Drift, selection, or migration? Processes affecting genetic differentiation and variation along a latitudinal gradient in an amphibian.

PubMed

Cortázar-Chinarro, Maria; Lattenkamp, Ella Z; Meyer-Lucht, Yvonne; Luquet, Emilien; Laurila, Anssi; Höglund, Jacob

2017-08-14

Past events like fluctuations in population size and post-glacial colonization processes may influence the relative importance of genetic drift, migration and selection when determining the present day patterns of genetic variation. We disentangle how drift, selection and migration shape neutral and adaptive genetic variation in 12 moor frog populations along a 1700 km latitudinal gradient. We studied genetic differentiation and variation at a MHC exon II locus and a set of 18 microsatellites. Using outlier analyses, we identified the MHC II exon 2 (corresponding to the β-2 domain) locus and one microsatellite locus (RCO8640) to be subject to diversifying selection, while five microsatellite loci showed signals of stabilizing selection among populations. STRUCTURE and DAPC analyses on the neutral microsatellites assigned populations to a northern and a southern cluster, reflecting two different post-glacial colonization routes found in previous studies. Genetic variation overall was lower in the northern cluster. The signature of selection on MHC exon II was weaker in the northern cluster, possibly as a consequence of smaller and more fragmented populations. Our results show that historical demographic processes combined with selection and drift have led to a complex pattern of differentiation along the gradient where some loci are more divergent among populations than predicted from drift expectations due to diversifying selection, while other loci are more uniform among populations due to stabilizing selection. Importantly, both overall and MHC genetic variation are lower at northern latitudes. Due to lower evolutionary potential, the low genetic variation in northern populations may increase the risk of extinction when confronted with emerging pathogens and climate change.

Genetic by environment interactions affect plant–soil linkages

PubMed Central

Pregitzer, Clara C; Bailey, Joseph K; Schweitzer, Jennifer A

2013-01-01

The role of plant intraspecific variation in plant–soil linkages is poorly understood, especially in the context of natural environmental variation, but has important implications in evolutionary ecology. We utilized three 18- to 21-year-old common gardens across an elevational gradient, planted with replicates of five Populus angustifolia genotypes each, to address the hypothesis that tree genotype (G), environment (E), and G × E interactions would affect soil carbon and nitrogen dynamics beneath individual trees. We found that soil nitrogen and carbon varied by over 50% and 62%, respectively, across all common garden environments. We found that plant leaf litter (but not root) traits vary by genotype and environment while soil nutrient pools demonstrated genotype, environment, and sometimes G × E interactions, while process rates (net N mineralization and net nitrification) demonstrated G × E interactions. Plasticity in tree growth and litter chemistry was significantly related to the variation in soil nutrient pools and processes across environments, reflecting tight plant–soil linkages. These data overall suggest that plant genetic variation can have differential affects on carbon storage and nitrogen cycling, with implications for understanding the role of genetic variation in plant–soil feedback as well as management plans for conservation and restoration of forest habitats with a changing climate. PMID:23919173

Genetics and variation

Treesearch

John R. Jones; Norbert V. DeByle

1985-01-01

The broad genotypic variability in quaking aspen (Populus tremuloides Michx.), that results in equally broad phenotypic variability among clones is important to the ecology and management of this species. This chapter considers principles of aspen genetics and variation, variation in aspen over its range, and local variation among clones. For a more...

Genetic variation in California oaks

Treesearch

Constance I. Millar; Diane L. Delany; Lawrence A. Riggs

1990-01-01

In forestry the importance of genetic variation for successful reproduction, survival and growth has been widely documented for commercial conifers; until recently, little genetic work has been done on the California oaks. Even before the nature of genetic variation was scientifically investigated, its importance was suspected in operational forestry. Many failures of...

Evolutionary response when selection and genetic variation covary across environments.

PubMed

Wood, Corlett W; Brodie, Edmund D

2016-10-01

Although models of evolution usually assume that the strength of selection on a trait and the expression of genetic variation in that trait are independent, whenever the same ecological factor impacts both parameters, a correlation between the two may arise that accelerates trait evolution in some environments and slows it in others. Here, we address the evolutionary consequences and ecological causes of a correlation between selection and expressed genetic variation. Using a simple analytical model, we show that the correlation has a modest effect on the mean evolutionary response and a large effect on its variance, increasing among-population or among-generation variation in the response when positive, and diminishing variation when negative. We performed a literature review to identify the ecological factors that influence selection and expressed genetic variation across traits. We found that some factors - temperature and competition - are unlikely to generate the correlation because they affected one parameter more than the other, and identified others - most notably, environmental novelty - that merit further investigation because little is known about their impact on one of the two parameters. We argue that the correlation between selection and genetic variation deserves attention alongside other factors that promote or constrain evolution in heterogeneous landscapes. © 2016 John Wiley & Sons Ltd/CNRS.

Genetic variation facilitates seedling establishment but not population growth rate of a perennial invader

PubMed Central

Li, Shou-Li; Vasemägi, Anti; Ramula, Satu

2016-01-01

variation may facilitate plant invasions by increasing seedling establishment, it may not necessarily affect the long-term population growth rate. Therefore, established invasions may be able to grow equally well regardless of their genetic diversity. PMID:26420202

Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau

PubMed Central

Leng, Shuguang; Picchi, Maria A.; Liu, Yushi; Thomas, Cynthia L.; Willis, Derall G.; Bernauer, Amanda M.; Carr, Teara G.; Mabel, Padilla T.; Han, Younghun; Amos, Christopher I.; Lin, Yong; Stidley, Christine A.; Gilliland, Frank D.; Jacobson, Marty R.; Belinsky, Steven A.

2013-01-01

Epidemiological studies of underground miners suggested that occupational exposure to radon causes lung cancer with squamous cell carcinoma (SCC) as the predominant histological type. However, the genetic determinants for susceptibility of radon-induced SCC in miners are unclear. Double-strand breaks induced by radioactive radon daughters are repaired primarily by non-homologous end joining (NHEJ) that is accompanied by the dynamic changes in surrounding chromatin, including nucleosome repositioning and histone modifications. Thus, a molecular epidemiological study was conducted to assess whether genetic variation in 16 genes involved in NHEJ and related histone modification affected susceptibility for SCC in radon-exposed former miners (267 SCC cases and 383 controls) from the Colorado plateau. A global association between genetic variation in the haplotype block where SIRT1 resides and the risk for SCC in miners (P = 0.003) was identified. Haplotype alleles tagged by the A allele of SIRT1 rs7097008 were associated with increased risk for SCC (odds ratio = 1.69, P = 8.2×10−5) and greater survival in SCC cases (hazard ratio = 0.79, P = 0.03) in miners. Functional validation of rs7097008 demonstrated that the A allele was associated with reduced gene expression in bronchial epithelial cells and compromised DNA repair capacity in peripheral lymphocytes. Together, these findings substantiate genetic variation in SIRT1 as a risk modifier for developing SCC in miners and suggest that SIRT1 may also play a tumor suppressor role in radon-induced cancer in miners. PMID:23354305

Additive genetic variation and evolvability of a multivariate trait can be increased by epistatic gene action.

PubMed

Griswold, Cortland K

2015-12-21

Epistatic gene action occurs when mutations or alleles interact to produce a phenotype. Theoretically and empirically it is of interest to know whether gene interactions can facilitate the evolution of diversity. In this paper, we explore how epistatic gene action affects the additive genetic component or heritable component of multivariate trait variation, as well as how epistatic gene action affects the evolvability of multivariate traits. The analysis involves a sexually reproducing and recombining population. Our results indicate that under stabilizing selection conditions a population with a mixed additive and epistatic genetic architecture can have greater multivariate additive genetic variation and evolvability than a population with a purely additive genetic architecture. That greater multivariate additive genetic variation can occur with epistasis is in contrast to previous theory that indicated univariate additive genetic variation is decreased with epistasis under stabilizing selection conditions. In a multivariate setting, epistasis leads to less relative covariance among individuals in their genotypic, as well as their breeding values, which facilitates the maintenance of additive genetic variation and increases a population׳s evolvability. Our analysis involves linking the combinatorial nature of epistatic genetic effects to the ancestral graph structure of a population to provide insight into the consequences of epistasis on multivariate trait variation and evolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

PubMed

McNally, Elizabeth M; Puckelwartz, Megan J

2015-01-01

With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli

PubMed Central

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-01-01

Individual genetic variation affects gene expression in response to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness QTLs; reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant acts as an activator of the antiviral response; using RNAi, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli. PMID:23503680

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

PubMed

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-04-01

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

Genetic variation facilitates seedling establishment but not population growth rate of a perennial invader.

PubMed

Li, Shou-Li; Vasemägi, Anti; Ramula, Satu

2016-01-01

Assessing the demographic consequences of genetic variation is fundamental to invasion biology. However, genetic and demographic approaches are rarely combined to explore the effects of genetic variation on invasive populations in natural environments. This study combined population genetics, demographic data and a greenhouse experiment to investigate the consequences of genetic variation for the population fitness of the perennial, invasive herb Lupinus polyphyllus. Genetic and demographic data were collected from 37 L. polyphyllus populations representing different latitudes in Finland, and genetic variation was characterized based on 13 microsatellite loci. Associations between genetic variation and population size, population density, latitude and habitat were investigated. Genetic variation was then explored in relation to four fitness components (establishment, survival, growth, fecundity) measured at the population level, and the long-term population growth rate (λ). For a subset of populations genetic variation was also examined in relation to the temporal variability of λ. A further assessment was made of the role of natural selection in the observed variation of certain fitness components among populations under greenhouse conditions. It was found that genetic variation correlated positively with population size, particularly at higher latitudes, and differed among habitat types. Average seedling establishment per population increased with genetic variation in the field, but not under greenhouse conditions. Quantitative genetic divergence (Q(ST)) based on seedling establishment in the greenhouse was smaller than allelic genetic divergence (F'(ST)), indicating that unifying selection has a prominent role in this fitness component. Genetic variation was not associated with average survival, growth or fecundity measured at the population level, λ or its variability. The study suggests that although genetic variation may facilitate plant invasions by

Sex reduces genetic variation: a multidisciplinary review.

PubMed

Gorelick, Root; Heng, Henry H Q

2011-04-01

For over a century, the paradigm has been that sex invariably increases genetic variation, despite many renowned biologists asserting that sex decreases most genetic variation. Sex is usually perceived as the source of additive genetic variance that drives eukaryotic evolution vis-à-vis adaptation and Fisher's fundamental theorem. However, evidence for sex decreasing genetic variation appears in ecology, paleontology, population genetics, and cancer biology. The common thread among many of these disciplines is that sex acts like a coarse filter, weeding out major changes, such as chromosomal rearrangements (that are almost always deleterious), but letting minor variation, such as changes at the nucleotide or gene level (that are often neutral), flow through the sexual sieve. Sex acts as a constraint on genomic and epigenetic variation, thereby limiting adaptive evolution. The diverse reasons for sex reducing genetic variation (especially at the genome level) and slowing down evolution may provide a sufficient benefit to offset the famed costs of sex. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Causal Genetic Variation Underlying Metabolome Differences.

PubMed

Swain-Lenz, Devjanee; Nikolskiy, Igor; Cheng, Jiye; Sudarsanam, Priya; Nayler, Darcy; Staller, Max V; Cohen, Barak A

2017-08-01

An ongoing challenge in biology is to predict the phenotypes of individuals from their genotypes. Genetic variants that cause disease often change an individual's total metabolite profile, or metabolome. In light of our extensive knowledge of metabolic pathways, genetic variants that alter the metabolome may help predict novel phenotypes. To link genetic variants to changes in the metabolome, we studied natural variation in the yeast Saccharomyces cerevisiae We used an untargeted mass spectrometry method to identify dozens of metabolite Quantitative Trait Loci (mQTL), genomic regions containing genetic variation that control differences in metabolite levels between individuals. We mapped differences in urea cycle metabolites to genetic variation in specific genes known to regulate amino acid biosynthesis. Our functional assays reveal that genetic variation in two genes, AUA1 and ARG81 , cause the differences in the abundance of several urea cycle metabolites. Based on knowledge of the urea cycle, we predicted and then validated a new phenotype: sensitivity to a particular class of amino acid isomers. Our results are a proof-of-concept that untargeted mass spectrometry can reveal links between natural genetic variants and metabolome diversity. The interpretability of our results demonstrates the promise of using genetic variants underlying natural differences in the metabolome to predict novel phenotypes from genotype. Copyright © 2017 by the Genetics Society of America.

Effects of functionally asexual reproduction on quantitative genetic variation in the evening primroses (Oenothera, Onagraceae).

PubMed

Godfrey, Ryan M; Johnson, Marc T J

2014-11-01

It has long been predicted that a loss of sexual reproduction leads to decreased heritable variation within populations and increased differentiation between populations. Despite an abundance of theory, there are few empirical tests of how sex affects genetic variation in phenotypic traits, especially for plants. Here we test whether repeated losses of two critical components of sex (recombination and segregation) in the evening primroses (Oenothera L., Onagraceae) affect quantitative genetic variation within and between populations. We sampled multiple genetic families from 3-5 populations from each of eight Oenothera species, which represented four independent transitions between sexual reproduction and a functionally asexual genetic system called "permanent translocation heterozygosity." We used quantitative genetics methods to partition genetic variation within and between populations for eight plant traits related to growth, leaf physiology, flowering, and resistance to herbivores. Heritability was, on average, 74% higher in sexual Oenothera populations than in functionally asexual populations, with plant growth rate, specific leaf area, and the percentage of leaf water content showing the strongest differences. By contrast, genetic differentiation among populations was 2.8× higher in functionally asexual vs. sexual Oenothera species. This difference was particularly strong for specific leaf area. Sexual populations tended to exhibit higher genetic correlations among traits, but this difference was weakly supported. These results support the prediction that sexual reproduction maintains higher genetic variation within populations, which may facilitate adaptive evolution. We also found partial support for the prediction that a loss of sex leads to greater population differentiation, which may elevate speciation rates. © 2014 Botanical Society of America, Inc.

Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

PubMed

Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

2014-09-01

Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

The contribution of additive genetic variation to personality variation: heritability of personality.

PubMed

Dochtermann, Ned A; Schwab, Tori; Sih, Andrew

2015-01-07

Individual animals frequently exhibit repeatable differences from other members of their population, differences now commonly referred to as 'animal personality'. Personality differences can arise, for example, from differences in permanent environmental effects--including parental and epigenetic contributors--and the effect of additive genetic variation. Although several studies have evaluated the heritability of behaviour, less is known about general patterns of heritability and additive genetic variation in animal personality. As overall variation in behaviour includes both the among-individual differences that reflect different personalities and temporary environmental effects, it is possible for personality to be largely genetically influenced even when heritability of behaviour per se is quite low. The relative contribution of additive genetic variation to personality variation can be estimated whenever both repeatability and heritability are estimated for the same data. Using published estimates to address this issue, we found that approximately 52% of animal personality variation was attributable to additive genetic variation. Thus, while the heritability of behaviour is often moderate or low, the heritability of personality is much higher. Our results therefore (i) demonstrate that genetic differences are likely to be a major contributor to variation in animal personality and (ii) support the phenotypic gambit: that evolutionary inferences drawn from repeatability estimates may often be justified. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Lost in Translation: Bioinformatic Analysis of Variations Affecting the Translation Initiation Codon in the Human Genome.

PubMed

Abad, Francisco; de la Morena-Barrio, María Eugenia; Fernández-Breis, Jesualdo Tomás; Corral, Javier

2018-06-01

Translation is a key biological process controlled in eukaryotes by the initiation AUG codon. Variations affecting this codon may have pathological consequences by disturbing the correct initiation of translation. Unfortunately, there is no systematic study describing these variations in the human genome. Moreover, we aimed to develop new tools for in silico prediction of the pathogenicity of gene variations affecting AUG codons, because to date, these gene defects have been wrongly classified as missense. Whole-exome analysis revealed the mean of 12 gene variations per person affecting initiation codons, mostly with high (> 0:01) minor allele frequency (MAF). Moreover, analysis of Ensembl data (December 2017) revealed 11,261 genetic variations affecting the initiation AUG codon of 7,205 genes. Most of these variations (99.5%) have low or unknown MAF, probably reflecting deleterious consequences. Only 62 variations had high MAF. Genetic variations with high MAF had closer alternative AUG downstream codons than did those with low MAF. Besides, the high-MAF group better maintained both the signal peptide and reading frame. These differentiating elements could help to determine the pathogenicity of this kind of variation. Data and scripts in Perl and R are freely available at https://github.com/fanavarro/hemodonacion. jfernand@um.es. Supplementary data are available at Bioinformatics online.

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

PubMed

De Luca, Maria; Roshina, Nataliya V; Geiger-Thornsberry, Gretchen L; Lyman, Richard F; Pasyukova, Elena G; Mackay, Trudy F C

2003-08-01

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

The effect of epistasis on sexually antagonistic genetic variation

PubMed Central

Arnqvist, Göran; Vellnow, Nikolas; Rowe, Locke

2014-01-01

There is increasing evidence of segregating sexually antagonistic (SA) genetic variation for fitness in laboratory and wild populations, yet the conditions for the maintenance of such variation can be restrictive. Epistatic interactions between genes can contribute to the maintenance of genetic variance in fitness and we suggest that epistasis between SA genes should be pervasive. Here, we explore its effect on SA genetic variation in fitness using a two locus model with negative epistasis. Our results demonstrate that epistasis often increases the parameter space showing polymorphism for SA loci. This is because selection in one locus is affected by allele frequencies at the other, which can act to balance net selection in males and females. Increased linkage between SA loci had more marginal effects. We also show that under some conditions, large portions of the parameter space evolve to a state where male benefit alleles are fixed at one locus and female benefit alleles at the other. This novel effect of epistasis on SA loci, which we term the ‘equity effect’, may have important effects on population differentiation and may contribute to speciation. More generally, these results support the suggestion that epistasis contributes to population divergence. PMID:24870040

Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail

PubMed Central

Seppälä, Otto; Langeloh, Laura

2016-01-01

Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals’ genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals’ genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID:27551822

Phenotypic and Genetic Variations in Obligate Parthenogenetic Populations of Eriosoma lanigerum Hausmann (Hemiptera: Aphididae).

PubMed

Ruiz-Montoya, L; Zúñiga, G; Cisneros, R; Salinas-Moreno, Y; Peña-Martínez, R; Machkour-M'Rabet, S

2015-12-01

The study of phenotypic and genetic variation of obligate parthenogenetic organisms contributes to an understanding of evolution in the absence of genetic variation produced by sexual reproduction. Eriosoma lanigerum Hausmann undergoes obligate parthenogenesis in Mexico City, Mexico, due to the unavailability of the host plants required for sexual reproduction. We analysed the phenotypic and genetic variation of E. lanigerum in relation to the dry and wet season and plant phenology. Aphids were collected on two occasions per season on a secondary host plant, Pyracantha koidzumii, at five different sites in the southern area of Mexico City, Mexico. Thirteen morphological characteristics were measured from 147 to 276 individuals per site and per season. A multivariate analysis of variance was performed to test the effect of the season, site and their interaction on morphological traits. Morphological variation was summarised using a principal component analysis. Genetic variation was described using six enzymatic loci, four of which were polymorphic. Our study showed that the site and season has a significant effect on morphological trait variation. The largest aphids were recorded during cold temperatures with low relative humidity and when the plant was at the end of the fruiting period. The mean genetic diversity was low (mean H e =  .161), and populations were genetically structured by season and site. Morphological and genetic variations appear to be associated with environmental factors that directly affect aphid development and/or indirectly by host plant phenology.

The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster.

PubMed

Hunter, Chad M; Huang, Wen; Mackay, Trudy F C; Singh, Nadia D

2016-04-01

Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms. Despite this crucial function, rates of recombination are highly variable within and between taxa, and the genetic basis of this variation remains poorly understood. Here, we exploit natural variation in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to map genetic variants affecting recombination rate. We used a two-step crossing scheme and visible markers to measure rates of recombination in a 33 cM interval on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP lines. Though we cannot exclude that some biases exist due to viability effects associated with the visible markers used in this study, we find ~2-fold variation in recombination rate among lines. Interestingly, we further find that recombination rates are uncorrelated between the two chromosomal intervals. We performed a genome-wide association study to identify genetic variants associated with recombination rate in each of the two intervals surveyed. We refined our list of candidate variants and genes associated with recombination rate variation and selected twenty genes for functional assessment. We present strong evidence that five genes are likely to contribute to natural variation in recombination rate in D. melanogaster; these genes lie outside the canonical meiotic recombination pathway. We also find a weak effect of Wolbachia infection on recombination rate and we confirm the interchromosomal effect. Our results highlight the magnitude of population variation in recombination rate present in D. melanogaster and implicate new genetic factors mediating natural variation in this quantitative trait.

Climatic suitability, isolation by distance and river resistance explain genetic variation in a Brazilian whiptail lizard.

PubMed

Oliveira, Eliana Faria; Martinez, Pablo Ariel; São-Pedro, Vinícius Avelar; Gehara, Marcelo; Burbrink, Frank Thomas; Mesquita, Daniel Oliveira; Garda, Adrian Antonio; Colli, Guarino Rinaldi; Costa, Gabriel Correa

2018-03-01

Spatial patterns of genetic variation can help understand how environmental factors either permit or restrict gene flow and create opportunities for regional adaptations. Organisms from harsh environments such as the Brazilian semiarid Caatinga biome may reveal how severe climate conditions may affect patterns of genetic variation. Herein we combine information from mitochondrial DNA with physical and environmental features to study the association between different aspects of the Caatinga landscape and spatial genetic variation in the whiptail lizard Ameivula ocellifera. We investigated which of the climatic, environmental, geographical and/or historical components best predict: (1) the spatial distribution of genetic diversity, and (2) the genetic differentiation among populations. We found that genetic variation in A. ocellifera has been influenced mainly by temperature variability, which modulates connectivity among populations. Past climate conditions were important for shaping current genetic diversity, suggesting a time lag in genetic responses. Population structure in A. ocellifera was best explained by both isolation by distance and isolation by resistance (main rivers). Our findings indicate that both physical and climatic features are important for explaining the observed patterns of genetic variation across the xeric Caatinga biome.

Genetic Variation Affects C-Reactive Protein Elevations in Crohn's Disease.

PubMed

Moran, Christopher J; Kaplan, Jess L; Winter, Harland S

2018-04-28

C-reactive protein (CRP) is a serum marker that is used to measure disease activity in Crohn's disease (CD). However, a subset of CD patients have normal CRP during flares. In rheumatoid arthritis and lupus, genetic variants can restrict CRP elevations during flares. This study sought to determine if common CRP genetic variants affect CRP values during active CD. Subjects with CD who participated in the Partners HealthCare BioBank were genotyped for 5 common CRP genetic variants (rs2794520, rs3122012, rs3093077, rs2808635, and rs1800947). Medical records were reviewed to determine disease activity and the highest CRP value during active CD. CRP values during active infection or malignancy at the time of the test were excluded. CRP values were compared by genotype using the Mann-Whitney test. The study included 199 subjects with active CD (21 to 86 years of age). Subjects with the rs2794520 TT genotype had a lower CRP than subjects with the CC genotype (58.3 mg/L vs 28.4 mg/L, P = 0.008). Subjects with the rs1800947 CG genotype had a lower CRP than those with the CC genotype (54.3 mg/L vs 22.4 mg/L, P < 0.0001); 41.6% of TT subjects had a normal CRP compared with 24.1% of CT subjects and 16.5% of CC subjects (P = 0.041). This study demonstrates that rs2794520 and rs1800947 are associated with a restriction of CRP elevations during active CD. While CRP is typically a reliable biomarker in CD, there is a subset of CD patients with a genetically determined restriction of CRP in whom other disease markers should be utilized.

Genetic variation in social environment construction influences the development of aggressive behavior in Drosophila melanogaster

PubMed Central

Saltz, J B

2017-01-01

Individuals are not merely subject to their social environments; they choose and create them, through a process called social environment (or social niche) construction. When genotypes differ in social environment-constructing behaviors, different genotypes are expected to experience different social environments. As social experience often affects behavioral development, quantitative genetics and psychology theories predict that genetic variation in social environment construction should have an important role in determining phenotypic variation; however, this hypothesis has not been tested directly. I identify multiple mechanisms of social environment construction that differ among natural genotypes of Drosophila melanogaster and investigate their consequences for the development of aggressive behavior. Male genotypes differed in the group sizes that they preferred and in their aggressive behavior; both of these behaviors influenced social experience, demonstrating that these behaviors function as social environment-constructing traits. Further, the effects of social experience—as determined in part by social environment construction—carried over to affect focal male aggression at a later time and with a new opponent. These results provide manipulative experimental support for longstanding hypotheses in psychology, that genetic variation in social environment construction has a causal role in behavioral development. More broadly, these results imply that studies of the genetic basis of complex traits should be expanded to include mechanisms by which genetic variation shapes the environments that individuals experience. PMID:27848947

Genetic variation in the USDA Chamaecrista fasciculata collection

USDA-ARS?s Scientific Manuscript database

Germplasm collections serve as critical repositories of genetic variation. Characterizing genetic diversity in existing collections is necessary to maximize their utility and to guide future collecting efforts. We have used AFLP markers to characterize genetic variation in the USDA germplasm collect...

Tissue culture-induced genetic and epigenetic variation in triticale (× Triticosecale spp. Wittmack ex A. Camus 1927) regenerants.

PubMed

Machczyńska, Joanna; Zimny, Janusz; Bednarek, Piotr Tomasz

2015-10-01

Plant regeneration via in vitro culture can induce genetic and epigenetic variation; however, the extent of such changes in triticale is not yet understood. In the present study, metAFLP, a variation of methylation-sensitive amplified fragment length polymorphism analysis, was used to investigate tissue culture-induced variation in triticale regenerants derived from four distinct genotypes using androgenesis and somatic embryogenesis. The metAFLP technique enabled identification of both sequence and DNA methylation pattern changes in a single experiment. Moreover, it was possible to quantify subtle effects such as sequence variation, demethylation, and de novo methylation, which affected 19, 5.5, 4.5% of sites, respectively. Comparison of variation in different genotypes and with different in vitro regeneration approaches demonstrated that both the culture technique and genetic background of donor plants affected tissue culture-induced variation. The results showed that the metAFLP approach could be used for quantification of tissue culture-induced variation and provided direct evidence that in vitro plant regeneration could cause genetic and epigenetic variation.

