of local extinction. These results have important implications for in situ conservation strategies of the only wild populations of O. glumaepatula in Costa Rica. PMID:27077002

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

PubMed

Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

2016-12-01

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Genetic considerations in human sex-mate selection: partners share human leukocyte antigen but not short-tandem-repeat identity markers.

PubMed

Israeli, Moshe; Kristt, Don; Nardi, Yuval; Klein, Tirza

2014-05-01

Previous studies support a role for MHC on mating preference, yet it remains unsettled as to whether mating occurs preferentially between individuals sharing human leukocyte antigen (HLA) determinants or not. Investigating sex-mate preferences in the contemporary Israeli population is of further curiosity being a population with distinct genetic characteristics, where multifaceted cultural considerations influence mate selection. Pairs of male-female sex partners were evaluated in three groups. Two groups represented unmarried (n = 1002) or married (n = 308) couples and a control group of fictitious male-female couples. HLA and short-tandem-repeat (STR) genetic identification markers were assessed for the frequency of shared antigens and alleles. Human leukocyte antigen results showed that Class I and/ or Class II single antigen as well as double antigen sharing was more common in sex partners than in control group couples (P < 0.001). Married versus unmarried pairs were not distinguishable. In contrast, STR-DNA markers failed to differentiate between sex-mates and controls (P = 0.78). Sex partnerships shared HLA determinants more frequently than randomly constituted male-female pairs. The observed phenomenon does not reflect a syngenetic background between sex-mates as STR markers were not selectively shared. Thus, sex-mate selection in man may contravene the evolutionary pressure for genetic diversity in regard to HLA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genomic and genetic analyses of diversity and plant interactions of Pseudomonas fluorescens

PubMed Central

Silby, Mark W; Cerdeño-Tárraga, Ana M; Vernikos, Georgios S; Giddens, Stephen R; Jackson, Robert W; Preston, Gail M; Zhang, Xue-Xian; Moon, Christina D; Gehrig, Stefanie M; Godfrey, Scott AC; Knight, Christopher G; Malone, Jacob G; Robinson, Zena; Spiers, Andrew J; Harris, Simon; Challis, Gregory L; Yaxley, Alice M; Harris, David; Seeger, Kathy; Murphy, Lee; Rutter, Simon; Squares, Rob; Quail, Michael A; Saunders, Elizabeth; Mavromatis, Konstantinos; Brettin, Thomas S; Bentley, Stephen D; Hothersall, Joanne; Stephens, Elton; Thomas, Christopher M; Parkhill, Julian; Levy, Stuart B; Rainey, Paul B; Thomson, Nicholas R

2009-01-01

Background Pseudomonas fluorescens are common soil bacteria that can improve plant health through nutrient cycling, pathogen antagonism and induction of plant defenses. The genome sequences of strains SBW25 and Pf0-1 were determined and compared to each other and with P. fluorescens Pf-5. A functional genomic in vivo expression technology (IVET) screen provided insight into genes used by P. fluorescens in its natural environment and an improved understanding of the ecological significance of diversity within this species. Results Comparisons of three P. fluorescens genomes (SBW25, Pf0-1, Pf-5) revealed considerable divergence: 61% of genes are shared, the majority located near the replication origin. Phylogenetic and average amino acid identity analyses showed a low overall relationship. A functional screen of SBW25 defined 125 plant-induced genes including a range of functions specific to the plant environment. Orthologues of 83 of these exist in Pf0-1 and Pf-5, with 73 shared by both strains. The P. fluorescens genomes carry numerous complex repetitive DNA sequences, some resembling Miniature Inverted-repeat Transposable Elements (MITEs). In SBW25, repeat density and distribution revealed 'repeat deserts' lacking repeats, covering approximately 40% of the genome. Conclusions P. fluorescens genomes are highly diverse. Strain-specific regions around the replication terminus suggest genome compartmentalization. The genomic heterogeneity among the three strains is reminiscent of a species complex rather than a single species. That 42% of plant-inducible genes were not shared by all strains reinforces this conclusion and shows that ecological success requires specialized and core functions. The diversity also indicates the significant size of genetic information within the Pseudomonas pan genome. PMID:19432983

Cognitive performance and BMI in childhood: Shared genetic influences between reaction time but not response inhibition

USDA-ARS?s Scientific Manuscript database

The aim of this work is to understand whether shared genetic influences can explain the associationbetween obesity and cognitive performance, including slower and more variable reaction times(RTs) and worse response inhibition. RT on a four-choice RT task and the go/no-go task, and commission errors...

Preschool Drawing and School Mathematics: The Nature of the Association

PubMed Central

Malanchini, M.; Tosto, M.G.; Garfield, V.; Czerwik, A.; Dirik, A.; Arden, R.; Malykh, S.

2016-01-01

The study examined the aetiology of individual differences in early drawing and of its longitudinal association with school mathematics. Participants (N = 14,760), members of the Twins Early Development Study, were assessed on their ability to draw a human figure, including number of features, symmetry and proportionality. Human figure drawing was moderately stable across six months (average r = .40). Individual differences in drawing at age 4½ were influenced by genetic (.21), shared environmental (.30) and non-shared environmental (.49) factors. Drawing was related to later (age 12) mathematical ability (average r = .24). This association was explained by genetic and shared environmental factors that also influenced general intelligence. Some genetic factors, unrelated to intelligence, also contributed to individual differences in drawing. PMID:27079561

Different Duck Species Infected Intramuscularly with Duck-Origin Genotype IX APMV-1 Show Discrepant Mortality and Indicate Another Fatal Genotype APMV-1 to Ducks.

PubMed

Fu, Guanghua; Cheng, Longfei; Fu, Qiuling; Qi, Baomin; Chen, Cuiteng; Shi, Shaohua; Chen, Hongmei; Wan, Chunhe; Liu, Rongchang; Huang, Yu

2017-03-01

Isolations of genotype IX (gIX) avian paramyxovirus type 1 (APMV-1) from various bird species have been more common recently, with isolates showing variable pathogenicity in different species of poultry. Here we sequenced the genome of a Muscovy duck origin gIX virus strain XBT14 and characterized the virulence and pathogenicity of this isolate in chickens and ducks. The genome sequence of strain XBT14 is 15,192 nt in length, containing multiple basic amino acids at the fusion protein cleavage site. The XBT14 strain shared 91.6%-91.9% nucleotide identities with early-genotype viruses (such as genotype III and IV) and shared 85.3%-85.9% nucleotide homologies with later genotype viruses (such as genotype VII). Pathogenicity tests showed that strain XBT14 could cause death in different duck breeds with a mortality rate of 44.4% in Muscovy duck, 25.9% in Sheldrake, and 11.1% in Cherry Valley duck, respectively. Similar mortality discrepancies were also observed in different ducks when infected with chicken-origin gIX virus strain F48E8. These results indicate that XBT14-like velogenic gIX APMV-1 (such as XBT14, F48E8, and GD09-2) could cause fatal infection in duck, and genotype IX is another genotype velogenic to duck as well as genotype VII. Accompanied by genetic differences in the vaccine strains or dominant strains prevailing in poultry, the virulent XBT14-like gIX viruses might become potentially endemic strains in poultry in the future.

A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood

PubMed Central

Reichborn-Kjennerud, T.; Czajkowski, N.; Ystrøm, E.; Ørstavik, R.; Aggen, S. H.; Tambs, K.; Torgersen, S.; Neale, M. C.; Røysamb, E.; Krueger, R. F.; Knudsen, G. P.; Kendler, K. S.

2015-01-01

Background Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. Method DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. Results The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. Conclusion ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD. PMID:26050739

A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood.

PubMed

Reichborn-Kjennerud, T; Czajkowski, N; Ystrøm, E; Ørstavik, R; Aggen, S H; Tambs, K; Torgersen, S; Neale, M C; Røysamb, E; Krueger, R F; Knudsen, G P; Kendler, K S

2015-10-01

Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.

Genetic counseling

MedlinePlus

... this page: //medlineplus.gov/ency/patientinstructions/000510.htm Genetic counseling To use the sharing features on this ... cystic fibrosis or Down syndrome. Who May Want Genetic Counseling? It is up to you whether or ...

Genetic Counseling

MedlinePlus

... Testing Evaluating Genomic Tests Epidemiology Pathogen Genomics Resources Genetic Counseling Recommend on Facebook Tweet Share Compartir In ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

Dengue — Quo tu et quo vadis?

PubMed Central

Chen, Rubing; Vasilakis, Nikos

2011-01-01

Dengue viruses (DENV) are by far the most important arboviral pathogens in the tropics around the world, putting at risk of infection nearly a third of the global human population. DENV are members of the genus Flavivirus in the Family Flaviviridae and comprise four antigenically distinct serotypes (DENV-1-4). Although they share almost identical epidemiological features, they are genetically distinct. Phylogenetic analyses have revealed valuable insights into the origins, epidemiology and the forces that shape DENV evolution in nature. In this review, we examine the current status of DENV evolution, including but not limited to rates of evolution, selection pressures, population sizes and evolutionary constraints, and we discuss how these factors influence transmission, pathogenesis and emergence. PMID:21994796

The origins of religious disbelief.

PubMed

Norenzayan, Ara; Gervais, Will M

2013-01-01

Although most people are religious, there are hundreds of millions of religious disbelievers in the world. What is religious disbelief and how does it arise? Recent developments in the scientific study of religious beliefs and behaviors point to the conclusion that religious disbelief arises from multiple interacting pathways, traceable to cognitive, motivational, and cultural learning mechanisms. We identify four such pathways, leading to four distinct forms of atheism, which we term mindblind atheism, apatheism, inCREDulous atheism, and analytic atheism. Religious belief and disbelief share the same underlying pathways and can be explained within a single evolutionary framework that is grounded in both genetic and cultural evolution. Copyright © 2012 Elsevier Ltd. All rights reserved.

Exploring links among imitation, mental development, and temperament

PubMed Central

Fenstermacher, Susan K.; Saudino, Kimberly J.

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children’s imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique. PMID:27840593

Exploring links among imitation, mental development, and temperament.

PubMed

Fenstermacher, Susan K; Saudino, Kimberly J

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children's imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique.

The Story of a Hitchhiker: Population Genetic Patterns in the Invasive Barnacle Balanus(Amphibalanus) improvisus Darwin 1854

PubMed Central

Wrange, Anna-Lisa; Charrier, Gregory; Thonig, Anne; Alm Rosenblad, Magnus; Blomberg, Anders; Havenhand, Jonathan N.; Jonsson, Per R.; André, Carl

2016-01-01

Understanding the ecological and evolutionary forces that determine the genetic structure and spread of invasive species is a key component of invasion biology. The bay barnacle, Balanus improvisus (= Amphibalanus improvisus), is one of the most successful aquatic invaders worldwide, and is characterised by broad environmental tolerance. Although the species can spread through natural larval dispersal, human-mediated transport through (primarily) shipping has almost certainly contributed to the current global distribution of this species. Despite its worldwide distribution, little is known about the phylogeography of this species. Here, we characterize the population genetic structure and model dispersal dynamics of the barnacle B. improvisus, and describe how human-mediated spreading via shipping as well as natural larval dispersal may have contributed to observed genetic variation. We used both mitochondrial DNA (cytochrome c oxidase subunit I: COI) and nuclear microsatellites to characterize the genetic structure in 14 populations of B. improvisus on a global and regional scale (Baltic Sea). Genetic diversity was high in most populations, and many haplotypes were shared among populations on a global scale, indicating that long-distance dispersal (presumably through shipping and other anthropogenic activities) has played an important role in shaping the population genetic structure of this cosmopolitan species. We could not clearly confirm prior claims that B. improvisus originates from the western margins of the Atlantic coasts; although there were indications that Argentina could be part of a native region. In addition to dispersal via shipping, we show that natural larval dispersal may play an important role for further colonisation following initial introduction. PMID:26821161

Demographic history and genetic adaptation in the Himalayan region inferred from genome-wide SNP genotypes of 49 populations.

PubMed

Arciero, Elena; Kraaijenbrink, Thirsa; Asan; Haber, Marc; Mezzavilla, Massimo; Ayub, Qasim; Wang, Wei; Pingcuo, Zhaxi; Yang, Huanming; Wang, Jian; Jobling, Mark A; van Driem, George; Xue, Yali; de Knijff, Peter; Tyler-Smith, Chris

2018-05-22

We genotyped 738 individuals belonging to 49 populations from Nepal, Bhutan, North India or Tibet at over 500,000 SNPs, and analysed the genotypes in the context of available worldwide population data in order to investigate the demographic history of the region and the genetic adaptations to the harsh environment. The Himalayan populations resembled other South and East Asians, but in addition displayed their own specific ancestral component and showed strong population structure and genetic drift. We also found evidence for multiple admixture events involving Himalayan populations and South/East Asians between 200 and 2,000 years ago. In comparisons with available ancient genomes, the Himalayans, like other East and South Asian populations, showed similar genetic affinity to Eurasian hunter-gatherers (a 24,000-year-old Upper Palaeolithic Siberian), and the related Bronze Age Yamnaya. The high-altitude Himalayan populations all shared a specific ancestral component, suggesting that genetic adaptation to life at high altitude originated only once in this region and subsequently spread. Combining four approaches to identifying specific positively-selected loci, we confirmed that the strongest signals of high-altitude adaptation were located near the Endothelial PAS domain-containing protein 1 (EPAS1) and Egl-9 Family Hypoxia Inducible Factor 1 (EGLN1) loci, and discovered eight additional robust signals of high-altitude adaptation, five of which have strong biological functional links to such adaptation. In conclusion, the demographic history of Himalayan populations is complex, with strong local differentiation, reflecting both genetic and cultural factors; these populations also display evidence of multiple genetic adaptations to high-altitude environments.

Developmental Origins of Low Mathematics Performance and Normal Variation in Twins from 7 to 9 Years

PubMed Central

Haworth, Claire M. A.; Kovas, Yulia; Petrill, Stephen A.; Plomin, Robert

2009-01-01

A previous publication reported the etiology of mathematics performance in 7-year-old twins (Oliver et al., 2004). As part of the same longitudinal study we investigated low mathematics performance and normal variation in a representative United Kingdom sample of 1713 same-sex 9-year-old twins based on teacher-assessed National Curriculum standards. Univariate individual differences and DeFries-Fulker extremes analyses were performed. Similar to our results at 7 years, all mathematics scores at 9 years showed high heritability (.62–.75) and low shared environmental estimates (.00–.11) for both the low performance group and the full sample. Longitudinal analyses were performed from 7 to 9 years. These longitudinal analyses indicated strong genetic continuity from 7 to 9 years for both low performance and mathematics in the normal range. We conclude that, despite the considerable differences in mathematics curricula from 7 to 9 years, the same genetic effects largely operate at the two ages. PMID:17539370

The evolutionary origins of beneficial alleles during the repeated adaptation of garter snakes to deadly prey.

PubMed

Feldman, Chris R; Brodie, Edmund D; Brodie, Edmund D; Pfrender, Michael E

2009-08-11

Where do the genetic variants underlying adaptive change come from? Are currently adaptive alleles recruited by selection from standing genetic variation within populations, moved through introgression from other populations, or do they arise as novel mutations? Here, we examine the molecular basis of repeated adaptation to the toxin of deadly prey in 3 species of garter snakes (Thamnophis) to determine whether adaptation has evolved through novel mutations, sieving of existing variation, or transmission of beneficial alleles across species. Functional amino acid substitutions in the skeletal muscle sodium channel (Na(v)1.4) are largely responsible for the physiological resistance of garter snakes to tetrodotoxin found in their newt (Taricha) prey. Phylogenetic analyses reject the hypotheses that the unique resistance alleles observed in multiple Thamnophis species were present before the split of these lineages, or that alleles were shared among species through occasional hybridization events. Our results demonstrate that adaptive evolution has occurred independently multiple times in garter snakes via the de novo acquisition of beneficial mutations.

Morphological and population genomic evidence that human faces have evolved to signal individual identity.

PubMed

Sheehan, Michael J; Nachman, Michael W

2014-09-16

Facial recognition plays a key role in human interactions, and there has been great interest in understanding the evolution of human abilities for individual recognition and tracking social relationships. Individual recognition requires sufficient cognitive abilities and phenotypic diversity within a population for discrimination to be possible. Despite the importance of facial recognition in humans, the evolution of facial identity has received little attention. Here we demonstrate that faces evolved to signal individual identity under negative frequency-dependent selection. Faces show elevated phenotypic variation and lower between-trait correlations compared with other traits. Regions surrounding face-associated single nucleotide polymorphisms show elevated diversity consistent with frequency-dependent selection. Genetic variation maintained by identity signalling tends to be shared across populations and, for some loci, predates the origin of Homo sapiens. Studies of human social evolution tend to emphasize cognitive adaptations, but we show that social evolution has shaped patterns of human phenotypic and genetic diversity as well.

Y chromosome STR typing in crime casework.

PubMed

Roewer, Lutz

2009-01-01

Since the beginning of the nineties the field of forensic Y chromosome analysis has been successfully developed to become commonplace in laboratories working in crime casework all over the world. The ability to identify male-specific DNA renders highly variable Y-chromosomal polymorphisms, the STR sequences, an invaluable addition to the standard panel of autosomal loci used in forensic genetics. The male-specificity makes the Y chromosome especially useful in cases of male/female cell admixture, namely in sexual assault cases. On the other hand, the haploidy and patrilineal inheritance complicates the interpretation of a Y-STR match, because male relatives share for several generations an identical Y-STR profile. Since paternal relatives tend to live in the geographic and cultural territory of their ancestors, the Y chromosome analysis has a potential to make inferences on the population of origin of a given DNA profile. This review addresses the fields of application of Y chromosome haplotyping, the interpretation of results, databasing efforts and population genetics aspects.

Developmental origins of low mathematics performance and normal variation in twins from 7 to 9 years.

PubMed

Haworth, Claire M A; Kovas, Yulia; Petrill, Stephen A; Plomin, Robert

2007-02-01

A previous publication reported the etiology of mathematics performance in 7-year-old twins (Oliver et al., 2004). As part of the same longitudinal study we investigated low mathematics performance and normal variation in a representative United Kingdom sample of 1713 same-sex 9-year-old twins based on teacher-assessed National Curriculum standards. Univariate individual differences and DeFries-Fulker extremes analyses were performed. Similar to our results at 7 years, all mathematics scores at 9 years showed high heritability (.62-.75) and low shared environmental estimates (.00-.11) for both the low performance group and the full sample. Longitudinal analyses were performed from 7 to 9 years. These longitudinal analyses indicated strong genetic continuity from 7 to 9 years for both low performance and mathematics in the normal range. We conclude that, despite the considerable differences in mathematics curricula from 7 to 9 years, the same genetic effects largely operate at the two ages.