The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster

PubMed Central

Hunter, Chad M.; Huang, Wen; Mackay, Trudy F. C.; Singh, Nadia D.

2016-01-01

Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms. Despite this crucial function, rates of recombination are highly variable within and between taxa, and the genetic basis of this variation remains poorly understood. Here, we exploit natural variation in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to map genetic variants affecting recombination rate. We used a two-step crossing scheme and visible markers to measure rates of recombination in a 33 cM interval on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP lines. Though we cannot exclude that some biases exist due to viability effects associated with the visible markers used in this study, we find ~2-fold variation in recombination rate among lines. Interestingly, we further find that recombination rates are uncorrelated between the two chromosomal intervals. We performed a genome-wide association study to identify genetic variants associated with recombination rate in each of the two intervals surveyed. We refined our list of candidate variants and genes associated with recombination rate variation and selected twenty genes for functional assessment. We present strong evidence that five genes are likely to contribute to natural variation in recombination rate in D. melanogaster; these genes lie outside the canonical meiotic recombination pathway. We also find a weak effect of Wolbachia infection on recombination rate and we confirm the interchromosomal effect. Our results highlight the magnitude of population variation in recombination rate present in D. melanogaster and implicate new genetic factors mediating natural variation in this quantitative trait. PMID:27035832

How spatio-temporal habitat connectivity affects amphibian genetic structure.

PubMed

Watts, Alexander G; Schlichting, Peter E; Billerman, Shawn M; Jesmer, Brett R; Micheletti, Steven; Fortin, Marie-Josée; Funk, W Chris; Hapeman, Paul; Muths, Erin; Murphy, Melanie A

2015-01-01

Heterogeneous landscapes and fluctuating environmental conditions can affect species dispersal, population genetics, and genetic structure, yet understanding how biotic and abiotic factors affect population dynamics in a fluctuating environment is critical for species management. We evaluated how spatio-temporal habitat connectivity influences dispersal and genetic structure in a population of boreal chorus frogs (Pseudacris maculata) using a landscape genetics approach. We developed gravity models to assess the contribution of various factors to the observed genetic distance as a measure of functional connectivity. We selected (a) wetland (within-site) and (b) landscape matrix (between-site) characteristics; and (c) wetland connectivity metrics using a unique methodology. Specifically, we developed three networks that quantify wetland connectivity based on: (i) P. maculata dispersal ability, (ii) temporal variation in wetland quality, and (iii) contribution of wetland stepping-stones to frog dispersal. We examined 18 wetlands in Colorado, and quantified 12 microsatellite loci from 322 individual frogs. We found that genetic connectivity was related to topographic complexity, within- and between-wetland differences in moisture, and wetland functional connectivity as contributed by stepping-stone wetlands. Our results highlight the role that dynamic environmental factors have on dispersal-limited species and illustrate how complex asynchronous interactions contribute to the structure of spatially-explicit metapopulations.

How spatio-temporal habitat connectivity affects amphibian genetic structure

PubMed Central

Watts, Alexander G.; Schlichting, Peter E.; Billerman, Shawn M.; Jesmer, Brett R.; Micheletti, Steven; Fortin, Marie-Josée; Funk, W. Chris; Hapeman, Paul; Muths, Erin; Murphy, Melanie A.

2015-01-01

Heterogeneous landscapes and fluctuating environmental conditions can affect species dispersal, population genetics, and genetic structure, yet understanding how biotic and abiotic factors affect population dynamics in a fluctuating environment is critical for species management. We evaluated how spatio-temporal habitat connectivity influences dispersal and genetic structure in a population of boreal chorus frogs (Pseudacris maculata) using a landscape genetics approach. We developed gravity models to assess the contribution of various factors to the observed genetic distance as a measure of functional connectivity. We selected (a) wetland (within-site) and (b) landscape matrix (between-site) characteristics; and (c) wetland connectivity metrics using a unique methodology. Specifically, we developed three networks that quantify wetland connectivity based on: (i) P. maculata dispersal ability, (ii) temporal variation in wetland quality, and (iii) contribution of wetland stepping-stones to frog dispersal. We examined 18 wetlands in Colorado, and quantified 12 microsatellite loci from 322 individual frogs. We found that genetic connectivity was related to topographic complexity, within- and between-wetland differences in moisture, and wetland functional connectivity as contributed by stepping-stone wetlands. Our results highlight the role that dynamic environmental factors have on dispersal-limited species and illustrate how complex asynchronous interactions contribute to the structure of spatially-explicit metapopulations. PMID:26442094

How spatio-temporal habitat connectivity affects amphibian genetic structure

USGS Publications Warehouse

Watts, Alexander G.; Schlichting, P; Billerman, S; Jesmer, B; Micheletti, S; Fortin, M.-J.; Funk, W.C.; Hapeman, P; Muths, Erin L.; Murphy, M.A.

2015-01-01

Heterogeneous landscapes and fluctuating environmental conditions can affect species dispersal, population genetics, and genetic structure, yet understanding how biotic and abiotic factors affect population dynamics in a fluctuating environment is critical for species management. We evaluated how spatio-temporal habitat connectivity influences dispersal and genetic structure in a population of boreal chorus frogs (Pseudacris maculata) using a landscape genetics approach. We developed gravity models to assess the contribution of various factors to the observed genetic distance as a measure of functional connectivity. We selected (a) wetland (within-site) and (b) landscape matrix (between-site) characteristics; and (c) wetland connectivity metrics using a unique methodology. Specifically, we developed three networks that quantify wetland connectivity based on: (i) P. maculata dispersal ability, (ii) temporal variation in wetland quality, and (iii) contribution of wetland stepping-stones to frog dispersal. We examined 18 wetlands in Colorado, and quantified 12 microsatellite loci from 322 individual frogs. We found that genetic connectivity was related to topographic complexity, within- and between-wetland differences in moisture, and wetland functional connectivity as contributed by stepping-stone wetlands. Our results highlight the role that dynamic environmental factors have on dispersal-limited species and illustrate how complex asynchronous interactions contribute to the structure of spatially-explicit metapopulations.

Natural Genetic Variation and Candidate Genes for Morphological Traits in Drosophila melanogaster

PubMed Central

Carreira, Valeria Paula; Mensch, Julián; Hasson, Esteban; Fanara, Juan José

2016-01-01

Body size is a complex character associated to several fitness related traits that vary within and between species as a consequence of environmental and genetic factors. Latitudinal and altitudinal clines for different morphological traits have been described in several species of Drosophila and previous work identified genomic regions associated with such variation in D. melanogaster. However, the genetic factors that orchestrate morphological variation have been barely studied. Here, our main objective was to investigate genetic variation for different morphological traits associated to the second chromosome in natural populations of D. melanogaster along latitudinal and altitudinal gradients in Argentina. Our results revealed weak clinal signals and a strong population effect on morphological variation. Moreover, most pairwise comparisons between populations were significant. Our study also showed important within-population genetic variation, which must be associated to the second chromosome, as the lines are otherwise genetically identical. Next, we examined the contribution of different candidate genes to natural variation for these traits. We performed quantitative complementation tests using a battery of lines bearing mutated alleles at candidate genes located in the second chromosome and six second chromosome substitution lines derived from natural populations which exhibited divergent phenotypes. Results of complementation tests revealed that natural variation at all candidate genes studied, invected, Fasciclin 3, toucan, Reticulon-like1, jing and CG14478, affects the studied characters, suggesting that they are Quantitative Trait Genes for morphological traits. Finally, the phenotypic patterns observed suggest that different alleles of each gene might contribute to natural variation for morphological traits. However, non-additive effects cannot be ruled out, as wild-derived strains differ at myriads of second chromosome loci that may interact

Does advertisement call variation coincide with genetic variation in the genetically diverse frog taxon currently known as Leptodactylus fuscus (Amphibia: Leptodactylidae)?

PubMed

Heyer, W Ronald; Reid, Yana R

2003-03-01

The frog Leptodactylus fuscus is found throughout much of South America in open and disturbed habitats. Previous study of genetic differentiation in L. fuscus demonstrated that there was lack of genetic exchange among population units consistent with multiple species, rather than a single species. We examine advertisement vocalizations of L. fuscus to determine whether call variation coincides with genetic differentiation. Calls were analyzed for 32 individual frogs from 25 localities throughout the distributional range of L. fuscus. Although there is variation in calls among geographic samples, call variation is not concordant with genetic variation or geographic distance and the call variation observed is less than that typically found among other closely related species of Leptodactylus. This study is an example of the rare pattern of strong genetic differentiation unaccompanied by salient differences in advertisement calls. The relative infrequency of this pattern as currently understood may only reflect the lack of detailed analyses of genetic and acoustic differentiation within population systems currently understood as single species with substantial geographic distributions.

Genetic variation in natural honeybee populations, Apis mellifera capensis

NASA Astrophysics Data System (ADS)

Hepburn, Randall; Neumann, Peter; Radloff, Sarah E.

2004-09-01

Genetic variation in honeybee, Apis mellifera, populations can be considerably influenced by breeding and commercial introductions, especially in areas with abundant beekeeping. However, in southern Africa apiculture is based on the capture of wild swarms, and queen rearing is virtually absent. Moreover, the introduction of European subspecies constantly failed in the Cape region. We therefore hypothesize a low human impact on genetic variation in populations of Cape honeybees, Apis mellifera capensis. A novel solution to studying genetic variation in honeybee populations based on thelytokous worker reproduction is applied to test this hypothesis. Environmental effects on metrical morphological characters of the phenotype are separated to obtain a genetic residual component. The genetic residuals are then re-calculated as coefficients of genetic variation. Characters measured included hair length on the abdomen, width and length of wax plate, and three wing angles. The data show for the first time that genetic variation in Cape honeybee populations is independent of beekeeping density and probably reflects naturally occurring processes such as gene flow due to topographic and climatic variation on a microscale.

Host genetic variation influences gene expression response to rhinovirus infection.

PubMed

Çalışkan, Minal; Baker, Samuel W; Gilad, Yoav; Ober, Carole

2015-04-01

Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs) in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs), namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5) and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

Genetic variation in insulin-induced kinase signaling

PubMed Central

Wang, Isabel Xiaorong; Ramrattan, Girish; Cheung, Vivian G

2015-01-01

Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20-fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis-acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance. PMID:26202599

Genetic architecture of natural variation in cuticular hydrocarbon composition in Drosophila melanogaster.

PubMed

Dembeck, Lauren M; Böröczky, Katalin; Huang, Wen; Schal, Coby; Anholt, Robert R H; Mackay, Trudy F C

2015-11-14

Insect cuticular hydrocarbons (CHCs) prevent desiccation and serve as chemical signals that mediate social interactions. Drosophila melanogaster CHCs have been studied extensively, but the genetic basis for individual variation in CHC composition is largely unknown. We quantified variation in CHC profiles in the D. melanogaster Genetic Reference Panel (DGRP) and identified novel CHCs. We used principal component (PC) analysis to extract PCs that explain the majority of CHC variation and identified polymorphisms in or near 305 and 173 genes in females and males, respectively, associated with variation in these PCs. In addition, 17 DGRP lines contain the functional Desat2 allele characteristic of African and Caribbean D. melanogaster females (more 5,9-C27:2 and less 7,11-C27:2, female sex pheromone isomers). Disruption of expression of 24 candidate genes affected CHC composition in at least one sex. These genes are associated with fatty acid metabolism and represent mechanistic targets for individual variation in CHC composition.

Genetical genomics of Populus leaf shape variation

DOE PAGES

Drost, Derek R.; Puranik, Swati; Novaes, Evandro; ...

2015-06-30

Leaf morphology varies extensively among plant species and is under strong genetic control. Mutagenic screens in model systems have identified genes and established molecular mechanisms regulating leaf initiation, development, and shape. However, it is not known whether this diversity across plant species is related to naturally occurring variation at these genes. Quantitative trait locus (QTL) analysis has revealed a polygenic control for leaf shape variation in different species suggesting that loci discovered by mutagenesis may only explain part of the naturally occurring variation in leaf shape. Here we undertook a genetical genomics study in a poplar intersectional pseudo-backcross pedigree tomore » identify genetic factors controlling leaf shape. Here, the approach combined QTL discovery in a genetic linkage map anchored to the Populus trichocarpa reference genome sequence and transcriptome analysis.« less

Population-level genetic variation and climate change in a biodiversity hotspot

PubMed Central

2017-01-01

Introduction Estimated future climate scenarios can be used to predict where hotspots of endemism may occur over the next century, but life history, ecological and genetic traits will be important in informing the varying responses within myriad taxa. Essential to predicting the consequences of climate change to individual species will be an understanding of the factors that drive genetic structure within and among populations. Here, I review the factors that influence the genetic structure of plant species in California, but are applicable elsewhere; existing levels of genetic variation, life history and ecological characteristics will affect the ability of an individual taxon to persist in the presence of anthropogenic change. Factors influencing the distribution of genetic variation Persistence in the face of climate change is likely determined by life history characteristics: dispersal ability, generation time, reproductive ability, degree of habitat specialization, plant–insect interactions, existing genetic diversity and availability of habitat or migration corridors. Existing levels of genetic diversity in plant populations vary based on a number of evolutionary scenarios that include endemism, expansion since the last glacial maximum, breeding system and current range sizes. Regional priorities and examples A number of well-documented examples are provided from the California Floristic Province. Some predictions can be made for the responses of plant taxa to rapid environmental changes based on geographic position, evolutionary history, existing genetic variation, and ecological amplitude. Conclusions, Solutions and Recommendations The prediction of how species will respond to climate change will require a synthesis drawing from population genetics, geography, palaeontology and ecology. The important integration of the historical factors that have shaped the distribution and existing genetic structure of California’s plant taxa will enable us to predict

Genetic Variation in the Vesicular Monoamine Transporter: Preliminary associations with Cognitive Outcomes after Severe Traumatic Brain Injury

PubMed Central

Markos, Steven; Failla, Michelle D.; Ritter, Anne C; Dixon, C. Edward; Conley, Yvette P.; Ricker, Joseph H; Arenth, Patricia M.; Juengst, Shannon B.; Wagner, Amy K.

2015-01-01

Introduction Traumatic brain injury (TBI) frequently results in impaired cognition, a function that can be modulated by monoaminergic signaling. Genetic variation among monoaminergic genes may affect post-TBI cognitive performance. The vesicular monoamine transporter 2 (VMAT2) gene may be a novel source of genetic variation important for cognitive outcomes post-TBI given VMAT2’s role in monoaminergic neurotransmission. Objective Evaluate associations between VMAT2 variability and cognitive outcomes post-TBI. Methods We evaluated 136 white adults with severe TBI for variation in VMAT2 using a tagging single nucleotide polymorphism (tSNP) approach (rs363223, rs363226, rs363251, and rs363341). We show genetic variation interacts with assessed cognitive impairment [cognitive composite T-scores (Comp-Cog)] to influence functional cognition [Functional Independence Measure Cognitive subscale (FIM-Cog)] 6 and 12 months post-injury. Results Multivariate analyses at 6-months post-injury showed rs363226 genotype was associated with Comp-Cog (p=0.040) and interacted with Comp-Cog to influence functional cognition (p<0.001). G-homozygotes had the largest cognitive impairment, and their cognitive impairment had the greatest adverse effect on functional cognition. Discussion We provide the first evidence that genetic variation within VMAT2 is associated with cognitive outcomes following TBI. Further work is needed to validate this finding and elucidate mechanisms by which genetic variation affects monoaminergic signaling, mediating differences in cognitive outcomes. PMID:26828714

Public Willingness to Participate in and Public Opinions About Genetic Variation Research: A Review of the Literature

PubMed Central

Sterling, Rene; Henderson, Gail E.; Corbie-Smith, Giselle

2006-01-01

Scientists are turning to genetic variation research in hopes of addressing persistent racial/ethnic disparities in health. Despite ongoing controversy, the advancement of genetic variation research is likely to produce new knowledge and technologies that will substantially change the ways in which we understand and value health. They also may affect the ways in which individuals and groups organize socially, politically, and economically. Addressing concerns that may exist in different communities is vital to the scientific and ethical advancement of genetic variation research. We review empirical studies of public willingness to participate in and opinions about genetic research with particular attention to differences in consent and opinion by racial/ethnic group membership. PMID:17018829

A High-Definition View of Functional Genetic Variation from Natural Yeast Genomes

PubMed Central

Bergström, Anders; Simpson, Jared T.; Salinas, Francisco; Barré, Benjamin; Parts, Leopold; Zia, Amin; Nguyen Ba, Alex N.; Moses, Alan M.; Louis, Edward J.; Mustonen, Ville; Warringer, Jonas; Durbin, Richard; Liti, Gianni

2014-01-01

The question of how genetic variation in a population influences phenotypic variation and evolution is of major importance in modern biology. Yet much is still unknown about the relative functional importance of different forms of genome variation and how they are shaped by evolutionary processes. Here we address these questions by population level sequencing of 42 strains from the budding yeast Saccharomyces cerevisiae and its closest relative S. paradoxus. We find that genome content variation, in the form of presence or absence as well as copy number of genetic material, is higher within S. cerevisiae than within S. paradoxus, despite genetic distances as measured in single-nucleotide polymorphisms being vastly smaller within the former species. This genome content variation, as well as loss-of-function variation in the form of premature stop codons and frameshifting indels, is heavily enriched in the subtelomeres, strongly reinforcing the relevance of these regions to functional evolution. Genes affected by these likely functional forms of variation are enriched for functions mediating interaction with the external environment (sugar transport and metabolism, flocculation, metal transport, and metabolism). Our results and analyses provide a comprehensive view of genomic diversity in budding yeast and expose surprising and pronounced differences between the variation within S. cerevisiae and that within S. paradoxus. We also believe that the sequence data and de novo assemblies will constitute a useful resource for further evolutionary and population genomics studies. PMID:24425782

The devil is in the details: genetic variation in introduced populations and its contributions to invasion.

PubMed

Dlugosch, Katrina M; Anderson, Samantha R; Braasch, Joseph; Cang, F Alice; Gillette, Heather D

2015-05-01

The influence of genetic variation on invasion success has captivated researchers since the start of the field of invasion genetics 50 years ago. We review the history of work on this question and conclude that genetic variation-as surveyed with molecular markers-appears to shape invasion rarely. Instead, there is a significant disconnect between marker assays and ecologically relevant genetic variation in introductions. We argue that the potential for adaptation to facilitate invasion will be shaped by the details of genotypes affecting phenotypes, and we highlight three areas in which we see opportunities to make powerful new insights. (i) The genetic architecture of adaptive variation. Traits shaped by large-effect alleles may be strongly impacted by founder events yet more likely to respond to selection when genetic drift is strong. Large-effect loci may be especially relevant for traits involved in biotic interactions. (ii) Cryptic genetic variation exposed during invasion. Introductions have strong potential to uncover masked variation due to alterations in genetic and ecological environments. (iii) Genetic interactions during admixture of multiple source populations. As divergence among sources increases, positive followed by increasingly negative effects of admixture should be expected. Although generally hypothesized to be beneficial during invasion, admixture is most often reported among sources of intermediate divergence, supporting the possibility that incompatibilities among divergent source populations might be limiting their introgression. Finally, we note that these details of invasion genetics can be coupled with comparative demographic analyses to link genetic changes to the evolution of invasiveness itself. © 2015 John Wiley & Sons Ltd.

Patterns of Genetic Variation across Altitude in Three Plant Species of Semi-Dry Grasslands

PubMed Central

Hahn, Thomas; Kettle, Chris J.; Ghazoul, Jaboury; Frei, Esther R.; Matter, Philippe; Pluess, Andrea R.

2012-01-01

Background Environmental gradients caused by altitudinal gradients may affect genetic variation within and among plant populations and inbreeding within populations. Populations in the upper range periphery of a species may be important source populations for range shifts to higher altitude in response to climate change. In this study we investigate patterns of population genetic variation at upper peripheral and lower more central altitudes in three common plant species of semi-dry grasslands in montane landscapes. Methodology/Principal Findings In Briza media, Trifolium montanum and Ranunculus bulbosus genetic diversity, inbreeding and genetic relatedness of individuals within populations and genetic differentiation among populations was characterized using AFLP markers. Populations were sampled in the Swiss Alps at 1800 (upper periphery of the study organisms) and at 1200 m a.s.l. Genetic diversity was not affected by altitude and only in B. media inbreeding was greater at higher altitudes. Genetic differentiation was slightly greater among populations at higher altitudes in B. media and individuals within populations were more related to each other compared to individuals in lower altitude populations. A similar but less strong pattern of differentiation and relatedness was observed in T. montanum, while in R. bulbosus there was no effect of altitude. Estimations of population size and isolation of populations were similar, both at higher and lower altitudes. Conclusions/Significance Our results suggest that altitude does not affect genetic diversity in the grassland species under study. Genetic differentiation of populations increased only slightly at higher elevation, probably due to extensive (historic) gene flow among altitudes. Potentially pre-adapted genes might therefore spread easily across altitudes. Our study indicates that populations at the upper periphery are not genetically depauperate or isolated and thus may be important source populations for

Collecting genetic variation on a small island

Treesearch

S. Kallow; C. Trivedi

2017-01-01

Genetic variation is the most powerful factor in ensuring the long term success of trees and forests in times of change. In order to protect against loss of genetic variation from threats, including pests and diseases and climate change, the Royal Botanic Gardens, Kew, is developing a national tree seed collection for the United Kingdom. This paper...

Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits.

PubMed

Yadav, Anupama; Dhole, Kaustubh; Sinha, Himanshu

2016-12-01

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets.

Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits

PubMed Central

Yadav, Anupama; Dhole, Kaustubh

2016-01-01

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets. PMID:28172852

High temperatures reveal cryptic genetic variation in a polymorphic female sperm storage organ.

PubMed

Berger, David; Bauerfeind, Stephanie Sandra; Blanckenhorn, Wolf Ulrich; Schäfer, Martin Andreas

2011-10-01

Variation in female reproductive morphology may play a decisive role in reproductive isolation by affecting the relative fertilization success of alternative male phenotypes. Yet, knowledge of how environmental variation may influence the development of the female reproductive tract and thus alter the arena of postcopulatory sexual selection is limited. Yellow dung fly females possess either three or four sperm storage compartments, a polymorphism with documented influence on sperm precedence. We performed a quantitative genetics study including 12 populations reared at three developmental temperatures complemented by extensive field data to show that warm developmental temperatures increase the frequency of females with four compartments, revealing striking hidden genetic variation for the polymorphism. Systematic genetic differentiation in growth rate and spermathecal number along latitude, and phenotypic covariance between the traits across temperature treatments suggest that the genetic architecture underlying the polymorphism is shaped by selection on metabolic rate. Our findings illustrate how temperature can modulate the preconditions for sexual selection by differentially exposing novel variation in reproductive morphology. This implies that environmental change may substantially alter the dynamics of sexual selection. We further discuss how temperature-dependent developmental plasticity may have contributed to observed rapid evolutionary transitions in spermathecal morphology. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

GENETIC VARIATION IN BABOON CRANIOFACIAL SEXUAL DIMORPHISM

PubMed Central

Willmore, Katherine E.; Roseman, Charles C.; Rogers, Jeffrey; Richtsmeier, Joan T.; Cheverud, James M.

2010-01-01

Sexual dimorphism is a widespread phenomenon and contributes greatly to intraspecies variation. Despite a long history of active research, the genetic basis of dimorphism for complex traits remains unknown. Understanding the sex-specific differences in genetic architecture for cranial traits in a highly dimorphic species could identify possible mechanisms through which selection acts to produce dimorphism. Using distances calculated from three-dimensional landmark data from CT scans of 402 baboon skulls from a known genealogy, we estimated genetic variance parameters in both sexes to determine the presence of gene-by-sex (G × S) interactions and X-linked heritability. We hypothesize that traits exhibiting the greatest degree of sexual dimorphism (facial traits in baboons) will demonstrate either stronger G × S interactions or X-linked effects. We found G × S interactions and X-linked effects for a few measures that span the areas connecting the face to the neurocranium but for no traits restricted to the face. This finding suggests that facial traits will have a limited response to selection for further evolution of dimorphism in this population. We discuss the implications of our results with respect to the origins of cranial sexual dimorphism in this baboon sample, and how the genetic architecture of these traits affects their potential for future evolution. PMID:19210535

Genetic variations in taste perception modify alcohol drinking behavior in Koreans.

PubMed

Choi, Jeong-Hwa; Lee, Jeonghee; Yang, Sarah; Kim, Jeongseon

2017-06-01

The sensory components of alcohol affect the onset of individual's drinking. Therefore, variations in taste receptor genes may lead to differential sensitivity for alcohol taste, which may modify an individual's drinking behavior. This study examined the influence of genetic variants in the taste-sensing mechanism on alcohol drinking behavior and the choice of alcoholic beverages. A total of 1829 Koreans were analyzed for their alcohol drinking status (drinker/non-drinker), total alcohol consumption (g/day), heavy drinking (≥30 g/day) and type of regularly consumed alcoholic beverages. Twenty-one genetic variations in bitterness, sweetness, umami and fatty acid sensing were also genotyped. Our findings suggested that multiple genetic variants modified individuals' alcohol drinking behavior. Genetic variations in the T2R bitterness receptor family were associated with overall drinking behavior. Subjects with the TAS2R38 AVI haplotype were less likely to be a drinker [odds ratio (OR): 0.75, 95% confidence interval (CI): 0.59-0.95], and TAS2R5 rs2227264 predicted the level of total alcohol consumption (p = 0.01). In contrast, the T1R sweet and umami receptor family was associated with heavy drinking. TAS1R3 rs307355 CT carriers were more likely to be heavy drinkers (OR: 1.53, 95% CI: 1.06-2.19). The genetic variants were also associated with the choice of alcoholic beverages. The homo-recessive type of TAS2R4 rs2233998 (OR: 1.62, 95% CI: 1.11-2.37) and TAS2R5 rs2227264 (OR: 1.72, 95% CI: 1.14-2.58) were associated with consumption of rice wine. However, TAS1R2 rs35874116 was associated with wine drinking (OR: 0.65, 95% CI: 0.43-0.98) and the consumption level (p = 0.04). These findings suggest that multiple genetic variations in taste receptors influence drinking behavior in Koreans. Genetic variations are also responsible for the preference of particular alcoholic beverages, which may contribute to an individual's alcohol drinking behavior. Copyright © 2017

Contribution of trans regulatory eQTL to cryptic genetic variation in C. elegans.