Design and development of genetically encoded fluorescent sensors to monitor intracellular chemical and physical parameters.

PubMed

Germond, Arno; Fujita, Hideaki; Ichimura, Taro; Watanabe, Tomonobu M

Over the past decades many researchers have made major contributions towards the development of genetically encoded (GE) fluorescent sensors derived from fluorescent proteins. GE sensors are now used to study biological phenomena by facilitating the measurement of biochemical behaviors at various scales, ranging from single molecules to single cells or even whole animals. Here, we review the historical development of GE fluorescent sensors and report on their current status. We specifically focus on the development strategies of the GE sensors used for measuring pH, ion concentrations (e.g., chloride and calcium), redox indicators, membrane potential, temperature, pressure, and molecular crowding. We demonstrate that these fluroescent protein-based sensors have a shared history of concepts and development strategies, and we highlight the most original concepts used to date. We believe that the understanding and application of these various concepts will pave the road for the development of future GE sensors and lead to new breakthroughs in bioimaging.

Design and development of genetically encoded fluorescent sensors to monitor intracellular chemical and physical parameters.

PubMed

Germond, Arno; Fujita, Hideaki; Ichimura, Taro; Watanabe, Tomonobu M

2016-06-01

Over the past decades many researchers have made major contributions towards the development of genetically encoded (GE) fluorescent sensors derived from fluorescent proteins. GE sensors are now used to study biological phenomena by facilitating the measurement of biochemical behaviors at various scales, ranging from single molecules to single cells or even whole animals. Here, we review the historical development of GE fluorescent sensors and report on their current status. We specifically focus on the development strategies of the GE sensors used for measuring pH, ion concentrations (e.g., chloride and calcium), redox indicators, membrane potential, temperature, pressure, and molecular crowding. We demonstrate that these fluroescent protein-based sensors have a shared history of concepts and development strategies, and we highlight the most original concepts used to date. We believe that the understanding and application of these various concepts will pave the road for the development of future GE sensors and lead to new breakthroughs in bioimaging.

Genetic Advances in Autism: Heterogeneity and Convergence on Shared Pathways

PubMed Central

Bill, Brent R.; Geschwind, Daniel H.

2009-01-01

The autism spectrum disorders (ASD) are a heterogeneous set of developmental disorders characterized at their core by deficits in social interaction and communication. Current psychiatric nosology groups this broad set of disorders with strong genetic liability and multiple etiologies into the same diagnostic category. This heterogeneity has challenged genetic analyses. But shared patient resources, genomic technologies, more refined phenotypes, and novel computational approaches have begun to yield dividends in defining the genetic mechanisms at work. Over the last five years, a large number of autism susceptibility loci have emerged, redefining our notion of autism’s etiologies, and reframing how we think about ASD. PMID:19477629

Oppositional Defiant Disorder dimensions: genetic influences and risk for later psychopathology

PubMed Central

Mikolajewski, Amy J.; Taylor, Jeanette; Iacono, William G.

2016-01-01

Background This study was undertaken to determine how well two Oppositional Defiant Disorder (ODD) dimensions (irritable and headstrong/hurtful) assessed in childhood predict late adolescent psychopathology and the degree to which these outcomes can be attributed to genetic influences shared with ODD dimensions. Methods Psychopathology was assessed via diagnostic interviews of 1225 twin pairs at ages 11 and 17. Results Consistent with hypotheses, the irritable dimension uniquely predicted overall internalizing problems, whereas the headstrong/hurtful dimension uniquely predicted substance use disorder symptoms. Both dimensions were predictive of antisocial behavior, and overall externalizing problems. The expected relationships between the irritable dimension and specific internalizing disorders were not found. Twin modeling showed the irritable and headstrong/hurtful dimensions were related to late adolescent psychopathology symptoms through common genetic influences. Conclusions Symptoms of ODD in childhood pose a significant risk for various mental health outcomes in late adolescence. Further, common genetic influences underlie the covariance between irritable symptoms in childhood and overall internalizing problems in late adolescence, whereas headstrong/hurtful symptoms share genetic influences with substance use disorder symptoms. Antisocial behavior and overall externalizing share common genetic influences with both the irritable and headstrong/hurtful dimensions. PMID:28059443

Suicidal ideation, depression, and conduct disorder in a sample of adolescent and young adult twins

PubMed Central

Linker, Julie; Gillespie, Nathan A; Maes, Hermine; Eaves, Lindon; Silberg, Judy L.

2012-01-01

Background The co-occurrence of suicidal ideation, depression, and conduct disturbance is likely explained in part by correlated genetic and environmental risk factors. Little is known about the specific nature of these associations. Method Structured interviews on 2814 twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and young adult follow-up (YAFU) yielded data on symptoms of depression, conduct disorder and adolescent and young adult suicidal ideation. Results Univariate analyses revealed that the familial aggregation for each trait was explained by a combination of additive genetic and shared environmental effects. Suicidal ideation in adolescence was explained in part by genetic influences, but predominantly accounted for by environmental factors. A mixture of genetic and shared environmental influences explained ideation occurring in young adulthood. Multivariate analyses revealed that there are genetic and shared environmental effects common to suicidal ideation, depression, and conduct disorder. The association between adolescent suicidal ideation and CD was attributable to the same genetic and environmental risk factors for depression. Conclusions These findings underscore that prevention and intervention strategies should reflect the different underlying mechanisms involving depression and conduct disorder to assist in identifying adolescents at suicidal risk. PMID:22646517

Suicidal ideation, depression, and conduct disorder in a sample of adolescent and young adult twins.

PubMed

Linker, Julie; Gillespie, Nathan A; Maes, Hermine; Eaves, Lindon; Silberg, Judy L

2012-08-01

The co-occurrence of suicidal ideation, depression, and conduct disturbance is likely explained in part by correlated genetic and environmental risk factors. Little is known about the specific nature of these associations. Structured interviews on 2,814 twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU) yielded data on symptoms of depression, conduct disorder, and adolescent and young adult suicidal ideation. Univariate analyses revealed that the familial aggregation for each trait was explained by a combination of additive genetic and shared environmental effects. Suicidal ideation in adolescence was explained in part by genetic influences, but predominantly accounted for by environmental factors. A mixture of genetic and shared environmental influences explained ideation occurring in young adulthood. Multivariate analyses revealed that there are genetic and shared environmental effects common to suicidal ideation, depression, and conduct disorder. The association between adolescent suicidal ideation and CD was attributable to the same genetic and environmental risk factors for depression. These findings underscore that prevention and intervention strategies should reflect the different underlying mechanisms involving depression and conduct disorder to assist in identifying adolescents at suicidal risk. © 2012 The American Association of Suicidology.

Oppositional defiant disorder dimensions: genetic influences and risk for later psychopathology.

PubMed

Mikolajewski, Amy J; Taylor, Jeanette; Iacono, William G

2017-06-01

This study was undertaken to determine how well two oppositional defiant disorder (ODD) dimensions (irritable and headstrong/hurtful) assessed in childhood predict late adolescent psychopathology and the degree to which these outcomes can be attributed to genetic influences shared with ODD dimensions. Psychopathology was assessed via diagnostic interviews of 1,225 twin pairs at ages 11 and 17. Consistent with hypotheses, the irritable dimension uniquely predicted overall internalizing problems, whereas the headstrong/hurtful dimension uniquely predicted substance use disorder symptoms. Both dimensions were predictive of antisocial behavior and overall externalizing problems. The expected relationships between the irritable dimension and specific internalizing disorders were not found. Twin modeling showed that the irritable and headstrong/hurtful dimensions were related to late adolescent psychopathology symptoms through common genetic influences. Symptoms of ODD in childhood pose a significant risk for various mental health outcomes in late adolescence. Further, common genetic influences underlie the covariance between irritable symptoms in childhood and overall internalizing problems in late adolescence, whereas headstrong/hurtful symptoms share genetic influences with substance use disorder symptoms. Antisocial behavior and overall externalizing share common genetic influences with both the irritable and headstrong/hurtful dimensions. © 2017 Association for Child and Adolescent Mental Health.

Genetic Variability of 27 Traits in a Core Collection of Flax (Linum usitatissimum L.)

PubMed Central

You, Frank M.; Jia, Gaofeng; Xiao, Jin; Duguid, Scott D.; Rashid, Khalid Y.; Booker, Helen M.; Cloutier, Sylvie

2017-01-01

Assessment of genetic variability of plant core germplasm is needed for efficient germplasm utilization in breeding improvement. A total of 391 accessions of a flax core collection, which preserves the variation present in the world collection of 3,378 accessions maintained by Plant Gene Resources of Canada (PGRC) and represents a broad range of geographical origins, different improvement statuses and two morphotypes, was evaluated in field trials in up to 8 year-location environments for 10 agronomic, eight seed quality, six fiber and three disease resistance traits. The large phenotypic variation in this subset was explained by morphotypes (22%), geographical origins (11%), and other variance components (67%). Both divergence and similarity between two basic morphotypes, namely oil or linseed and fiber types, were observed, whereby linseed accessions had greater thousand seed weight, seeds m−2, oil content, branching capability and resistance to powdery mildew while fiber accessions had greater straw weight, plant height, protein content and resistance to pasmo and fusarium wilt diseases, but they had similar performance in many traits and some of them shared common characteristics of fiber and linseed types. Weak geographical patterns within either fiber or linseed accessions were confirmed, but specific trait performance was identified in East Asia for fiber type, and South Asia and North America for linseed type. Relatively high broad-sense heritability was obtained for seed quality traits, followed by agronomic traits and resistance to powdery mildew and fusarium wilt. Diverse phenotypic and genetic variability in the flax core collection constitutes a useful resource for breeding. PMID:28993783

Genetic Variability of 27 Traits in a Core Collection of Flax (Linum usitatissimum L.).

PubMed

You, Frank M; Jia, Gaofeng; Xiao, Jin; Duguid, Scott D; Rashid, Khalid Y; Booker, Helen M; Cloutier, Sylvie

2017-01-01

Assessment of genetic variability of plant core germplasm is needed for efficient germplasm utilization in breeding improvement. A total of 391 accessions of a flax core collection, which preserves the variation present in the world collection of 3,378 accessions maintained by Plant Gene Resources of Canada (PGRC) and represents a broad range of geographical origins, different improvement statuses and two morphotypes, was evaluated in field trials in up to 8 year-location environments for 10 agronomic, eight seed quality, six fiber and three disease resistance traits. The large phenotypic variation in this subset was explained by morphotypes (22%), geographical origins (11%), and other variance components (67%). Both divergence and similarity between two basic morphotypes, namely oil or linseed and fiber types, were observed, whereby linseed accessions had greater thousand seed weight, seeds m -2 , oil content, branching capability and resistance to powdery mildew while fiber accessions had greater straw weight, plant height, protein content and resistance to pasmo and fusarium wilt diseases, but they had similar performance in many traits and some of them shared common characteristics of fiber and linseed types. Weak geographical patterns within either fiber or linseed accessions were confirmed, but specific trait performance was identified in East Asia for fiber type, and South Asia and North America for linseed type. Relatively high broad-sense heritability was obtained for seed quality traits, followed by agronomic traits and resistance to powdery mildew and fusarium wilt. Diverse phenotypic and genetic variability in the flax core collection constitutes a useful resource for breeding.

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents.

PubMed

Maes, Hermine H; Prom-Wormley, Elizabeth; Eaves, Lindon J; Rhee, Soo Hyun; Hewitt, John K; Young, Susan; Corley, Robin; McGue, Matt; Iacono, William G; Legrand, Lisa; Samek, Diana R; Murrelle, E Lenn; Silberg, Judy L; Miles, Donna R; Schieken, Richard M; Beunen, Gaston P; Thomis, Martine; Rose, Richard J; Dick, Danielle M; Boomsma, Dorret I; Bartels, Meike; Vink, Jacqueline M; Lichtenstein, Paul; White, Victoria; Kaprio, Jaakko; Neale, Michael C

2017-04-01

Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation (SI) across adolescence. Mega-analysis of pooled genetically informative data on SI was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N = 19 313 pairs) between ages 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the United States, Europe, and Australia. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of SI across developed countries. The estimate of additive genetic contributions to liability of SI increased from approximately 15% to 45% from ages 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to SI at age 13 (70%) and gradually less by age 19 (40%). Both additive genetic and shared environmental factors significantly contribute to variance in SI throughout adolescence. The present study, the largest genetic epidemiological study on SI to date, found consistent results across 11 studies for the etiology of SI. Environmental factors, especially those shared by siblings in a family, primarily influence SI variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. This is the first study to find evidence of genetic factors in liability to SI at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic and environmental overlap between borderline personality disorder traits and psychopathy: evidence for promotive effects of factor 2 and protective effects of factor 1.

PubMed

Hunt, E; Bornovalova, M A; Patrick, C J

2015-05-01

Previous studies have reported strong genetic and environmental overlap between antisocial-externalizing (factor 2; F2) features of psychopathy and borderline personality disorder (BPD) tendencies. However, this line of research has yet to examine etiological associations of affective-interpersonal (factor 1, F1) features of psychopathy with BPD tendencies. The current study investigated differential phenotypic and genetic overlap of psychopathy factors 1 and 2 with BPD tendencies in a sample of over 250 male and female community-recruited adult twin pairs. Consistent with previous research, biometric analyses revealed strong genetic and non-shared environmental correlations of F2 with BPD tendencies, suggesting that common genetic and non-shared environmental factors contribute to both phenotypes. In contrast, negative genetic and non-shared environmental correlations were observed between F1 and BPD tendencies, indicating that the genetic factors underlying F1 serve as protective factors against BPD. No gender differences emerged in the analyses. These findings provide further insight into associations of psychopathic features - F1 as well as F2 - and BPD tendencies. Implications for treatment and intervention are discussed, along with how psychopathic traits may differentially influence the manifestation of BPD tendencies.

Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies.

PubMed

Yutin, Natalya; Raoult, Didier; Koonin, Eugene V

2013-05-23

Recent advances of genomics and metagenomics reveal remarkable diversity of viruses and other selfish genetic elements. In particular, giant viruses have been shown to possess their own mobilomes that include virophages, small viruses that parasitize on giant viruses of the Mimiviridae family, and transpovirons, distinct linear plasmids. One of the virophages known as the Mavirus, a parasite of the giant Cafeteria roenbergensis virus, shares several genes with large eukaryotic self-replicating transposon of the Polinton (Maverick) family, and it has been proposed that the polintons evolved from a Mavirus-like ancestor. We performed a comprehensive phylogenomic analysis of the available genomes of virophages and traced the evolutionary connections between the virophages and other selfish genetic elements. The comparison of the gene composition and genome organization of the virophages reveals 6 conserved, core genes that are organized in partially conserved arrays. Phylogenetic analysis of those core virophage genes, for which a sufficient diversity of homologs outside the virophages was detected, including the maturation protease and the packaging ATPase, supports the monophyly of the virophages. The results of this analysis appear incompatible with the origin of polintons from a Mavirus-like agent but rather suggest that Mavirus evolved through recombination between a polinton and an unknown virus. Altogether, virophages, polintons, a distinct Tetrahymena transposable element Tlr1, transpovirons, adenoviruses, and some bacteriophages form a network of evolutionary relationships that is held together by overlapping sets of shared genes and appears to represent a distinct module in the vast total network of viruses and mobile elements. The results of the phylogenomic analysis of the virophages and related genetic elements are compatible with the concept of network-like evolution of the virus world and emphasize multiple evolutionary connections between bona fide viruses and other classes of capsid-less mobile elements.

Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies

PubMed Central

2013-01-01

Background Recent advances of genomics and metagenomics reveal remarkable diversity of viruses and other selfish genetic elements. In particular, giant viruses have been shown to possess their own mobilomes that include virophages, small viruses that parasitize on giant viruses of the Mimiviridae family, and transpovirons, distinct linear plasmids. One of the virophages known as the Mavirus, a parasite of the giant Cafeteria roenbergensis virus, shares several genes with large eukaryotic self-replicating transposon of the Polinton (Maverick) family, and it has been proposed that the polintons evolved from a Mavirus-like ancestor. Results We performed a comprehensive phylogenomic analysis of the available genomes of virophages and traced the evolutionary connections between the virophages and other selfish genetic elements. The comparison of the gene composition and genome organization of the virophages reveals 6 conserved, core genes that are organized in partially conserved arrays. Phylogenetic analysis of those core virophage genes, for which a sufficient diversity of homologs outside the virophages was detected, including the maturation protease and the packaging ATPase, supports the monophyly of the virophages. The results of this analysis appear incompatible with the origin of polintons from a Mavirus-like agent but rather suggest that Mavirus evolved through recombination between a polinton and an unknownvirus. Altogether, virophages, polintons, a distinct Tetrahymena transposable element Tlr1, transpovirons, adenoviruses, and some bacteriophages form a network of evolutionary relationships that is held together by overlapping sets of shared genes and appears to represent a distinct module in the vast total network of viruses and mobile elements. Conclusions The results of the phylogenomic analysis of the virophages and related genetic elements are compatible with the concept of network-like evolution of the virus world and emphasize multiple evolutionary connections between bona fide viruses and other classes of capsid-less mobile elements. PMID:23701946

Genetics of phenotypic plasticity and biomass traits in hybrid willows across contrasting environments and years.

PubMed

Berlin, Sofia; Hallingbäck, Henrik R; Beyer, Friderike; Nordh, Nils-Erik; Weih, Martin; Rönnberg-Wästljung, Ann-Christin

2017-07-01

Phenotypic plasticity can affect the geographical distribution of taxa and greatly impact the productivity of crops across contrasting and variable environments. The main objectives of this study were to identify genotype-phenotype associations in key biomass and phenology traits and the strength of phenotypic plasticity of these traits in a short-rotation coppice willow population across multiple years and contrasting environments to facilitate marker-assisted selection for these traits. A hybrid Salix viminalis  × ( S. viminalis × Salix schwerinii ) population with 463 individuals was clonally propagated and planted in three common garden experiments comprising one climatic contrast between Sweden and Italy and one water availability contrast in Italy. Several key phenotypic traits were measured and phenotypic plasticity was estimated as the trait value difference between experiments. Quantitative trait locus (QTL) mapping analyses were conducted using a dense linkage map and phenotypic effects of S. schwerinii haplotypes derived from detected QTL were assessed. Across the climatic contrast, clone predictor correlations for biomass traits were low and few common biomass QTL were detected. This indicates that the genetic regulation of biomass traits was sensitive to environmental variation. Biomass QTL were, however, frequently shared across years and across the water availability contrast. Phenology QTL were generally shared between all experiments. Substantial phenotypic plasticity was found among the hybrid offspring, that to a large extent had a genetic origin. Individuals carrying influential S. schwerinii haplotypes generally performed well in Sweden but less well in Italy in terms of biomass production. The results indicate that specific genetic elements of S. schwerinii are more suited to Swedish conditions than to those of Italy. Therefore, selection should preferably be conducted separately for such environments in order to maximize biomass production in admixed S. viminalis × S. schwerinii populations. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

Dispersal of the Japanese Pine Sawyer, Monochamus alternatus (Coleoptera: Cerambycidae), in Mainland China as Inferred from Molecular Data and Associations to Indices of Human Activity

PubMed Central

Fu, Da-ying; Haack, Robert A.; Zhang, Zhen; Chen, De-dao; Ma, Xue-yu; Ye, Hui

2013-01-01

The Japanese pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae), is an important forest pest as well as the principal vector of the pinewood nematode (PWN), Bursaphelenchus xylophilus (Steiner et Buhrer), in mainland China. Despite the economic importance of this insect-disease complex, only a few studies are available on the population genetic structure of M. alternatus and the relationship between its historic dispersal pattern and various human activities. The aim of the present study was to further explore aspects of human activity on the population genetic structure of M. alternatus in mainland China. The molecular data based on the combined mitochondrial cox1 and cox2 gene fragments from 140 individuals representing 14 Chinese populations yielded 54 haplotypes. Overall, a historical (natural) expansion that originated from China’s eastern coast to the western interior was revealed by the haplotype network, as well as several recent, long-distant population exchanges. Correlation analysis suggested that regional economic status and proximity to marine ports significantly influenced the population genetic structure of M. alternatus as indicated by both the ratio of shared haplotypes and the haplotype diversity, however, the PWN distribution in China was significantly correlated with only the ratio of shared haplotypes. Our results suggested that the modern logistical network (i.e., the transportation system) in China is a key medium by which humans have brought about population exchange of M. alternatus in mainland China, likely through inadvertent movement of infested wood packaging material associated with trade, and that this genetic exchange was primarily from the economically well-developed east coast of China, westward, to the less-developed interior. In addition, this study demonstrated the existence of non-local M. alternatus in new PWN-infested localities in China, but not all sites with non-local M. alternatus were infested with PWN. PMID:23469026

Shared and unique components of human population structure and genome-wide signals of positive selection in South Asia.

PubMed

Metspalu, Mait; Romero, Irene Gallego; Yunusbayev, Bayazit; Chaubey, Gyaneshwer; Mallick, Chandana Basu; Hudjashov, Georgi; Nelis, Mari; Mägi, Reedik; Metspalu, Ene; Remm, Maido; Pitchappan, Ramasamy; Singh, Lalji; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas

2011-12-09

South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Y-chromosome and mtDNA variation confirms independent domestications and directional hybridization in South American camelids.

PubMed

Marín, J C; Romero, K; Rivera, R; Johnson, W E; González, B A

2017-10-01

Investigations of genetic diversity and domestication in South American camelids (SAC) have relied on autosomal microsatellite and maternally-inherited mitochondrial data. We present the first integrated analysis of domestic and wild SAC combining male and female sex-specific markers (male specific Y-chromosome and female-specific mtDNA sequence variation) to assess: (i) hypotheses about the origin of domestic camelids, (ii) directionality of introgression among domestic and/or wild taxa as evidence of hybridization and (iii) currently recognized subspecies patterns. Three male-specific Y-chromosome markers and control region sequences of mitochondrial DNA are studied here. Although no sequence variation was found in SRY and ZFY, there were seven variable sites in DBY generating five haplotypes on the Y-chromosome. The haplotype network showed clear separation between haplogroups of guanaco-llama and vicuña-alpaca, indicating two genetically distinct patrilineages with near absence of shared haplotypes between guanacos and vicuñas. Although we document some examples of directional hybridization, the patterns strongly support the hypothesis that llama (Lama glama) is derived from guanaco (Lama guanicoe) and the alpaca (Vicugna pacos) from vicuña (Vicugna vicugna). Within male guanacos we identified a haplogroup formed by three haplotypes with different geographical distributions, the northernmost of which (Peru and northern Chile) was also observed in llamas, supporting the commonly held hypothesis that llamas were domesticated from the northernmost populations of guanacos (L. g. cacilensis). Southern guanacos shared the other two haplotypes. A second haplogroup, consisting of two haplotypes, was mostly present in vicuñas and alpacas. However, Y-chromosome variation did not distinguish the two subspecies of vicuñas. © 2017 Stichting International Foundation for Animal Genetics.

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases

PubMed Central

Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G.; Nalls, Michael A.; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J.; Graff-Radford, Neill R.; Ross, Owen A.; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J.; Halliday, Glenda M.; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K.; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

2016-01-01

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. PMID:26643944

Genetic Diversity and Evidence for Transmission of Streptococcus mutans by DiversiLab rep-PCR.

PubMed

Momeni, Stephanie S; Whiddon, Jennifer; Cheon, Kyounga; Ghazal, Tariq; Moser, Stephen A; Childers, Noel K

2016-09-01

This two-part study investigated the genetic diversity and transmission of Streptococcus mutans using the DiversiLab repetitive extragenic palindromic PCR (rep-PCR) approach. For children with S. mutans and participating household members, analysis for evidence of unrelated child-to-child as well as intra-familial transmission was evaluated based on commonality of genotypes. A total of 169 index children and 425 household family members from Uniontown, Alabama were evaluated for genetic diversity using rep-PCR. Thirty-four unique rep-PCR genotypes were observed for 13,906 S. mutans isolates. For transmission, 117 child and household isolates were evaluated for shared genotype (by child and by genotype cases, multiple matches possible for each child). Overall, children had 1-9 genotypes and those with multiple genotypes were 2.3 times more likely to have caries experience (decayed, missing and filled teeth/surfaces>0). Only 28% of children shared all genotypes within the household, while 72% had at least 1 genotype not shared with anyone in the household. Children had genotype(s) not shared with any household members in 157 cases. In 158 cases children and household members shared a genotype in which 55% (87/158 cases) were shared with more than one family member. Children most frequently shared genotypes with their mothers (54%; 85/158), siblings (46%; 72/158) and cousins (23%; 37/158). A reference library for S. mutans for epidemiological surveillance using the DiversiLab rep-PCR approach is detailed. The genetic diversity of S. mutans in this population demonstrated frequent commonality of genotypes. Evidence for both child-to-child and intra-familial transmission of S. mutans was observed by rep-PCR. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic Diversity and Evidence for Transmission of Streptococcus mutans by DiversiLab rep-PCR

PubMed Central

Momeni, Stephanie S.; Whiddon, Jennifer; Cheon, Kyounga; Ghazal, Tariq; Moser, Stephen A.; Childers, Noel K.

2016-01-01

This two-part study investigated the genetic diversity and transmission of Streptococcus mutans using the DiversiLab repetitive extragenic palindromic PCR (rep-PCR) approach. For children with S. mutans and participating household members, analysis for evidence of unrelated child-to-child as well as intra-familial transmission was evaluated based on commonality of genotypes. A total of 169 index children and 425 household family members from Uniontown, Alabama were evaluated for genetic diversity using rep-PCR. Thirty-four unique rep-PCR genotypes were observed for 13,906 S. mutans isolates. For transmission, 117 child and household isolates were evaluated for shared genotype (by child and by genotype cases, multiple matches possible for each child). Overall, children had 1–9 genotypes and those with multiple genotypes were 2.3 times more likely to have caries experience (decayed, missing and filled teeth/surfaces>0). Only 28% of children shared all genotypes within the household, while 72% had at least 1 genotype not shared with anyone in the household. Children had genotype(s) not shared with any household members in 155 cases. In 158 cases children and household members shared a genotype in which 55% (87/158 cases) were shared with more than one family member. Children most frequently shared genotypes with their mothers (54%; 85/158), siblings (46%; 72/158) and cousins (23%; 37/158). A reference library for S. mutans for epidemiological surveillance using the DiversiLab rep-PCR approach is detailed. The genetic diversity of S. mutans in this population demonstrated frequent commonality of genotypes. Evidence for both child-to-child and intra-familial transmission of S. mutans was observed by rep-PCR. PMID:27432341

All things rhabdoid and SMARC: An enigmatic exploration with Dr. Louis P. Dehner.

PubMed

Fuller, Christine E

2016-11-01

Over the past several decades, our understanding of malignant rhabdoid tumors (MRT) and the central nervous system equivalent atypical teratoid/rhabdoid tumor (ATRT) has undergone considerable refinement, particularly in terms of genetic characterization. MRT (both renal and extra-renal) and ATRT share phenotypic similarities and a common genetic signature, that being inactivating alterations of the SWI/SNF complex component SMARCB1 (or rarely SMARCA4). Unfortunately, a wide array of tumors bears significantly overlapping phenotypic characteristics to MRT/ATRT, posing a formidable diagnostic challenge. Likewise, the list of tumors bearing SMARC-related alterations has grown at a dizzying pace, and the original assumption that SMARCB1 alterations were unique to MRT/ATRT has been essentially negated. It should come as no surprise that Dr. Louis P. Dehner, no stranger to enigmatic lesions, participated significantly in this pathologic controversy, and the circuitous journey of entity discovery and clarification. This review aims to (1) summarize our current knowledge of MRT and ATRT with an emphasis on genetic characterization, (2) present insight into so-called "composite rhabdoid tumors" (CRTs), and (3) and provide an updated account of others tumors bearing SMARC alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

Temporal and spatial scaling of the genetic structure of a vector-borne plant pathogen.

PubMed

Coletta-Filho, Helvécio D; Francisco, Carolina S; Almeida, Rodrigo P P

2014-02-01

The ecology of plant pathogens of perennial crops is affected by the long-lived nature of their immobile hosts. In addition, changes to the genetic structure of pathogen populations may affect disease epidemiology and management practices; examples include local adaptation of more fit genotypes or introduction of novel genotypes from geographically distant areas via human movement of infected plant material or insect vectors. We studied the genetic structure of Xylella fastidiosa populations causing disease in sweet orange plants in Brazil at multiple scales using fast-evolving molecular markers (simple-sequence DNA repeats). Results show that populations of X. fastidiosa were regionally isolated, and that isolation was maintained for populations analyzed a decade apart from each other. However, despite such geographic isolation, local populations present in year 2000 were largely replaced by novel genotypes in 2009 but not as a result of migration. At a smaller spatial scale (individual trees), results suggest that isolates within plants originated from a shared common ancestor. In summary, new insights on the ecology of this economically important plant pathogen were obtained by sampling populations at different spatial scales and two different time points.

Genetic Factors Influence Serological Measures of Common Infections

PubMed Central

Rubicz, Rohina; Leach, Charles T.; Kraig, Ellen; Dhurandhar, Nikhil V.; Duggirala, Ravindranath; Blangero, John; Yolken, Robert; Göring, Harald H.H.

2011-01-01

Background/Aims Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and −2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses. Results Serological phenotypes were significantly heritable for most pathogens (h2 = 0.17–0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c2 = 0.10–0.32). The underlying genetic etiology appears to be largely different for most pathogens. Conclusions Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance. PMID:21996708

Posterior Communicating Artery Giving Rise to Shared-Origin Anterior Choroidal Artery: Case Illustration.

PubMed

Tonetti, Daniel A; Andrews, Edward G; Stabingas, Kristen; Tyler-Kabara, Elizabeth; Gross, Bradley A; Jadhav, Ashutosh

2018-01-01

The origin point of the anterior choroidal artery (AChA) is variable, typically arising from the supraclinoid internal carotid artery (ICA) distal to the posterior communicating artery (PComA) on either the posterolateral or posterior aspect of the ICA. Variations of AChA origin have important clinical implications, and rare origins reported previously include the ICA bifurcation and middle cerebral artery. We provide illustrations of a case of a shared-origin PComA and AChA. A young girl presented with intracranial hemorrhage and underwent angiography to evaluate for an underlying cause. Ultimately, 3-dimensional rotational angiography incidentally demonstrated a common origin of the AChA with the PComA. A rare case of a shared-origin AChA and PComA is reported for angiographic illustration. The radiologic findings, embryology behind the development of the AChA, and neurosurgical and neurovascular relevance of this variant are discussed. The importance of recognizing the origin of the AChA is emphasized. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic specificity of face recognition.

PubMed

Shakeshaft, Nicholas G; Plomin, Robert

2015-10-13

Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities.

Genetic specificity of face recognition

PubMed Central

Shakeshaft, Nicholas G.; Plomin, Robert

2015-01-01

Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities. PMID:26417086

Shared Genetic Aetiology between Cognitive Ability and Cardiovascular Disease Risk Factors: Generation Scotland's Scottish Family Health Study

ERIC Educational Resources Information Center

Luciano, Michelle; Batty, G. David; McGilchrist, Mark; Linksted, Pamela; Fitzpatrick, Bridie; Jackson, Cathy; Pattie, Alison; Dominiczak, Anna F.; Morris, Andrew D.; Smith, Blair H.; Porteous, David; Deary, Ian J.

2010-01-01

People with higher general cognitive ability in early life have more favourable levels of cardiovascular disease (CVD) risk factors in adulthood and CVD itself. The mechanism of these associations is not known. Here we examine whether general cognitive ability and CVD risk factors share genetic and/or environmental aetiology. In this large,…

Literacy outcomes of children with early childhood speech sound disorders: impact of endophenotypes.

PubMed

Lewis, Barbara A; Avrich, Allison A; Freebairn, Lisa A; Hansen, Amy J; Sucheston, Lara E; Kuo, Iris; Taylor, H Gerry; Iyengar, Sudha K; Stein, Catherine M

2011-12-01

To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Children with SSD and their siblings were assessed at early childhood (ages 4-6 years) and followed at school age (7-12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills.

Literacy Outcomes of Children With Early Childhood Speech Sound Disorders: Impact of Endophenotypes

PubMed Central

Lewis, Barbara A.; Avrich, Allison A.; Freebairn, Lisa A.; Hansen, Amy J.; Sucheston, Lara E.; Kuo, Iris; Taylor, H. Gerry; Iyengar, Sudha K.; Stein, Catherine M.

2012-01-01

Purpose To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Method Children with SSD and their siblings were assessed at early childhood (ages 4–6 years) and followed at school age (7–12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. Results Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. Conclusions Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills. PMID:21930616

Genetics of Attention Deficit Hyperactivity Disorder: A Current Review and Future Prospects

ERIC Educational Resources Information Center

Levy, Florence; Hay, David A.; Bennett, Kellie S.

2006-01-01

While there have been significant advances in both the behaviour genetics and molecular genetics of Attention Deficit Hyperactivity Disorder (ADHD), researchers are now beginning to develop hypotheses about relationships between phenotypes and genetic mechanisms. Twin studies are able to model genetic, shared environmental and non-shared…

Combination of Sharing Matrix and Image Encryption for Lossless $(k,n)$ -Secret Image Sharing.

PubMed

Bao, Long; Yi, Shuang; Zhou, Yicong

2017-12-01

This paper first introduces a (k,n) -sharing matrix S (k, n) and its generation algorithm. Mathematical analysis is provided to show its potential for secret image sharing. Combining sharing matrix with image encryption, we further propose a lossless (k,n) -secret image sharing scheme (SMIE-SIS). Only with no less than k shares, all the ciphertext information and security key can be reconstructed, which results in a lossless recovery of original information. This can be proved by the correctness and security analysis. Performance evaluation and security analysis demonstrate that the proposed SMIE-SIS with arbitrary settings of k and n has at least five advantages: 1) it is able to fully recover the original image without any distortion; 2) it has much lower pixel expansion than many existing methods; 3) its computation cost is much lower than the polynomial-based secret image sharing methods; 4) it is able to verify and detect a fake share; and 5) even using the same original image with the same initial settings of parameters, every execution of SMIE-SIS is able to generate completely different secret shares that are unpredictable and non-repetitive. This property offers SMIE-SIS a high level of security to withstand many different attacks.

The Market Dynamics of Generic Medicines in the Private Sector of 19 Low and Middle Income Countries between 2001 and 2011: A Descriptive Time Series Analysis

PubMed Central

Kaplan, Warren A.; Wirtz, Veronika J.; Stephens, Peter

2013-01-01

This observational study investigates the private sector, retail pharmaceutical market of 19 low and middle income countries (LMICs) in Latin America, Asia and the Middle East/South Africa analyzing the relationships between volume market share of generic and originator medicines over a time series from 2001 to 2011. Over 5000 individual pharmaceutical substances were divided into generic (unbranded generic, branded generic medicines) and originator categories for each country, including the United States as a comparator. In 9 selected LMICs, the market share of those originator substances with the largest decrease over time was compared to the market share of their counterpart generic versions. Generic medicines (branded generic plus unbranded generic) represent between 70 and 80% of market share in the private sector of these LMICs which exceeds that of most European countries. Branded generic medicine market share is higher than that of unbranded generics in all three regions and this is in contrast to the U.S. Although switching from an originator to its generic counterpart can save money, this narrative in reality is complex at the level of individual medicines. In some countries, the market behavior of some originator medicines that showed the most temporal decrease, showed switching to their generic counterpart. In other countries such as in the Middle East/South Africa and Asia, the loss of these originators was not accompanied by any change at all in market share of the equivalent generic version. For those countries with a significant increase in generic medicines market share and/or with evidence of comprehensive “switching” to generic versions, notably in Latin America, it would be worthwhile to establish cause-effect relationships between pharmaceutical policies and uptake of generic medicines. The absence of change in the generic medicines market share in other countries suggests that, at a minimum, generic medicines have not been strongly promoted. PMID:24098644

The market dynamics of generic medicines in the private sector of 19 low and middle income countries between 2001 and 2011: a descriptive time series analysis.

PubMed

Kaplan, Warren A; Wirtz, Veronika J; Stephens, Peter

2013-01-01

This observational study investigates the private sector, retail pharmaceutical market of 19 low and middle income countries (LMICs) in Latin America, Asia and the Middle East/South Africa analyzing the relationships between volume market share of generic and originator medicines over a time series from 2001 to 2011. Over 5000 individual pharmaceutical substances were divided into generic (unbranded generic, branded generic medicines) and originator categories for each country, including the United States as a comparator. In 9 selected LMICs, the market share of those originator substances with the largest decrease over time was compared to the market share of their counterpart generic versions. Generic medicines (branded generic plus unbranded generic) represent between 70 and 80% of market share in the private sector of these LMICs which exceeds that of most European countries. Branded generic medicine market share is higher than that of unbranded generics in all three regions and this is in contrast to the U.S. Although switching from an originator to its generic counterpart can save money, this narrative in reality is complex at the level of individual medicines. In some countries, the market behavior of some originator medicines that showed the most temporal decrease, showed switching to their generic counterpart. In other countries such as in the Middle East/South Africa and Asia, the loss of these originators was not accompanied by any change at all in market share of the equivalent generic version. For those countries with a significant increase in generic medicines market share and/or with evidence of comprehensive "switching" to generic versions, notably in Latin America, it would be worthwhile to establish cause-effect relationships between pharmaceutical policies and uptake of generic medicines. The absence of change in the generic medicines market share in other countries suggests that, at a minimum, generic medicines have not been strongly promoted.