PubMed

Snoek, Basten L; Sterken, Mark G; Bevers, Roel P J; Volkers, Rita J M; Van't Hof, Arjen; Brenchley, Rachel; Riksen, Joost A G; Cossins, Andrew; Kammenga, Jan E

2017-06-29

Cryptic genetic variation (CGV) is the hidden genetic variation that can be unlocked by perturbing normal conditions. CGV can drive the emergence of novel complex phenotypes through changes in gene expression. Although our theoretical understanding of CGV has thoroughly increased over the past decade, insight into polymorphic gene expression regulation underlying CGV is scarce. Here we investigated the transcriptional architecture of CGV in response to rapid temperature changes in the nematode Caenorhabditis elegans. We analyzed regulatory variation in gene expression (and mapped eQTL) across the course of a heat stress and recovery response in a recombinant inbred population. We measured gene expression over three temperature treatments: i) control, ii) heat stress, and iii) recovery from heat stress. Compared to control, exposure to heat stress affected the transcription of 3305 genes, whereas 942 were affected in recovering animals. These affected genes were mainly involved in metabolism and reproduction. The gene expression pattern in recovering animals resembled both the control and the heat-stress treatment. We mapped eQTL using the genetic variation of the recombinant inbred population and detected 2626 genes with an eQTL in the heat-stress treatment, 1797 in the control, and 1880 in the recovery. The cis-eQTL were highly shared across treatments. A considerable fraction of the trans-eQTL (40-57%) mapped to 19 treatment specific trans-bands. In contrast to cis-eQTL, trans-eQTL were highly environment specific and thus cryptic. Approximately 67% of the trans-eQTL were only induced in a single treatment, with heat-stress showing the most unique trans-eQTL. These results illustrate the highly dynamic pattern of CGV across three different environmental conditions that can be evoked by a stress response over a relatively short time-span (2 h) and that CGV is mainly determined by response related trans regulatory eQTL.

Multiple capacitors for natural genetic variation in Drosophila melanogaster.

PubMed

Takahashi, Kazuo H

2013-03-01

Cryptic genetic variation (CGV) or a standing genetic variation that is not ordinarily expressed as a phenotype is released when the robustness of organisms is impaired under environmental or genetic perturbations. Evolutionary capacitors modulate the amount of genetic variation exposed to natural selection and hidden cryptically; they have a fundamental effect on the evolvability of traits on evolutionary timescales. In this study, I have demonstrated the effects of multiple genomic regions of Drosophila melanogaster on CGV in wing shape. I examined the effects of 61 genomic deficiencies on quantitative and qualitative natural genetic variation in the wing shape of D. melanogaster. I have identified 10 genomic deficiencies that do not encompass a known candidate evolutionary capacitor, Hsp90, exposing natural CGV differently depending on the location of the deficiencies in the genome. Furthermore, five genomic deficiencies uncovered qualitative CGV in wing morphology. These findings suggest that CGV in wing shape of wild-type D. melanogaster is regulated by multiple capacitors with divergent functions. Future analysis of genes encompassed by these genomic regions would help elucidate novel capacitor genes and better understand the general features of capacitors regarding natural genetic variation. © 2012 Blackwell Publishing Ltd.

Effects of Genetic Drift and Gene Flow on the Selective Maintenance of Genetic Variation

PubMed Central

Star, Bastiaan; Spencer, Hamish G.

2013-01-01

Explanations for the genetic variation ubiquitous in natural populations are often classified by the population–genetic processes they emphasize: natural selection or mutation and genetic drift. Here we investigate models that incorporate all three processes in a spatially structured population, using what we call a construction approach, simulating finite populations under selection that are bombarded with a steady stream of novel mutations. As expected, the amount of genetic variation compared to previous models that ignored the stochastic effects of drift was reduced, especially for smaller populations and when spatial structure was most profound. By contrast, however, for higher levels of gene flow and larger population sizes, the amount of genetic variation found after many generations was greater than that in simulations without drift. This increased amount of genetic variation is due to the introduction of slightly deleterious alleles by genetic drift and this process is more efficient when migration load is higher. The incorporation of genetic drift also selects for fitness sets that exhibit allele-frequency equilibria with larger domains of attraction: they are “more stable.” Moreover, the finiteness of populations strongly influences levels of local adaptation, selection strength, and the proportion of allele-frequency vectors that can be distinguished from the neutral expectation. PMID:23457235

Genetic and Environmental Contributions to the Development of Positive Affect in Infancy

PubMed Central

Planalp, Elizabeth M.; Van Hulle, Carol; Lemery-Chalfant, Kathryn; Goldsmith, H. Hill

2016-01-01

We studied developmental changes in infant positive affect from 6 to 12 months of age, a time marked by increasing use of positive vocalizations, laughter, and social smiles. We estimated the magnitude of genetic and environmental influences on observed and parent reported infant positive affect across development. Participants were drawn from a longitudinal twin study of infancy and toddlerhood (N=536 twin pairs). Mothers and fathers reported on infant temperament and infants were videotaped during two observational tasks assessing positive affect. Parents also reported on their own affect and emotional expression within the family. Biometric models examined genetic and environmental influences that contribute to the developmental continuity of positive affect. Infant positive affect was associated with increased parent positive affect and family expressions of positive affect although not with family expressions of negative affect. In addition, the shared environment accounted for a large portion of variation in infant positive affect and continuity over time. These findings highlight the importance of the family environment in relation to infant positive emotional development. PMID:27797564

Genetic and environmental contributions to the development of positive affect in infancy.

PubMed

Planalp, Elizabeth M; Van Hulle, Carol; Lemery-Chalfant, Kathryn; Goldsmith, H Hill

2017-04-01

We studied developmental changes in infant positive affect from 6 to 12 months of age, a time marked by increasing use of positive vocalizations, laughter, and social smiles. We estimated the magnitude of genetic and environmental influences on observed and parent reported infant positive affect across development. Participants were drawn from a longitudinal twin study of infancy and toddlerhood (N = 536 twin pairs). Mothers and fathers reported on infant temperament and infants were videotaped during 2 observational tasks assessing positive affect. Parents also reported on their own affect and emotional expression within the family. Biometric models examined genetic and environmental influences that contribute to the developmental continuity of positive affect. Infant positive affect was associated with increased parent positive affect and family expressions of positive affect although not with family expressions of negative affect. In addition, the shared environment accounted for a large portion of variation in infant positive affect and continuity over time. These findings highlight the importance of the family environment in relation to infant positive emotional development. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Common genetic variation drives molecular heterogeneity in human iPSCs.

PubMed

Kilpinen, Helena; Goncalves, Angela; Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard; Stegle, Oliver; Gaffney, Daniel J

2017-06-15

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

Common genetic variation drives molecular heterogeneity in human iPSCs

PubMed Central

Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard

2017-01-01

Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study outlines the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells. PMID:28489815

Molecular Darwinism: The Contingency of Spontaneous Genetic Variation

PubMed Central

Arber, Werner

2011-01-01

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions. PMID:21979160

Molecular Darwinism: the contingency of spontaneous genetic variation.

PubMed

Arber, Werner

2011-01-01

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions.

A global reference for human genetic variation

PubMed Central

2016-01-01

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. PMID:26432245

Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy.

PubMed

Heinig, Matthias; Adriaens, Michiel E; Schafer, Sebastian; van Deutekom, Hanneke W M; Lodder, Elisabeth M; Ware, James S; Schneider, Valentin; Felkin, Leanne E; Creemers, Esther E; Meder, Benjamin; Katus, Hugo A; Rühle, Frank; Stoll, Monika; Cambien, François; Villard, Eric; Charron, Philippe; Varro, Andras; Bishopric, Nanette H; George, Alfred L; Dos Remedios, Cristobal; Moreno-Moral, Aida; Pesce, Francesco; Bauerfeind, Anja; Rüschendorf, Franz; Rintisch, Carola; Petretto, Enrico; Barton, Paul J; Cook, Stuart A; Pinto, Yigal M; Bezzina, Connie R; Hubner, Norbert

2017-09-14

Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage, and allele-specific expression. Systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome-wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome-wide association signals in two independent cohorts. RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics.

Genetic variation in social mammals: the marmot model.

PubMed

Schwartz, O A; Armitage, K B

1980-02-08

The social substructure and the distribution of genetic variation among colonies of yellow-bellied marmots, when analyzed as an evolutionary system, suggests that this substructure enhances the intercolony variance and retards the fixation of genetic variation. This result supports a traditional theory of gradual evolution rather than recent theories suggesting accelerated evolution in social mammals.

Cordova: Web-based management of genetic variation data

PubMed Central

Ephraim, Sean S.; Anand, Nikhil; DeLuca, Adam P.; Taylor, Kyle R.; Kolbe, Diana L.; Simpson, Allen C.; Azaiez, Hela; Sloan, Christina M.; Shearer, A. Eliot; Hallier, Andrea R.; Casavant, Thomas L.; Scheetz, Todd E.; Smith, Richard J. H.; Braun, Terry A.

2014-01-01

Summary: Cordova is an out-of-the-box solution for building and maintaining an online database of genetic variations integrated with pathogenicity prediction results from popular algorithms. Our primary motivation for developing this system is to aid researchers and clinician–scientists in determining the clinical significance of genetic variations. To achieve this goal, Cordova provides an interface to review and manually or computationally curate genetic variation data as well as share it for clinical diagnostics and the advancement of research. Availability and implementation: Cordova is open source under the MIT license and is freely available for download at https://github.com/clcg/cordova. Contact: sean.ephraim@gmail.com or terry-braun@uiowa.edu PMID:25123904

Relating Human Genetic Variation to Variation in Drug Responses

PubMed Central

Madian, Ashraf G.; Wheeler, Heather E.; Jones, Richard Baker; Dolan, M. Eileen

2012-01-01

Although sequencing a single human genome was a monumental effort a decade ago, more than one thousand genomes have now been sequenced. The task ahead lies in transforming this information into personalized treatment strategies that are tailored to the unique genetics of each individual. One important aspect of personalized medicine is patient-to-patient variation in drug response. Pharmacogenomics addresses this issue by seeking to identify genetic contributors to human variation in drug efficacy and toxicity. Here, we present a summary of the current status of this field, which has evolved from studies of single candidate genes to comprehensive genome-wide analyses. Additionally, we discuss the major challenges in translating this knowledge into a systems-level understanding of drug physiology with the ultimate goal of developing more effective personalized clinical treatment strategies. PMID:22840197

The Impact of Accelerating Faster than Exponential Population Growth on Genetic Variation

PubMed Central

Reppell, Mark; Boehnke, Michael; Zöllner, Sebastian

2014-01-01

Current human sequencing projects observe an abundance of extremely rare genetic variation, suggesting recent acceleration of population growth. To better understand the impact of such accelerating growth on the quantity and nature of genetic variation, we present a new class of models capable of incorporating faster than exponential growth in a coalescent framework. Our work shows that such accelerated growth affects only the population size in the recent past and thus large samples are required to detect the models’ effects on patterns of variation. When we compare models with fixed initial growth rate, models with accelerating growth achieve very large current population sizes and large samples from these populations contain more variation than samples from populations with constant growth. This increase is driven almost entirely by an increase in singleton variation. Moreover, linkage disequilibrium decays faster in populations with accelerating growth. When we instead condition on current population size, models with accelerating growth result in less overall variation and slower linkage disequilibrium decay compared to models with exponential growth. We also find that pairwise linkage disequilibrium of very rare variants contains information about growth rates in the recent past. Finally, we demonstrate that models of accelerating growth may substantially change estimates of present-day effective population sizes and growth times. PMID:24381333

The impact of accelerating faster than exponential population growth on genetic variation.

PubMed

Reppell, Mark; Boehnke, Michael; Zöllner, Sebastian

2014-03-01

Current human sequencing projects observe an abundance of extremely rare genetic variation, suggesting recent acceleration of population growth. To better understand the impact of such accelerating growth on the quantity and nature of genetic variation, we present a new class of models capable of incorporating faster than exponential growth in a coalescent framework. Our work shows that such accelerated growth affects only the population size in the recent past and thus large samples are required to detect the models' effects on patterns of variation. When we compare models with fixed initial growth rate, models with accelerating growth achieve very large current population sizes and large samples from these populations contain more variation than samples from populations with constant growth. This increase is driven almost entirely by an increase in singleton variation. Moreover, linkage disequilibrium decays faster in populations with accelerating growth. When we instead condition on current population size, models with accelerating growth result in less overall variation and slower linkage disequilibrium decay compared to models with exponential growth. We also find that pairwise linkage disequilibrium of very rare variants contains information about growth rates in the recent past. Finally, we demonstrate that models of accelerating growth may substantially change estimates of present-day effective population sizes and growth times.

Host genetic variation impacts microbiome composition across human body sites.

PubMed

Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

2015-09-15

The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation.

PubMed

Babak, Tomas; Garrett-Engele, Philip; Armour, Christopher D; Raymond, Christopher K; Keller, Mark P; Chen, Ronghua; Rohl, Carol A; Johnson, Jason M; Attie, Alan D; Fraser, Hunter B; Schadt, Eric E

2010-08-13

Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing.

Cordova: web-based management of genetic variation data.

PubMed

Ephraim, Sean S; Anand, Nikhil; DeLuca, Adam P; Taylor, Kyle R; Kolbe, Diana L; Simpson, Allen C; Azaiez, Hela; Sloan, Christina M; Shearer, A Eliot; Hallier, Andrea R; Casavant, Thomas L; Scheetz, Todd E; Smith, Richard J H; Braun, Terry A

2014-12-01

Cordova is an out-of-the-box solution for building and maintaining an online database of genetic variations integrated with pathogenicity prediction results from popular algorithms. Our primary motivation for developing this system is to aid researchers and clinician-scientists in determining the clinical significance of genetic variations. To achieve this goal, Cordova provides an interface to review and manually or computationally curate genetic variation data as well as share it for clinical diagnostics and the advancement of research. Cordova is open source under the MIT license and is freely available for download at https://github.com/clcg/cordova. Published by Oxford University Press. This work is written by US Government employees and is in the public domain in the US.

Parents' communication with siblings of children affected by an inherited genetic condition.

PubMed

Plumridge, Gillian; Metcalfe, Alison; Coad, Jane; Gill, Paramjit

2011-08-01

The objective of this study was to explore parents' communication about risk with siblings of children affected by an inherited genetic condition, and to ascertain what level of support, if any, is required from health professionals. Semi-structured interviews were conducted with affected and unaffected children and their parents. Families were affected by one of six genetic conditions representing different patterns of inheritance and variations in age of onset, life expectancy and impact on families. Interviews were analysed using constructivist grounded theory and informed by models which focused on three different aspects of family communication. Interviews with 33 families showed that siblings' information and support needs go largely unrecognized by health professionals and sometimes by parents. Some siblings were actively informed about the genetic condition by parents, others were left to find out and assimilate information by themselves. Siblings were given information about the current symptoms and management of the genetic condition but were less likely to know about its hereditary nature and their own potential risk. When siblings were fully informed about the condition and included in family discussion, they had a better understanding of their role within their family, and family relationships were reported to be more harmonious. The information and support needs of siblings can be overlooked. Parents with the responsibility for caring for a child affected by a genetic condition may require support from health professionals to understand and respond to their unaffected children's need for more information about the genetic condition and its implications for the children's own future health and reproductive decision-making.

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

PubMed

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

2014-12-01

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

Genetic Variation within a Lotic Population of Janthinobacterium lividum

PubMed Central

Saeger, Jennifer L.; Hale, Alan B.

1993-01-01

An understanding of the genetic variation within and between populations should allow scientists to address many problems, including those associated with endangered species and the release of genetically modified organisms into the environment. With respect to microorganisms, the release of genetically engineered microorganisms is likely to increase dramatically given the current growth in the bioremediation industry. In this study, genetic variation within a lotic, bacterial population of Janthinobacterium lividum was measured with restriction fragment length polymorphism analysis. Chromosomal DNA from 10 Kettle Creek (Hawk Mountain Sanctuary, Kempton, Pa.) J. lividum isolates was digested with six restriction endonucleases and probed with a 7.5-kb pKK3535 fragment containing the E. coli rrnB rRNA operon. Genetic variation, as measured in terms of nucleotide diversity, was high within the population. The 0.0781 value for genetic variation was especially high given the conservative nature of the genetic probe. The average percent similarity among isolates within the population was 67.25%. Pairwise comparisons of nucleotide diversity values (π) and similarity coefficients (F) yielded values ranging from 0.0032 to 0.1816 and 0.3363 to 0.9808, respectively. Putative clonemates were not present within the group of isolates; however, all isolates shared 14 fragments across a spectrum of six restriction enzymes. The presence of these common fragments indicates that restriction fragment length polymorphism analysis may provide population- or species-specific diagnostic markers for J. lividum. Data that suggest a plume effect with respect to the downstream movement of J. lividum are also presented. An increase in genetic variation within groups of isolates along the longitudinal gradient of Kettle Creek is also suggested. PMID:16348995

Genetic Variation within a Lotic Population of Janthinobacterium lividum.

PubMed

Saeger, J L; Hale, A B

1993-07-01

An understanding of the genetic variation within and between populations should allow scientists to address many problems, including those associated with endangered species and the release of genetically modified organisms into the environment. With respect to microorganisms, the release of genetically engineered microorganisms is likely to increase dramatically given the current growth in the bioremediation industry. In this study, genetic variation within a lotic, bacterial population of Janthinobacterium lividum was measured with restriction fragment length polymorphism analysis. Chromosomal DNA from 10 Kettle Creek (Hawk Mountain Sanctuary, Kempton, Pa.) J. lividum isolates was digested with six restriction endonucleases and probed with a 7.5-kb pKK3535 fragment containing the E. coli rrnB rRNA operon. Genetic variation, as measured in terms of nucleotide diversity, was high within the population. The 0.0781 value for genetic variation was especially high given the conservative nature of the genetic probe. The average percent similarity among isolates within the population was 67.25%. Pairwise comparisons of nucleotide diversity values (pi) and similarity coefficients (F) yielded values ranging from 0.0032 to 0.1816 and 0.3363 to 0.9808, respectively. Putative clonemates were not present within the group of isolates; however, all isolates shared 14 fragments across a spectrum of six restriction enzymes. The presence of these common fragments indicates that restriction fragment length polymorphism analysis may provide population- or species-specific diagnostic markers for J. lividum. Data that suggest a plume effect with respect to the downstream movement of J. lividum are also presented. An increase in genetic variation within groups of isolates along the longitudinal gradient of Kettle Creek is also suggested.

Variation in Recombination Rate and Its Genetic Determinism in Sheep Populations.

PubMed

Petit, Morgane; Astruc, Jean-Michel; Sarry, Julien; Drouilhet, Laurence; Fabre, Stéphane; Moreno, Carole R; Servin, Bertrand

2017-10-01

Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and data sets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified ∼50,000 crossover hotspots on the genome, and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting interindividual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly two other loci of smaller effects including the KCNJ15 and FSHR genes. The comparison of these new results to those obtained previously in a distantly related population of domestic sheep (the Soay) revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome. The two data sets were thus combined to create more precise male meiotic recombination maps in Sheep. However, despite their similar recombination maps, Soay and Lacaune males were found to exhibit different heritabilities and QTL effects for interindividual variation in genome-wide recombination rates. This highlights the robustness of recombination patterns to underlying variation in their genetic determinism. Copyright © 2017 by the Genetics Society

Genetic diversity affects the strength of population regulation in a marine fish.

PubMed

Johnson, D W; Freiwald, J; Bernardi, G

2016-03-01

Variation is an essential feature of biological populations, yet much of ecological theory treats individuals as though they are identical. This simplifying assumption is often justified by the perception that variation among individuals does not have significant effects on the dynamics of whole populations. However, this perception may be skewed by a historic focus on studying single populations. A true evaluation of the extent to which among-individual variation affects the dynamics of populations requires the study of multiple populations. In this study, we examined variation in the dynamics of populations of a live-bearing, marine fish (black surfperch; Embiotoca jacksoni). In collaboration with an organization of citizen scientists (Reef Check California), we were able to examine the dynamics of eight populations that were distributed throughout approximately 700 km of coastline, a distance that encompasses much of this species' range. We hypothesized that genetic variation within a local population would be related to the intensity of competition and to the strength of population regulation. To test this hypothesis, we examined whether genetic diversity (measured by the diversity of mitochondrial DNA haplotypes) was related to the strength of population regulation. Low-diversity populations experienced strong density dependence in population growth rates and population sizes were regulated much more tightly than they were in high-diversity populations. Mechanisms that contributed to this pattern include links between genetic diversity, habitat use, and spatial crowding. On average, low-diversity populations used less of the available habitat and exhibited greater spatial clustering (and more intense competition) for a given level of density (measured at the scale of the reef). Although the populations we studied also varied with respect to exogenous characteristics (habitat complexity, densities of predators, and interspecific competitors), none of these

Evolutionary implications of mitochondrial genetic variation: mitochondrial genetic effects on OXPHOS respiration and mitochondrial quantity change with age and sex in fruit flies.

PubMed

Wolff, J N; Pichaud, N; Camus, M F; Côté, G; Blier, P U; Dowling, D K

2016-04-01

The ancient acquisition of the mitochondrion into the ancestor of modern-day eukaryotes is thought to have been pivotal in facilitating the evolution of complex life. Mitochondria retain their own diminutive genome, with mitochondrial genes encoding core subunits involved in oxidative phosphorylation. Traditionally, it was assumed that there was little scope for genetic variation to accumulate and be maintained within the mitochondrial genome. However, in the past decade, mitochondrial genetic variation has been routinely tied to the expression of life-history traits such as fertility, development and longevity. To examine whether these broad-scale effects on life-history trait expression might ultimately find their root in mitochondrially mediated effects on core bioenergetic function, we measured the effects of genetic variation across twelve different mitochondrial haplotypes on respiratory capacity and mitochondrial quantity in the fruit fly, Drosophila melanogaster. We used strains of flies that differed only in their mitochondrial haplotype, and tested each sex separately at two different adult ages. Mitochondrial haplotypes affected both respiratory capacity and mitochondrial quantity. However, these effects were highly context-dependent, with the genetic effects contingent on both the sex and the age of the flies. These sex- and age-specific genetic effects are likely to resonate across the entire organismal life-history, providing insights into how mitochondrial genetic variation may contribute to sex-specific trajectories of life-history evolution. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors.

PubMed

Patin, Etienne; Hasan, Milena; Bergstedt, Jacob; Rouilly, Vincent; Libri, Valentina; Urrutia, Alejandra; Alanio, Cécile; Scepanovic, Petar; Hammer, Christian; Jönsson, Friederike; Beitz, Benoît; Quach, Hélène; Lim, Yoong Wearn; Hunkapiller, Julie; Zepeda, Magge; Green, Cherie; Piasecka, Barbara; Leloup, Claire; Rogge, Lars; Huetz, François; Peguillet, Isabelle; Lantz, Olivier; Fontes, Magnus; Di Santo, James P; Thomas, Stéphanie; Fellay, Jacques; Duffy, Darragh; Quintana-Murci, Lluís; Albert, Matthew L

2018-03-01

The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.

Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia.

PubMed

Churchman, Michelle L; Qian, Maoxiang; Te Kronnie, Geertruy; Zhang, Ranran; Yang, Wenjian; Zhang, Hui; Lana, Tobia; Tedrick, Paige; Baskin, Rebekah; Verbist, Katherine; Peters, Jennifer L; Devidas, Meenakshi; Larsen, Eric; Moore, Ian M; Gu, Zhaohui; Qu, Chunxu; Yoshihara, Hiroki; Porter, Shaina N; Pruett-Miller, Shondra M; Wu, Gang; Raetz, Elizabeth; Martin, Paul L; Bowman, W Paul; Winick, Naomi; Mardis, Elaine; Fulton, Robert; Stanulla, Martin; Evans, William E; Relling, Mary V; Pui, Ching-Hon; Hunger, Stephen P; Loh, Mignon L; Handgretinger, Rupert; Nichols, Kim E; Yang, Jun J; Mullighan, Charles G

2018-05-14

Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL. Copyright © 2018 Elsevier Inc. All rights reserved.

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation

PubMed Central

2010-01-01

Background Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Results Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Conclusion Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing. PMID:20707912

Harnessing Genetic Variation in Leaf Angle to Increase Productivity of Sorghum bicolor

PubMed Central

Truong, Sandra K.; McCormick, Ryan F.; Rooney, William L.; Mullet, John E.

2015-01-01

The efficiency with which a plant intercepts solar radiation is determined primarily by its architecture. Understanding the genetic regulation of plant architecture and how changes in architecture affect performance can be used to improve plant productivity. Leaf inclination angle, the angle at which a leaf emerges with respect to the stem, is a feature of plant architecture that influences how a plant canopy intercepts solar radiation. Here we identify extensive genetic variation for leaf inclination angle in the crop plant Sorghum bicolor, a C4 grass species used for the production of grain, forage, and bioenergy. Multiple genetic loci that regulate leaf inclination angle were identified in recombinant inbred line populations of grain and bioenergy sorghum. Alleles of sorghum dwarf-3, a gene encoding a P-glycoprotein involved in polar auxin transport, are shown to change leaf inclination angle by up to 34° (0.59 rad). The impact of heritable variation in leaf inclination angle on light interception in sorghum canopies was assessed using functional-structural plant models and field experiments. Smaller leaf inclination angles caused solar radiation to penetrate deeper into the canopy, and the resulting redistribution of light is predicted to increase the biomass yield potential of bioenergy sorghum by at least 3%. These results show that sorghum leaf angle is a heritable trait regulated by multiple loci and that genetic variation in leaf angle can be used to modify plant architecture to improve sorghum crop performance. PMID:26323882

Genetic variation in arthropod vectors of disease-causing organisms: obstacles and opportunities.