Cross-Cultural Comparison of Genetic and Cultural Transmission of Smoking Initiation Using an Extended Twin Kinship Model.

PubMed

Maes, Hermine H; Morley, Kate; Neale, Michael C; Kendler, Kenneth S; Heath, Andrew C; Eaves, Lindon J; Martin, Nicholas G

2018-06-01

Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime 'ever' smoking measure was obtained from twins and relatives in the 'Virginia 30,000' sample and the 'Australian 25,000'. Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI.

A phylogeographic investigation of the hybrid origin of a species of swordtail fish from Mexico.

PubMed

Jones, Julia C; Perez-Sato, Juan-Antonio; Meyer, Axel

2012-06-01

Hybrid speciation may contribute significantly to generating biodiversity, but only a few well-documented examples for it exist so far that do not involve polyploidization as a mechanism. The swordtail fish, Xiphophorus clemenciae, shows common hallmarks of a hybrid origin and still overlaps in its current geographic distribution with its putative ancestral species (Xiphophorus hellerii and Xiphophorus maculatus). Xiphophorus clemenciae provides an ideal system for investigating the possible continued genetic interactions between a hybrid and its parental species. Here, we use microsatellite and mitochondrial markers to investigate the population structure of these species of swordtails and search for signs of recent hybridization. Individuals were sampled from 21 localities across the known range of X. clemenciae- the Isthmus of Tehuantepec (IT) Mexico, and several environmental parameters that might represent barriers to dispersal were recorded. The hybridization event that gave rise to X. clemenciae appears to be rather ancient, and a single origin is likely. We find negligible evidence for ongoing hybridization and introgression between the putative ancestral species, because they now occupy distinct ecological niches, and a common haplotype is shared by most populations of X. clemenciae. The population structure within these species shows an isolation-by-distance (IBD) pattern and genetic differentiation between most populations is significant and high. We infer that tectonic evolution in the Isthmus has greatly restricted gene flow between the southern and central IT populations of X. clemenciae and X. helleriii and provide preliminary information to aid in conservation management of this geographically restricted hybrid species, X. clemenciae. © 2012 Blackwell Publishing Ltd.

Admixture into and within sub-Saharan Africa

PubMed Central

Busby, George BJ; Band, Gavin; Si Le, Quang; Jallow, Muminatou; Bougama, Edith; Mangano, Valentina D; Amenga-Etego, Lucas N; Enimil, Anthony; Apinjoh, Tobias; Ndila, Carolyne M; Manjurano, Alphaxard; Nyirongo, Vysaul; Doumba, Ogobara; Rockett, Kirk A; Kwiatkowski, Dominic P; Spencer, Chris CA

2016-01-01

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology. DOI: http://dx.doi.org/10.7554/eLife.15266.001 PMID:27324836

Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci

NASA Astrophysics Data System (ADS)

Law, Philip J.; Sud, Amit; Mitchell, Jonathan S.; Henrion, Marc; Orlando, Giulia; Lenive, Oleg; Broderick, Peter; Speedy, Helen E.; Johnson, David C.; Kaiser, Martin; Weinhold, Niels; Cooke, Rosie; Sunter, Nicola J.; Jackson, Graham H.; Summerfield, Geoffrey; Harris, Robert J.; Pettitt, Andrew R.; Allsup, David J.; Carmichael, Jonathan; Bailey, James R.; Pratt, Guy; Rahman, Thahira; Pepper, Chris; Fegan, Chris; von Strandmann, Elke Pogge; Engert, Andreas; Försti, Asta; Chen, Bowang; Filho, Miguel Inacio Da Silva; Thomsen, Hauke; Hoffmann, Per; Noethen, Markus M.; Eisele, Lewin; Jöckel, Karl-Heinz; Allan, James M.; Swerdlow, Anthony J.; Goldschmidt, Hartmut; Catovsky, Daniel; Morgan, Gareth J.; Hemminki, Kari; Houlston, Richard S.

2017-01-01

B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10-9) with opposing effects between CLL (P = 1.97 × 10-8) and HL (P = 3.31 × 10-3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10-12) was associated with increased CLL and HL risk (P = 4.68 × 10-12), and reduced MM risk (P = 1.12 × 10-2), and Gly70 in HLA-DQB1 (P = 3.15 × 10-10) showed opposing effects between CLL (P = 3.52 × 10-3) and HL (P = 3.41 × 10-9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs.

Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function.

PubMed

Smeland, Olav B; Frei, Oleksandr; Kauppi, Karolina; Hill, W David; Li, Wen; Wang, Yunpeng; Krull, Florian; Bettella, Francesco; Eriksen, Jon A; Witoelar, Aree; Davies, Gail; Fan, Chun C; Thompson, Wesley K; Lam, Max; Lencz, Todd; Chen, Chi-Hua; Ueland, Torill; Jönsson, Erik G; Djurovic, Srdjan; Deary, Ian J; Dale, Anders M; Andreassen, Ole A

2017-10-01

Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction. To identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains. Combining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). Genetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined. Among the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10-7), general cognitive function (z score, -4.43; P = 9.42 × 10-6), and verbal-numerical reasoning (z score, -5.43; P = 5.64 × 10-8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain. The discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.

Alcohol use disorder and divorce: evidence for a genetic correlation in a population-based Swedish sample.

PubMed

Salvatore, Jessica E; Larsson Lönn, Sara; Sundquist, Jan; Lichtenstein, Paul; Sundquist, Kristina; Kendler, Kenneth S

2017-04-01

We tested the association between alcohol use disorder (AUD) and divorce; estimated the genetic and environmental influences on divorce; estimated how much genetic and environmental influences accounted for covariance between AUD and divorce; and estimated latent genetic and environmental correlations between AUD and divorce. We tested sex differences in these effects. We identified twin and sibling pairs with AUD and divorce information in Swedish national registers. We described the association between AUD and divorce using tetrachorics and used twin and sibling models to estimate genetic and environmental influences on divorce, on the covariance between AUD and divorce and the latent genetic and environmental correlations between AUD and divorce. Sweden. A total of 670 836 individuals (53% male) born 1940-1965. Life-time measures of AUD and divorce. AUD and divorce were related strongly (males: r tet  = +0.44, 95% CI = 0.43, 0.45; females r tet  = +0.37, 95% CI = 0.36, 0.38). Genetic factors accounted for a modest proportion of the variance in divorce (males: 21.3%, 95% CI = 7.6, 28.5; females: 31.0%, 95% CI = 18.8, 37.1). Genetic factors accounted for most of the covariance between AUD and divorce (males: 52.0%, 95% CI = 48.8, 67.9; females: 53.74%, 95% CI = 17.6, 54.5), followed by non-shared environmental factors (males: 45.0%, 95% CI = 37.5, 54.9; females: 41.6%, 95% CI = 40.3, 60.2). Shared environmental factors accounted for a negligible proportion of the covariance (males: 3.0%, 95% CI = -3.0, 13.5; females: 4.75%, 95% CI = 0.0, 6.6). The AUD-divorce genetic correlations were high (males: rA = +0.76, 95% CI = 0.53, 0.90; females +0.52, 95% CI = 0.24, 0.67). The non-shared environmental correlations were modest (males: rE = +0.32, 95% CI = 0.31, 0.40; females: +0.27, 95% CI = 0.27, 0.36). Divorce and alcohol use disorder are correlated strongly in the Swedish population, and the heritability of divorce is consistent with previous studies. Covariation between AUD and divorce results from overlapping genetic and non-shared environmental factors. Latent genetic and non-shared environmental correlations for alcohol use disorder and divorce are high and moderate. © 2016 Society for the Study of Addiction.

The genetic relationship between cannabis and tobacco cigarette use in European- and African-American female twins and siblings.

PubMed

Agrawal, Arpana; Grant, Julia D; Lynskey, Michael T; Madden, Pamela A F; Heath, Andrew C; Bucholz, Kathleen K; Sartor, Carolyn E

2016-06-01

Use of cigarettes and cannabis frequently co-occurs. We examine the role of genetic and environmental influences on variation in and covariation between tobacco cigarette and cannabis use across European-American (EA) and African-American (AA) women. Data on lifetime cannabis and cigarette use were drawn from interviews of 956 AA and 3557 EA young adult female twins and non-twin same sex female full siblings. Twin modeling was used to decompose variance in and covariance between cigarette and cannabis use into additive genetic, shared, special twin and non-shared environmental sources. Cigarette use was more common in EAs (75.3%, 95% C.I. 73.8-76.7%) than AAs (64.2%, 95% C.I. 61.2-67.2%) while cannabis use was marginally more commonly reported by AAs (55.5%, 95% C.I. 52.5-58.8%) than EAs (52.4%, 95% C.I. 50.7-54.0%). Additive genetic factors were responsible for 43-66% of the variance in cigarette and cannabis use. Broad shared environmental factors (shared+special twin) played a more significant role in EA (23-29%) than AA (2-15%) women. In AA women, the influence of non-shared environment was more pronounced (42-45% vs. 11-19% in EA women). There was strong evidence for the same familial influences underlying use of both substances (rA=0.82-0.89; rC+T=0.70-0.75). Non-shared environmental factors were also correlated but less so (rE=0.48-0.66). No racial/ethnic differences were apparent in these sources of covariation. Heritability of cigarette and cannabis use is comparable across racial/ethnic groups. Differences in the contribution of shared and non-shared environmental influences indicate that different factors may shape substance use in EA and AA women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

78 FR 13286 - Sharing Certain Business Information Regarding the Introduction of Genetically Engineered...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

... Information Regarding the Introduction of Genetically Engineered Organisms With State and Tribal Government... proposing to amend our regulations regarding genetically engineered organisms regulated by the United States...). The regulations refer to such genetically engineered (GE) organisms and products as ``regulated...

Bartonellae are Prevalent and Diverse in Costa Rican Bats and Bat Flies.

PubMed

Judson, S D; Frank, H K; Hadly, E A

2015-12-01

Species in the bacterial genus, Bartonella, can cause disease in both humans and animals. Previous reports of Bartonella in bats and ectoparasitic bat flies suggest that bats could serve as mammalian hosts and bat flies as arthropod vectors. We compared the prevalence and genetic similarity of bartonellae in individual Costa Rican bats and their bat flies using molecular and sequencing methods targeting the citrate synthase gene (gltA). Bartonellae were more prevalent in bat flies than in bats, and genetic variants were sometimes, but not always, shared between bats and their bat flies. The detected bartonellae genetic variants were diverse, and some were similar to species known to cause disease in humans and other mammals. The high prevalence and sharing of bartonellae in bat flies and bats support a role for bat flies as a potential vector for Bartonella, while the genetic diversity and similarity to known species suggest that bartonellae could spill over into humans and animals sharing the landscape. © 2015 Blackwell Verlag GmbH.

Has the "Equal Environments" assumption been tested in twin studies?

PubMed

Eaves, Lindon; Foley, Debra; Silberg, Judy

2003-12-01

A recurring criticism of the twin method for quantifying genetic and environmental components of human differences is the necessity of the so-called "equal environments assumption" (EEA) (i.e., that monozygotic and dizygotic twins experience equally correlated environments). It has been proposed to test the EEA by stratifying twin correlations by indices of the amount of shared environment. However, relevant environments may also be influenced by genetic differences. We present a model for the role of genetic factors in niche selection by twins that may account for variation in indices of the shared twin environment (e.g., contact between members of twin pairs). Simulations reveal that stratification of twin correlations by amount of contact can yield spurious evidence of large shared environmental effects in some strata and even give false indications of genotype x environment interaction. The stratification approach to testing the equal environments assumption may be misleading and the results of such tests may actually be consistent with a simpler theory of the role of genetic factors in niche selection.

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

Similarities and distinctions in Y chromosome gene pool of Western Slavs.

PubMed

Woźniak, Marcin; Malyarchuk, Boris; Derenko, Miroslava; Vanecek, Tomas; Lazur, Jan; Gomolcak, Pavol; Grzybowski, Tomasz

2010-08-01

Analysis of Y chromosome Y-STRs has proven to be a useful tool in the field of population genetics, especially in the case of closely related populations. We collected DNA samples from 169 males of Czech origin, 80 males of Slovakian origin, and 142 males dwelling Northern Poland. We performed Y-STR analysis of 12 loci in the samples collected (PowerPlex Y system from Promega) and compared the Y chromosome haplotype frequencies between the populations investigated. Also, we used Y-STR data available from the literature for comparison purposes. We observed significant differences between Y chromosome pools of Czechs and Slovaks compared to other Slavic and European populations. At the same time we were able to point to a specific group of Y-STR haplotypes belonging to an R1a haplogroup that seems to be shared by Slavic populations dwelling in Central Europe. The observed Y chromosome diversity may be explained by taking into consideration archeological and historical data regarding early Slav migrations. Copyright 2010 Wiley-Liss, Inc.

The origin and distribution of human lice in the world.

PubMed

Boutellis, Amina; Abi-Rached, Laurent; Raoult, Didier

2014-04-01

Two genera of lice parasitize humans: Pthirus and Pediculus. The latter is of significant public health importance and comprises two ecotypes: the body louse and the head louse. These ecotypes are morphologically and genetically notably similar; the body louse is responsible for three infectious diseases: Louse-borne epidemic typhus, relapsing fever, and trench fever. Mitochondrial DNA studies have shown that there are three obviously divergent clades of head lice (A, B and C), and only one clade of body lice is shared with head lice (clade A). Each clade has a unique geographic distribution. Lice have been parasitizing humans for millions of years and likely dispersed throughout the World with the human migrations out of Africa, so they can be good markers for studying human evolution. Here, we present an overview of the origin of human lice and their role in vector pathogenic bacteria that caused epidemics, and we review the association between lice clades and human migrations. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

PubMed Central

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Background Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation. PMID:21760939

Genomic characterization of H14 subtype influenza A viruses in New World waterfowl and experimental infectivity in mallards Anas platyrhynchos

USGS Publications Warehouse

Ramey, Andy M.; Poulson, Rebecca L.; Gonzalez-Reiche, Ana S.; Perez, Daniel R.; Stalknecht, David E.; Brown, Justin D.

2014-01-01

Recent repeated isolation of H14 hemagglutinin subtype influenza A viruses (IAVs) in the New World waterfowl provides evidence to suggest that host and/or geographic ranges for viruses of this subtype may be expanding. In this study, we used genomic analyses to gain inference on the origin and evolution of H14 viruses in New World waterfowl and conducted an experimental challenge study in mallards (Anas platyrhynchos) to evaluate pathogenicity, viral replication, and transmissibility of a representative viral strain in a natural host species. Genomic characterization of H14 subtype IAVs isolated from New World waterfowl, including three isolates sequenced specifically for this study, revealed high nucleotide identity among individual gene segments (e.g. ≥95% shared identity among H14 HA gene segments). In contrast, lower shared identity was observed among internal gene segments. Furthermore, multiple neuraminidase subtypes were observed for H14 IAVs isolated in the New World. Gene segments of H14 viruses isolated after 2010 shared ancestral genetic lineages with IAVs isolated from wild birds throughout North America. Thus, genomic characterization provided evidence for viral evolution in New World waterfowl through genetic drift and genetic shift since purported introduction from Eurasia. In the challenge study, no clinical disease or lesions were observed among mallards experimentally inoculated with A/blue-winged teal/Texas/AI13-1028/2013(H14N5) or exposed via contact with infected birds. Titers of viral shedding for mallards challenged with the H14N5 IAV were highest at two days post-inoculation (DPI); however shedding was detected up to nine DPI using cloacal swabs. The distribution of viral antigen among mallards infected with H14N5 IAV was largely restricted to enterocytes lining the villi in the lower intestinal tract and in the epithelium of the bursa of Fabricius. Characterization of the infectivity of A/blue-winged teal/Texas/AI13-1028/2013(H14N5) in mallards provides support for similarities in viral replication and shedding as compared to previously described waterfowl-adapted, low pathogenic IAV strains in ducks.

Redefining genomic privacy: trust and empowerment.

PubMed

Erlich, Yaniv; Williams, James B; Glazer, David; Yocum, Kenneth; Farahany, Nita; Olson, Maynard; Narayanan, Arvind; Stein, Lincoln D; Witkowski, Jan A; Kain, Robert C

2014-11-01

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research.

Examining the genetic and environmental associations among spelling, reading fluency, reading comprehension and a high stakes reading test in a combined sample of third and fourth grade students

PubMed Central

Little, Callie W.

2015-01-01

The present study is an examination of the genetic and environmental effects on the associations among reading fluency, spelling and earlier reading comprehension on a later reading comprehension outcome (FCAT) in a combined sample of 3rd and 4th grade students using data from the 2011-2012 school year of the Florida Twin project on Reading (Taylor et al., 2013). A genetically sensitive model was applied to the data with results indicating a common genetic component among all four measures, along with shared and non-shared environmental influences common between reading fluency, spelling and FCAT. PMID:26770052

Redefining Genomic Privacy: Trust and Empowerment

PubMed Central

Erlich, Yaniv; Williams, James B.; Glazer, David; Yocum, Kenneth; Farahany, Nita; Olson, Maynard; Narayanan, Arvind; Stein, Lincoln D.; Witkowski, Jan A.; Kain, Robert C.

2014-01-01

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research. PMID:25369215

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.

PubMed

Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G; Nalls, Michael A; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J; Graff-Radford, Neill R; Ross, Owen A; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J; Halliday, Glenda M; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

2016-02-01

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Research Data in Core Journals in Biology, Chemistry, Mathematics, and Physics.

PubMed

Womack, Ryan P

2015-01-01

This study takes a stratified random sample of articles published in 2014 from the top 10 journals in the disciplines of biology, chemistry, mathematics, and physics, as ranked by impact factor. Sampled articles were examined for their reporting of original data or reuse of prior data, and were coded for whether the data was publicly shared or otherwise made available to readers. Other characteristics such as the sharing of software code used for analysis and use of data citation and DOIs for data were examined. The study finds that data sharing practices are still relatively rare in these disciplines' top journals, but that the disciplines have markedly different practices. Biology top journals share original data at the highest rate, and physics top journals share at the lowest rate. Overall, the study finds that within the top journals, only 13% of articles with original data published in 2014 make the data available to others.

Research Data in Core Journals in Biology, Chemistry, Mathematics, and Physics

PubMed Central

Womack, Ryan P.

2015-01-01

This study takes a stratified random sample of articles published in 2014 from the top 10 journals in the disciplines of biology, chemistry, mathematics, and physics, as ranked by impact factor. Sampled articles were examined for their reporting of original data or reuse of prior data, and were coded for whether the data was publicly shared or otherwise made available to readers. Other characteristics such as the sharing of software code used for analysis and use of data citation and DOIs for data were examined. The study finds that data sharing practices are still relatively rare in these disciplines’ top journals, but that the disciplines have markedly different practices. Biology top journals share original data at the highest rate, and physics top journals share at the lowest rate. Overall, the study finds that within the top journals, only 13% of articles with original data published in 2014 make the data available to others. PMID:26636676

Genetic overlap between diagnostic subtypes of ischemic stroke.

PubMed

Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Steve; Falcone, Guido; Hopewell, Jemma C; Cheng, Yu-Ching; Cotlarciuc, Ioana; Bis, Joshua C; Boerwinkle, Eric; Boncoraglio, Giorgio B; Clarke, Robert; Cole, John W; Fornage, Myriam; Furie, Karen L; Ikram, M Arfan; Jannes, Jim; Kittner, Steven J; Lincz, Lisa F; Maguire, Jane M; Meschia, James F; Mosley, Thomas H; Nalls, Mike A; Oldmeadow, Christopher; Parati, Eugenio A; Psaty, Bruce M; Rothwell, Peter M; Seshadri, Sudha; Scott, Rodney J; Sharma, Pankaj; Sudlow, Cathie; Wiggins, Kerri L; Worrall, Bradford B; Rosand, Jonathan; Mitchell, Braxton D; Dichgans, Martin; Markus, Hugh S; Levi, Christopher; Attia, John; Wray, Naomi R

2015-03-01

Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene. Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes. © 2015 American Heart Association, Inc.

Overlap and specificity of genetic and environmental influences on mathematics and reading disability in 10-year-old twins

PubMed Central

Kovas, Y.; Haworth, C.M.A.; Harlaar, N.; Petrill, S.A.; Dale, P.S.; Plomin, R.

2009-01-01

Background To what extent do genetic and environmental influences on reading disability overlap with those on mathematics disability? Multivariate genetic research on the normal range of variation in unselected samples has led to a Generalist Genes Hypothesis which posits that the same genes largely affect individual differences in these abilities in the normal range. However, little is known about the etiology of co-morbidity for the disability extremes of reading and mathematics. Method From 2596 pairs of 10-year-old monozygotic and dizygotic twins assessed on a web-based battery of reading and mathematics tests, we selected the lowest 15% on reading and on mathematics. We conducted bivariate DeFries–Fulker (DF) extremes analyses to assess overlap and specificity of genetic and environmental influences on reading and mathematics disability defined by a 15% cut-off. Results Both reading and mathematics disability are moderately heritable (47% and 43%, respectively) and show only modest shared environmental influence (16% and 20%). There is substantial phenotypic co-morbidity between reading and mathematics disability. Bivariate DF extremes analyses yielded a genetic correlation of .67 between reading disability and mathematics disability, suggesting that they are affected largely by the same genetic factors. The shared environmental correlation is .96 and the non-shared environmental correlation is .08. Conclusions In line with the Generalist Genes Hypothesis, the same set of generalist genes largely affects mathematical and reading disabilities. The dissociation between the disabilities occurs largely due to independent non-shared environmental influences. PMID:17714376

Approaching confidentiality at a familial level in genomic medicine: a focus group study with healthcare professionals

PubMed Central

Dheensa, Sandi; Fenwick, Angela; Lucassen, Anneke

2017-01-01

Objectives Clinical genetics guidelines from 2011 conceptualise genetic information as confidential to families, not individuals. The normative consequence of this is that the family's interest is the primary consideration and genetic information is shared unless there are good reasons not to do so. We investigated healthcare professionals' (HCPs') views about, and reasoning around, individual and familial approaches to confidentiality and how such views influenced their practice. Method 16 focus groups with 80 HCPs working in/with clinical genetics services were analysed, drawing on grounded theory. Results Participants raised seven problems with, and arguments against, going beyond the individual approach to confidentiality. These problems fell into two overlapping categories: ‘relationships’ and ‘structures’. Most participants had never considered ways to—or thought it was impossible to—treat familial genetic information and personal information differently. They worried that putting the familial approach into practice could disrupt family dynamics and erode patient trust in the health service. They also thought they had insufficient resources to share information and feared that sharing might change the standard of care and make them more vulnerable to liability. Conclusions A familial approach to confidentiality has not been accepted or adopted as a standard, but wider research suggests that some of the problems HCPs perceived are surmountable and sharing in the interest of the family can be achieved. However, further research is needed to explore how personal and familial genetic information can be separated in practice. Our findings are relevant to HCPs across health services who are starting to use genome tests as part of their routine investigations. PMID:28159847

To share or not to share? Expected pros and cons of data sharing in radiological research.

PubMed

Sardanelli, Francesco; Alì, Marco; Hunink, Myriam G; Houssami, Nehmat; Sconfienza, Luca M; Di Leo, Giovanni

2018-06-01

The aims of this paper are to illustrate the trend towards data sharing, i.e. the regulated availability of the original patient-level data obtained during a study, and to discuss the expected advantages (pros) and disadvantages (cons) of data sharing in radiological research. Expected pros include the potential for verification of original results with alternative or supplementary analyses (including estimation of reproducibility), advancement of knowledge by providing new results by testing new hypotheses (not explored by the original authors) on pre-existing databases, larger scale analyses based on individual-patient data, enhanced multidisciplinary cooperation, reduced publication of false studies, improved clinical practice, and reduced cost and time for clinical research. Expected cons are outlined as the risk that the original authors could not exploit the entire potential of the data they obtained, possible failures in patients' privacy protection, technical barriers such as the lack of standard formats, and possible data misinterpretation. Finally, open issues regarding data ownership, the role of individual patients, advocacy groups and funding institutions in decision making about sharing of data and images are discussed. • Regulated availability of patient-level data of published clinical studies (data-sharing) is expected. • Expected benefits include verification/advancement of knowledge, reduced cost/time of research, clinical improvement. • Potential drawbacks include faults in patients' identity protection and data misinterpretation.

Crying without a cause and being easily upset in two-year-olds: heritability and predictive power of behavioral problems.

PubMed

Groen-Blokhuis, Maria M; Middeldorp, Christel M; M van Beijsterveldt, Catharina E; Boomsma, Dorret I

2011-10-01

In order to estimate the influence of genetic and environmental factors on 'crying without a cause' and 'being easily upset' in 2-year-old children, a large twin study was carried out. Prospective data were available for ~18,000 2-year-old twin pairs from the Netherlands Twin Register. A bivariate genetic analysis was performed using structural equation modeling in the Mx software package. The influence of maternal personality characteristics and demographic and lifestyle factors was tested to identify specific risk factors that may underlie the shared environment of twins. Furthermore, it was tested whether crying without a cause and being easily upset were predictive of later internalizing, externalizing and attention problems. Crying without a cause yielded a heritability estimate of 60% in boys and girls. For easily upset, the heritability was estimated at 43% in boys and 31% in girls. The variance explained by shared environment varied between 35% and 63%. The correlation between crying without a cause and easily upset (r = .36) was explained both by genetic and shared environmental factors. Birth cohort, gestational age, socioeconomic status, parental age, parental smoking behavior and alcohol use during pregnancy did not explain the shared environmental component. Neuroticism of the mother explained a small proportion of the additive genetic, but not of the shared environmental effects for easily upset. Crying without a cause and being easily upset at age 2 were predictive of internalizing, externalizing and attention problems at age 7, with effect sizes of .28-.42. A large influence of shared environmental factors on crying without a cause and easily upset was detected. Although these effects could be specific to these items, we could not explain them by personality characteristics of the mother or by demographic and lifestyle factors, and we recognize that these effects may reflect other maternal characteristics. A substantial influence of genetic factors was found for the two items, which are predictive of later behavioral problems.

Molecular evolution of shattering loci in U.S. weedy rice

PubMed Central

Thurber, Carrie S.; Reagon, Michael; Gross, Briana L.; Olsen, Kenneth M.; Jia, Yulin; Caicedo, Ana L.

2010-01-01

Cultivated rice fields worldwide are plagued with weedy rice, a conspecific weed of cultivated rice (Oryza sativa L.). The persistence of weedy rice has been attributed, in part, to its ability to shatter (disperse) seed prior to crop harvesting. In the United States, separately evolved weedy rice groups have been shown to share genomic identity with exotic domesticated cultivars. Here, we investigate the shattering phenotype in a collection of U.S. weedy rice accessions, as well as wild and cultivated relatives. We find that all U.S. weedy rice groups shatter seeds easily, despite multiple origins, and in contrast to a decrease in shattering ability seen in cultivated groups. We assessed allelic identity and diversity at the major shattering locus, sh4, in weedy rice; we find that all cultivated and weedy rice, regardless of population, share similar haplotypes at sh4, and all contain a single derived mutation associated with decreased seed shattering. Our data constitute the strongest evidence to date of an evolution of weeds from domesticated backgrounds. The combination of a shared cultivar sh4 allele and a highly shattering phenotype, suggests that U.S. weedy rice have re-acquired the shattering trait after divergence from their progenitors through alternative genetic mechanisms. PMID:20584132

The Locus Preservation Hypothesis: Shared Linguistic Profiles across Developmental Disorders and the Resilient Part of the Human Language Faculty

PubMed Central

Leivada, Evelina; Kambanaros, Maria; Grohmann, Kleanthes K.

2017-01-01

Grammatical markers are not uniformly impaired across speakers of different languages, even when speakers share a diagnosis and the marker in question is grammaticalized in a similar way in these languages. The aim of this work is to demarcate, from a cross-linguistic perspective, the linguistic phenotype of three genetically heterogeneous developmental disorders: specific language impairment, Down syndrome, and autism spectrum disorder. After a systematic review of linguistic profiles targeting mainly English-, Greek-, Catalan-, and Spanish-speaking populations with developmental disorders (n = 880), shared loci of impairment are identified and certain domains of grammar are shown to be more vulnerable than others. The distribution of impaired loci is captured by the Locus Preservation Hypothesis which suggests that specific parts of the language faculty are immune to impairment across developmental disorders. Through the Locus Preservation Hypothesis, a classical chicken and egg question can be addressed: Do poor conceptual resources and memory limitations result in an atypical grammar or does a grammatical breakdown lead to conceptual and memory limitations? Overall, certain morphological markers reveal themselves as highly susceptible to impairment, while syntactic operations are preserved, granting support to the first scenario. The origin of resilient syntax is explained from a phylogenetic perspective in connection to the “syntax-before-phonology” hypothesis. PMID:29081756

Prevalence and healthcare actions of women in a large health system with a family history meeting the 2005 USPSTF recommendation for BRCA genetic counseling referral.

PubMed

Bellcross, Cecelia A; Leadbetter, Steven; Alford, Sharon Hensley; Peipins, Lucy A

2013-04-01

In 2005, the United States Preventive Services Task Force (USPSTF) released guidelines which outlined specific family history patterns associated with an increased risk for BRCA1/2 mutations, and recommended at-risk individuals be referred for genetic counseling and evaluation for BRCA testing. The purpose of this study was to assess the prevalence of individuals with a USPSTF increased-risk family history pattern, the frequency with which specific patterns were met, and resulting healthcare actions among women from the Henry Ford Health System. As part of a study evaluating ovarian cancer risk perception and screening, 2,524 randomly selected participants completed a detailed interview (response rate 76%) from an initial eligible cohort of 16,720 women. Approximately 6% of participants had a family history fulfilling one or more of the USPSTF patterns. Although 90% of these women had shared their family history with their provider, less than 20% had been referred for genetic counseling and only 8% had undergone genetic testing. Caucasian women with higher income and education levels were more likely to receive referrals. Among the 95 participants in the total study cohort who reported BRCA testing, 78% did not have a family history that met one of the USPSTF patterns. These results suggest a higher prevalence of women with an increased-risk family history than originally predicted by the USPSTF, and lack of provider recognition and referral for genetic services. Improvements in healthcare infrastructure and clinician education will be required to realize population level benefits from BRCA genetic counseling and testing.

Investigating Environmental Links Between Parent Depression and Child Depressive/Anxiety Symptoms Using an Assisted Conception Design

PubMed Central

Lewis, Gemma; Rice, Frances; Harold, Gordon T.; Collishaw, Stephan; Thapar, Anita

2011-01-01

Objective Links between maternal and offspring depression symptoms could arise from inherited factors, direct environmental exposure, or shared adversity. A novel genetically sensitive design was used to test the extent of environmental links between maternal depression symptoms and child depression/anxiety symptoms, accounting for inherited effects, shared adversity, and child age and gender. Method Eight hundred fifty-two families with a child born by assisted conception provided questionnaire data. Mothers and fathers were genetically related or unrelated to the child depending on conception method. Parental depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Child depression/anxiety symptoms were assessed using the Short Mood and Feelings questionnaire and six items tapping generalized anxiety disorder symptoms. Associations between maternal and child symptoms were examined separately for genetically unrelated and related mother–child pairs, adjusting for three measurements of shared adversity: negative life events, family income, and socioeconomic status. Analyses were then run separately for boys and girls and for children and adolescents, and the role of paternal depression symptoms was also examined. Results Significant associations between parent and child symptoms were found for genetically unrelated mother–child (r = 0.32, p < .001) and father–child (r = 0.17, p < .05) pairs and genetically related mother–child (r = 0.31, p < .001) and father–child (r = 0.23, p < .001) pairs and were not explained by the shared adversity measurements. Environmental links were present for children and adolescents and were stronger for girls. Conclusions The transmission of depression symptoms is due in part to environmental processes independent of inherited effects and is not accounted for by shared adversity measurements. Girls may be more sensitive to the negative effects of maternal depression symptoms than boys through environmental processes. PMID:21515194

Transcriptional signatures of ancient floral developmental genetics in avocado (Persea americana; Lauraceae).

PubMed

Chanderbali, André S; Albert, Victor A; Leebens-Mack, Jim; Altman, Naomi S; Soltis, Douglas E; Soltis, Pamela S

2009-06-02

The debate on the origin and evolution of flowers has recently entered the field of developmental genetics, with focus on the design of the ancestral floral regulatory program. Flowers can differ dramatically among angiosperm lineages, but in general, male and female reproductive organs surrounded by a sterile perianth of sepals and petals constitute the basic floral structure. However, the basal angiosperm lineages exhibit spectacular diversity in the number, arrangement, and structure of floral organs, whereas the evolutionarily derived monocot and eudicot lineages share a far more uniform floral ground plan. Here we show that broadly overlapping transcriptional programs characterize the floral transcriptome of the basal angiosperm Persea americana (avocado), whereas floral gene expression domains are considerably more organ specific in the model eudicot Arabidopsis thaliana. Our findings therefore support the "fading borders" model for organ identity determination in basal angiosperm flowers and extend it from the action of regulatory genes to downstream transcriptional programs. Furthermore, the declining expression of components of the staminal transcriptome in central and peripheral regions of Persea flowers concurs with elements of a previous hypothesis for developmental regulation in a gymnosperm "floral progenitor." Accordingly, in contrast to the canalized organ-specific regulatory apparatus of Arabidopsis, floral development may have been originally regulated by overlapping transcriptional cascades with fading gradients of influence from focal to bordering organs.

The epidemiological characteristics and genetic diversity of dengue virus during the third largest historical outbreak of dengue in Guangdong, China, in 2014.

PubMed

Sun, Jiufeng; Wu, De; Zhou, Huiqiong; Zhang, Huan; Guan, Dawei; He, Xiang; Cai, Songwu; Ke, Changwen; Lin, Jinyan

2016-01-01

The third largest historical outbreak of dengue occurred during July to December 2014, in 20 of 21 cities of Guangdong, China. The epidemiological and molecular characteristics of the introduction, expansion and phylogeny of the DENV isolates involved in this outbreak were investigated. A combination analyses of epidemiological characteristics and genetic diversity of dengue virus was performed in this study. In total, 45,236 cases and 6 fatalities were reported. Unemployed individuals, retirees and retailers were the most affected populations. A total of 6024 cases were verified to have DENV infections by nucleic acid detection, of which 5947, 74 and 3 were confirmed to have DENV-1, -2, and -3 infections, respectively. Phylogenetic analyses of DENV-1 isolates were assigned into three genotypes (I, IV, and V). Genotype V was the predominant genotype that likely originated from Singapore. The DENV-2 isolates were assigned to the Cosmopolitan and Asian I genotypes. A unique DENV-3 isolate (genotype III) shared high similarity with isolates obtained from Guangdong in 2013. A combination analyses demonstrated the multiple geographical origins of this outbreak, and highlight the importance of early detection, the case management and vector surveillance for preventing further dengue epidemics in Guangdong. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