PubMed Central

Gooding, R H

1996-01-01

An overview of the genetic variation in arthropods that transmit pathogens to vertebrates is presented, emphasizing the genetics of vector-pathogen relationships and the biochemical genetics of vectors. Vector-pathogen interactions are reviewed briefly as a prelude to a discussion of the genetics of susceptibility and refractoriness in vectors. Susceptibility to pathogens is controlled by maternally inherited factors, sex-linked dominant alleles, and dominant and recessive autosomal genes. There is widespread interpopulation (including intercolony) and temporal variation in susceptibility to pathogens. The amount of biochemical genetic variation in vectors is similar to that found in other invertebrates. However, the amount varies widely among species, among populations within species, and temporally within populations. Biochemical genetic studies show that there is considerable genetic structuring of many vectors at the local, regional, and global levels. It is argued that genetic variation in vectors is critical in understanding vector-pathogen interactions and that genetic variation in vectors creates both obstacles to and opportunities for application of genetic techniques to the control of vectors. PMID:8809462

Genetic variation in steelhead of Oregon and northern California

USGS Publications Warehouse

Reisenbichler, R.R.; McIntyre, J.D.; Solazzi, M.F.; Landino, S.W

1992-01-01

Steelhead Oncorhynchus mykiss from various sites between the Columbia River and the Mad River, California, were genetically characterized at 10 protein-coding loci or pairs of loci by starch gel electrophoresis. Fish from coastal streams differed from fish east of the Cascade Mountains and from fish of the Willamette River (a tributary of the Columbia River, west of the Cascade Mountains). Coastal steelhead from the northern part of the study area differed from those in the southern part. Genetic differentiation within and among drainages was not statistically significant; however, gene diversity analysis and the life history of steelhead suggested that fish from different drainages should be considered as separate populations. Genetic variation among fish in separate drainages was similar to that reported in northwestern Washington and less than that reported in British Columbia. Allele frequencies varied significantly among year-classes. Genetic variation within samples accounted for 98.3% of the total genetic variation observed in this study. Most hatchery populations differed from wild populations, suggesting that conservation of genetic diversity among and within wild populations could be facilitated by altering hatchery programs.

[Research progress of molecular genetic analysis in Schistosoma variation].

PubMed

Zheng, Su-Yue; Li, Fei

2014-02-01

The development of molecular biology techniques makes important contributions to the researches of heritable variation of Schistosoma. In recent years, the molecular genetic analysis in the Schistosoma variation researches mainly includes the restriction fragment length polymorphism (RFLP), random amplified polymorphism technology (RAPD), microsatellite anchored PCR (SSR-PCR), and polymerase reaction single-strand conformation polymorphism (PCR-SSCP). This article reviews the research progress of molecular genetic analysis in Schistosoma variation in recent years.

The Roles of Standing Genetic Variation and Evolutionary History in Determining the Evolvability of Anti-Predator Strategies

PubMed Central

Dworkin, Ian; Wagner, Aaron P.

2014-01-01

Standing genetic variation and the historical environment in which that variation arises (evolutionary history) are both potentially significant determinants of a population's capacity for evolutionary response to a changing environment. Using the open-ended digital evolution software Avida, we evaluated the relative importance of these two factors in influencing evolutionary trajectories in the face of sudden environmental change. We examined how historical exposure to predation pressures, different levels of genetic variation, and combinations of the two, affected the evolvability of anti-predator strategies and competitive abilities in the presence or absence of threats from new, invasive predator populations. We show that while standing genetic variation plays some role in determining evolutionary responses, evolutionary history has the greater influence on a population's capacity to evolve anti-predator traits, i.e. traits effective against novel predators. This adaptability likely reflects the relative ease of repurposing existing, relevant genes and traits, and the broader potential value of the generation and maintenance of adaptively flexible traits in evolving populations. PMID:24955847

The role of latitudinal, genetic and temperature variation in the induction of diapause of Papilio glaucus (Lepidoptera: Papilionidae).

PubMed

Ryan, Sean F; Valella, Patti; Thivierge, Gabrielle; Aardema, Matthew L; Scriber, J Mark

2018-04-01

A key adaptation in insects for dealing with variable environmental conditions is the ability to diapause. The tiger swallowtail butterflies, Papilio glaucus and P. canadensis are ideal species to explore the genetic causes and population genetic consequences of diapause because divergence in this trait is believed to be a salient factor in maintaining a hybrid zone between these species. Yet little is known about the factors that influence diapause induction in this system. Here we explored how spatial (latitudinal), environmental (temperature) and genetic (hybridization) factors affect diapause induction in this system. Specifically, a series of growth chamber experiments using wild caught individuals from across the eastern United States were performed to: (1) evaluate how critical photoperiod varies with latitude, (2) isolate the stage in which induction occurs, (3) test whether changes in temperature affected rates of diapause induction, and (4) explore how the incidence of diapause is affected in hybrid offspring. We find that induction occurs in the larval stage, is not sensitive to a relatively broad range of temperatures, appears to have a complex genetic basis (i.e., is not simply a dominant trait following a Mendelian inheritance pattern) and that the critical photoperiod increases by 0.4 h with each increasing degree in latitude. This work deepens our understanding of how spatial, environmental and genetic variation influences a key seasonal adaptation (diapause induction) in a well-developed ecological model system and will make possible future studies that explore how climatic variation affects the population dynamics and genetics of this system. © 2016 Institute of Zoology, Chinese Academy of Sciences.

Variations in 5-HTTLPR: relation to familiar risk of affective disorder, life events, neuroticism and cortisol.

PubMed

Vinberg, Maj; Mellerup, Erling; Andersen, Per Kragh; Bennike, Bente; Kessing, Lars Vedel

2010-02-01

Variations in the serotonin transporter gene (5-HTTLPR) and stressful life events are associated with affective disorders. To investigate whether the distribution of the alleles of the 5-HTTLPR is associated with a genetic predisposition to affective disorder and whether these variations interact with life events in relation to depressive symptoms, neuroticism and salivary cortisol. In a high-risk population study, healthy monozygotic and dizygotic twins with (high-risk twins) and without (low-risk twins) a co-twin history of affective disorder were identified through nationwide registers. When comparing the 81 individuals homozygote for the long allele with the 125 individuals hetero- and homozygote for the short allele no associations between the allele distribution and a genetic predisposition were found. The presence of the short allele of the 5-HTTLPR and the experience of SLE was associated with a higher neuroticism score, but not with depressive symptoms nor awakening or evening salivary cortisol. A combination of variants in 5-HTTLPR and environmental stress seems to increase neuroticism in healthy individuals. Copyright 2009 Elsevier Inc. All rights reserved.

Short communication: milk protein genetic variation and casein haplotype structure in the Original Pinzgauer cattle.

PubMed

Caroli, A; Rizzi, R; Lühken, G; Erhardt, G

2010-03-01

Milk protein genetic polymorphisms are often used for characterizing domesticated mammalian species and breeds, and for studying associations with economic traits. The aim of this work was to analyze milk protein genetic variation in the Original Pinzgauer, a dual-purpose (dairy and beef) cattle breed of European origin that was influenced in the past by human movements from different regions as well as by crossbreeding with Red Holstein. A total of 485 milk samples from Original Pinzgauer from Austria (n=275) and Germany (n=210) were typed at milk proteins alpha(S1)-casein, beta-casein, kappa-casein, alpha-lactalbumin, and beta-lactoglobulin by isoelectrofocusing to analyze the genetic variation affecting the protein amino acid charge. The Original Pinzgauer breed is characterized by a rather high genetic variation affecting the amino acid charge of milk proteins, with a total of 15 alleles, 12 of which were found at a frequency >0.05. The most polymorphic protein was beta-casein with 4 alleles detected. The prevalent alleles were CSN1S1*B, CSN2*A(2), CSN1S2*A, CSN3*A, LGB*A, and LAA*B. A relatively high frequency of CSN1S2*B (0.202 in the whole data set) was found, mainly occurring within the C-A(2)-B-A haplotype (in the order CSN1S1-CSN2-CSN1S2-CSN3), which seems to be peculiar to the Original Pinzgauer, possibly because the survival of an ancestral haplotype or the introgression of Bos indicus.

Genetic Variation Sampled in Three California Oaks

Treesearch

Lawrence A. Riggs; Constance I. Millar; Diane L. Delany

1991-01-01

As a first step in acquiring genetic information about oak species indigenous to California's hardwood rangelands we drew on experience from both forest regeneration and species conservation and applied biochemical techniques for rapidly assaying patterns of genetic variation. In a study sponsored by the California Integrated Hardwood Range Management Program we...

When Does Frequency-Independent Selection Maintain Genetic Variation?

PubMed

Novak, Sebastian; Barton, Nicholas H

2017-10-01

Frequency-independent selection is generally considered as a force that acts to reduce the genetic variation in evolving populations, yet rigorous arguments for this idea are scarce. When selection fluctuates in time, it is unclear whether frequency-independent selection may maintain genetic polymorphism without invoking additional mechanisms. We show that constant frequency-independent selection with arbitrary epistasis on a well-mixed haploid population eliminates genetic variation if we assume linkage equilibrium between alleles. To this end, we introduce the notion of frequency-independent selection at the level of alleles, which is sufficient to prove our claim and contains the notion of frequency-independent selection on haploids. When selection and recombination are weak but of the same order, there may be strong linkage disequilibrium; numerical calculations show that stable equilibria are highly unlikely. Using the example of a diallelic two-locus model, we then demonstrate that frequency-independent selection that fluctuates in time can maintain stable polymorphism if linkage disequilibrium changes its sign periodically. We put our findings in the context of results from the existing literature and point out those scenarios in which the possible role of frequency-independent selection in maintaining genetic variation remains unclear. Copyright © 2017 by the Genetics Society of America.

GEMINI: Integrative Exploration of Genetic Variation and Genome Annotations

PubMed Central

Paila, Umadevi; Chapman, Brad A.; Kirchner, Rory; Quinlan, Aaron R.

2013-01-01

Modern DNA sequencing technologies enable geneticists to rapidly identify genetic variation among many human genomes. However, isolating the minority of variants underlying disease remains an important, yet formidable challenge for medical genetics. We have developed GEMINI (GEnome MINIng), a flexible software package for exploring all forms of human genetic variation. Unlike existing tools, GEMINI integrates genetic variation with a diverse and adaptable set of genome annotations (e.g., dbSNP, ENCODE, UCSC, ClinVar, KEGG) into a unified database to facilitate interpretation and data exploration. Whereas other methods provide an inflexible set of variant filters or prioritization methods, GEMINI allows researchers to compose complex queries based on sample genotypes, inheritance patterns, and both pre-installed and custom genome annotations. GEMINI also provides methods for ad hoc queries and data exploration, a simple programming interface for custom analyses that leverage the underlying database, and both command line and graphical tools for common analyses. We demonstrate GEMINI's utility for exploring variation in personal genomes and family based genetic studies, and illustrate its ability to scale to studies involving thousands of human samples. GEMINI is designed for reproducibility and flexibility and our goal is to provide researchers with a standard framework for medical genomics. PMID:23874191

Individual differences in cognition, affect, and performance: Behavioral, neuroimaging, and molecular genetic approaches

PubMed Central

Parasuraman, Raja; Jiang, Yang

2012-01-01

We describe the use of behavioral, neuroimaging, and genetic methods to examine individual differences in cognition and affect, guided by three criteria: (1) relevance to human performance in work and everyday settings; (2) interactions between working memory, decision-making, and affective processing; and (3) examination of individual differences. The results of behavioral, functional MRI (fMRI), event-related potential (ERP), and molecular genetic studies show that analyses at the group level often mask important findings associated with sub-groups of individuals. Dopaminergic/noradrenergic genes influencing prefrontal cortex activity contribute to inter-individual variation in working memory and decision behavior, including performance in complex simulations of military decision-making. The interactive influences of individual differences in anxiety, sensation seeking, and boredom susceptibility on evaluative decision-making can be systematically described using ERP and fMRI methods. We conclude that a multi-modal neuroergonomic approach to examining brain function (using both neuroimaging and molecular genetics) can be usefully applied to understanding individual differences in cognition and affect and has implications for human performance at work. PMID:21569853

Aggregation of population‐based genetic variation over protein domain homologues and its potential use in genetic diagnostics

PubMed Central

Wiel, Laurens; Venselaar, Hanka; Veltman, Joris A.; Vriend, Gert

2017-01-01

Abstract Whole exomes of patients with a genetic disorder are nowadays routinely sequenced but interpretation of the identified genetic variants remains a major challenge. The increased availability of population‐based human genetic variation has given rise to measures of genetic tolerance that have been used, for example, to predict disease‐causing genes in neurodevelopmental disorders. Here, we investigated whether combining variant information from homologous protein domains can improve variant interpretation. For this purpose, we developed a framework that maps population variation and known pathogenic mutations onto 2,750 “meta‐domains.” These meta‐domains consist of 30,853 homologous Pfam protein domain instances that cover 36% of all human protein coding sequences. We find that genetic tolerance is consistent across protein domain homologues, and that patterns of genetic tolerance faithfully mimic patterns of evolutionary conservation. Furthermore, for a significant fraction (68%) of the meta‐domains high‐frequency population variation re‐occurs at the same positions across domain homologues more often than expected. In addition, we observe that the presence of pathogenic missense variants at an aligned homologous domain position is often paired with the absence of population variation and vice versa. The use of these meta‐domains can improve the interpretation of genetic variation. PMID:28815929

Striking Phenotypic Variation yet Low Genetic Differentiation in Sympatric Lake Trout (Salvelinus namaycush)

PubMed Central

Coon, Andrew; Carson, Robert; Debes, Paul V.

2016-01-01

The study of population differentiation in the context of ecological speciation is commonly assessed using populations with obvious discreteness. Fewer studies have examined diversifying populations with occasional adaptive variation and minor reproductive isolation, so factors impeding or facilitating the progress of early stage differentiation are less understood. We detected non-random genetic structuring in lake trout (Salvelinus namaycush) inhabiting a large, pristine, postglacial lake (Mistassini Lake, Canada), with up to five discernible genetic clusters having distinctions in body shape, size, colouration and head shape. However, genetic differentiation was low (FST = 0.017) and genetic clustering was largely incongruent between several population- and individual-based clustering approaches. Genotype- and phenotype-environment associations with spatial habitat, depth and fish community structure (competitors and prey) were either inconsistent or weak. Striking morphological variation was often more continuous within than among defined genetic clusters. Low genetic differentiation was a consequence of relatively high contemporary gene flow despite large effective population sizes, not migration-drift disequilibrium. Our results suggest a highly plastic propensity for occupying multiple habitat niches in lake trout and a low cost of morphological plasticity, which may constrain the speed and extent of adaptive divergence. We discuss how factors relating to niche conservatism in this species may also influence how plasticity affects adaptive divergence, even where ample ecological opportunity apparently exists. PMID:27680019

Intracolonial genetic variation in the scleractinian coral Seriatopora hystrix

NASA Astrophysics Data System (ADS)

Maier, E.; Buckenmaier, A.; Tollrian, R.; Nürnberger, B.

2012-06-01

In recent years, increasing numbers of studies revealed intraorganismal genetic variation, primarily in modular organisms like plants or colonial marine invertebrates. Two underlying mechanisms are distinguished: Mosaicism is caused by somatic mutation, whereas chimerism originates from allogeneic fusion. We investigated the occurrence of intracolonial genetic variation at microsatellite loci in five natural populations of the scleractinian coral Seriatopora hystrix on the Great Barrier Reef. This coral is a widely distributed, brooding species that is at present a target of intensive population genetic research on reproduction and dispersal patterns. From each of 155 S. hystrix colonies, either two or three samples were genotyped at five or six loci. Twenty-seven (~17%) genetically heterogeneous colonies were found. Statistical analyses indicated the occurrence of both mosaicism and chimerism. In most cases, intracolonial variation was found only at a single allele. Our analyses suggest that somatic mutations present a major source of genetic heterogeneity within a single colony. Moreover, we observed large, apparently stable chimeric colonies that harbored clearly distinct genotypes and contrast these findings with the patterns typically observed in laboratory-based experiments. We discuss the error that mosaicism and chimerism introduce into population genetic analyses.

Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan.

PubMed

Akuta, Norio; Kawamura, Yusuke; Arase, Yasuji; Suzuki, Fumitaka; Sezaki, Hitomi; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Suzuki, Yoshiyuki; Ikeda, Kenji; Kumada, Hiromitsu

2016-05-23

It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.

Androgens and doping tests: genetic variation and pit-falls

PubMed Central

Rane, Anders; Ekström, Lena

2012-01-01

The large variation in disposition known for most drugs is also true for anabolic androgenic steroids. Genetic factors are probably the single most important cause of this variation. Further, there are reasons to believe that there is a corresponding variation in efficacy of doping agents. Doped individuals employ a large variety of doping strategies in respect of choice of substance, dose, dose interval, duration of treatment and use of other drugs for enforcement of effects or correction of side effects. Metabolic steps up-stream and down-stream of testosterone are genetically variable and contribute substantially to the variation in disposition of testosterone, the most common doping agent in sports and in society. Large inter- and intra-ethnic variation in testosterone glucuronidation and excretion is described as well as the pit-falls in evaluation of testosterone doping test results. The hydrolysis and bioactivation of testosterone enanthate is also genetically variable yielding a 2–3 fold variation in excretion rate and serum concentration, thereby implicating a substantial variation in ‘efficacy’ of testosterone. Given this situation it is logical to adopt the new findings in the doping control programme. The population based cut-off level for the testosterone : epitestosterone ratio should be replaced by a Bayesian interpretation of consecutive tests in the same individual. When combined with the above genetic information the sensitivity of the test is considerably improved. The combination of the three approaches should reduce the rate of falsely negative or positive results and the number of expensive follow-up tests, stipulated by the World Anti-Doping Agency. PMID:22506612

Normal Genetic Variation, Cognition, and Aging

PubMed Central

Greenwood, P. M.; Parasuraman, Raja

2005-01-01

This article reviews the modulation of cognitive function by normal genetic variation. Although the heritability of “g” is well established, the genes that modulate specific cognitive functions are largely unidentified. Application of the allelic association approach to individual differences in cognition has begun to reveal the effects of single nucleotide polymorphisms on specific and general cognitive functions. This article proposes a framework for relating genotype to cognitive phenotype by considering the effect of genetic variation on the protein product of specific genes within the context of the neural basis of particular cognitive domains. Specificity of effects is considered, from genes controlling part of one receptor type to genes controlling agents of neuronal repair, and evidence is reviewed of cognitive modulation by polymorphisms in dopaminergic and cholinergic receptor genes, dopaminergic enzyme genes, and neurotrophic genes. Although allelic variation in certain genes can be reliably linked to cognition—specifically to components of attention, working memory, and executive function in healthy adults—the specificity, generality, and replicability of the effects are not fully known. PMID:15006290

Genetic variation among interconnected populations of Catostomus occidentalis: Implications for distinguishing impacts of contaminants from biogeographical structuring

USGS Publications Warehouse

Whitehead, A.; Anderson, S.L.; Kuivila, K.M.; Roach, J.L.; May, B.

2003-01-01

Exposure to contaminants can affect survivorship, recruitment, reproductive success, mutation rates and migration, and may play a significant role in the partitioning of genetic variation among exposed and nonexposed populations. However, the application of molecular population genetic data to evaluate such influences has been uncommon and often flawed. We tested whether patterns of genetic variation among native fish populations (Sacramento sucker, Catostomus occidentalis) in the Central Valley of California were consistent with long-term pesticide exposure history, or primarily with expectations based on biogeography. Field sampling was designed to rigorously test for both geographical and contamination influences. Fine-scale structure of these interconnected populations was detected with both amplified fragment length polymorphisms (AFLP) and microsatellite markers, and patterns of variation elucidated by the two marker systems were highly concordant. Analyses indicated that biogeographical hypotheses described the data set better than hypotheses relating to common historical pesticide exposure. Downstream populations had higher genetic diversity than upstream populations, regardless of exposure history, and genetic distances showed that populations from the same river system tended to cluster together. Relatedness among populations reflected primarily directions of gene flow, rather than convergence among contaminant-exposed populations. Watershed geography accounted for significant partitioning of genetic variation among populations, whereas contaminant exposure history did not. Genetic patterns indicating contaminant-induced selection, increased mutation rates or recent bottlenecks were weak or absent. We stress the importance of testing contaminant-induced genetic change hypotheses within a biogeographical context. Strategic application of molecular markers for analysis of fine-scale structure, and for evaluating contaminant impacts on gene pools, is

Evolutionary Determinants of Genetic Variation in Susceptibility to Infectious Diseases in Humans

PubMed Central

Baker, Christi; Antonovics, Janis

2012-01-01

Although genetic variation among humans in their susceptibility to infectious diseases has long been appreciated, little focus has been devoted to identifying patterns in levels of variation in susceptibility to different diseases. Levels of genetic variation in susceptibility associated with 40 human infectious diseases were assessed by a survey of studies on both pedigree-based quantitative variation, as well as studies on different classes of marker alleles. These estimates were correlated with pathogen traits, epidemiological characteristics, and effectiveness of the human immune response. The strongest predictors of levels of genetic variation in susceptibility were disease characteristics negatively associated with immune effectiveness. High levels of genetic variation were associated with diseases with long infectious periods and for which vaccine development attempts have been unsuccessful. These findings are consistent with predictions based on theoretical models incorporating fitness costs associated with the different types of resistance mechanisms. An appreciation of these observed patterns will be a valuable tool in directing future research given that genetic variation in disease susceptibility has large implications for vaccine development and epidemiology. PMID:22242158

Most genetic risk for autism resides with common variation.

PubMed

Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J; Bodea, Corneliu A; Goldberg, Arthur P; Lee, Ann B; Mahajan, Milind; Manaa, Dina; Pawitan, Yudi; Reichert, Jennifer; Ripke, Stephan; Sandin, Sven; Sklar, Pamela; Svantesson, Oscar; Reichenberg, Abraham; Hultman, Christina M; Devlin, Bernie; Roeder, Kathryn; Buxbaum, Joseph D

2014-08-01

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse. At issue is how much of an impact relative to rare variation this common variation has. Using a unique epidemiological sample from Sweden, new methods that distinguish total narrow-sense heritability from that due to common variation and synthesis of results from other studies, we reach several conclusions about autism's genetic architecture: its narrow-sense heritability is ∼52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation.

Population-level genetic variation and climate change in a biodiversity hotspot.

PubMed

Schierenbeck, Kristina A

2017-01-01

Estimated future climate scenarios can be used to predict where hotspots of endemism may occur over the next century, but life history, ecological and genetic traits will be important in informing the varying responses within myriad taxa. Essential to predicting the consequences of climate change to individual species will be an understanding of the factors that drive genetic structure within and among populations. Here, I review the factors that influence the genetic structure of plant species in California, but are applicable elsewhere; existing levels of genetic variation, life history and ecological characteristics will affect the ability of an individual taxon to persist in the presence of anthropogenic change. Persistence in the face of climate change is likely determined by life history characteristics: dispersal ability, generation time, reproductive ability, degree of habitat specialization, plant-insect interactions, existing genetic diversity and availability of habitat or migration corridors. Existing levels of genetic diversity in plant populations vary based on a number of evolutionary scenarios that include endemism, expansion since the last glacial maximum, breeding system and current range sizes. A number of well-documented examples are provided from the California Floristic Province. Some predictions can be made for the responses of plant taxa to rapid environmental changes based on geographic position, evolutionary history, existing genetic variation, and ecological amplitude. The prediction of how species will respond to climate change will require a synthesis drawing from population genetics, geography, palaeontology and ecology. The important integration of the historical factors that have shaped the distribution and existing genetic structure of California's plant taxa will enable us to predict and prioritize the conservation of species and areas most likely to be impacted by rapid climate change, human disturbance and invasive species. �

Maintenance of genetic variation in human personality: Testing evolutionary models by estimating heritability due to common causal variants and investigating the effect of distant inbreeding

PubMed Central

Verweij, Karin J.H.; Yang, Jian; Lahti, Jari; Veijola, Juha; Hintsanen, Mirka; Pulkki-Råback, Laura; Heinonen, Kati; Pouta, Anneli; Pesonen, Anu-Katriina; Widen, Elisabeth; Taanila, Anja; Isohanni, Matti; Miettunen, Jouko; Palotie, Aarno; Penke, Lars; Service, Susan K.; Heath, Andrew C.; Montgomery, Grant W.; Raitakari, Olli; Kähönen, Mika; Viikari, Jorma; Räikkönen, Katri; Eriksson, Johan G; Keltikangas-Järvinen, Liisa; Lehtimäki, Terho; Martin, Nicholas G.; Järvelin, Marjo-Riitta; Visscher, Peter M.; Keller, Matthew C.; Zietsch, Brendan P.

2012-01-01

Personality traits are basic dimensions of behavioural variation, and twin, family, and adoption studies show that around 30% of the between-individual variation is due to genetic variation. There is rapidly-growing interest in understanding the evolutionary basis of this genetic variation. Several evolutionary mechanisms could explain how genetic variation is maintained in traits, and each of these makes predictions in terms of the relative contribution of rare and common genetic variants to personality variation, the magnitude of nonadditive genetic influences, and whether personality is affected by inbreeding. Using genome-wide SNP data from >8,000 individuals, we estimated that little variation in the Cloninger personality dimensions (7.2% on average) is due to the combined effect of common, additive genetic variants across the genome, suggesting that most heritable variation in personality is due to rare variant effects and/or a combination of dominance and epistasis. Furthermore, higher levels of inbreeding were associated with less socially-desirable personality trait levels in three of the four personality dimensions. These findings are consistent with genetic variation in personality traits having been maintained by mutation-selection balance. PMID:23025612

Demographic History and Reproductive Output Correlates with Intraspecific Genetic Variation in Seven Species of Indo-Pacific Mangrove Crabs

PubMed Central

Fratini, Sara; Ragionieri, Lapo; Cannicci, Stefano

2016-01-01

The spatial distribution and the amount of intraspecific genetic variation of marine organisms are strongly influenced by many biotic and abiotic factors. Comparing biological and genetic data characterizing species living in the same habitat can help to elucidate the processes driving these variation patterns. Here, we present a comparative multispecies population genetic study on seven mangrove crabs co-occurring in the West Indian Ocean characterized by planktotrophic larvae with similar pelagic larval duration. Our main aim was to investigate whether a suite of biological, behavioural and ecological traits could affect genetic diversities of the study species in combination with historical demographic parameters. As possible current explanatory factors, we used the intertidal micro-habitat colonised by adult populations, various parameters of individual and population fecundity, and the timing of larval release. As the genetic marker, we used partial sequences of cytochrome oxidase subunit I gene. Genetic and ecological data were collected by the authors and/or gathered from primary literature. Permutational multiple regression models and ANOVA tests showed that species density and their reproductive output in combination with historical demographic parameters could explain the intraspecific genetic variation indexes across the seven species. In particular, species producing consistently less eggs per spawning event showed higher values of haplotype diversity. Moreover, Tajima’s D parameters well explained the recorded values for haplotype diversity and average γst. We concluded that current intraspecific gene diversities in crabs inhabiting mangrove forests were affected by population fecundity as well as past demographic history. The results were also discussed in terms of management and conservation of fauna in the Western Indian Ocean mangroves. PMID:27379532

Demographic History and Reproductive Output Correlates with Intraspecific Genetic Variation in Seven Species of Indo-Pacific Mangrove Crabs.

PubMed

Fratini, Sara; Ragionieri, Lapo; Cannicci, Stefano

2016-01-01

The spatial distribution and the amount of intraspecific genetic variation of marine organisms are strongly influenced by many biotic and abiotic factors. Comparing biological and genetic data characterizing species living in the same habitat can help to elucidate the processes driving these variation patterns. Here, we present a comparative multispecies population genetic study on seven mangrove crabs co-occurring in the West Indian Ocean characterized by planktotrophic larvae with similar pelagic larval duration. Our main aim was to investigate whether a suite of biological, behavioural and ecological traits could affect genetic diversities of the study species in combination with historical demographic parameters. As possible current explanatory factors, we used the intertidal micro-habitat colonised by adult populations, various parameters of individual and population fecundity, and the timing of larval release. As the genetic marker, we used partial sequences of cytochrome oxidase subunit I gene. Genetic and ecological data were collected by the authors and/or gathered from primary literature. Permutational multiple regression models and ANOVA tests showed that species density and their reproductive output in combination with historical demographic parameters could explain the intraspecific genetic variation indexes across the seven species. In particular, species producing consistently less eggs per spawning event showed higher values of haplotype diversity. Moreover, Tajima's D parameters well explained the recorded values for haplotype diversity and average γst. We concluded that current intraspecific gene diversities in crabs inhabiting mangrove forests were affected by population fecundity as well as past demographic history. The results were also discussed in terms of management and conservation of fauna in the Western Indian Ocean mangroves.

Genetic integration of molar cusp size variation in baboons

PubMed Central

Koh, Christina; Bates, Elizabeth; Broughton, Elizabeth; Do, Nicholas T.; Fletcher, Zachary; Mahaney, Michael C.; Hlusko, Leslea J.

2010-01-01

Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded our study to include data from the maxillary molar cusps. Here we report on these later analyses, as well as inter-arch comparisons with the mandibular data. We analyzed variation in two-dimensional maxillary molar cusp size using data collected from a captive pedigreed breeding colony of baboons, Papio hamadryas, housed at the Southwest National Primate Research Center. These analyses show that variation in maxillary molar cusp size is heritable and sexually dimorphic. We also estimated additive genetic correlations between cusps on the same crown, homologous cusps along the tooth row, and maxillary and mandibular cusps. The pattern for maxillary molars yields genetic correlations of one between the paracone-metacone and protocone-hypocone. Bivariate analyses of cuspal homologues on adjacent teeth yield correlations that are high or not significantly different from one. Between dental arcades, the non-occluding cusps consistently yield high genetic correlations, especially the metaconid-paracone and metaconid-metacone. This pattern of genetic correlation does not immediately accord with the pattern of development and/or calcification, however these results do follow predictions that can be made from the evolutionary history of the tribosphenic molar. PMID:20034010

Genetic integration of molar cusp size variation in baboons.

PubMed

Koh, Christina; Bates, Elizabeth; Broughton, Elizabeth; Do, Nicholas T; Fletcher, Zachary; Mahaney, Michael C; Hlusko, Leslea J

2010-06-01

Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded our study to include data from the maxillary molar cusps. Here we report on these later analyses, as well as inter-arch comparisons with the mandibular data. We analyzed variation in two-dimensional maxillary molar cusp size using data collected from a captive pedigreed breeding colony of baboons, Papio hamadryas, housed at the Southwest National Primate Research Center. These analyses show that variation in maxillary molar cusp size is heritable and sexually dimorphic. We also estimated additive genetic correlations between cusps on the same crown, homologous cusps along the tooth row, and maxillary and mandibular cusps. The pattern for maxillary molars yields genetic correlations of one between the paracone-metacone and protocone-hypocone. Bivariate analyses of cuspal homologues on adjacent teeth yield correlations that are high or not significantly different from one. Between dental arcades, the nonoccluding cusps consistently yield high genetic correlations, especially the metaconid-paracone and metaconid-metacone. This pattern of genetic correlation does not immediately accord with the pattern of development and/or calcification, however these results do follow predictions that can be made from the evolutionary history of the tribosphenic molar. Copyright 2009 Wiley-Liss, Inc.

Most genetic risk for autism resides with common variation

PubMed Central

Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J.; Bodea, Corneliu A.; Goldberg, Arthur P.; Lee, Ann B.; Mahajan, Milind; Manaa, Dina; Pawitan, Yudi; Reichert, Jennifer; Ripke, Stephan; Sandin, Sven; Sklar, Pamela; Svantesson, Oscar; Reichenberg, Abraham; Hultman, Christina M.; Devlin, Bernie

2014-01-01

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (henceforth autism) the nature of its allelic spectrum is uncertain. Individual risk genes have been identified from rare variation, especially de novo mutations1–8. From this evidence one might conclude that rare variation dominates its allelic spectrum, yet recent studies show that common variation, individually of small effect, has substantial impact en masse9,10. At issue is how much of an impact relative to rare variation. Using a unique epidemiological sample from Sweden, novel methods that distinguish total narrow-sense heritability from that due to common variation, and by synthesizing results from other studies, we reach several conclusions about autism’s genetic architecture: its narrow-sense heritability is ≈54% and most traces to common variation; rare de novo mutations contribute substantially to individuals’ liability; still their contribution to variance in liability, 2.6%, is modest compared to heritable variation. PMID:25038753

Identification of rare genetic variation of NLRP1 gene in familial multiple sclerosis.

PubMed

Maver, Ales; Lavtar, Polona; Ristić, Smiljana; Stopinšek, Sanja; Simčič, Saša; Hočevar, Keli; Sepčić, Juraj; Drulović, Jelena; Pekmezović, Tatjana; Novaković, Ivana; Alenka, Hodžić; Rudolf, Gorazd; Šega, Saša; Starčević-Čizmarević, Nada; Palandačić, Anja; Zamolo, Gordana; Kapović, Miljenko; Likar, Tina; Peterlin, Borut

2017-06-16

The genetic etiology and the contribution of rare genetic variation in multiple sclerosis (MS) has not yet been elucidated. Although familial forms of MS have been described, no convincing rare and penetrant variants have been reported to date. We aimed to characterize the contribution of rare genetic variation in familial and sporadic MS and have identified a family with two sibs affected by concomitant MS and malignant melanoma (MM). We performed whole exome sequencing in this primary family and 38 multiplex MS families and 44 sporadic MS cases and performed transcriptional and immunologic assessment of the identified variants. We identified a potentially causative homozygous missense variant in NLRP1 gene (Gly587Ser) in the primary family. Further possibly pathogenic NLRP1 variants were identified in the expanded cohort of patients. Stimulation of peripheral blood mononuclear cells from MS patients with putatively pathogenic NLRP1 variants showed an increase in IL-1B gene expression and active cytokine IL-1β production, as well as global activation of NLRP1-driven immunologic pathways. We report a novel familial association of MS and MM, and propose a possible underlying genetic basis in NLRP1 gene. Furthermore, we provide initial evidence of the broader implications of NLRP1-related pathway dysfunction in MS.

A multi-perspective view of genetic variation in Cameroon.

PubMed

Coia, V; Brisighelli, F; Donati, F; Pascali, V; Boschi, I; Luiselli, D; Battaggia, C; Batini, C; Taglioli, L; Cruciani, F; Paoli, G; Capelli, C; Spedini, G; Destro-Bisol, G

2009-11-01

In this study, we report the genetic variation of autosomal and Y-chromosomal microsatellites in a large Cameroon population dataset (a total of 11 populations) and jointly analyze novel and previous genetic data (mitochondrial DNA and protein coding loci) taking geographic and cultural factors into consideration. The complex pattern of genetic variation of Cameroon can in part be described by contrasting two geographic areas (corresponding to the northern and southern part of the country), which differ substantially in environmental, biological, and cultural aspects. Northern Cameroon populations show a greater within- and among-group diversity, a finding that reflects the complex migratory patterns and the linguistic heterogeneity of this area. A striking reduction of Y-chromosomal genetic diversity was observed in some populations of the northern part of the country (Podokwo and Uldeme), a result that seems to be related to their demographic history rather than to sampling issues. By exploring patterns of genetic, geographic, and linguistic variation, we detect a preferential correlation between genetics and geography for mtDNA. This finding could reflect a female matrimonial mobility that is less constrained by linguistic factors than in males. Finally, we apply the island model to mitochondrial and Y-chromosomal data and obtain a female-to-male migration Nnu ratio that was more than double in the northern part of the country. The combined effect of the propensity to inter-populational admixture of females, favored by cultural contacts, and of genetic drift acting on Y-chromosomal diversity could account for the peculiar genetic pattern observed in northern Cameroon.

Standing genetic variation as a major contributor to adaptation in the Virginia chicken lines selection experiment.

PubMed

Sheng, Zheya; Pettersson, Mats E; Honaker, Christa F; Siegel, Paul B; Carlborg, Örjan

2015-10-01

Artificial selection provides a powerful approach to study the genetics of adaptation. Using selective-sweep mapping, it is possible to identify genomic regions where allele-frequencies have diverged during selection. To avoid false positive signatures of selection, it is necessary to show that a sweep affects a selected trait before it can be considered adaptive. Here, we confirm candidate, genome-wide distributed selective sweeps originating from the standing genetic variation in a long-term selection experiment on high and low body weight of chickens. Using an intercross between the two divergent chicken lines, 16 adaptive selective sweeps were confirmed based on their association with the body weight at 56 days of age. Although individual additive effects were small, the fixation for alternative alleles across the loci contributed at least 40 % of the phenotypic difference for the selected trait between these lines. The sweeps contributed about half of the additive genetic variance present within and between the lines after 40 generations of selection, corresponding to a considerable portion of the additive genetic variance of the base population. Long-term, single-trait, bi-directional selection in the Virginia chicken lines has resulted in a gradual response to selection for extreme phenotypes without a drastic reduction in the genetic variation. We find that fixation of several standing genetic variants across a highly polygenic genetic architecture made a considerable contribution to long-term selection response. This provides new fundamental insights into the dynamics of standing genetic variation during long-term selection and adaptation.

Genetic variation in foundation species governs the dynamics of trophic interactions

PubMed Central

Valencia-Cuevas, Leticia; Mussali-Galante, Patricia; Cano-Santana, Zenón; Pujade-Villar, Juli; Equihua-Martínez, Armando

2018-01-01

Abstract Various studies have demonstrated that the foundation species genetic diversity can have direct effects that extend beyond the individual or population level, affecting the dependent communities. Additionally, these effects may be indirectly extended to higher trophic levels throughout the entire community. Quercus castanea is an oak species with characteristics of foundation species beyond presenting a wide geographical distribution and being a dominant element of Mexican temperate forests. In this study, we analyzed the influence of population (He) and individual (HL) genetic diversity of Q. castanea on its canopy endophagous insect community and associated parasitoids. Specifically, we studied the composition, richness (S) and density of leaf-mining moths (Lepidoptera: Tischeridae, Citheraniidae), gall-forming wasps (Hymenoptera: Cynipidae), and canopy parasitoids of Q. castanea. We sampled 120 trees belonging to six populations (20/site) through the previously recognized gradient of genetic diversity. In total, 22 endophagous insect species belonging to three orders (Hymenoptera, Lepidoptera, and Diptera) and 20 parasitoid species belonging to 13 families were identified. In general, we observed that the individual genetic diversity of the host plant (HL) has a significant positive effect on the S and density of the canopy endophagous insect communities. In contrast, He has a significant negative effect on the S of endophagous insects. Additionally, indirect effects of HL were observed, affecting the S and density of parasitoid insects. Our results suggest that genetic variation in foundation species can be one of the most important factors governing the dynamics of tritrophic interactions that involve oaks, herbivores, and parasitoids. PMID:29492034

Characterizing Male–Female Interactions Using Natural Genetic Variation in Drosophila melanogaster

PubMed Central

Reinhart, Michael; Carney, Tara; Clark, Andrew G.

2015-01-01

Drosophila melanogaster females commonly mate with multiple males establishing the opportunity for pre- and postcopulatory sexual selection. Traits impacting sexual selection can be affected by a complex interplay of the genotypes of the competing males, the genotype of the female, and compatibilities between the males and females. We scored males from 96 2nd and 94 3rd chromosome substitution lines for traits affecting reproductive success when mated with females from 3 different genetic backgrounds. The traits included male-induced female refractoriness, male remating ability, the proportion of offspring sired under competitive conditions and male-induced female fecundity. We observed significant effects of male line, female genetic background, and strong male by female interactions. Some males appeared to be “generalists” and performed consistently across the different females; other males appeared to be “specialists” and performed very well with a particular female and poorly with others. “Specialist” males did not, however, prefer to court those females with whom they had the highest reproductive fitness. Using 143 polymorphisms in male reproductive genes, we mapped several genes that had consistent effects across the different females including a derived, high fitness allele in Acp26Aa that may be the target of adaptive evolution. We also identified a polymorphism upstream of PebII that may interact with the female genetic background to affect male-induced refractoriness to remating. These results suggest that natural variation in PebII might contribute to the observed male–female interactions. PMID:25425680

Genetic Brain Disorders

MedlinePlus

A genetic brain disorder is caused by a variation or a mutation in a gene. A variation is a different form ... mutation is a change in a gene. Genetic brain disorders affect the development and function of the ...

Conservation genetics of bull trout: Geographic distribution of variation at microsatellite loci.

Treesearch

P. Spruell; A.R. Hemmingsen; P.J. Howell; N. Kanda; F.W. Allendorf

2003-01-01

We describe the genetic population structure of 65 bull trout (Salvelinus confluentus) populations from the northwestern United States using four microsatellite loci. The distribution of genetic variation as measured by microsatellites is consistent with previous allozyme and mitochondrial DNA analysis. There is relatively little genetic variation...

Identifying environmental correlates of intraspecific genetic variation.

PubMed

Harrisson, K A; Yen, J D L; Pavlova, A; Rourke, M L; Gilligan, D; Ingram, B A; Lyon, J; Tonkin, Z; Sunnucks, P

2016-09-01

Genetic variation is critical to the persistence of populations and their capacity to adapt to environmental change. The distribution of genetic variation across a species' range can reveal critical information that is not necessarily represented in species occurrence or abundance patterns. We identified environmental factors associated with the amount of intraspecific, individual-based genetic variation across the range of a widespread freshwater fish species, the Murray cod Maccullochella peelii. We used two different approaches to statistically quantify the relative importance of predictor variables, allowing for nonlinear relationships: a random forest model and a Bayesian approach. The latter also accounted for population history. Both approaches identified associations between homozygosity by locus and both disturbance to the natural flow regime and mean annual flow. Homozygosity by locus was negatively associated with disturbance to the natural flow regime, suggesting that river reaches with more disturbed flow regimes may support larger, more genetically diverse populations. Our findings are consistent with the hypothesis that artificially induced perennial flows in regulated channels may provide greater and more consistent habitat and reduce the frequency of population bottlenecks that can occur frequently under the highly variable and unpredictable natural flow regime of the system. Although extensive river regulation across eastern Australia has not had an overall positive effect on Murray cod numbers over the past century, regulation may not represent the primary threat to Murray cod survival. Instead, pressures other than flow regulation may be more critical to the persistence of Murray cod (for example, reduced frequency of large floods, overfishing and chemical pollution).

ALDH1A2 (RALDH2) genetic variation in human congenital heart disease

PubMed Central

2009-01-01

Background Signaling by the vitamin A-derived morphogen retinoic acid (RA) is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2) is critical for cardiac development, we screened patients with congenital heart disease (CHDs) for genetic variation at the ALDH1A2 locus. Methods One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430) at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM) simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay. Results We describe in Tetralogy of Fallot (TOF) the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT) design using single marker genotype, or haplotype information do not show differences between cases and controls. Conclusion In summary, our screen indicates that ALDH1A2 genetic

[Genetic variation of geographical provenance of Pinus massoniana--review and analysis].

PubMed

Li, D; Peng, S

2000-04-01

Pinus massoniana is a significant tree species constituting the subtropical forests in China. Based on morphological, physio-ecological, chromosome, and molecular levels, the genetic variation of geographical provenance of P. massoniana and its distribution were reviewed, and the methodologies on genetic diversity and the genetic variation patterns of geographical provenance of P. massoniana were synthetically analyzed. The Key problems on molecular ecology of P. massoniana were discussed.

Genetic Variation in an Inbred Plant: Variation in Tissue Cultures of Soybean [Glycine Max (L.) Merrill

PubMed Central

Roth, E. J.; Frazier, B. L.; Apuya, N. R.; Lark, K. G.

1989-01-01

Although soybean [Glycine max (L.) Merrill] grows as an inbreeding, generally homozygous, plant, the germplasm of the species contains large amounts of genetic variation. Analysis of soybean DNA has indicated that variation of RFLP (restriction fragment length polymorphism) markers within the species usually entails only two alleles at any one locus and that mixtures of such dimorphic loci account for virtually all of the restriction fragment variation seen in soybean (G. max), and in its ancestors, G. soja and G. gracilis. We report here that tissue cultures prepared from root tissue of individual soybean plants develop RFLP allelic differences at various loci. However, these newly generated alleles are almost always the same as ones previously found and characterized in other varieties of cultivated soybean (cultivars). This repeated generation of particular alleles suggests that much of the genetic variation seen in soybean could be the consequence of specific, relatively frequently employed, recombinational events. Such a mechanism would allow inbred cultivars to generate genetic variation (in the form of alternative alleles) in a controlled manner, perhaps in response to stress. PMID:2567263

Quantitative Genetics Identifies Cryptic Genetic Variation Involved in the Paternal Regulation of Seed Development

PubMed Central

Pires, Nuno D.; Bemer, Marian; Müller, Lena M.; Baroux, Célia; Spillane, Charles; Grossniklaus, Ueli

2016-01-01

Embryonic development requires a correct balancing of maternal and paternal genetic information. This balance is mediated by genomic imprinting, an epigenetic mechanism that leads to parent-of-origin-dependent gene expression. The parental conflict (or kinship) theory proposes that imprinting can evolve due to a conflict between maternal and paternal alleles over resource allocation during seed development. One assumption of this theory is that paternal alleles can regulate seed growth; however, paternal effects on seed size are often very low or non-existent. We demonstrate that there is a pool of cryptic genetic variation in the paternal control of Arabidopsis thaliana seed development. Such cryptic variation can be exposed in seeds that maternally inherit a medea mutation, suggesting that MEA acts as a maternal buffer of paternal effects. Genetic mapping using recombinant inbred lines, and a novel method for the mapping of parent-of-origin effects using whole-genome sequencing of segregant bulks, indicate that there are at least six loci with small, paternal effects on seed development. Together, our analyses reveal the existence of a pool of hidden genetic variation on the paternal control of seed development that is likely shaped by parental conflict. PMID:26811909

Quantitative Genetics Identifies Cryptic Genetic Variation Involved in the Paternal Regulation of Seed Development.

PubMed

Pires, Nuno D; Bemer, Marian; Müller, Lena M; Baroux, Célia; Spillane, Charles; Grossniklaus, Ueli

2016-01-01

Embryonic development requires a correct balancing of maternal and paternal genetic information. This balance is mediated by genomic imprinting, an epigenetic mechanism that leads to parent-of-origin-dependent gene expression. The parental conflict (or kinship) theory proposes that imprinting can evolve due to a conflict between maternal and paternal alleles over resource allocation during seed development. One assumption of this theory is that paternal alleles can regulate seed growth; however, paternal effects on seed size are often very low or non-existent. We demonstrate that there is a pool of cryptic genetic variation in the paternal control of Arabidopsis thaliana seed development. Such cryptic variation can be exposed in seeds that maternally inherit a medea mutation, suggesting that MEA acts as a maternal buffer of paternal effects. Genetic mapping using recombinant inbred lines, and a novel method for the mapping of parent-of-origin effects using whole-genome sequencing of segregant bulks, indicate that there are at least six loci with small, paternal effects on seed development. Together, our analyses reveal the existence of a pool of hidden genetic variation on the paternal control of seed development that is likely shaped by parental conflict.

Genetic variation in Toll-like receptors and disease susceptibility.

PubMed

Netea, Mihai G; Wijmenga, Cisca; O'Neill, Luke A J

2012-05-18

Toll-like receptors (TLRs) are key initiators of the innate immune response and promote adaptive immunity. Much has been learned about the role of TLRs in human immunity from studies linking TLR genetic variation with disease. First, monogenic disorders associated with complete deficiency in certain TLR pathways, such as MyD88-IRAK4 or TLR3-Unc93b-TRIF-TRAF3, have demonstrated the specific roles of these pathways in host defense against pyogenic bacteria and herpesviruses, respectively. Second, common polymorphisms in genes encoding several TLRs and associated genes have been associated with both infectious and autoimmune diseases. The study of genetic variation in TLRs in various populations combined with information on infection has demonstrated complex interaction between genetic variation in TLRs and environmental factors. This interaction explains the differences in the effect of TLR polymorphisms on susceptibility to infection and autoimmune disease in various populations.

Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size.

PubMed

Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T; Weiss, Kenneth M; Mahaney, Michael C; Rogers, Jeffrey; Cheverud, James M

2018-02-01

Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (V P ) and additive genetic (V A ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. Covariates account for 1.2-91% of craniofacial V P . EID V A decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. Because a relatively large proportion of EID V A is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual V P patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes. © 2017 Wiley Periodicals, Inc.

Genetic variation assessed with microsatellites in mass selection lines of the Pacific oyster ( Crassostrea gigas) in China

NASA Astrophysics Data System (ADS)

Wang, Xubo; Li, Qi; Yu, Hong; Kong, Lingfeng

2016-12-01

Four successive mass selection lines of the Pacific oyster, Crassostrea gigas, selected for faster growth in breeding programs in China were examined at ten polymorphic microsatellite loci to assess the level of allelic diversity and estimate the effective population size. These data were compared with those of their base population. The results showed that the genetic variation of the four generations were maintained at high levels with an average allelic richness of 18.8-20.6, and a mean expected heterozygosity of 0.902-0.921. They were not reduced compared with those of their base population. Estimated effective population sizes based on temporal variances in microsatellite frequencies were smaller to that of sex ratio-corrected broodstock count estimates. Using a relatively large number of broodstock and keeping an equal sex ratio in the broodstock each generation may have contributed to retaining the original genetic diversity and maintaining relatively large effective population size. The results obtained in this study showed that the genetic variation was not affected greatly by mass selection progress and high genetic variation still existed in the mass selection lines, suggesting that there is still potential for increasing the gains in future generations of C. gigas. The present study provided important information for future genetic improvement by selective breeding, and for the design of suitable management guidelines for genetic breeding of C. gigas.

Variation in Recombination Rate and Its Genetic Determinism in Sheep Populations

PubMed Central

Petit, Morgane; Astruc, Jean-Michel; Sarry, Julien; Drouilhet, Laurence; Fabre, Stéphane; Moreno, Carole R.; Servin, Bertrand

2017-01-01

Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and data sets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified ∼50,000 crossover hotspots on the genome, and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting interindividual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly two other loci of smaller effects including the KCNJ15 and FSHR genes. The comparison of these new results to those obtained previously in a distantly related population of domestic sheep (the Soay) revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome. The two data sets were thus combined to create more precise male meiotic recombination maps in Sheep. However, despite their similar recombination maps, Soay and Lacaune males were found to exhibit different heritabilities and QTL effects for interindividual variation in genome-wide recombination rates. This highlights the robustness of recombination patterns to underlying variation in their genetic determinism. PMID:28978774

Genetic constraints on wing pattern variation in Lycaeides butterflies: A case study on mapping complex, multifaceted traits in structured populations.

PubMed

Lucas, Lauren K; Nice, Chris C; Gompert, Zachariah

2018-03-13

Patterns of phenotypic variation within and among species can be shaped and constrained by trait genetic architecture. This is particularly true for complex traits, such as butterfly wing patterns, that consist of multiple elements. Understanding the genetics of complex trait variation across species boundaries is difficult, as it necessitates mapping in structured populations and can involve many loci with small or variable phenotypic effects. Here, we investigate the genetic architecture of complex wing pattern variation in Lycaeides butterflies as a case study of mapping multivariate traits in wild populations that include multiple nominal species or groups. We identify conserved modules of integrated wing pattern elements within populations and species. We show that trait covariances within modules have a genetic basis and thus represent genetic constraints that can channel evolution. Consistent with this, we find evidence that evolutionary changes in wing patterns among populations and species occur in the directions of genetic covariances within these groups. Thus, we show that genetic constraints affect patterns of biological diversity (wing pattern) in Lycaeides, and we provide an analytical template for similar work in other systems. © 2018 John Wiley & Sons Ltd.

AFLP analysis of Cynodon dactylon (L.) Pers. var. dactylon genetic variation.