PubMed

Lee, S Hong; Ripke, Stephan; Neale, Benjamin M; Faraone, Stephen V; Purcell, Shaun M; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breen, Gerome; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Buitelaar, Jan K; Bunney, William E; Buxbaum, Joseph D; Byerley, William F; Byrne, Enda M; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C Robert; Collier, David A; Cook, Edwin H; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H; Craig, David W; Craig, Ian W; Crosbie, Jennifer; Cuccaro, Michael L; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J; Doyle, Alysa E; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P; Edenberg, Howard J; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E; Ferrier, I Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B; Freitag, Christine M; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V; Georgieva, Lyudmila; Gershon, Elliot S; Geschwind, Daniel H; Giegling, Ina; Gill, Michael; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Greenwood, Tiffany A; Grice, Dorothy E; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P; Hamshere, Marian L; Hansen, Thomas F; Hartmann, Annette M; Hautzinger, Martin; Heath, Andrew C; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A; Holsboer, Florian; Hoogendijk, Witte J; Hottenga, Jouke-Jan; Hultman, Christina M; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K; Kahn, René S; Kandaswamy, Radhika; Keller, Matthew C; Kennedy, James L; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K; Klauck, Sabine M; Klei, Lambertus; Knowles, James A; Kohli, Martin A; Koller, Daniel L; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Långström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B; Leboyer, Marion; Ledbetter, David H; Lee, Phil H; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F; Lewis, Cathryn M; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Liu, Chunyu; Lohoff, Falk W; Loo, Sandra K; Lord, Catherine; Lowe, Jennifer K; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela A F; Maestrini, Elena; Magnusson, Patrik K E; Mahon, Pamela B; Maier, Wolfgang; Malhotra, Anil K; Mane, Shrikant M; Martin, Christa L; Martin, Nicholas G; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A; McGhee, Kevin A; McGough, James J; McGrath, Patrick J; McGuffin, Peter; McInnis, Melvin G; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W; McMahon, Francis J; McMahon, William M; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P; Montgomery, Grant W; Moran, Jennifer L; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W; Morrow, Eric M; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W; Muir, Walter J; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M; Myin-Germeys, Inez; Neale, Michael C; Nelson, Stan F; Nievergelt, Caroline M; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A; Nöthen, Markus M; Nurnberger, John I; Nwulia, Evaristus A; Nyholt, Dale R; O'Dushlaine, Colm; Oades, Robert D; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A; Osby, Urban; Owen, Michael J; Palotie, Aarno; Parr, Jeremy R; Paterson, Andrew D; Pato, Carlos N; Pato, Michele T; Penninx, Brenda W; Pergadia, Michele L; Pericak-Vance, Margaret A; Pickard, Benjamin S; Pimm, Jonathan; Piven, Joseph; Posthuma, Danielle; Potash, James B; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J; Quinn, Emma M; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rossin, Lizzy; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R; Sanders, Stephan J; Santangelo, Susan L; Sergeant, Joseph A; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F; Scheftner, William A; Schellenberg, Gerard D; Scherer, Stephen W; Schork, Nicholas J; Schulze, Thomas G; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J; Shi, Jianxin; Shilling, Paul D; Shyn, Stanley I; Silverman, Jeremy M; Slager, Susan L; Smalley, Susan L; Smit, Johannes H; Smith, Erin N; Sonuga-Barke, Edmund J S; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S; Strohmaier, Jana; Stroup, T Scott; Sutcliffe, James S; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C; Todorov, Alexandre A; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M; Vieland, Veronica J; Vincent, John B; Visscher, Peter M; Walsh, Christopher A; Wassink, Thomas H; Watson, Stanley J; Weissman, Myrna M; Werge, Thomas; Wienker, Thomas F; Wijsman, Ellen M; Willemsen, Gonneke; Williams, Nigel; Willsey, A Jeremy; Witt, Stephanie H; Xu, Wei; Young, Allan H; Yu, Timothy W; Zammit, Stanley; Zandi, Peter P; Zhang, Peng; Zitman, Frans G; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R; Sklar, Pamela; Daly, Mark J; O'Donovan, Michael C; Craddock, Nicholas; Sullivan, Patrick F; Smoller, Jordan W; Kendler, Kenneth S; Wray, Naomi R

2013-09-01

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Bivariate Heritability of Total and Regional Brain Volumes: the Framingham Study

PubMed Central

DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles

2009-01-01

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging (MRI) who were free of stroke and other neurological disorders that might influence brain volumes and who were members of families with at least two Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60, were observed for total brain, white matter hyperintensity, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for white matter hyperintensity, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and white matter hyperintensity volumes. These data extend current knowledge by showing that these two different types of MRI measures do not share underlying genetic or environmental influences. PMID:19812462

Low extraversion and high neuroticism as indices of genetic and environmental risk for social phobia, agoraphobia, and animal phobia.

PubMed

Bienvenu, O Joseph; Hettema, John M; Neale, Michael C; Prescott, Carol A; Kendler, Kenneth S

2007-11-01

The authors examined the extent to which two major personality dimensions (extraversion and neuroticism) index the genetic and environmental risk for three phobias (social phobia, agoraphobia, and animal phobia) in twins ascertained from a large, population-based registry. Lifetime phobias and personality traits were assessed through diagnostic interview and self-report questionnaire, respectively, in 7,800 twins from female-female, male-male, and opposite-sex pairs. Sex-limited trivariate Cholesky structural equation models were used to decompose the correlations among extraversion, neuroticism, and each phobia. In the best-fitting models, genetic correlations were moderate and negative between extraversion and both social phobia and agoraphobia, and that between extraversion and animal phobia was effectively zero. Genetic correlations were high and positive between neuroticism and both social phobia and agoraphobia, and that between neuroticism and animal phobia was moderate. All of the genetic risk factors for social phobia and agoraphobia were shared with those that influence extraversion and neuroticism; in contrast, only a small proportion of the genetic risk factors for animal phobia (16%) was shared with those that influence personality. Shared environmental experiences were not a source of correlations between personality traits and phobias, and unique environmental correlations were relatively modest. Genetic factors that influence individual variation in extraversion and neuroticism appear to account entirely for the genetic liability to social phobia and agoraphobia, but not animal phobia. These findings underline the importance of both introversion (low extraversion) and neuroticism in some psychiatric disorders.

mtDNA data indicate a single origin for dogs south of Yangtze River, less than 16,300 years ago, from numerous wolves.

PubMed

Pang, Jun-Feng; Kluetsch, Cornelya; Zou, Xiao-Ju; Zhang, Ai-bing; Luo, Li-Yang; Angleby, Helen; Ardalan, Arman; Ekström, Camilla; Sköllermo, Anna; Lundeberg, Joakim; Matsumura, Shuichi; Leitner, Thomas; Zhang, Ya-Ping; Savolainen, Peter

2009-12-01

There is no generally accepted picture of where, when, and how the domestic dog originated. Previous studies of mitochondrial DNA (mtDNA) have failed to establish the time and precise place of origin because of lack of phylogenetic resolution in the so far studied control region (CR), and inadequate sampling. We therefore analyzed entire mitochondrial genomes for 169 dogs to obtain maximal phylogenetic resolution and the CR for 1,543 dogs across the Old World for a comprehensive picture of geographical diversity. Hereby, a detailed picture of the origins of the dog can for the first time be suggested. We obtained evidence that the dog has a single origin in time and space and an estimation of the time of origin, number of founders, and approximate region, which also gives potential clues about the human culture involved. The analyses showed that dogs universally share a common homogenous gene pool containing 10 major haplogroups. However, the full range of genetic diversity, all 10 haplogroups, was found only in southeastern Asia south of Yangtze River, and diversity decreased following a gradient across Eurasia, through seven haplogroups in Central China and five in North China and Southwest (SW)Asia, down to only four haplogroups in Europe. The mean sequence distance to ancestral haplotypes indicates an origin 5,400-16,300 years ago (ya) from at least 51 female wolf founders. These results indicate that the domestic dog originated in southern China less than 16,300 ya, from several hundred wolves. The place and time coincide approximately with the origin of rice agriculture, suggesting that the dogs may have originated among sedentary hunter-gatherers or early farmers, and the numerous founders indicate that wolf taming was an important culture trait.

Modeling and Dynamic Analysis of Paralleled dc/dc Converters With Master-Slave Current Sharing Control

NASA Technical Reports Server (NTRS)

Rajagopalan, J.; Xing, K.; Guo, Y.; Lee, F. C.; Manners, Bruce

1996-01-01

A simple, application-oriented, transfer function model of paralleled converters employing Master-Slave Current-sharing (MSC) control is developed. Dynamically, the Master converter retains its original design characteristics; all the Slave converters are forced to depart significantly from their original design characteristics into current-controlled current sources. Five distinct loop gains to assess system stability and performance are identified and their physical significance is described. A design methodology for the current share compensator is presented. The effect of this current sharing scheme on 'system output impedance' is analyzed.

Heterogeneity in the development of proactive and reactive aggression in childhood: Common and specific genetic - environmental factors

PubMed Central

Lacourse, Eric; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard Ernest; Boivin, Michel

2017-01-01

Background Few studies are grounded in a developmental framework to study proactive and reactive aggression. Furthermore, although distinctive correlates, predictors and outcomes have been highlighted, proactive and reactive aggression are substantially correlated. To our knowledge, no empirical study has examined the communality of genetic and environmental underpinning of the development of both subtypes of aggression. The current study investigated the communality and specificity of genetic-environmental factors related to heterogeneity in proactive and reactive aggression’s development throughout childhood. Methods Participants were 223 monozygotic and 332 dizygotic pairs. Teacher reports of aggression were obtained at 6, 7, 9, 10 and 12 years of age. Joint development of both phenotypes were analyzed through a multivariate latent growth curve model. Set point, differentiation, and genetic maturation/environmental modulation hypotheses were tested using a biometric decomposition of intercepts and slopes. Results Common genetic factors accounted for 64% of the total variation of proactive and reactive aggression’s intercepts. Two other sets of uncorrelated genetic factors accounted for reactive aggression’s intercept (17%) on the one hand, and for proactive (43%) and reactive (13%) aggression’s slopes on the other. Common shared environmental factors were associated with proactive aggression’s intercept (21%) and slope (26%) and uncorrelated shared environmental factors were also associated with reactive aggression’s slope (14%). Common nonshared environmental factors explained most of the remaining variability of proactive and reactive aggression slopes. Conclusions A genetic differentiation hypothesis common to both phenotypes was supported by common genetic factors associated with the developmental heterogeneity of proactive and reactive aggression in childhood. A genetic maturation hypothesis common to both phenotypes, albeit stronger for proactive aggression, was supported by common genetic factors associated with proactive and reactive aggression slopes. A shared environment set point hypothesis for proactive aggression was supported by shared environmental factors associated with proactive aggression baseline and slope. Although there are many common features to proactive and reactive aggression, the current research underscores the advantages of differentiating them when studying aggression. PMID:29211810

Genomic instability in cancer: Teetering on the limit of tolerance

PubMed Central

Andor, Noemi; Maley, Carlo C.; Ji, Hanlee P.

2017-01-01

Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared to intermediate levels under this threshold. This has been observed in clonal subpopulations of larger size, especially when genomic instability is shared among a limited number of clones. We hypothesize that cancers with extreme levels of genomic instability may be teetering on the brink of a threshold where so much of their genome is adversely altered that cells rarely replicate successfully. Another possibility is that tumors with high levels of genomic instability are more immunogenic than other cancers with a less extensive burden of genetic aberrations. Regardless of the exact mechanism, but hinging on our ability to quantify how a tumor’s burden of genetic aberrations is distributed among coexisting clones – genomic instability has important therapeutic implications. Herein, we explore the possibility that a high genomic instability could be the basis for a tumor’s sensitivity to DNA damaging therapies. We primarily focus on studies of epithelial-derived solid tumors. PMID:28432052

Pre-Columbian origins of Native American dog breeds, with only limited replacement by European dogs, confirmed by mtDNA analysis.

PubMed

van Asch, Barbara; Zhang, Ai-bing; Oskarsson, Mattias C R; Klütsch, Cornelya F C; Amorim, António; Savolainen, Peter

2013-09-07

Dogs were present in pre-Columbian America, presumably brought by early human migrants from Asia. Studies of free-ranging village/street dogs have indicated almost total replacement of these original dogs by European dogs, but the extent to which Arctic, North and South American breeds are descendants of the original population remains to be assessed. Using a comprehensive phylogeographic analysis, we traced the origin of the mitochondrial DNA lineages for Inuit, Eskimo and Greenland dogs, Alaskan Malamute, Chihuahua, xoloitzcuintli and perro sín pelo del Peru, by comparing to extensive samples of East Asian (n = 984) and European dogs (n = 639), and previously published pre-Columbian sequences. Evidence for a pre-Columbian origin was found for all these breeds, except Alaskan Malamute for which results were ambigous. No European influence was indicated for the Arctic breeds Inuit, Eskimo and Greenland dog, and North/South American breeds had at most 30% European female lineages, suggesting marginal replacement by European dogs. Genetic continuity through time was shown by the sharing of a unique haplotype between the Mexican breed Chihuahua and ancient Mexican samples. We also analysed free-ranging dogs, confirming limited pre-Columbian ancestry overall, but also identifying pockets of remaining populations with high proportion of indigenous ancestry, and we provide the first DNA-based evidence that the Carolina dog, a free-ranging population in the USA, may have an ancient Asian origin.

Initiative for standardization of reporting genetics of male infertility.

PubMed

Traven, Eva; Ogrinc, Ana; Kunej, Tanja

2017-02-01

The number of publications on research of male infertility is increasing. Technologies used in research of male infertility generate complex results and various types of data that need to be appropriately managed, arranged, and made available to other researchers for further use. In our previous study, we collected over 800 candidate loci for male fertility in seven mammalian species. However, the continuation of the work towards a comprehensive database of candidate genes associated with different types of idiopathic human male infertility is challenging due to fragmented information, obtained from a variety of technologies and various omics approaches. Results are published in different forms and usually need to be excavated from the text, which hinders the gathering of information. Standardized reporting of genetic anomalies as well as causative and risk factors of male infertility therefore presents an important issue. The aim of the study was to collect examples of diverse genomic loci published in association with human male infertility and to propose a standardized format for reporting genetic causes of male infertility. From the currently available data we have selected 75 studies reporting 186 representative genomic loci which have been proposed as genetic risk factors for male infertility. Based on collected and formatted data, we suggested a first step towards unification of reporting the genetics of male infertility in original and review studies. The proposed initiative consists of five relevant data types: 1) genetic locus, 2) race/ethnicity, number of participants (infertile/controls), 3) methodology, 4) phenotype (clinical data, disease ontology, and disease comorbidity), and 5) reference. The proposed form for standardized reporting presents a baseline for further optimization with additional genetic and clinical information. This data standardization initiative will enable faster multi-omics data integration, database development and sharing, establishing more targeted hypotheses, and facilitating biomarker discovery.

MtDNA and Y-chromosomal diversity in the Chachapoya, a population from the northeast Peruvian Andes-Amazon divide.

PubMed

Guevara, Evelyn K; Palo, Jukka U; Guillén, Sonia; Sajantila, Antti

2016-11-01

The ancient Chachapoya were an aggregate of several ethnic groups that shared a common language, religion, and material culture. They inhabited a territory at the juncture of the Andes and the Amazon basin. Their position between those ecozones most likely influenced their genetic composition. We attempted to better understand their population history by assessing the contemporary genetic diversity in the Chachapoya and three of their immediate neighbors (Huancas, Jivaro, and Cajamarca). We inferred signatures of demographic history and genetic affinities, and contrasted the findings with data from other populations on local and continental scales. We studied mitochondrial DNA (mtDNA; hypervariable segment [HVSI and HVSII]) and Y chromosome (23 short tandem repeats (STRs)) marker data in 382 modern individuals. We used Sanger sequencing for mtDNA and a commercially available kit for Y-chromosomal STR typing. The Chachapoya had affinities with various populations of Andean and Amazonian origin. When examining the Native American component, the Chachapoya displayed high levels of genetic diversity. Together with other parameters, for example, large Tajima's D and Fu's Fs, the data indicated no drastic reduction of the population size in the past. The high level of diversity in the Chachapoya, the lack of evidence of drift in the past, and genetic affinities with a broad range of populations in the Americas reflects an intricate population history in the region. The new genetic data from the Chachapoya indeed seems to point to a genetic complexity that is not yet resolved but beginning to be elucidated. Am. J. Hum. Biol. 28:857-867, 2016. © 2016Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genetic Relationships Between Schizophrenia, Bipolar Disorder, and Schizoaffective Disorder

PubMed Central

Cardno, Alastair G.

2014-01-01

There is substantial evidence for partial overlap of genetic influences on schizophrenia and bipolar disorder, with family, twin, and adoption studies showing a genetic correlation between the disorders of around 0.6. Results of genome-wide association studies are consistent with commonly occurring genetic risk variants, contributing to both the shared and nonshared aspects, while studies of large, rare chromosomal structural variants, particularly copy number variants, show a stronger influence on schizophrenia than bipolar disorder to date. Schizoaffective disorder has been less investigated but shows substantial familial overlap with both schizophrenia and bipolar disorder. A twin analysis is consistent with genetic influences on schizoaffective episodes being entirely shared with genetic influences on schizophrenic and manic episodes, while association studies suggest the possibility of some relatively specific genetic influences on broadly defined schizoaffective disorder, bipolar subtype. Further insights into genetic relationships between these disorders are expected as studies continue to increase in sample size and in technical and analytical sophistication, information on phenotypes beyond clinical diagnoses are increasingly incorporated, and approaches such as next-generation sequencing identify additional types of genetic risk variant. PMID:24567502

Continuity of Genetic and Environmental Influences on Cognition across the Life Span: A Meta-Analysis of Longitudinal Twin and Adoption Studies

PubMed Central

Tucker-Drob, Elliot M.; Briley, Daniel A.

2014-01-01

The longitudinal rank-order stability of cognitive ability increases dramatically over the lifespan. Multiple theoretical perspectives have proposed that genetic and/or environmental mechanisms underlie the longitudinal stability of cognition, and developmental trends therein. However, the patterns of stability of genetic and environmental influences on cognition over the lifespan largely remain poorly understood. We searched for longitudinal studies of cognition that reported raw genetically-informative longitudinal correlations or parameter estimates from longitudinal behavior genetic models. We identified 150 combinations of time points and measures from 15 independent longitudinal samples. In total, longitudinal data came from 4,538 monozygotic twin pairs raised together, 7,777 dizygotic twin pairs raised together, 34 monozygotic twin pairs raised apart, 78 dizygotic twin pairs raised apart, 141 adoptive sibling pairs, and 143 non-adoptive sibling pairs, ranging in age from infancy through late adulthood. At all ages, cross-time genetic correlations and shared environmental correlations were substantially larger than cross-time nonshared environmental correlations. Cross-time correlations for genetic and shared environmental components were low during early childhood, increased sharply over child development, and remained relatively high from adolescence through late adulthood. Cross-time correlations for nonshared environmental components were low across childhood and increased gradually to moderate magnitudes in adulthood. Increasing phenotypic stability over child development was almost entirely mediated by genetic factors. Time-based decay of genetic and shared environmental stability was more pronounced earlier in child development. Results are interpreted in reference to theories of gene-environment interaction and correlation. PMID:24611582

A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

PubMed

Lacourse, E; Boivin, M; Brendgen, M; Petitclerc, A; Girard, A; Vitaro, F; Paquin, S; Ouellet-Morin, I; Dionne, G; Tremblay, R E

2014-09-01

Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.

A classical twin study of PTSD symptoms and resilience: Evidence for a single spectrum of vulnerability to traumatic stress.