PubMed

Wu, Y Q; Taliaferro, C M; Bai, G H; Anderson, M P

2004-08-01

Cynodon dactylon (L.) Pers. var. dactylon (common bermudagrass) is geographically widely distributed between about lat 45 degrees N and lat 45 degrees S, penetrating to about lat 53 degrees N in Europe. The extensive variation of morphological and adaptive characteristics of the taxon is substantially documented, but information is lacking on DNA molecular variation in geographically disparate forms. Accordingly, this study was conducted to assess molecular genetic variation and genetic relatedness among 28 C. dactylon var. dactylon accessions originating from 11 countries on 4 continents (Africa, Asia, Australia, and Europe). A fluorescence-labeled amplified fragment length polymorphism (AFLP) DNA profiling method was used to detect the genetic diversity and relatedness. On the basis of 443 polymorphic AFLP fragments from 8 primer combinations, the accessions were grouped into clusters and subclusters associating with their geographic origins. Genetic similarity coefficients (SC) for the 28 accessions ranged from 0.53 to 0.98. Accessions originating from Africa, Australia, Asia, and Europe formed major groupings as indicated by cluster and principal coordinate analysis. Accessions from Australia and Asia, though separately clustered, were relatively closely related and most distantly related to accessions of European origin. African accessions formed two distant clusters and had the greatest variation in genetic relatedness relative to accessions from other geographic regions. Sampling the full extent of genetic variation in C. dactylon var. dactylon would require extensive germplasm collection in the major geographic regions of its distributional range.

Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways

PubMed Central

Singh, Kapil Dev; Roschitzki, Bernd; Snoek, L. Basten; Grossmann, Jonas; Zheng, Xue; Elvin, Mark; Kamkina, Polina; Schrimpf, Sabine P.; Poulin, Gino B.; Kammenga, Jan E.; Hengartner, Michael O.

2016-01-01

Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch, and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans. We used selected reaction monitoring to analyse proteins from the abovementioned four pathways in a set of recombinant inbred lines (RILs) generated from the wild-type strains N2 (Bristol) and CB4856 (Hawaii) to enable quantitative trait locus (QTL) mapping. About half of the cases from the 44 genes tested showed a statistically significant change in protein abundance between various strains, most of these were however very weak (below 1.3-fold change). We detected a distant QTL on the left arm of chromosome II that affected protein abundance of the phosphatidylserine receptor protein PSR-1, and two separate QTLs that influenced embryonic and ionizing radiation-induced apoptosis on chromosome IV. Our results demonstrate that natural variation in C. elegans is sufficient to cause significant changes in signalling pathways both at the gene expression (transcript and protein abundance) and phenotypic levels. PMID:26985669

Lack of genetic variation in tree ring delta13C suggests a uniform, stomatally-driven response to drought stress across Pinus radiata genotypes.

PubMed

Rowell, Douglas M; Ades, Peter K; Tausz, Michael; Arndt, Stefan K; Adams, Mark A

2009-02-01

We assessed the variation in delta(13)C signatures of Pinus radiata D. Don stemwood taken from three genetic trials in southern Australia. We sought to determine the potential of using delta(13)C signatures as selection criteria for drought tolerance. Increment cores were taken from P. radiata and were used to determine the basal area increment and the delta(13)C signature of extracted cellulose. Both growth increment and cellulose delta(13)C were affected by water availability. Growth increment and delta(13)C were negatively correlated suggesting that growth was water-limited. While there was significant genetic variation in growth, there was no significant genetic variation in cellulose delta(13)C of tree rings. This suggests that different genotypes of P. radiata display significant differences in growth and yet respond similarly to drought stress. The delta(13)C response to drought stress was more due to changes in stomatal conductance than to the variation in photosynthetic capacity, and this may explain the lack of genetic variation in delta(13)C. The lack of genetic variation in cellulose delta(13)C of tree rings precludes its use as a selection criterion for drought tolerance among P. radiata genotypes.

Antigenic variation: Molecular and genetic mechanisms of relapsing disease

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

Cruse, J.M.; Lewis, R.E.

1987-01-01

This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

Unique genetic variation at a species' rear edge is under threat from global climate change

PubMed Central

Provan, Jim; Maggs, Christine A.

2012-01-01

Global climate change is having a significant effect on the distributions of a wide variety of species, causing both range shifts and population extinctions. To date, however, no consensus has emerged on how these processes will affect the range-wide genetic diversity of impacted species. It has been suggested that species that recolonized from low-latitude refugia might harbour high levels of genetic variation in rear-edge populations, and that loss of these populations could cause a disproportionately large reduction in overall genetic diversity in such taxa. In the present study, we have examined the distribution of genetic diversity across the range of the seaweed Chondrus crispus, a species that has exhibited a northward shift in its southern limit in Europe over the last 40 years. Analysis of 19 populations from both sides of the North Atlantic using mitochondrial single nucleotide polymorphisms (SNPs), sequence data from two single-copy nuclear regions and allelic variation at eight microsatellite loci revealed unique genetic variation for all marker classes in the rear-edge populations in Iberia, but not in the rear-edge populations in North America. Palaeodistribution modelling and statistical testing of alternative phylogeographic scenarios indicate that the unique genetic diversity in Iberian populations is a result not only of persistence in the region during the last glacial maximum, but also because this refugium did not contribute substantially to the recolonization of Europe after the retreat of the ice. Consequently, loss of these rear-edge populations as a result of ongoing climate change will have a major effect on the overall genetic diversity of the species, particularly in Europe, and this could compromise the adaptive potential of the species as a whole in the face of future global warming. PMID:21593035

Levels of genetic variation in trees: influence of life history characteristics

Treesearch

J. L Hamrick; J. B. Milton; Y. B. Linhart

1981-01-01

In a previous study, levels of genetic variation, as measured by isozyme analyses, were compared for 113 taxa of vascular plants. Each species was classified for 12 life history and ecological traits and three measures of genetic variation were calculated. Plants with large ranges, high fecundities, an outcrossing mode of reproduction, wind pollination, a long...

Genetic variation within and between strains of outbred Swiss mice.

PubMed

Cui, S; Chesson, C; Hope, R

1993-04-01

The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. Ten to 15 animals from each strain (NIH, Q(S), ARC, IMVS and STUD) were typed, using allozyme electrophoresis, at 10 gene loci: Mod-1, Idh-1, Gpi-I, Es-1, Es-3, Hbb, Pep-3, Gr-1, Got-2 and Pgm-1. Polymorphic variation in at least one of the 5 strains was detected at all 10 loci. The proportion of polymorphic loci ranged from 0.3 (NIH) to 0.8 (IMVS) with a mean of 0.52. Average expected heterozygosities ranged from 0.08 (NIH) to 0.37 (IMVS) with a mean of 0.21. The inbred strain SWR was, as expected, homozygous at all 10 loci. The amount of allelic substitution between pairs of strains was quantified using Nei's genetic distance, and a dendrogram based on these genetic distances showed a close overall similarity in its branching pattern to the known genealogy of the strains. This survey showed that a considerable degree of genetic variation persists in the 5 strains examined, a level of variation similar to that previously detected by Rice and O'Brien (1980) in 3 other outbred Swiss strains.

Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior

PubMed Central

Shorter, John; Couch, Charlene; Huang, Wen; Carbone, Mary Anna; Peiffer, Jason; Anholt, Robert R. H.; Mackay, Trudy F. C.

2015-01-01

Aggression is an evolutionarily conserved complex behavior essential for survival and the organization of social hierarchies. With the exception of genetic variants associated with bioamine signaling, which have been implicated in aggression in many species, the genetic basis of natural variation in aggression is largely unknown. Drosophila melanogaster is a favorable model system for exploring the genetic basis of natural variation in aggression. Here, we performed genome-wide association analyses using the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and replicate advanced intercross populations derived from the most and least aggressive DGRP lines. We identified genes that have been previously implicated in aggressive behavior as well as many novel loci, including gustatory receptor 63a (Gr63a), which encodes a subunit of the receptor for CO2, and genes associated with development and function of the nervous system. Although genes from the two association analyses were largely nonoverlapping, they mapped onto a genetic interaction network inferred from an analysis of pairwise epistasis in the DGRP. We used mutations and RNAi knock-down alleles to functionally validate 79% of the candidate genes and 75% of the candidate epistatic interactions tested. Epistasis for aggressive behavior causes cryptic genetic variation in the DGRP that is revealed by changing allele frequencies in the outbred populations derived from extreme DGRP lines. This phenomenon may pertain to other fitness traits and species, with implications for evolution, applied breeding, and human genetics. PMID:26100892

Evolutionary developmental genetics of fruit morphological variation within the Solanaceae

PubMed Central

Wang, Li; Li, Jing; Zhao, Jing; He, Chaoying

2015-01-01

Morphological variations of fruits such as shape and size, and color are a result of adaptive evolution. The evolution of morphological novelties is particularly intriguing. An understanding of these evolutionary processes calls for the elucidation of the developmental and genetic mechanisms that result in particular fruit morphological characteristics, which determine seed dispersal. The genetic and developmental basis for fruit morphological variation was established at a microevolutionary time scale. Here, we summarize the progress on the evolutionary developmental genetics of fruit size, shape and color in the Solanaceae. Studies suggest that the recruitment of a pre-existing gene and subsequent modification of its interaction and regulatory networks are frequently involved in the evolution of morphological diversity. The basic mechanisms underlying changes in plant morphology are alterations in gene expression and/or gene function. We also deliberate on the future direction in evolutionary developmental genetics of fruit morphological variation such as fruit type. These studies will provide insights into plant developmental processes and will help to improve the productivity and fruit quality of crops. PMID:25918515

SRD5A1 Genetic Variation and Prostate Cancer Epidemiology

DTIC Science & Technology

2006-05-01

DAMD17-03-1-0136 TITLE: SRD5A1 Genetic Variation and Prostate Cancer Epidemiology PRINCIPAL INVESTIGATOR: Troy Phipps...DATES COVERED (From - To) 1 May 2003 – 30 Apr 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER SRD5A1 Genetic Variation and Prostate Cancer...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The human steroid 5-alpha reductase type I ( SRD5A1 ) gene was sequenced in 101

Quantitative Genetic Architecture at Latitudinal Range Boundaries: Reduced Variation but Higher Trait Independence.

PubMed

Paccard, Antoine; Van Buskirk, Josh; Willi, Yvonne

2016-05-01

Species distribution limits are hypothesized to be caused by small population size and limited genetic variation in ecologically relevant traits, but earlier studies have not evaluated genetic variation in multivariate phenotypes. We asked whether populations at the latitudinal edges of the distribution have altered quantitative genetic architecture of ecologically relevant traits compared with midlatitude populations. We calculated measures of evolutionary potential in nine Arabidopsis lyrata populations spanning the latitudinal range of the species in eastern and midwestern North America. Environments at the latitudinal extremes have reduced water availability, and therefore plants were assessed under wet and dry treatments. We estimated genetic variance-covariance (G-) matrices for 10 traits related to size, development, and water balance. Populations at southern and northern distribution edges had reduced levels of genetic variation across traits, but their G-matrices were more spherical; G-matrix orientation was unrelated to latitude. As a consequence, the predicted short-term response to selection was at least as strong in edge populations as in central populations. These results are consistent with genetic drift eroding variation and reducing the effectiveness of correlational selection at distribution margins. We conclude that genetic variation of isolated traits poorly predicts the capacity to evolve in response to multivariate selection and that the response to selection may frequently be greater than expected at species distribution margins because of genetic drift.

Drosophila melanogaster Natural Variation Affects Growth Dynamics of Infecting Listeria monocytogenes

PubMed Central

Hotson, Alejandra Guzmán; Schneider, David S.

2015-01-01

We find that in a Listeria monocytogenes/Drosophila melanogaster infection model, L. monocytogenes grows according to logistic kinetics, which means we can measure both a maximal growth rate and growth plateau for the microbe. Genetic variation of the host affects both of the pathogen growth parameters, and they can vary independently. Because growth rates and ceilings both correlate with host survival, both properties could drive evolution of the host. We find that growth rates and ceilings are sensitive to the initial infectious dose in a host genotype–dependent manner, implying that experimental results differ as we change the original challenge dose within a single strain of host. PMID:26438294

Genetic variation and factors affecting the genetic structure of the lichenicolous fungus Heterocephalacria bachmannii (Filobasidiales, Basidiomycota)

PubMed Central

Laakso, Into; Stenroos, Soili

2017-01-01

Heterocephalacria bachmannii is a lichenicolous fungus that takes as hosts numerous lichen species of the genus Cladonia. In the present study we analyze whether the geographical distance, the host species or the host secondary metabolites determine the genetic structure of this parasite. To address the question, populations mainly from the Southern Europe, Southern Finland and the Azores were sampled. The specimens were collected from 20 different host species representing ten chemotypes. Three loci, ITS rDNA, LSU rDNA and mtSSU, were sequenced. The genetic structure was assessed by AMOVA, redundance analyses and Bayesian clustering methods. The results indicated that the host species and the host secondary metabolites are the most influential factors over the genetic structure of this lichenicolous fungus. In addition, the genetic structure of H. bachmannii was compared with that of one of its hosts, Cladonia rangiformis. The population structure of parasite and host were discordant. The contents in phenolic compounds and fatty acids of C. rangiformis were quantified in order to test whether it had some influence on the genetic structure of the species. But no correlation was found with the genetic clusters of H. bachmannii. PMID:29253026

Loss of Mhc and Neutral Variation in Peary Caribou: Genetic Drift Is Not Mitigated by Balancing Selection or Exacerbated by Mhc Allele Distributions

PubMed Central

Taylor, Sabrina S.; Jenkins, Deborah A.; Arcese, Peter

2012-01-01

Theory and empirical results suggest that the rate of loss of variation at Mhc and neutral microsatellite loci may differ because selection influences Mhc genes, and because a high proportion of rare alleles at Mhc loci may result in high rates of loss via drift. Most published studies compare Mhc and microsatellite variation in various contemporary populations to infer the effects of population size on genetic variation, even though different populations are likely to have different demographic histories that may also affect contemporary genetic variation. We directly compared loss of variation at Mhc and microsatellite loci in Peary caribou by comparing historical and contemporary samples. We observed that similar proportions of genetic variation were lost over time at each type of marker despite strong evidence for selection at Mhc genes. These results suggest that microsatellites can be used to estimate genome-wide levels of variation, but also that adaptive potential is likely to be lost following population bottlenecks. However, gene conversion and recombination at Mhc loci may act to increase variation following bottlenecks. PMID:22655029

The relative effects of habitat loss and fragmentation on population genetic variation in the red-cockaded woodpecker (Picoides borealis).

PubMed

Bruggeman, Douglas J; Wiegand, Thorsten; Fernández, Néstor

2010-09-01

The relative influence of habitat loss, fragmentation and matrix heterogeneity on the viability of populations is a critical area of conservation research that remains unresolved. Using simulation modelling, we provide an analysis of the influence both patch size and patch isolation have on abundance, effective population size (N(e)) and F(ST). An individual-based, spatially explicit population model based on 15 years of field work on the red-cockaded woodpecker (Picoides borealis) was applied to different landscape configurations. The variation in landscape patterns was summarized using spatial statistics based on O-ring statistics. By regressing demographic and genetics attributes that emerged across the landscape treatments against proportion of total habitat and O-ring statistics, we show that O-ring statistics provide an explicit link between population processes, habitat area, and critical thresholds of fragmentation that affect those processes. Spatial distances among land cover classes that affect biological processes translated into critical scales at which the measures of landscape structure correlated best with genetic indices. Therefore our study infers pattern from process, which contrasts with past studies of landscape genetics. We found that population genetic structure was more strongly affected by fragmentation than population size, which suggests that examining only population size may limit recognition of fragmentation effects that erode genetic variation. If effective population size is used to set recovery goals for endangered species, then habitat fragmentation effects may be sufficiently strong to prevent evaluation of recovery based on the ratio of census:effective population size alone.

Genetic Variation in Populations of a Tropical Mysid, Mysidium gracile

NASA Astrophysics Data System (ADS)

Chapina, R.; Ramos-Chavez, J.; Walsh, E.

2016-02-01

Genetic diversity allows organisms to adapt to environmental factors such as climate change and ocean acidification. Greater genetic diversity among organisms allows a higher probability of adaptation to changing environments. The mysid Mysidium gracile is a shrimp-like crustacean that aggregates into swarms near coral reefs. They are important in reef systems since they occupy an important intermediate level of marine food webs by transferring energy from planktonic species to reef fishes. Thus, there is concern regarding the tolerance of reef- associated organisms to climatic changes and overall coral reef health. The objective of this study is to determine the level of genetic variation within and among Caribbean M. gracile populations. Mysids from 7 islands were collected and preserved for genetic analysis. The CO1 gene was amplified and sequenced for 100 mysids representing 14 swarms. Haplotype diversity was determined using DnaSP5.0. Twenty- three haplotypes were detected with a haplotype diversity of 0.94, thus indicating a high level of haplotypic variation. Mysids from two populations shared a haplotype, implying that there is potential gene flow between these populations. Mysids from additional swarms are in process of being characterized. Overall, these results show that there is substantial genetic variation within and among mysid populations that may allow them to adapt environmental factors.

Genetic variation, climate models and the ecological genetics of Larix occidentalis

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

Rehfeldt, G.E.

1995-12-31

Provenance tests of 138 populations of Larix occidentalis revealed genetic differentiation for eight variables describing growth, phenology, tolerance to spring frosts, effects of Meria laricis needle cast, and survival. Geographic variables accounted for as much as 34% of the variance among Rocky Mountain populations. Patterns of genetic variation were dominated by the effects of latitude and elevation, with populations from the north and from high elevations having the lowest growth potential, the least tolerance to the needle cast, and the lowest survival. However, the slope of the geographic clines was relatively flat. Populations in the same geographic area, for instance,more » need to be separated by about 500 m in elevation before genetic differentiation can be expected.« less

Genetic and non-genetic factors affecting morphometry of Sirohi goats

PubMed Central

Dudhe, S. D.; Yadav, S. B. S.; Nagda, R. K.; Pannu, Urmila; Gahlot, G. C.

2015-01-01

Aim: The aim was to estimate genetic and non-genetic factors affecting morphometric traits of Sirohi goats under field condition. Materials and Methods: The detailed information of all animals on body measurements at birth, 3, 6, 9, and 12 months of age was collected from farmer’s flock under field condition born during 2007-2013 to analyze the effect of genetic and non-genetic factors. The least squares maximum likelihood program was used to estimate genetic and non-genetic parameters affecting morphometric traits. Results and Discussion: Effect of sire, cluster, year of birth, and sex was found to be highly significant (p<0.01) on all three morphometric traits, parity was highly significant (p<0.01) for body height (BH) and body girth (BG) at birth. The h2 estimates for morphometric traits ranged among 0.528±0.163 to 0.709±0.144 for BH, 0.408±0.159 to 0.605±0.192 for body length (BL), and 0.503±0.197 to 0.695±0.161 for BG. Conclusion: The effect of sire was highly significant (p<0.01) and also h² estimate of all morphometric traits were medium to high; therefore, it could be concluded on the basis of present findings that animals with higher body measurements at initial phases of growth will perform better with respect to even body weight traits at later stages of growth. PMID:27047043

Genetic variation in the endangered Southwestern Willow Flycatcher

USGS Publications Warehouse

Busch, Joseph; Miller, Mark P.; Paxton, E.H.; Sogge, M.K.; Keim, Paul

2000-01-01

The Southwestern Willow Flycatcher (Empidonax traillii extimus) is an endangered Neotropical migrant that breeds in isolated remnants of dense riparian habitat in the southwestern United States. We estimated genetic variation at 20 breeding sites of the Southwestern Willow Flycatcher (290 individuals) using 38 amplified fragment length polymorphisms (AFLPs). Our results suggest that considerable genetic diversity exists within the subspecies and within local breeding sites. Statistical analyses of genetic variation revealed only slight, although significant, differentiation among breeding sites (Mantel's r = 0.0705, P < 0.0005; θ = 0.0816, 95% CI = 0.0608 to 0.1034; ΦST = 0.0458, P < 0.001). UPGMA cluster analysis of the AFLP markers indicates that extensive gene flow has occurred among breeding sites. No one site stood out as being genetically unique or isolated. Therefore, the small level of genetic structure that we detected may not be biologically significant. Ongoing field studies are consistent with this conclusion. Of the banded birds that were resighted or recaptured in Arizona during the 1996 to 1998 breeding seasons, one-third moved between breeding sites and two-thirds were philopatric. Low differentiation may be the result of historically high rangewide diversity followed by recent geographic isolation of breeding sites, although observational data indicate that gene flow is a current phenomenon. Our data suggest that breeding groups of E. t. extimus act as a metapopulation.

Genetic identity affects performance of species in grasslands of different plant diversity: an experiment with Lolium perenne cultivars.

PubMed

Roscher, Christiane; Schumacher, Jens; Weisser, Wolfgang W; Schulze, Ernst-Detlef

2008-07-01

Recent biodiversity research has focused on ecosystem processes, but less is known about responses of populations of individual plant species to changing community diversity and implications of genetic variation within species. To address these issues, effects of plant community diversity on the performance of different cultivars of Lolium perenne were analysed. Populations of 15 genetic cultivars of Lolium perenne were established in experimental grasslands varying in richness of species (from 1 to 60) and functional groups (from 1 to 4). Population sizes, mean size of individual plants, biomass of individual shoots and seed production were measured in the first and second growing season after establishment. Population sizes of all cultivars decreased with increasing community species richness. Plant individuals formed fewer shoots with a lower shoot mass in more species-rich plant communities. A large proportion of variation in plant size and relative population growth was attributable to effects of community species and functional group richness, but the inclusion of cultivar identity explained additional 4-7 % of variation. Cultivar identity explained most variation (28-51 %) at the shoot level (biomass of individual tillers and reproductive shoots, seed production, heading stage). Coefficients of variation of the measured variables across plant communities were larger in cultivars with a lower average performance, indicating that this variation was predominantly due to passive growth reductions and not a consequence of larger adaptive plastic responses. No single cultivar performed best in all communities. The decreasing performance of Lolium perenne in plant communities of increasing species richness suggests a regulation of competitive interactions by species diversity. Genetic variation within species provides a base for larger phenotypic variation and may affect competitive ability. However, heterogeneous biotic environments (= plant communities of

Aging, Genetic Variations, and Ethnopharmacology: Building Cultural Competence Through Awareness of Drug Responses in Ethnic Minority Elders.

PubMed

Woods, Diana Lynn; Mentes, Janet C; Cadogan, Mary; Phillips, Linda R

2017-01-01

Unique drug responses that may result in adverse events are among the ethnocultural differences described by the Agency for Healthcare Research and Quality. These differences, often attributed to a lack of adherence on the part of the older adult, may be linked to genetic variations that influence drug responses in different ethnic groups. The paucity of research coupled with a lack of knowledge among health care providers compound the problem, contributing to further disparities, especially in this era of personalized medicine and pharmacogenomics. This article examines how age-related changes and genetic differences influence variations in drug responses among older adults in unique ethnocultural groups. The article starts with an overview of age-related changes and ethnopharmacology, moves to describing genetic differences that affect drug responses, with a focus on medications commonly prescribed for older adults, and ends with application of these issues to culturally congruent health care. © The Author(s) 2015.

The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel

PubMed Central

Wang, Jonathan B.

2017-01-01

Individuals vary extensively in the way they respond to disease but the genetic basis of this variation is not fully understood. We found substantial individual variation in resistance and tolerance to the fungal pathogen Metarhizium anisopliae Ma549 using the Drosophila melanogaster Genetic Reference Panel (DGRP). In addition, we found that host defense to Ma549 was correlated with defense to the bacterium Pseudomonas aeruginosa Pa14, and several previously published DGRP phenotypes including oxidative stress sensitivity, starvation stress resistance, hemolymph glucose levels, and sleep indices. We identified polymorphisms associated with differences between lines in both their mean survival times and microenvironmental plasticity, suggesting that lines differ in their ability to adapt to variable pathogen exposures. The majority of polymorphisms increasing resistance to Ma549 were sex biased, located in non-coding regions, had moderately large effect and were rare, suggesting that there is a general cost to defense. Nevertheless, host defense was not negatively correlated with overall longevity and fecundity. In contrast to Ma549, minor alleles were concentrated in the most Pa14-susceptible as well as the most Pa14-resistant lines. A pathway based analysis revealed a network of Pa14 and Ma549-resistance genes that are functionally connected through processes that encompass phagocytosis and engulfment, cell mobility, intermediary metabolism, protein phosphorylation, axon guidance, response to DNA damage, and drug metabolism. Functional testing with insertional mutagenesis lines indicates that 12/13 candidate genes tested influence susceptibility to Ma549. Many candidate genes have homologs identified in studies of human disease, suggesting that genes affecting variation in susceptibility are conserved across species. PMID:28257468

Genetic variation in personality traits explains genetic overlap between borderline personality features and substance use disorders.

PubMed

Few, Lauren R; Grant, Julia D; Trull, Timothy J; Statham, Dixie J; Martin, Nicholas G; Lynskey, Michael T; Agrawal, Arpana

2014-12-01

To examine the genetic overlap between borderline personality features (BPF) and substance use disorders (SUDs) and the extent to which variation in personality traits contributes to this covariance. Genetic structural equation modelling was used to partition the variance in and covariance between personality traits, BPF and SUDs into additive genetic, shared and individual-specific environmental factors. All participants were registered with the Australian Twin Registry. A total of 3127 Australian adult twins participated in the study. Diagnoses of DSM-IV alcohol and cannabis abuse/dependence (AAD; CAD) and nicotine dependence (ND) were derived via computer-assisted telephone interview. BPF and five-factor model personality traits were derived via self-report questionnaires. Personality traits, BPF and substance use disorders were partially influenced by genetic factors with heritability estimates ranging from 0.38 (neuroticism; 95% confidence interval: 0.30-0.45) to 0.78 (CAD; 95% confidence interval: 0.67-0.86). Genetic and individual-specific environmental correlations between BPF and SUDs ranged from 0.33 to 0.56 (95% CI = 0.19-0.74) and 0.19-0.32 (95% CI = 0.06-0.43), respectively. Overall, there was substantial support for genetic influences that were specific to AAD, ND and CAD (30.76-68.60%). Finally, genetic variation in personality traits was responsible for 11.46% (extraversion for CAD) to 59.30% (neuroticism for AAD) of the correlation between BPF and SUDs. Both genetic and individual-specific environmental factors contribute to comorbidity between borderline personality features and substance use disorders. A substantial proportion of this comorbidity can be attributed to variation in normal personality traits, particularly neuroticism. © 2014 Society for the Study of Addiction.

The Evolution of Human Genetic and Phenotypic Variation in Africa

PubMed Central

Campbell, Michael C.