PubMed

Wolf, Erika J; Miller, Mark W; Sullivan, Danielle R; Amstadter, Ananda B; Mitchell, Karen S; Goldberg, Jack; Magruder, Kathryn M

2018-02-01

To examine shared genetic and environmental risk factors across PTSD symptoms and resilience. Classical twin study of 2010-2012 survey data conducted among 3,318 male twin pairs in the Vietnam Era Twin Registry. Analyses included: (a) estimates of genetic and environmental influences on PTSD symptom severity (as measured by the PTSD Checklist) and resilience (assessed with the Connor-Davidson Resilience Scale-10); (b) development of a latent model of traumatic stress, spanning both PTSD and resilience; and (c) estimates of genetic and environmental influences on this spectrum. The heritability of PTSD was 49% and of resilience was 25%. PTSD and resilience were correlated at r = -.59, and 59% of this correlation was attributable to a single genetic factor, whereas the remainder was due to a single non-shared environment factor. Resilience was also influenced by common and unique environmental factors not shared with PTSD, but there was no genetic factor specific to resilience. Confirmatory factor analysis supported the Development of a revised phenotype reflecting the broader dimension of traumatic stress, with biometric models suggesting increased heritability (66%) of this spectrum compared to PTSD or resilience individually. Genetic factors contribute to a single spectrum of traumatic stress reflecting resilience at one end and high symptom severity at the other. This carries implications for phenotype refinement in the search for molecular genetic markers of trauma-related psychopathology. Rather than focusing only on genetic risk for PTSD, molecular genetics research may benefit from evaluation of the broader spectrum of traumatic stress. © 2017 Wiley Periodicals, Inc.

Species delimitation and biogeography of two fir species (Abies) in central China: cytoplasmic DNA variation.

PubMed

Wang, J; Abbott, R J; Peng, Y L; Du, F K; Liu, J-Q

2011-10-01

It remains unclear how speciation history might contribute to species-specific variation and affect species delimitation. We examined concordance between cytoplasmic genetic variation and morphological taxonomy in two fir species, Abies chensiensis and A. fargesii, with overlapping distributions in central China. Range-wide genetic variation was investigated using mitochondrial (mt) and plastid (pt) DNA sequences, which contrast in their rates of gene flow. Four mtDNA haplotypes were recovered and showed no obvious species' bias in terms of relative frequency. In contrast, a high level of ptDNA variation was recorded in both species with 3 common ptDNA haplotypes shared between them and 21 rare ptDNA haplotypes specific to one or other species. We argue that the lack of concordance between morphological and molecular variation between the two fir species most likely reflects extensive ancestral polymorphism sharing for both forms of cytoplasmic DNA variation. It is feasible that a relatively fast mutation rate for ptDNA contributed to the production of many species-specific ptDNA haplotypes, which remained rare due to insufficient time passing for their spread and fixation in either species, despite high levels of intraspecific ptDNA gene flow. Our phylogeographic analyses further suggest that polymorphisms in both organelle genomes most likely originated during and following glacial intervals preceding the last glacial maximum, when species distributions became fragmented into several refugia and then expanded in range across central China.

Genetic diversity reflects geographical origin of Ralstonia solanacearum strains isolated from plant and water sources in Spain.

PubMed

Caruso, Paola; Biosca, Elena G; Bertolini, Edson; Marco-Noales, Ester; Gorris, María Teresa; Licciardello, Concetta; López, María M

2017-12-01

The characterization and intraspecific diversity of a collection of 45 Ralstonia solanacearum strains isolated in Spain from different sources and geographical origins is reported. To test the influence of the site and the host on strain diversity, phenotypic and genotypic analysis were performed by a polyphasic approach. Biochemical and metabolic profiles were compared. Serological relationship was evaluated by Indirect-ELISA using polyclonal and monoclonal antibodies. For genotypic analysis, hrpB and egl DNA sequence analysis, repetitive sequences (rep-PCR), amplified fragment length polymorphism (AFLP) profiles and macrorestriction with XbaI followed by pulsed field gel electrophoresis (PFGE) were performed. The biochemical and metabolic characterization, serological tests, rep-PCR typing and phylogenetic analysis showed that all analysed strains belonged to phylotype II sequevar 1 and shared homogeneous profiles. However, interesting differences among strains were found by AFLP and macrorestriction with XbaI followed by PFGE techniques, some profiles being related to the geographical origin of the strains. Diversity results obtained offer new insights into the biogeography of this quarantine organism and its possible sources and reservoirs in Spain and Mediterranean countries. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

Character trees from transcriptome data: Origin and individuation of morphological characters and the so-called "species signal".

PubMed

Musser, Jacob M; Wagner, Günter P

2015-11-01

We elaborate a framework for investigating the evolutionary history of morphological characters. We argue that morphological character trees generated by phylogenetic analysis of transcriptomes provide a useful tool for identifying causal gene expression differences underlying the development and evolution of morphological characters. They also enable rigorous testing of different models of morphological character evolution and origination, including the hypothesis that characters originate via divergence of repeated ancestral characters. Finally, morphological character trees provide evidence that character transcriptomes undergo concerted evolution. We argue that concerted evolution of transcriptomes can explain the so-called "species signal" found in several recent comparative transcriptome studies. The species signal is the phenomenon that transcriptomes cluster by species rather than character type, even though the characters are older than the respective species. We suggest the species signal is a natural consequence of concerted gene expression evolution resulting from mutations that alter gene regulatory network interactions shared by the characters under comparison. Thus, character trees generated from transcriptomes allow us to investigate the variational independence, or individuation, of morphological characters at the level of genetic programs. © 2015 Wiley Periodicals, Inc.

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.

A population-based study of anxiety as a precursor for depression in childhood and adolescence.

PubMed

Rice, Frances; van den Bree, Marianne B M; Thapar, Anita

2004-12-13

Anxiety and depression co-occur in children and adolescents with anxiety commonly preceding depression. Although there is some evidence to suggest that the association between early anxiety and later depression is explained by a shared genetic aetiology, the contribution of environmental factors is less well examined and it is unknown whether anxiety itself is a phenotypic risk factor for later depression. These explanations of the association between early anxiety and later depression were evaluated. Anxiety and depressive symptoms were assessed longitudinally in a U.K. population-based sample of 676 twins aged 5-17 at baseline. At baseline, anxiety and depression were assessed by parental questionnaire. Depression was assessed three years later by parental and adolescent questionnaire. Shared genetic effects between early anxiety and later depression were found. A model of a phenotypic risk effect from early anxiety on later depression provided a poor fit to the data. However, there were significant genetic effects specific to later depression, showing that early anxiety and later depression do not index entirely the same genetic risk. Anxiety and depression are associated over time because they share a partly common genetic aetiology rather than because the anxiety phenotype leads to later depression.

Genetic and environmental sources of individual religiousness: the roles of individual personality traits and perceived environmental religiousness.

PubMed

Kandler, Christian; Riemann, Rainer

2013-07-01

In the current study, we examined the genetic and environmental sources of the links between individual religiousness and individual personality traits, perceived parental religiousness, and perceived peer religiousness. Data from 870 individuals (incl. 394 twin pairs) were analyzed. Variance in individual religiousness was significantly influenced by genetic effects, environmental influences shared by twins reared together, and individual-specific environmental influences. Individual religiousness showed significant associations with age, sex, specific personality traits (e.g., agreeableness, openness to values), and perceived religiousness of important social interaction partners, such as parents, best friends, and spouses. The links to personality traits were relatively small and primarily genetically mediated. The associations between individual religiousness and parental religiousness were substantial and mediated by shared environmental effects. These links significantly decreased across age accompanying a significant decrease of shared environmental influences on individual religiousness. The correlations between individual religiousness and perceived religiousness of spouses and best friends were relatively moderate but increased with age. These associations were mediated by genetic as well as nonshared environmental sources accompanying an increase of nonshared environmental influences on individual religiousness with age. The results suggest that inter-individual differences in religiousness are due to multiple sources.

Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants

PubMed Central

Bagley, Steven C.; Sirota, Marina; Chen, Richard; Butte, Atul J.; Altman, Russ B.

2016-01-01

Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups. PMID:27115429

Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants.

PubMed

Bagley, Steven C; Sirota, Marina; Chen, Richard; Butte, Atul J; Altman, Russ B

2016-04-01

Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups.

Stability and change in temperament during adolescence.

PubMed

Ganiban, Jody M; Saudino, Kimberly J; Ulbricht, Jennifer; Neiderhiser, Jenae M; Reiss, David

2008-07-01

This study assessed genetic and environmental contributions to temperament during adolescence within the Nonshared Environment and Adolescent Development project (NEAD; D. Reiss, J. M. Neiderhiser, E. M. Hetherington, & R. Plomin, 2000). NEAD is a national study that includes twins and other sibling types who vary in regard to genetic relatedness. Seven hundred twenty sibling pairs (aged 12.1-13.5 years) participated at Time 1, and 395 sibling pairs (aged 14.7-16.2 years) participated again at Time 2. At both Times, mothers and fathers rated their children's temperament (emotionality, activity, sociability, and shyness). At Times 1 and 2, genetic and nonshared environmental factors accounted for variance in temperament, whereas shared environmental contributions were negligible. However, at Time 1, genetic contributions were inflated, and shared environmental contributions were masked if sibling contrast effects were not taken into account. At Time 2, sibling interaction effects had little impact on estimates of genetic and environmental contributions to temperament. Last, temperament stability was primarily explained by genetic factors, whereas both genetic and nonshared environmental factors accounted for change.

[Prospect and application of microsatellite population genetics in study of geoherbs].

PubMed

Zhang, Wen-Jing; Zhang, Yong-Qing; Yuan, Qing-Jun; Huang, Lu-Qi; Jiang, Dan; Jing, Li

2013-12-01

The author introduces the basic concepts of microsatellite and population genetics and its characteristics, expounds the application of these theories for population genetic structure and genetic diversity, gene flow and evolutionary significant unit ESU division research. This paper discuss its applicationin study of genetic causes, origin of cultivation, different regional origins of geoherbs, aiming at providing a new theory and method for geoherbs.

Microsatellite analysis of chloroquine resistance associated alleles and neutral loci reveal genetic structure of Indian Plasmodium falciparum

PubMed Central

Mallick, Prashant K.; Sutton, Patrick L.; Singh, Ruchi; Singh, Om P.; Dash, Aditya P.; Singh, Ashok K.; Carlton, Jane M.; Bhasin, Virendra K.

2013-01-01

Efforts to control malignant malaria caused by Plasmodium falciparum are hampered by the parasite’s acquisition of resistance to antimalarial drugs, e.g., chloroquine. This necessitates evaluating the spread of chloroquine resistance in any malaria-endemic area. India displays highly variable malaria epidemiology and also shares porous international borders with malaria-endemic Southeast Asian countries having multi-drug resistant malaria. Malaria epidemiology in India is believed to be affected by two major factors: high genetic diversity and evolving drug resistance in P. falciparum. How transmission intensity of malaria can influence the genetic structure of chloroquine-resistant P. falciparum population in India is unknown. Here, genetic diversity within and among P. falciparum populations is analyzed with respect to their prevalence and chloroquine resistance observed in 13 different locations in India. Microsatellites developed for P. falciparum, including three putatively neutral and seven microsatellites thought to be under a hitchhiking effect due to chloroquine selection were used. Genetic hitchhiking is observed in five of seven microsatellites flanking the gene responsible for chloroquine resistance. Genetic admixture analysis and F-statistics detected genetically distinct groups in accordance with transmission intensity of different locations and the probable use of chloroquine. A large genetic break between the chloroquine-resistant parasite of the Northeast-East-Island group and Southwest group (FST = 0.253, P<0.001) suggests a long period of isolation or a possibility of different origin between them. A pattern of significant isolation by distance was observed in low transmission areas (r = 0.49, P=0.003, N = 83, Mantel test). An unanticipated pattern of spread of hitchhiking suggests genetic structure for Indian P. falciparum population. Overall, the study suggests that transmission intensity can be an efficient driver for genetic differentiation at both neutral and adaptive loci across India. PMID:23871774

Microsatellite analysis of chloroquine resistance associated alleles and neutral loci reveal genetic structure of Indian Plasmodium falciparum.

PubMed

Mallick, Prashant K; Sutton, Patrick L; Singh, Ruchi; Singh, Om P; Dash, Aditya P; Singh, Ashok K; Carlton, Jane M; Bhasin, Virendra K

2013-10-01

Efforts to control malignant malaria caused by Plasmodium falciparum are hampered by the parasite's acquisition of resistance to antimalarial drugs, e.g., chloroquine. This necessitates evaluating the spread of chloroquine resistance in any malaria-endemic area. India displays highly variable malaria epidemiology and also shares porous international borders with malaria-endemic Southeast Asian countries having multi-drug resistant malaria. Malaria epidemiology in India is believed to be affected by two major factors: high genetic diversity and evolving drug resistance in P. falciparum. How transmission intensity of malaria can influence the genetic structure of chloroquine-resistant P. falciparum population in India is unknown. Here, genetic diversity within and among P. falciparum populations is analyzed with respect to their prevalence and chloroquine resistance observed in 13 different locations in India. Microsatellites developed for P. falciparum, including three putatively neutral and seven microsatellites thought to be under a hitchhiking effect due to chloroquine selection were used. Genetic hitchhiking is observed in five of seven microsatellites flanking the gene responsible for chloroquine resistance. Genetic admixture analysis and F-statistics detected genetically distinct groups in accordance with transmission intensity of different locations and the probable use of chloroquine. A large genetic break between the chloroquine-resistant parasite of the Northeast-East-Island group and Southwest group (FST=0.253, P<0.001) suggests a long period of isolation or a possibility of different origin between them. A pattern of significant isolation by distance was observed in low transmission areas (r=0.49, P=0.003, N=83, Mantel test). An unanticipated pattern of spread of hitchhiking suggests genetic structure for Indian P. falciparum population. Overall, the study suggests that transmission intensity can be an efficient driver for genetic differentiation at both neutral and adaptive loci across India. Copyright © 2013 Elsevier B.V. All rights reserved.

The Genetic Overlap of Attention-Deficit/Hyperactivity Disorder and Autistic-like Traits: an Investigation of Individual Symptom Scales and Cognitive markers.

PubMed

Pinto, Rebecca; Rijsdijk, Fruhling; Ronald, Angelica; Asherson, Philip; Kuntsi, Jonna

2016-02-01

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) frequently co-occur. However, due to previous exclusionary diagnostic criteria, little is known about the underlying causes of this covariation. Twin studies assessing ADHD symptoms and autistic-like traits (ALTs) suggest substantial genetic overlap, but have largely failed to take into account the genetic heterogeneity of symptom subscales. This study aimed to clarify the phenotypic and genetic relations between ADHD and ASD by distinguishing between symptom subscales that characterise the two disorders. Moreover, we aimed to investigate whether ADHD-related cognitive impairments show a relationship with ALT symptom subscales; and whether potential shared cognitive impairments underlie the genetic risk shared between the ADHD and ALT symptoms. Multivariate structural equation modelling was conducted on a population-based sample of 1312 twins aged 7-10. Social-communication ALTs correlated moderately with both ADHD symptom domains (phenotypic correlations around 0.30) and showed substantial genetic overlap with both inattention and hyperactivity-impulsivity (genetic correlation = 0.52 and 0.44, respectively). In addition to previously reported associations with ADHD traits, reaction time variability (RTV) showed significant phenotypic (0.18) and genetic (0.32) association with social-communication ALTs. RTV captured a significant proportion (24 %) of the genetic influences shared between inattention and social-communication ALTs. Our findings suggest that social-communication ALTs underlie the previously observed phenotypic and genetic covariation between ALTs and ADHD symptoms. RTV is not specific to ADHD symptoms, but is also associated with social-communication ALTs and can, in part, contribute to an explanation of the co-occurrence of ASD and ADHD.

Common genetic architecture underlying young children's food fussiness and liking for vegetables and fruit.

PubMed

Fildes, Alison; van Jaarsveld, Cornelia H M; Cooke, Lucy; Wardle, Jane; Llewellyn, Clare H

2016-04-01

Food fussiness (FF) is common in early childhood and is often associated with the rejection of nutrient-dense foods such as vegetables and fruit. FF and liking for vegetables and fruit are likely all heritable phenotypes; the genetic influence underlying FF may explain the observed genetic influence on liking for vegetables and fruit. Twin analyses make it possible to get a broad-based estimate of the extent of the shared genetic influence that underlies these traits. We quantified the extent of the shared genetic influence that underlies FF and liking for vegetables and fruit in early childhood with the use of a twin design. Data were from the Gemini cohort, which is a population-based sample of twins born in England and Wales in 2007. Parents of 3-y-old twins (n= 1330 pairs) completed questionnaire measures of their children's food preferences (liking for vegetables and fruit) and the FF scale from the Children's Eating Behavior Questionnaire. Multivariate quantitative genetic modeling was used to estimate common genetic influences that underlie FF and liking for vegetables and fruit. Genetic correlations were significant and moderate to large in size between FF and liking for both vegetables (-0.65) and fruit (-0.43), which indicated that a substantial proportion of the genes that influence FF also influence liking. Common genes that underlie FF and liking for vegetables and fruit largely explained the observed phenotypic correlations between them (68-70%). FF and liking for fruit and vegetables in young children share a large proportion of common genetic factors. The genetic influence on FF may determine why fussy children typically reject fruit and vegetables.

Population Structure of Pythium irregulare, P. ultimum, and P. sylvaticum in Forest Nursery Soils of Oregon and Washington.

PubMed

Weiland, Jerry E; Garrido, Patricia; Kamvar, Zhian N; Espíndola, Andrés S; Marek, Stephen M; Grünwald, Niklaus J; Garzón, Carla D

2015-05-01

Pythium species are important soilborne pathogens occurring in the forest nursery industry of the Pacific Northwest. However, little is known about their genetic diversity or population structure and it is suspected that isolates are moved among forest nurseries on seedling stock and shared field equipment. In order to address these concerns, a total of 115 isolates of three Pythium species (P. irregulare, P. sylvaticum, and P. ultimum) were examined at three forest nurseries using simple sequence repeat (SSR) and amplified fragment length polymorphism (AFLP) markers. Analyses revealed distinct patterns of intraspecific variation for the three species. P. sylvaticum exhibited the most diversity, followed by P. irregulare, while substantial clonality was found in P. ultimum. For both P. irregulare and P. sylvaticum, but not P. ultimum, there was evidence for significant variation among nurseries. However, all three species also exhibited at least two distinct lineages not associated with the nursery of origin. Finally, evidence was found that certain lineages and clonal genotypes, including fungicide-resistant isolates, are shared among nurseries, indicating that pathogen movement has occurred.

Common genetic variants explain the majority of the correlation between height and intelligence: the generation Scotland study.

PubMed

Marioni, Riccardo E; Batty, G David; Hayward, Caroline; Kerr, Shona M; Campbell, Archie; Hocking, Lynne J; Porteous, David J; Visscher, Peter M; Deary, Ian J

2014-03-01

Greater height and higher intelligence test scores are predictors of better health outcomes. Here, we used molecular (single-nucleotide polymorphism) data to estimate the genetic correlation between height and general intelligence (g) in 6,815 unrelated subjects (median age 57, IQR 49-63) from the Generation Scotland: Scottish Family Health Study cohort. The phenotypic correlation between height and g was 0.16 (SE 0.01). The genetic correlation between height and g was 0.28 (SE 0.09) with a bivariate heritability estimate of 0.71. Understanding the molecular basis of the correlation between height and intelligence may help explain any shared role in determining health outcomes. This study identified a modest genetic correlation between height and intelligence with the majority of the phenotypic correlation being explained by shared genetic influences.