2010-01-01

Africa is the birthplace of modern humans, and is the source of the geographic expansion of ancestral populations into other regions of the world. Indigenous Africans are characterized by high levels of genetic diversity within and between populations. The pattern of genetic variation in these populations has been shaped by demographic events occurring over the last 200,000 years. The dramatic variation in climate, diet, and exposure to infectious disease across the continent has also resulted in novel genetic and phenotypic adaptations in extant Africans. This review summarizes some recent advances in our understanding of the demographic history and selective pressures that have influenced levels and patterns of diversity in African populations. PMID:20178763

Extensive genetic and DNA methylation variation contribute to heterosis in triploid loquat hybrids.

PubMed

Liu, Chao; Wang, Mingbo; Wang, Lingli; Guo, Qigao; Liang, Guolu

2018-04-24

We aim to overcome the unclear origin of the loquat and elucidate the heterosis mechanism of the triploid loquat. Here we investigated the genetic and epigenetic variations between the triploid plant and its parental lines using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified fragment length polymorphism (MSAP) analyses. We show that in addition to genetic variations, extensive DNA methylation variation occurred during the formation process of triploid loquat, with the triploid hybrid having increased DNA methylation compared to the parents. Furthermore, a correlation existed between genetic variation and DNA methylation remodeling, suggesting that genome instability may lead to DNA methylation variation or vice versa. Sequence analysis of the MSAP bands revealed that over 53% of them overlap with protein-coding genes, which may indicate a functional role of the differential DNA methylation in gene regulation and hence heterosis phenotypes. Consistent with this, the genetic and epigenetic alterations were associated closely to the heterosis phenotypes of triploid loquat, and this association varied for different traits. Our results suggested that the formation of triploid is accompanied by extensive genetic and DNA methylation variation, and these changes contribute to the heterosis phenotypes of the triploid loquats from the two cross lines.

Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach.

PubMed

Giardine, Belinda; Borg, Joseph; Higgs, Douglas R; Peterson, Kenneth R; Philipsen, Sjaak; Maglott, Donna; Singleton, Belinda K; Anstee, David J; Basak, A Nazli; Clark, Barnaby; Costa, Flavia C; Faustino, Paula; Fedosyuk, Halyna; Felice, Alex E; Francina, Alain; Galanello, Renzo; Gallivan, Monica V E; Georgitsi, Marianthi; Gibbons, Richard J; Giordano, Piero C; Harteveld, Cornelis L; Hoyer, James D; Jarvis, Martin; Joly, Philippe; Kanavakis, Emmanuel; Kollia, Panagoula; Menzel, Stephan; Miller, Webb; Moradkhani, Kamran; Old, John; Papachatzopoulou, Adamantia; Papadakis, Manoussos N; Papadopoulos, Petros; Pavlovic, Sonja; Perseu, Lucia; Radmilovic, Milena; Riemer, Cathy; Satta, Stefania; Schrijver, Iris; Stojiljkovic, Maja; Thein, Swee Lay; Traeger-Synodinos, Jan; Tully, Ray; Wada, Takahito; Waye, John S; Wiemann, Claudia; Zukic, Branka; Chui, David H K; Wajcman, Henri; Hardison, Ross C; Patrinos, George P

2011-03-20

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.

Heritability and genetic basis of protein level variation in an outbred population

PubMed Central

Liu, Yi-Chun; Tekkedil, Manu M.; Steinmetz, Lars M.; Caudy, Amy A.; Fraser, Andrew G.

2014-01-01

The genetic basis of heritable traits has been studied for decades. Although recent mapping efforts have elucidated genetic determinants of transcript levels, mapping of protein abundance has lagged. Here, we analyze levels of 4084 GFP-tagged yeast proteins in the progeny of a cross between a laboratory and a wild strain using flow cytometry and high-content microscopy. The genotype of trans variants contributed little to protein level variation between individual cells but explained >50% of the variance in the population’s average protein abundance for half of the GFP fusions tested. To map trans-acting factors responsible, we performed flow sorting and bulk segregant analysis of 25 proteins, finding a median of five protein quantitative trait loci (pQTLs) per GFP fusion. Further, we find that cis-acting variants predominate; the genotype of a gene and its surrounding region had a large effect on protein level six times more frequently than the rest of the genome combined. We present evidence for both shared and independent genetic control of transcript and protein abundance: More than half of the expression QTLs (eQTLs) contribute to changes in protein levels of regulated genes, but several pQTLs do not affect their cognate transcript levels. Allele replacements of genes known to underlie trans eQTL hotspots confirmed the correlation of effects on mRNA and protein levels. This study represents the first genome-scale measurement of genetic contribution to protein levels in single cells and populations, identifies more than a hundred trans pQTLs, and validates the propagation of effects associated with transcript variation to protein abundance. PMID:24823668

Comprehensive Evaluation of the Association of APOE Genetic Variation with Plasma Lipoprotein Traits in U.S. Whites and African Blacks

PubMed Central

Radwan, Zaheda H.; Wang, Xingbin; Waqar, Fahad; Pirim, Dilek; Niemsiri, Vipavee; Hokanson, John E.; Hamman, Richard F.; Bunker, Clareann H.; Barmada, M. Michael; Demirci, F. Yesim; Kamboh, M. Ilyas

2014-01-01

Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE*2 and APOE*4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol. PMID:25502880

Additive genetic variation for tolerance to estrogen pollution in natural populations of Alpine whitefish (Coregonus sp., Salmonidae).

PubMed

Brazzola, Gregory; Chèvre, Nathalie; Wedekind, Claus

2014-11-01

The evolutionary potential of natural populations to adapt to anthropogenic threats critically depends on whether there exists additive genetic variation for tolerance to the threat. A major problem for water-dwelling organisms is chemical pollution, and among the most common pollutants is 17α-ethinylestradiol (EE2), the synthetic estrogen that is used in oral contraceptives and that can affect fish at various developmental stages, including embryogenesis. We tested whether there is variation in the tolerance to EE2 within Alpine whitefish. We sampled spawners from two species of different lakes, bred them in vitro in a full-factorial design each, and studied growth and mortality of embryos. Exposure to EE2 turned out to be toxic in all concentrations we tested (≥1 ng/L). It reduced embryo viability and slowed down embryogenesis. We found significant additive genetic variation in EE2-induced mortality in both species, that is, genotypes differed in their tolerance to estrogen pollution. We also found maternal effects on embryo development to be influenced by EE2, that is, some maternal sib groups were more susceptible to EE2 than others. In conclusion, the toxic effects of EE2 were strong, but both species demonstrated the kind of additive genetic variation that is necessary for an evolutionary response to this type of pollution.

Genetic variation in personality traits explains genetic overlap between borderline personality features and substance use disorders

PubMed Central

Few, Lauren R.; Grant, Julia D; Trull, Timothy J.; Statham, Dixie J.; Martin, Nicholas G.; Lynskey, Michael T.; Agrawal, Arpana

2014-01-01

Aims To examine the genetic overlap between borderline personality features (BPF) and substance use disorders (SUDs) and the extent to which variation in personality traits contributes to this covariance. Design Genetic structural equation modelling was used to partition the variance in and covariance between personality traits, BPF, and SUDs into additive genetic, shared, and individual-specific environmental factors. Setting All participants were registered with the Australian Twin Registry. Participants A total of 3,127 Australian adult twins participated in the study. Measurements Diagnoses of DSM-IV alcohol and cannabis abuse/dependence (AAD; CAD), and nicotine dependence (ND) were derived via computer-assisted telephone interview. BPF and five-factor model personality traits were derived via self-report questionnaires. Findings Genetic factors were responsible for 49% (95%CI: 42%–55%) of the variance in BPF, 38–42% (95%CI range: 32%–49%) for personality traits and 47% (95%CI: 17%–77%), 54% (95%CI: 43%–64%), and 78% (67%–86%) for ND, AAD and CAD, respectively. Genetic and individual-specific environmental correlations between BPF and SUDs ranged from .33–.56 (95%CI range: .19–.74) and .19–.32 (95%CI range: .06–.43), respectively. Overall, there was substantial support for genetic influences that were specific to AAD, ND and CAD (31%–69%). Finally, genetic variation in personality traits was responsible for 11% (Extraversion for CAD) to 59% (Neuroticism for AAD) of the correlation between BPF and SUDs. Conclusions Both genetic and individual-specific environmental factors contribute to comorbidity between borderline personality features and substance use disorders. A substantial proportion of this comorbidity can be attributed to variation in normal personality traits, particularly Neuroticism. PMID:25041562

Unleashing the power of human genetic variation knowledge: New Zealand stakeholder perspectives.

PubMed

Gu, Yulong; Warren, James Roy; Day, Karen Jean

2011-01-01

This study aimed to characterize the challenges in using genetic information in health care and to identify opportunities for improvement. Taking a grounded theory approach, semistructured interviews were conducted with 48 participants to collect multiple stakeholder perspectives on genetic services in New Zealand. Three themes emerged from the data: (1) four service delivery models were identified in operation, including both those expected models involving genetic counselors and variations that do not route through the formal genetic service program; (2) multiple barriers to sharing and using genetic information were perceived, including technological, organizational, institutional, legal, ethical, and social issues; and (3) impediments to wider use of genetic testing technology, including variable understanding of genetic test utilities among clinicians and the limited capacity of clinical genetic services. Targeting these problems, information technologies and knowledge management tools have the potential to support key tasks in genetic services delivery, improve knowledge processes, and enhance knowledge networks. Because of the effect of issues in genetic information and knowledge management, the potential of human genetic variation knowledge to enhance health care delivery has been put on a "leash."

The Grandest Genetic Experiment Ever Performed on Man? - A Y-Chromosomal Perspective on Genetic Variation in India.

PubMed

Carvalho-Silva, Denise R; Tyler-Smith, Chris

2008-05-01

We have analysed Y-chromosomal data from Indian caste, Indian tribal and East Asian populations in order to investigate the impact of the caste system on male genetic variation. We find that variation within populations is lower in India than in East Asia, while variation between populations is overall higher. This observation can be explained by greater subdivision within the Indian population, leading to more genetic drift. However, the effect is most marked in the tribal populations, and the level of variation between caste populations is similar to the level between Chinese populations. The caste system has therefore had a detectable impact on Y-chromosomal variation, but this has been less strong than the influence of the tribal system, perhaps because of larger population sizes in the castes, more gene flow or a shorter period of time.

P450 GENETIC VARIATION: IMPLICATIONS FOR ENVIRONMENTAL AND WORKPLACE EXPOSURE

EPA Science Inventory

The Cytochrome P450 array detoxifies many chemicals by catalyzing the conversion of mostly hydrophobic chemicals into more hydrophilic forms that can subsequently be excreted by the body. Human genetic variation in the genes for these enzymes produces wide variations in the abili...

Intraspecific variation in social organization by genetic variation, developmental plasticity, social flexibility or entirely extrinsic factors.

PubMed

Schradin, Carsten

2013-05-19

Previously, it was widely believed that each species has a specific social organization, but we know now that many species show intraspecific variation in their social organization. Four different processes can lead to intraspecific variation in social organization: (i) genetic variation between individuals owing to local adaptation (between populations) or evolutionarily stable strategies within populations; (ii) developmental plasticity evolved in long-term (more than one generation) unpredictable and short-term (one generation) predictable environments, which is mediated by organizational physiological effects during early ontogeny; (iii) social flexibility evolved in highly unpredictable environments, which is mediated by activational physiological effects in adults; (iv) entirely extrinsic factors such as the death of a dominant breeder. Variation in social behaviour occurs between individuals in the case of genetic variation and developmental plasticity, but within individuals in the case of social flexibility. It is important to study intraspecific variation in social organization to understand the social systems of species because it reveals the mechanisms by which species can adapt to changing environments, offers a useful tool to study the ultimate and proximate causes of sociality, and is an interesting phenomenon by itself that needs scientific explanation.

Maintenance of genetic variation in sexual ornaments: a review of the mechanisms.

PubMed

Radwan, Jacek

2008-09-01

Female preferences for elaborate male sexual traits have been documented in a number of species in which males contribute only genes to the next generation. In such systems, mate choice has been hypothesised to benefit females genetically. For the genetic benefits to be possible there must be additive genetic variation (V A) for sexual ornaments, such that highly ornamented males can pass fitter genes on to the progeny of choosy females. Here, I review the mechanisms that can contribute to the maintenance of this variation. The variation may be limited to sexual ornaments, resulting in Fisherian benefits in terms of the increased reproductive success of male progeny produced by choosy females. Alternatively, ornaments may capture V A in other life-history traits. In the latter case, "good genes" benefits may apply in terms of improved performance of the progeny of either sex. Some mechanisms, however, such as negative pleiotropy, sexually antagonistic variation or overdominance, can maintain V A in ornaments and other life-history traits with little variation in total fitness, leaving little room for any genetic benefits of mate choice. Distinguishing between these mechanisms has consequences not only for the theory of sexual selection, but also for evolution of sex and for biological conservation. I discuss how the traditional ways of testing for genetic benefits can usefully be supplemented by tests detecting benefits resulting from specific mechanisms maintaining V A in sexual ornaments.

Population-genetic properties of differentiated copy number variations in cattle.

PubMed

Xu, Lingyang; Hou, Yali; Bickhart, Derek M; Zhou, Yang; Hay, El Hamidi Abdel; Song, Jiuzhou; Sonstegard, Tad S; Van Tassell, Curtis P; Liu, George E

2016-03-23

While single nucleotide polymorphism (SNP) is typically the variant of choice for population genetics, copy number variation (CNV) which comprises insertion, deletion and duplication of genomic sequence, is an informative type of genetic variation. CNVs have been shown to be both common in mammals and important for understanding the relationship between genotype and phenotype. However, CNV differentiation, selection and its population genetic properties are not well understood across diverse populations. We performed a population genetics survey based on CNVs derived from the BovineHD SNP array data of eight distinct cattle breeds. We generated high resolution results that show geographical patterns of variations and genome-wide admixture proportions within and among breeds. Similar to the previous SNP-based studies, our CNV-based results displayed a strong correlation of population structure and geographical location. By conducting three pairwise comparisons among European taurine, African taurine, and indicine groups, we further identified 78 unique CNV regions that were highly differentiated, some of which might be due to selection. These CNV regions overlapped with genes involved in traits related to parasite resistance, immunity response, body size, fertility, and milk production. Our results characterize CNV diversity among cattle populations and provide a list of lineage-differentiated CNVs.

Comparison of the levels of intra-specific genetic variation within Giardia muris and Giardia intestinalis.

PubMed

Andrews, R H; Monis, P T; Ey, P L; Mayrhofer, G

1998-08-01

The extent of intra-specific genetic variation between isolates of Giardia muris was assessed by allozyme electrophoresis. Additionally, the levels of allozymic variation detected within G. muris were compared with those observed between members of the two major assemblages of the morphologically distinct species Giardia intestinalis. Four isolates of G. muris were analysed. Three (Ad-120, -150, -151) were isolated from mice in Australia, while the fourth (R-T) was isolated from a golden hamster in North America. The 11 isolates of G. intestinalis (Ad-1, -12, -2, -62, representing genetic Groups I and II of Assemblage A and BAH-12, BRIS/87/HEPU/694, Ad-19, -22, -28, -45, -52, representing genetic Groups III and IV of Assemblage B) were from humans in Australia. Intra-specific genetic variation was detected between G. muris isolates at four of the 23 enzyme loci examined. Similar levels of variation were found within the genetic groups that comprise Assemblages A and B of G. intestinalis. These levels of intra-specific variation are similar to those observed within other morphologically-distinct species of protozoan parasites. We suggest that the magnitude of the genetic differences detected within G. muris provides an indication of the range of genetic variation within other species of Giardia and that this can be used as a model to delineate morphologically similar but genetically distinct (cryptic) species within this genus.

Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation.

PubMed

Delviks-Frankenberry, Krista A; Nikolaitchik, Olga A; Burdick, Ryan C; Gorelick, Robert J; Keele, Brandon F; Hu, Wei-Shau; Pathak, Vinay K

2016-05-01

Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10-5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10-21 and1 × 10-11, respectively) and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic

Hsp90 and environmental stress transform the adaptive value of natural genetic variation.

PubMed

Jarosz, Daniel F; Lindquist, Susan

2010-12-24

How can species remain unaltered for long periods yet also undergo rapid diversification? By linking genetic variation to phenotypic variation via environmental stress, the Hsp90 protein-folding reservoir might promote both stasis and change. However, the nature and adaptive value of Hsp90-contingent traits remain uncertain. In ecologically and genetically diverse yeasts, we find such traits to be both common and frequently adaptive. Most are based on preexisting variation, with causative polymorphisms occurring in coding and regulatory sequences alike. A common temperature stress alters phenotypes similarly. Both selective inhibition of Hsp90 and temperature stress increase correlations between genotype and phenotype. This system broadly determines the adaptive value of standing genetic variation and, in so doing, has influenced the evolution of current genomes.

Within-population Y-linked genetic variation for lifespan in Drosophila melanogaster.

PubMed

Griffin, R M; Le Gall, D; Schielzeth, H; Friberg, U

2015-11-01

The view that the Y chromosome is of little importance for phenotypic evolution stems from early studies of Drosophila melanogaster. This species' Y chromosome contains only 13 protein-coding genes, is almost entirely heterochromatic and is not necessary for male viability. Population genetic theory further suggests that non-neutral variation can only be maintained at the Y chromosome under special circumstances. Yet, recent studies suggest that the D. melanogaster Y chromosome trans-regulates hundreds to thousands of X and autosomal genes. This finding suggests that the Y chromosome may play a far more active role in adaptive evolution than has previously been assumed. To evaluate the potential for the Y chromosome to contribute to phenotypic evolution from standing genetic variation, we test for Y-linked variation in lifespan within a population of D. melanogaster. Assessing variation for lifespan provides a powerful test because lifespan (i) shows sexual dimorphism, which the Y is primarily predicted to contribute to, (ii) is influenced by many genes, which provides the Y with many potential regulatory targets and (iii) is sensitive to heterochromatin remodelling, a mechanism through which the Y chromosome is believed to regulate gene expression. Our results show a small but significant effect of the Y chromosome and thus suggest that the Y chromosome has the potential to respond to selection from standing genetic variation. Despite its small effect size, Y-linked variation may still be important, in particular when evolution of sexual dimorphism is genetically constrained elsewhere in the genome. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

PubMed

Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C

2017-09-12

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol

PubMed Central

Alvarez, Monica I.; Glover, Luke C.; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H.; Walton, Eric M.; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I.; McClean, Colleen M.; Chinh, Nguyen Tran; Medina, Marisa W.; Dunstan, Sarah J.

2017-01-01

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi (S. Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S. Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches. PMID:28827342

Genetic Architectures of Quantitative Variation in RNA Editing Pathways

PubMed Central

Gu, Tongjun; Gatti, Daniel M.; Srivastava, Anuj; Snyder, Elizabeth M.; Raghupathy, Narayanan; Simecek, Petr; Svenson, Karen L.; Dotu, Ivan; Chuang, Jeffrey H.; Keller, Mark P.; Attie, Alan D.; Braun, Robert E.; Churchill, Gary A.

2016-01-01

RNA editing refers to post-transcriptional processes that alter the base sequence of RNA. Recently, hundreds of new RNA editing targets have been reported. However, the mechanisms that determine the specificity and degree of editing are not well understood. We examined quantitative variation of site-specific editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specific sites for A-to-I editing. An allelic series in the C-to-U editing enzyme Apobec1 influences the editing efficiency of Apob and 58 additional C-to-U editing targets. We identified 49 A-to-I editing sites with polymorphisms in the edited transcript that alter editing efficiency. In contrast to the shared genetic control of C-to-U editing, most of the variable A-to-I editing sites were determined by local nucleotide polymorphisms in proximity to the editing site in the RNA secondary structure. Our results indicate that RNA editing is a quantitative trait subject to genetic variation and that evolutionary constraints have given rise to distinct genetic architectures in the two canonical types of RNA editing. PMID:26614740

Genetic component of flammability variation in a Mediterranean shrub.

PubMed

Moreira, B; Castellanos, M C; Pausas, J G

2014-03-01

Recurrent fires impose a strong selection pressure in many ecosystems worldwide. In such ecosystems, plant flammability is of paramount importance because it enhances population persistence, particularly in non-resprouting species. Indeed, there is evidence of phenotypic divergence of flammability under different fire regimes. Our general hypothesis is that flammability-enhancing traits are adaptive; here, we test whether they have a genetic component. To test this hypothesis, we used the postfire obligate seeder Ulex parviflorus from sites historically exposed to different fire recurrence. We associated molecular variation in potentially adaptive loci detected with a genomic scan (using AFLP markers) with individual phenotypic variability in flammability across fire regimes. We found that at least 42% of the phenotypic variation in flammability was explained by the genetic divergence in a subset of AFLP loci. In spite of generalized gene flow, the genetic variability was structured by differences in fire recurrence. Our results provide the first field evidence supporting that traits enhancing plant flammability have a genetic component and thus can be responding to natural selection driven by fire. These results highlight the importance of flammability as an adaptive trait in fire-prone ecosystems. © 2014 John Wiley & Sons Ltd.

Conservation Genetics of the Philippine Tarsier: Cryptic Genetic Variation Restructures Conservation Priorities for an Island Archipelago Primate

PubMed Central

Brown, Rafe M.; Weghorst, Jennifer A.; Olson, Karen V.; Duya, Mariano R. M.; Barley, Anthony J.; Duya, Melizar V.; Shekelle, Myron; Neri-Arboleda, Irene; Esselstyn, Jacob A.; Dominy, Nathaniel J.; Ong, Perry S.; Moritz, Gillian L.; Luczon, Adrian; Diesmos, Mae Lowe L.; Diesmos, Arvin C.; Siler, Cameron D.

2014-01-01

Establishment of conservation priorities for primates is a particular concern in the island archipelagos of Southeast Asia, where rates of habitat destruction are among the highest in the world. Conservation programs require knowledge of taxonomic diversity to ensure success. The Philippine tarsier is a flagship species that promotes environmental awareness and a thriving ecotourism economy in the Philippines. However, assessment of its conservation status has been impeded by taxonomic uncertainty, a paucity of field studies, and a lack of vouchered specimens and genetic samples available for study in biodiversity repositories. Consequently, conservation priorities are unclear. In this study we use mitochondrial and nuclear DNA to empirically infer geographic partitioning of genetic variation and to identify evolutionarily distinct lineages for conservation action. The distribution of Philippine tarsier genetic diversity is neither congruent with expectations based on biogeographical patterns documented in other Philippine vertebrates, nor does it agree with the most recent Philippine tarsier taxonomic arrangement. We identify three principal evolutionary lineages that do not correspond to the currently recognized subspecies, highlight the discovery of a novel cryptic and range-restricted subcenter of genetic variation in an unanticipated part of the archipelago, and identify additional geographically structured genetic variation that should be the focus of future studies and conservation action. Conservation of this flagship species necessitates establishment of protected areas and targeted conservation programs within the range of each genetically distinct variant of the Philippine tarsier. PMID:25136854

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.

Standing Genetic Variation and the Evolution of Drug Resistance in HIV

PubMed Central

Pennings, Pleuni Simone

2012-01-01

Drug resistance remains a major problem for the treatment of HIV. Resistance can occur due to mutations that were present before treatment starts or due to mutations that occur during treatment. The relative importance of these two sources is unknown. Resistance can also be transmitted between patients, but this process is not considered in the current study. We study three different situations in which HIV drug resistance may evolve: starting triple-drug therapy, treatment with a single dose of nevirapine and interruption of treatment. For each of these three cases good data are available from literature, which allows us to estimate the probability that resistance evolves from standing genetic variation. Depending on the treatment we find probabilities of the evolution of drug resistance due to standing genetic variation between and . For patients who start triple-drug combination therapy, we find that drug resistance evolves from standing genetic variation in approximately 6% of the patients. We use a population-dynamic and population-genetic model to understand the observations and to estimate important evolutionary parameters under the assumption that treatment failure is caused by the fixation of a single drug resistance mutation. We find that both the effective population size of the virus before treatment, and the fitness of the resistant mutant during treatment, are key-parameters which determine the probability that resistance evolves from standing genetic variation. Importantly, clinical data indicate that both of these parameters can be manipulated by the kind of treatment that is used. PMID:22685388

Regeneration Methods Affect Genetic Variation and Structure in Shortleaf Pine (Pinus Echinata Mill.)

Treesearch

Rajiv G. Raja; Charles G. Tauer; Robert F. Wittwer; Yinghua Huang

1998-01-01

The effects of regene ration methods on genetic diversity and structure in shortleaf pine (Pinus echinata Mill.) were examined by quantifying the changes in genetic composition of shortleaf pine stands following harvest by monitoring changes in allele number and frequency at heterozygous loci over time. The results were also compared to the genetic...

Natural genetic variation of root system architecture from Arabidopsis to Brachypodium: towards adaptive value.

PubMed

Pacheco-Villalobos, David; Hardtke, Christian S

2012-06-05

Root system architecture is a trait that displays considerable plasticity because of its sensitivity to environmental stimuli. Nevertheless, to a significant degree it is genetically constrained as suggested by surveys of its natural genetic variation. A few regulators of root system architecture have been isolated as quantitative trait loci through the natural variation approach in the dicotyledon model, Arabidopsis. This provides proof of principle that allelic variation for root system architecture traits exists, is genetically tractable, and might be exploited for crop breeding. Beyond Arabidopsis, Brachypodium could serve as both a credible and experimentally accessible model for root system architecture variation in monocotyledons, as suggested by first glimpses of the different root morphologies of Brachypodium accessions. Whether a direct knowledge transfer gained from molecular model system studies will work in practice remains unclear however, because of a lack of comprehensive understanding of root system physiology in the native context. For instance, apart from a few notable exceptions, the adaptive value of genetic variation in root system modulators is unknown. Future studies should thus aim at comprehensive characterization of the role of genetic players in root system architecture variation by taking into account the native environmental conditions, in particular soil characteristics.

Neutral mutation as the source of genetic variation in life history traits.