Added value measures in education show genetic as well as environmental influence.

PubMed

Haworth, Claire M A; Asbury, Kathryn; Dale, Philip S; Plomin, Robert

2011-02-02

Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%). The pervasiveness of genetic influence in how and how much children learn is compatible with an active view of learning in which children create their own educational experiences in part on the basis of their genetic propensities.

Genetic architecture of verbal abilities in children and adolescents.

PubMed

Hoekstra, Rosa A; Bartels, Meike; van Leeuwen, Marieke; Boomsma, Dorret I

2009-11-01

The etiology of individual differences in general verbal ability, verbal learning and letter and category fluency were examined in two independent samples of 9- and 18-year-old twin pairs and their siblings. In both age groups, we observed strong familial resemblance for general verbal ability and moderate familial resemblance for verbal learning, letter and category fluency. All familial resemblance was explained by genetic factors. There was significant covariance among the tests, which was stronger in magnitude in the adolescent cohort. The covariance was mainly explained by genetic effects shared by subtests, both in middle childhood and in late adolescence. In addition to a shared set of genes that influenced all phenotypes, there were also genetic influences specific to the different verbal phenotypes.

An overview of human genetic privacy

PubMed Central

Shi, Xinghua; Wu, Xintao

2016-01-01

The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. PMID:27626905

'Candidatus Phytoplasma phoenicium' associated with almond witches'-broom disease: from draft genome to genetic diversity among strain populations.

PubMed

Quaglino, Fabio; Kube, Michael; Jawhari, Maan; Abou-Jawdah, Yusuf; Siewert, Christin; Choueiri, Elia; Sobh, Hana; Casati, Paola; Tedeschi, Rosemarie; Lova, Marina Molino; Alma, Alberto; Bianco, Piero Attilio

2015-07-30

Almond witches'-broom (AlmWB), a devastating disease of almond, peach and nectarine in Lebanon, is associated with 'Candidatus Phytoplasma phoenicium'. In the present study, we generated a draft genome sequence of 'Ca. P. phoenicium' strain SA213, representative of phytoplasma strain populations from different host plants, and determined the genetic diversity among phytoplasma strain populations by phylogenetic analyses of 16S rRNA, groEL, tufB and inmp gene sequences. Sequence-based typing and phylogenetic analysis of the gene inmp, coding an integral membrane protein, distinguished AlmWB-associated phytoplasma strains originating from diverse host plants, whereas their 16S rRNA, tufB and groEL genes shared 100 % sequence identity. Moreover, dN/dS analysis indicated positive selection acting on inmp gene. Additionally, the analysis of 'Ca. P. phoenicium' draft genome revealed the presence of integral membrane proteins and effector-like proteins and potential candidates for interaction with hosts. One of the integral membrane proteins was predicted as BI-1, an inhibitor of apoptosis-promoting Bax factor. Bioinformatics analyses revealed the presence of putative BI-1 in draft and complete genomes of other 'Ca. Phytoplasma' species. The genetic diversity within 'Ca. P. phoenicium' strain populations in Lebanon suggested that AlmWB disease could be associated with phytoplasma strains derived from the adaptation of an original strain to diverse hosts. Moreover, the identification of a putative inhibitor of apoptosis-promoting Bax factor (BI-1) in 'Ca. P. phoenicium' draft genome and within genomes of other 'Ca. Phytoplasma' species suggested its potential role as a phytoplasma fitness-increasing factor by modification of the host-defense response.

Mitochondrial DNA perspective of Serbian genetic diversity.

PubMed

Davidovic, Slobodan; Malyarchuk, Boris; Aleksic, Jelena M; Derenko, Miroslava; Topalovic, Vladanka; Litvinov, Andrey; Stevanovic, Milena; Kovacevic-Grujicic, Natasa

2015-03-01

Although south-Slavic populations have been studied to date from various aspects, the population of Serbia, occupying the central part of the Balkan Peninsula, is still genetically understudied at least at the level of mitochondrial DNA (mtDNA) variation. We analyzed polymorphisms of the first and the second mtDNA hypervariable segments (HVS-I and HVS-II) and informative coding-region markers in 139 Serbians to shed more light on their mtDNA variability, and used available data on other Slavic and neighboring non-Slavic populations to assess their interrelations in a broader European context. The contemporary Serbian mtDNA profile is consistent with the general European maternal landscape having a substantial proportion of shared haplotypes with eastern, central, and southern European populations. Serbian population was characterized as an important link between easternmost and westernmost south-Slavic populations due to the observed lack of genetic differentiation with all other south-Slavic populations and its geographical positioning within the Balkan Peninsula. An increased heterogeneity of south Slavs, most likely mirroring turbulent demographic events within the Balkan Peninsula over time (i.e., frequent admixture and differential introgression of various gene pools), and a marked geographical stratification of Slavs to south-, east-, and west-Slavic groups, were also found. A phylogeographic analyses of 20 completely sequenced Serbian mitochondrial genomes revealed not only the presence of mtDNA lineages predominantly found within the Slavic gene pool (U4a2a*, U4a2a1, U4a2c, U4a2g, HV10), supporting a common Slavic origin, but also lineages that may have originated within the southern Europe (H5*, H5e1, H5a1v) and the Balkan Peninsula in particular (H6a2b and L2a1k). © 2014 Wiley Periodicals, Inc.

Genetic variability, phylogenetic relationships and gene flow in Triatoma infestans dark morphs from the Argentinean Chaco

PubMed Central

Piccinali, R. V.; Marcet, P. L.; Ceballos, L. A.; Kitron, U.; Gürtler, R. E.; Dotson, E. M.

2011-01-01

The recent discovery of sylvatic populations of Triatoma infestans outside the Andean Valleys of Bolivia prompted an evolutionary question about the putative ancestral area of origin and dispersal of the species, and an epidemiological question regarding the possible role of these sylvatic populations in the recolonization process of insecticide-treated houses. The finding of a population of sylvatic melanic T. infestans (dark morphs) in the Argentinean dry Chaco at 7 km from a peridomestic bug population of typical coloration gave us the opportunity to test both questions simultaneously by employing phylogenetic and population genetic approaches. For this purpose we analyzed sylvatic and peridomestic bugs using sequence-based mitochondrial and nuclear markers (mtCOI and ITS-1) and microsatellites. Sylvatic bugs were confirmed to be T. infestans and not hybrids, and showed high levels of genetic variability and departures from neutral expectations for mtCOI variation. New ITS-1 and mtCOI haplotypes were recorded, as well as haplotypes shared with peridomestic and/or domestic bugs from previous records. The peridomestic population was invariant for ITS-1 and mtCOI, but showed variability for microsatellites and signatures of a population bottleneck, probably due to a limited number of founders. Phylogenetic analyses were consistent with the presence of ancestral haplotypes in sylvatic bugs. According to F-statistics and assignment methods there was a significant differentiation between sylvatic and peridomestic bugs and gene flow was low and asymmetric, with more bugs moving from the peridomicile to the sylvatic environment. These results support the hypothesis of the Chaco region as the area of origin of T. infestans, and a limited role of sylvatic melanic T. infestans in peridomestic infestation in the Argentinean Chaco. PMID:21352954

Sex differences in genetic and environmental contributions to alcohol consumption from early adolescence to young adulthood.

PubMed

Seglem, Karoline B; Waaktaar, Trine; Ask, Helga; Torgersen, Svenn

2016-07-01

To estimate genetic and environmental contributions to alcohol consumption from early adolescence to young adulthood, and test whether gender moderates these effects. Longitudinal twin cohort design. Population-based sample from Norway. A total of 2862 male and female twins, aged 14-22 years, were assessed at one (n = 881), two (n = 898) or three (n = 1083) occasions. The percentage of females was between 56 and 63 in the different age groups (in the different waves). Alcohol consumption was measured by two questionnaire items about frequency of alcohol use and frequency of being drunk. Additive genetic effects showed low to moderate contributions [proportion estimate, 95% confidence interval (CI) = range from 0.03 (0.00-0.14) to 0.49 (0.37-0.59) in males and from 0.09 (0.00-0.57) to 0.41 (0.24-0.58) in females] from adolescence to young adulthood, while environmental influences shared by twin pairs and contributing to twin similarity were moderate to highly influential during this developmental period [proportion estimate, 95% CI = range from 0.04 (0.00-0.13) to 0.45 (0.26-0.60) in males for shared environment in common with females, from 0.25 (0.09-0.42) to 0.54 (0.06-0.78) for shared environment specific to males and from 0.36 (0.20-0.52) to 0.51 (0.37-0.71) in females]. There was evidence of qualitative sex differences with shared environmental influences being largely sex-specific from middle adolescence onwards. Alcohol consumption from early adolescence to young adulthood appears to be influenced to a small to moderate degree by genetic factors and to a moderate to high degree by shared environmental factors (e.g. rearing influences, shared friends). The shared environmental factors influencing alcohol consumption appear to be largely gender-specific. © 2016 Society for the Study of Addiction.

A Twin Study of Normative Personality and DSM-IV Personality Disorder Criterion Counts: Evidence for Separate Genetic Influences.

PubMed

Czajkowski, Nikolai; Aggen, Steven H; Krueger, Robert F; Kendler, Kenneth S; Neale, Michael C; Knudsen, Gun Peggy; Gillespie, Nathan A; Røysamb, Espen; Tambs, Kristian; Reichborn-Kjennerud, Ted

2018-03-21

Both normative personality and DSM-IV personality disorders have been found to be heritable. However, there is limited knowledge about the extent to which the genetic and environmental influences underlying DSM personality disorders are shared with those of normative personality. The aims of this study were to assess the phenotypic similarity between normative and pathological personality and to investigate the extent to which genetic and environmental influences underlying individual differences in normative personality account for symptom variance across DSM-IV personality disorders. A large population-based sample of adult twins was assessed for DSM-IV personality disorder criteria with structured interviews at two waves spanning a 10-year interval. At the second assessment, participants also completed the Big Five Inventory, a self-report instrument assessing the five-factor normative personality model. The proportion of genetic and environmental liabilities unique to the individual personality disorder measures, and hence not shared with the five Big Five Inventory domains, were estimated by means of multivariate Cholesky twin decompositions. The median percentage of genetic liability to the 10 DSM-IV personality disorders assessed at wave 1 that was not shared with the Big Five domains was 64%, whereas for the six personality disorders that were assessed concurrently at wave 2, the median was 39%. Conversely, the median proportions of unique environmental liability in the personality disorders for wave 1 and wave 2 were 97% and 96%, respectively. The results indicate that a moderate-to-sizable proportion of the genetic influence underlying DSM-IV personality disorders is not shared with the domain constructs of the Big Five model of normative personality. Caution should be exercised in assuming that normative personality measures can serve as proxies for DSM personality disorders when investigating the etiology of these disorders.

The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry

PubMed Central

Davidson, Natalie R.; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L.; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

2016-01-01

The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19–33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so. PMID:27010569

The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry.

PubMed

Waldman, Yedael Y; Biddanda, Arjun; Davidson, Natalie R; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

2016-01-01

The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19-33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so.

The dog originated south of Yangtse river less than 16,000 years ago, from numerous wolves

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

Leitner, Thomas; Pang, Jun - Feng; Kluetsch, Cornelya

We here present a detailed picture of the origins of the dog, giving strong and precise evidence for 'where and when', and thereby also a first tentative picture of 'how, why and by whom' the wolf was domesticated. Previous studies of mitochondrial DNA (mtDNA) have failed to definitely establish the time and place of origin because of lack in phylogenetic resolution for the so far studied 582 bp region, and inadequate sampling across the world. We therefore analysed 169 mtDNA genomes, selected from partial sequences (582 bp) from 1,576 dogs worldwide. This shows that dogs universally share a common genemore » pool, but the three earlier identified universally occurring phylogenetic clades ofhigh age consist often much younger subclades, which originated 5,000-16,000 ya from at least 48 wolf founders. The full range of genetic diversity, all 10 subclades, is found only in south-eastern Asia south of Yangtze River, and the diversity decreases gradually across Eurasia down to only four sub clades in Europe. This establishes that the dog has a single origin in time and space from a large number ofwolves, less than 16,000 ya, probably in China south of Y angtzeRiver. The place and time coincide with the origin of rice agriculture, suggesting an origin among sedentary hunter-gatherers or early rice farmers. The numerous founders indicate that wolf taming was an important cultural trait, and it is noticeable that in this region dogs are since ancient times used as food, offering a possible reason for the wolf domestication.« less

Modeling and Dynamic Analysis of Paralleled of dc/dc Converters with Master-Slave Current Sharing Control

NASA Technical Reports Server (NTRS)

Rajagopalan, J.; Xing, K.; Guo, Y.; Lee, F. C.; Manners, Bruce

1996-01-01

A simple, application-oriented, transfer function model of paralleled converters employing Master-Slave Current-sharing (MSC) control is developed. Dynamically, the Master converter retains its original design characteristics; all the Slave converters are forced to depart significantly from their original design characteristics into current-controlled current sources. Five distinct loop gains to assess system stability and performance are identified and their physical significance is described. A design methodology for the current share compensator is presented. The effect of this current sharing scheme on 'system output impedance' is analyzed.

Association between genetic risk scoring for schizophrenia and bipolar disorder with regional subcortical volumes.

PubMed

Caseras, X; Tansey, K E; Foley, S; Linden, D

2015-12-08

Previous research has shown coincident abnormal regional brain volume in patients with schizophrenia (SCZ) and bipolar disorder (BD) compared with controls. Whether these abnormalities are genetically driven or explained by secondary effects of the disorder or environmental factors is unknown. We aimed to investigate the association between genetic risk scoring (GRS) for SCZ and BD with volume of brain areas previously shown to be different between these clinical groups and healthy controls. We obtained subcortical brain volume measures and GRS for SCZ and BD from a sample of 274 healthy volunteers (71.4% females, mean age 24.7 (s.d. 6.9)). Volume of the globus pallidus was associated with the shared GRS between SCZ and BD, and also with the independent GRS for each of these disorders. Volume of the amygdala was associated with the non-shared GRS between SCZ and BD, and with the independent GRS for BD. Our results for volume of the globus pallidus support the idea of SCZ and BD sharing a common underlying neurobiological abnormality associated with a common genetic risk for both these disorders. Results for volume of the amygdala, though, would suggest the existence of a distinct mechanism only associated with genetic risk for BD. Finally, the lack of association between genetic risk and volume of most subcortical structures suggests that the volumetric differences reported in patient-control comparisons may not be genetically driven, but a consequence of the disorder or co-occurring environmental factors.

Genetic and environmental influences on conduct and antisocial personality problems in childhood, adolescence, and adulthood.

PubMed

Wesseldijk, Laura W; Bartels, Meike; Vink, Jacqueline M; van Beijsterveldt, Catharina E M; Ligthart, Lannie; Boomsma, Dorret I; Middeldorp, Christel M

2017-06-21

Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and unique environmental factors on variation in conduct problems measured at childhood and adolescence and antisocial personality problems measured at adulthood and on the covariation across ages. We also tested whether these estimates differed by sex. Longitudinal data were collected in the Netherlands Twin Register over a period of 27 years. Age appropriate and comparable measures of conduct and antisocial personality problems, assessed with the Achenbach System of Empirically Based Assessment, were available for 9783 9-10-year-old, 6839 13-18-year-old, and 7909 19-65-year-old twin pairs, respectively; 5114 twins have two or more assessments. At all ages, men scored higher than women. There were no sex differences in the estimates of the genetic and environmental influences. During childhood, genetic and environmental factors shared by children in families explained 43 and 44% of the variance of conduct problems, with the remaining variance due to unique environment. During adolescence and adulthood, genetic and unique environmental factors equally explained the variation. Longitudinal correlations across age varied between 0.20 and 0.38 and were mainly due to stable genetic factors. We conclude that shared environment is mainly of importance during childhood, while genetic factors contribute to variation in conduct and antisocial personality problems at all ages, and also underlie its stability over age.

Offering to Share: How to Put Heads Together in Autism Neuroimaging

ERIC Educational Resources Information Center

Belmonte, Matthew K.; Mazziotta, John C.; Minshew, Nancy J.; Evans, Alan C.; Courchesne, Eric; Dager, Stephen R.; Bookheimer, Susan Y.; Aylward, Elizabeth H.; Amaral, David G.; Cantor, Rita M.; Chugani, Diane C.; Dale, Anders M.; Davatzikos, Christos; Gerig, Guido; Herbert, Martha R.; Lainhart, Janet E.; Murphy, Declan G.; Piven, Joseph; Reiss, Allan L.; Schultz, Robert T.; Zeffiro, Thomas A.; Levi-Pearl, Susan; Lajonchere, Clara; Colamarino, Sophia A.

2008-01-01

Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including…

Psychopathology in 7-year-old children: Differences in maternal and paternal ratings and the genetic epidemiology.

PubMed

Wesseldijk, Laura W; Fedko, Iryna O; Bartels, Meike; Nivard, Michel G; van Beijsterveldt, Catharina E M; Boomsma, Dorret I; Middeldorp, Christel M

2017-04-01

The assessment of children's psychopathology is often based on parental report. Earlier studies have suggested that rater bias can affect the estimates of genetic, shared environmental and unique environmental influences on differences between children. The availability of a large dataset of maternal as well as paternal ratings of psychopathology in 7-year old children enabled (i) the analysis of informant effects on these assessments, and (ii) to obtain more reliable estimates of the genetic and non-genetic effects. DSM-oriented measures of affective, anxiety, somatic, attention-deficit/hyperactivity, oppositional-defiant, conduct, and obsessive-compulsive problems were rated for 12,310 twin pairs from the Netherlands Twin Register by mothers (N = 12,085) and fathers (N = 8,516). The effects of genetic and non-genetic effects were estimated on the common and rater-specific variance. For all scales, mean scores on maternal ratings exceeded paternal ratings. Parents largely agreed on the ranking of their child's problems (r 0.60-0.75). The heritability was estimated over 55% for maternal and paternal ratings for all scales, except for conduct problems (44-46%). Unbiased shared environmental influences, i.e., on the common variance, were significant for affective (13%), oppositional (13%), and conduct problems (37%). In clinical settings, different cutoffs for (sub)clinical scores could be applied to paternal and maternal ratings of their child's psychopathology. Only for conduct problems, shared environmental and genetic influences explain an equal amount in differences between children. For the other scales, genetic factors explain the majority of the variance, especially for the common part that is free of rater bias. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.