PubMed

Brcić-Kostić, Krunoslav

2005-08-01

The mechanism underlying the maintenance of adaptive genetic variation is a long-standing question in evolutionary genetics. There are two concepts (mutation-selection balance and balancing selection) which are based on the phenotypic differences between alleles. Mutation - selection balance and balancing selection cannot properly explain the process of gene substitution, i.e. the molecular evolution of quantitative trait loci affecting fitness. I assume that such loci have non-essential functions (small effects on fitness), and that they have the potential to evolve into new functions and acquire new adaptations. Here I show that a high amount of neutral polymorphism at these loci can exist in real populations. Consistent with this, I propose a hypothesis for the maintenance of genetic variation in life history traits which can be efficient for the fixation of alleles with very small selective advantage. The hypothesis is based on neutral polymorphism at quantitative trait loci and both neutral and adaptive gene substitutions. The model of neutral - adaptive conversion (NAC) assumes that neutral alleles are not neutral indefinitely, and that in specific and very rare situations phenotypic (relative fitness) differences between them can appear. In this paper I focus on NAC due to phenotypic plasticity of neutral alleles. The important evolutionary consequence of NAC could be the increased adaptive potential of a population. Loci responsible for adaptation should be fast evolving genes with minimally discernible phenotypic effects, and the recent discovery of genes with such characteristics implicates them as suitable candidates for loci involved in adaptation.

Intraspecific morphological and genetic variation of common species predicts ranges of threatened ones

PubMed Central

Fuller, Trevon L.; Thomassen, Henri A.; Peralvo, Manuel; Buermann, Wolfgang; Milá, Borja; Kieswetter, Charles M.; Jarrín-V, Pablo; Devitt, Susan E. Cameron; Mason, Eliza; Schweizer, Rena M.; Schlunegger, Jasmin; Chan, Janice; Wang, Ophelia; Schneider, Christopher J.; Pollinger, John P.; Saatchi, Sassan; Graham, Catherine H.; Wayne, Robert K.; Smith, Thomas B.

2013-01-01

Predicting where threatened species occur is useful for making informed conservation decisions. However, because they are usually rare, surveying threatened species is often expensive and time intensive. Here, we show how regions where common species exhibit high genetic and morphological divergence among populations can be used to predict the occurrence of species of conservation concern. Intraspecific variation of common species of birds, bats and frogs from Ecuador were found to be a significantly better predictor for the occurrence of threatened species than suites of environmental variables or the occurrence of amphibians and birds. Fully 93 per cent of the threatened species analysed had their range adequately represented by the geographical distribution of the morphological and genetic variation found in seven common species. Both higher numbers of threatened species and greater genetic and morphological variation of common species occurred along elevation gradients. Higher levels of intraspecific divergence may be the result of disruptive selection and/or introgression along gradients. We suggest that collecting data on genetic and morphological variation in common species can be a cost effective tool for conservation planning, and that future biodiversity inventories include surveying genetic and morphological data of common species whenever feasible. PMID:23595273

Genetic variation in bioaccumulation and partitioning of cadmium in Theobroma cacao L.

PubMed

Lewis, Caleb; Lennon, Adrian M; Eudoxie, Gaius; Umaharan, Pathmanathan

2018-06-02

Cadmium (Cd) is a non-essential heavy metal that is toxic to both plants and animals and chocolates have been identified as a contributor to the human dietary Cd intake. One hundred accessions representing the various genetic groups and hybrid populations in Theobroma cacao L. held at the International Cocoa Genebank, Trinidad were evaluated for leaf and bean cadmium levels with three tree replications. Representative samples of soil from the drip zone around each tree were evaluated for bioavailable cadmium. Although there were significant differences (P ≤ 0.05) among genetic groups for leaf and bean Cd much of the variation was between accessions. There was a 13-fold variation in bean Cd and a 7-fold variation in leaf Cd between accessions despite the bioavailable Cd in the soil being uniform. There were differences in the level of partitioning into beans evident by significant variation (P ≤ 0.05) in bean Cd as a percentage of the cumulative leaf and bean Cd concentration (15-52%) between accessions. Although in general there was a higher concentration of cadmium in the testa than the cotyledon of the cocoa bean there was considerable genetic variation. These results point to the potential of using a genetic strategy to mitigate cadmium within cocoa beans either through breeding or through the use of low cadmium uptake rootstocks in grafting. The results will fuel further work into the understanding of mechanisms and genetics of cadmium uptake and partitioning in cocoa. Copyright © 2018. Published by Elsevier B.V.

Patterns of molecular genetic variation among cat breeds.

PubMed

Menotti-Raymond, Marilyn; David, Victor A; Pflueger, Solveig M; Lindblad-Toh, Kerstin; Wade, Claire M; O'Brien, Stephen J; Johnson, Warren E

2008-01-01

Genetic variation in cat breeds was assessed utilizing a panel of short tandem repeat (STR) loci genotyped in 38 cat breeds and 284 single-nucleotide polymorphisms (SNPs) genotyped in 24 breeds. Population structure in cat breeds generally reflects their recent ancestry and absence of strong breed barriers between some breeds. There is a wide range in the robustness of population definition, from breeds demonstrating high definition to breeds with as little as a third of their genetic variation partitioning into a single population. Utilizing the STRUCTURE algorithm, there was no clear demarcation of the number of population subdivisions; 16 breeds could not be resolved into independent populations, the consequence of outcrossing in established breeds to recently developed breeds with common ancestry. These 16 breeds were divided into 6 populations. Ninety-six percent of cats in a sample set of 1040 were correctly assigned to their classified breed or breed group/population. Average breed STR heterozygosities ranged from moderate (0.53; Havana, Korat) to high (0.85; Norwegian Forest Cat, Manx). Most of the variation in cat breeds was observed within a breed population (83.7%), versus 16.3% of the variation observed between populations. The hierarchical relationships of cat breeds is poorly defined as demonstrated by phylogenetic trees generated from both STR and SNP data, though phylogeographic grouping of breeds derived completely or in part from Southeast Asian ancestors was apparent.

Molar intercuspal dimensions: genetic input to phenotypic variation.

PubMed

Townsend, G; Richards, L; Hughes, T

2003-05-01

Molecular studies indicate that epigenetic events are important in determining how the internal enamel epithelium folds during odontogenesis. Since this process of folding leads to the subsequent arrangement of cusps on molar teeth, we hypothesized that intercuspal distances of human molar teeth would display greater phenotypic variation but lower heritabilities than overall crown diameters. Intercuspal distances and maximum crown diameters were recorded from digitized images of dental casts in 100 monozygotic and 74 dizygotic twin pairs. Intercuspal distances displayed less sexual dimorphism in mean values but greater relative variability and fluctuating asymmetry than overall crown measures. Correlations between intercuspal distances and overall crown measures were low. Models incorporating only environmental effects accounted for observed variation in several intercuspal measures. For those intercuspal variables displaying significant additive genetic variance, estimates of heritability ranged from 43 to 79%, whereas those for overall crown size were higher generally, ranging from 60 to 82%. Our finding of high phenotypic variation in intercuspal distances with only moderate genetic contribution is consistent with substantial epigenetic influence on the progressive folding of the internal enamel epithelium, following formation of the primary and secondary enamel knots.

Elevational patterns of genetic variation in the cosmopolitan moss Bryum argenteum (Bryaceae).

PubMed

Pisa, Sergio; Werner, Olaf; Vanderpoorten, Alain; Magdy, Mahmoud; Ros, Rosa M

2013-10-01

The Baas Becking tenet posits that 'everything is everywhere, but the environment selects' to explain cosmopolitan distributions in highly vagile taxa. Bryophyte species show wider distributions than vascular plants and include examples of truly cosmopolitan ranges, which have been interpreted as a result of high dispersal capacities and ecological plasticity. In the current study, we documented patterns of genetic structure and diversity in the cosmopolitan moss Bryum argenteum along an elevational gradient to determine if genetic diversity and structure is homogenized by intense migrations in the lack of ecological differentiation. • 60 specimens were collected in the Sierra Nevada Mountains (Spain) between 100 and 2870 m and sequenced for ITS and rps4. Comparative analyses, genetic diversity estimators, and Mantel's tests were employed to determine the relationship between genetic variation, elevation, and geographic distance and to look for signs of demographic shifts. • Genetic diversity peaked above 1900 m and no signs of demographic shifts were detected at any elevation. There was a strong phylogenetic component in elevational variation. Genetic variation was significantly correlated with elevation, but not with geographic distance. • The results point to the long-term persistence of Bryum argenteum in a range that was glaciated during the Late Pleistocene. Evidence for an environmentally driven pattern of genetic differentiation suggests adaptive divergence. This supports the Baas Becking tenet and indicates that ecological specialization might play a key role in explaining patterns of genetic structure in cosmopolitan mosses.

The Genetic Basis for Variation in Sensitivity to Lead Toxicity in Drosophila melanogaster.

PubMed

Zhou, Shanshan; Morozova, Tatiana V; Hussain, Yasmeen N; Luoma, Sarah E; McCoy, Lenovia; Yamamoto, Akihiko; Mackay, Trudy F C; Anholt, Robert R H

2016-07-01

Lead toxicity presents a worldwide health problem, especially due to its adverse effects on cognitive development in children. However, identifying genes that give rise to individual variation in susceptibility to lead toxicity is challenging in human populations. Our goal was to use Drosophila melanogaster to identify evolutionarily conserved candidate genes associated with individual variation in susceptibility to lead exposure. To identify candidate genes associated with variation in susceptibility to lead toxicity, we measured effects of lead exposure on development time, viability and adult activity in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association analyses to identify candidate genes. We used mutants to assess functional causality of candidate genes and constructed a genetic network associated with variation in sensitivity to lead exposure, on which we could superimpose human orthologs. We found substantial heritabilities for all three traits and identified candidate genes associated with variation in susceptibility to lead exposure for each phenotype. The genetic architectures that determine variation in sensitivity to lead exposure are highly polygenic. Gene ontology and network analyses showed enrichment of genes associated with early development and function of the nervous system. Drosophila melanogaster presents an advantageous model to study the genetic underpinnings of variation in susceptibility to lead toxicity. Evolutionary conservation of cellular pathways that respond to toxic exposure allows predictions regarding orthologous genes and pathways across phyla. Thus, studies in the D. melanogaster model system can identify candidate susceptibility genes to guide subsequent studies in human populations. Zhou S, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, Mackay TF, Anholt RR. 2016. The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster. Environ Health

The Genetic Basis for Variation in Sensitivity to Lead Toxicity in Drosophila melanogaster

PubMed Central

Zhou, Shanshan; Morozova, Tatiana V.; Hussain, Yasmeen N.; Luoma, Sarah E.; McCoy, Lenovia; Yamamoto, Akihiko; Mackay, Trudy F.C.; Anholt, Robert R.H.

2016-01-01

Background: Lead toxicity presents a worldwide health problem, especially due to its adverse effects on cognitive development in children. However, identifying genes that give rise to individual variation in susceptibility to lead toxicity is challenging in human populations. Objectives: Our goal was to use Drosophila melanogaster to identify evolutionarily conserved candidate genes associated with individual variation in susceptibility to lead exposure. Methods: To identify candidate genes associated with variation in susceptibility to lead toxicity, we measured effects of lead exposure on development time, viability and adult activity in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association analyses to identify candidate genes. We used mutants to assess functional causality of candidate genes and constructed a genetic network associated with variation in sensitivity to lead exposure, on which we could superimpose human orthologs. Results: We found substantial heritabilities for all three traits and identified candidate genes associated with variation in susceptibility to lead exposure for each phenotype. The genetic architectures that determine variation in sensitivity to lead exposure are highly polygenic. Gene ontology and network analyses showed enrichment of genes associated with early development and function of the nervous system. Conclusions: Drosophila melanogaster presents an advantageous model to study the genetic underpinnings of variation in susceptibility to lead toxicity. Evolutionary conservation of cellular pathways that respond to toxic exposure allows predictions regarding orthologous genes and pathways across phyla. Thus, studies in the D. melanogaster model system can identify candidate susceptibility genes to guide subsequent studies in human populations. Citation: Zhou S, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, Mackay TF, Anholt RR. 2016. The genetic basis for variation in

Variation in recombination rate may bias human genetic disease mapping studies.

PubMed

Boyle, A Susannah; Noor, Mohamed A F

2004-11-01

The availability of the human genome sequence and variability information (as from the International HapMap project) will enhance our ability to map genetic disorders and choose targets for therapeutic intervention. However, several factors, such as regional variation in recombination rate, can bias conclusions from genetic mapping studies. Here, we examine the impact of regional variation in recombination rate across the human genome. Through computer simulations and literature surveys, we conclude that genetic disorders have been mapped to regions of low recombination more often than expected if such diseases were randomly distributed across the genome. This concentration in low recombination regions may be an artifact, and disorders appearing to be caused by a few genes of large effect may be polygenic. Future genetic mapping studies should be conscious of this potential complication by noting the regional recombination rate of regions implicated in diseases.

Genetic effects on gene expression across human tissues

PubMed Central

2017-01-01

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease. PMID:29022597

Genetic effects on gene expression across human tissues.

PubMed

Battle, Alexis; Brown, Christopher D; Engelhardt, Barbara E; Montgomery, Stephen B

2017-10-11

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Genetic diversity is related to climatic variation and vulnerability in threatened bull trout

USGS Publications Warehouse

Kovach, Ryan; Muhlfeld, Clint C.; Wade, Alisa A.; Hand, Brian K.; Whited, Diane C.; DeHaan, Patrick W.; Al-Chokhachy, Robert K.; Luikart, Gordon

2015-01-01

Understanding how climatic variation influences ecological and evolutionary processes is crucial for informed conservation decision-making. Nevertheless, few studies have measured how climatic variation influences genetic diversity within populations or how genetic diversity is distributed across space relative to future climatic stress. Here, we tested whether patterns of genetic diversity (allelic richness) were related to climatic variation and habitat features in 130 bull trout (Salvelinus confluentus) populations from 24 watersheds (i.e., ~4–7th order river subbasins) across the Columbia River Basin, USA. We then determined whether bull trout genetic diversity was related to climate vulnerability at the watershed scale, which we quantified on the basis of exposure to future climatic conditions (projected scenarios for the 2040s) and existing habitat complexity. We found a strong gradient in genetic diversity in bull trout populations across the Columbia River Basin, where populations located in the most upstream headwater areas had the greatest genetic diversity. After accounting for spatial patterns with linear mixed models, allelic richness in bull trout populations was positively related to habitat patch size and complexity, and negatively related to maximum summer temperature and the frequency of winter flooding. These relationships strongly suggest that climatic variation influences evolutionary processes in this threatened species and that genetic diversity will likely decrease due to future climate change. Vulnerability at a watershed scale was negatively correlated with average genetic diversity (r = −0.77;P < 0.001); watersheds containing populations with lower average genetic diversity generally had the lowest habitat complexity, warmest stream temperatures, and greatest frequency of winter flooding. Together, these findings have important conservation implications for bull trout and other imperiled species. Genetic diversity is already

Genetic variation and genetic structure of the endangered species Sinowilsonia henryi Hemsi. (Hamamelidaceae) revealed by amplified fragment length polymorphism (AFLP) markers.

PubMed

Zhang, H; Ji, W L; Li, M; Zhou, L Y

2015-10-14

Comprehensive research of genetic variation is crucial in designing conservation strategies for endangered and threatened species. Sinowilsonia henryi Hemsi. is a tertiary relic with a limited geographical distribution in the central and western areas of China. It is endangered because of climate change and habitat fragmentation over the last thousands of years. In this study, amplified fragment length polymorphism markers were utilized to estimate genetic diversity and genetic structure in and among S. henryi. In this study, Nei's genetic diversity and Shannon's information index were found to be 0.192 and 0.325 respectively, indicating a moderate-to-high genetic diversity in species. According to analysis of molecular variation results, 32% of the genetic variation was shown to be partitioned among populations, demonstrating a relatively high genetic divergence; this was supported by principal coordinate analysis and unweighted pair-group method with arithmetic average analysis. Moreover, the Mantel test showed that there was no significant correlation between genetic and geographical distances. The above results can be explained by the effects of habitat fragmentation, history traits, and gene drift. Based on the results, several implications were indicated and suggestions proposed for preservation strategies for this species.

Heredity vs. Environment: The Effects of Genetic Variation with Age

ERIC Educational Resources Information Center

Gourlay, N.

1978-01-01

Major problems in the field are presented through a brief review of Burt's work and a critical account of the Hawaiian and British schools of biometrical genetics. The merits and demerits of Christopher Jencks' study are also discussed. There follows an account of the principle of genetic variation with age, a new concept to the…

Oral infection of Aedes aegypti with yellow fever virus: geographic variation and genetic considerations.

PubMed

Tabachnick, W J; Wallis, G P; Aitken, T H; Miller, B R; Amato, G D; Lorenz, L; Powell, J R; Beaty, B J

1985-11-01

Twenty-eight populations representing a worldwide distribution of Aedes aegypti were tested for their ability to become orally infected with yellow fever virus (YFV). Populations had been analyzed for genetic variations at 11 isozyme loci and assigned to one of 8 genetic geographic groups of Ae. aegypti. Infection rates suggest that populations showing isozyme genetic relatedness also demonstrate similarity to oral infection rates with YFV. The findings support the hypothesis that genetic variation exists for oral susceptibility to YFV in Ae. aegypti.

Oxytocin Receptor Genetic Variation Promotes Human Trust Behavior

PubMed Central

Krueger, Frank; Parasuraman, Raja; Iyengar, Vijeth; Thornburg, Matthew; Weel, Jaap; Lin, Mingkuan; Clarke, Ellen; McCabe, Kevin; Lipsky, Robert H.

2012-01-01

Given that human trust behavior is heritable and intranasal administration of oxytocin enhances trust, the oxytocin receptor (OXTR) gene is an excellent candidate to investigate genetic contributions to individual variations in trust behavior. Although a single-nucleotide polymorphism involving an adenine (A)/guanine (G) transition (rs53576) has been associated with socio-emotional phenotypes, its link to trust behavior is unclear. We combined genotyping of healthy male students (n = 108) with the administration of a trust game experiment. Our results show that a common occurring genetic variation (rs53576) in the OXTR gene is reliably associated with trust behavior rather than a general increase in trustworthy or risk behaviors. Individuals homozygous for the G allele (GG) showed higher trust behavior than individuals with A allele carriers (AA/AG). Although the molecular functionality of this polymorphism is still unknown, future research should clarify how the OXTR gene interacts with other genes and the environment in promoting socio-emotional behaviors. PMID:22347177

Genetic Variation and Structure in Contrasting Geographic Distributions: Widespread Versus Restricted Black-Tailed Prairie Dogs (Subgenus Cynomys).

PubMed

Castellanos-Morales, Gabriela; Ortega, Jorge; Castillo-Gámez, Reyna A; Sackett, Loren C; Eguiarte, Luis E

2015-01-01

Species of restricted distribution are considered more vulnerable to extinction because of low levels of genetic variation relative to widespread taxa. Species of the subgenus Cynomys are an excellent system to compare genetic variation and degree of genetic structure in contrasting geographic distributions. We assessed levels of genetic variation, genetic structure, and genetic differentiation in widespread Cynomys ludovicianus and restricted C. mexicanus using 1997bp from the cytochrome b and control region (n = 223 C. ludovicianus; 77 C. mexicanus), and 10 nuclear microsatellite loci (n = 207 and 78, respectively). Genetic variation for both species was high, and genetic structure in the widespread species was higher than in the restricted species. C. mexicanus showed values of genetic variation, genetic structure, and genetic differentiation similar to C. ludovicianus at smaller geographic scales. Results suggest the presence of at least 2 historical refuges for C. ludovicianus and that the Sierra Madre Occidental represents a barrier to gene flow. Chihuahua and New Mexico possess high levels of genetic diversity and should be protected, while Sonora should be treated as an independent management unit. For C. mexicanus, connectivity among colonies is very important and habitat fragmentation and habitat loss should be mitigated to maintain gene flow. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic alterations affecting cholesterol metabolism and human fertility.

PubMed

DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

2014-11-01

Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.

Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

PubMed Central

Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

2014-01-01

Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.

PubMed

Bou Sleiman, Maroun S; Osman, Dani; Massouras, Andreas; Hoffmann, Ary A; Lemaitre, Bruno; Deplancke, Bart

2015-07-27

Gut immunocompetence involves immune, stress and regenerative processes. To investigate the determinants underlying inter-individual variation in gut immunocompetence, we perform enteric infection of 140 Drosophila lines with the entomopathogenic bacterium Pseudomonas entomophila and observe extensive variation in survival. Using genome-wide association analysis, we identify several novel immune modulators. Transcriptional profiling further shows that the intestinal molecular state differs between resistant and susceptible lines, already before infection, with one transcriptional module involving genes linked to reactive oxygen species (ROS) metabolism contributing to this difference. This genetic and molecular variation is physiologically manifested in lower ROS activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance and higher stem cell activity in resistant versus susceptible lines. This study provides novel insights into the determinants underlying population-level variability in gut immunocompetence, revealing how relatively minor, but systematic genetic and transcriptional variation can mediate overt physiological differences that determine enteric infection susceptibility.

Detection of genetic variation affecting milk coagulation properties in Danish Holstein dairy cattle by analyses of pooled whole-genome sequences from phenotypically extreme samples (pool-seq).

PubMed

Bertelsen, H P; Gregersen, V R; Poulsen, N; Nielsen, R O; Das, A; Madsen, L B; Buitenhuis, A J; Holm, L-E; Panitz, F; Larsen, L B; Bendixen, C

2016-04-01

Rennet-induced milk coagulation is an important trait for cheese production. Recent studies have reported an alarming frequency of cows producing poorly coagulating milk unsuitable for cheese production. Several genetic factors are known to affect milk coagulation, including variation in the major milk proteins; however, recent association studies indicate genetic effects from other genomic regions as well. The aim of this study was to detect genetic variation affecting milk coagulation properties, measured as curd-firming rate (CFR) and milk pH. This was achieved by examining allele frequency differences between pooled whole-genome sequences of phenotypically extreme samples (pool-seq).. Curd-firming rate and raw milk pH were measured for 415 Danish Holstein cows, and each animal was sequenced at low coverage. Pools were created containing whole genome sequence reads from samples with "extreme" values (high or low) for both phenotypic traits. A total of 6,992,186 and 5,295,501 SNP were assessed in relation to CFR and milk pH, respectively. Allele frequency differences were calculated between pools and 32 significantly different SNP were detected, 1 for milk pH and 31 for CFR, of which 19 are located on chromosome 6. A total of 9 significant SNP, which were selected based on the possible function of proximal candidate genes, were genotyped in the entire sample set ( = 415) to test for an association. The most significant SNP was located proximal to , explaining 33% of the phenotypic variance. , coding for κ-casein, is the most studied in relation to milk coagulation due to its position on the surface of the casein micelles and the direct involvement in milk coagulation. Three additional SNP located on chromosome 6 showed significant associations explaining 7, 3.6, and 1.3% of the phenotypic variance of CFR. The significant SNP on chromosome 6 were shown to be in linkage disequilibrium with the SNP peaking proximal to ; however, after accounting for the genotype of

Population genetic analysis and bioclimatic modeling in Agave striata in the Chihuahuan Desert indicate higher genetic variation and lower differentiation in drier and more variable environments.

PubMed

Trejo, Laura; Alvarado-Cárdenas, Leonardo O; Scheinvar, Enrique; Eguiarte, Luis E

2016-06-01

Is there an association between bioclimatic variables and genetic variation within species? This question can be approached by a detailed analysis of population genetics parameters along environmental gradients in recently originated species (so genetic drift does not further obscure the patterns). The genus Agave, with more than 200 recent species encompassing a diversity of morphologies and distributional patterns, is an adequate system for such analyses. We studied Agave striata, a widely distributed species from the Chihuahuan Desert, with a distinctive iteroparous reproductive ecology and two recognized subspecies with clear morphological differences. We used population genetic analyses along with bioclimatic studies to understand the effect of environment on the genetic variation and differentiation of this species. We analyzed six populations of the subspecies A. striata subsp. striata, with a southern distribution, and six populations of A. striata subsp. falcata, with a northern distribution, using 48 ISSR loci and a total of 541 individuals (averaging 45 individuals per population). We assessed correlations between population genetics parameters (the levels of genetic variation and differentiation) and the bioclimatic variables of each population. We modeled each subspecies distribution and used linear correlations and multifactorial analysis of variance. Genetic variation (measured as expected heterozygosity) increased at higher latitudes. Higher levels of genetic variation in populations were associated with a higher variation in environmental temperature and lower precipitation. Stronger population differentiation was associated with wetter and more variable precipitation in the southern distribution of the species. The two subspecies have genetic differences, which coincide with their climatic differences and potential distributions. Differences in genetic variation among populations and the genetic differentiation between A. striata subsp. striata

Defining the consequences of genetic variation on a proteome–wide scale

PubMed Central

Chick, Joel M.; Munger, Steven C.; Simecek, Petr; Huttlin, Edward L.; Choi, Kwangbom; Gatti, Daniel M.; Raghupathy, Narayanan; Svenson, Karen L.; Churchill, Gary A.; Gygi, Steven P.

2016-01-01

Genetic variation modulates protein expression through both transcriptional and post-transcriptional mechanisms. To characterize the consequences of natural genetic diversity on the proteome, here we combine a multiplexed, mass spectrometry-based method for protein quantification with an emerging outbred mouse model containing extensive genetic variation from eight inbred founder strains. By measuring genome-wide transcript and protein expression in livers from 192 Diversity outbred mice, we identify 2,866 protein quantitative trait loci (pQTL) with twice as many local as distant genetic variants. These data support distinct transcriptional and post-transcriptional models underlying the observed pQTL effects. Using a sensitive approach to mediation analysis, we often identified a second protein or transcript as the causal mediator of distant pQTL. Our analysis reveals an extensive network of direct protein–protein interactions. Finally, we show that local genotype can provide accurate predictions of protein abundance in an independent cohort of collaborative cross mice. PMID:27309819

Genetic and epigenetic variation in the lineage specification of regulatory T cells

PubMed Central

Arvey, Aaron; van der Veeken, Joris; Plitas, George; Rich, Stephen S; Concannon, Patrick; Rudensky, Alexander Y

2015-01-01

Regulatory T (Treg) cells, which suppress autoimmunity and other inflammatory states, are characterized by a distinct set of genetic elements controlling their gene expression. However, the extent of genetic and associated epigenetic variation in the Treg cell lineage and its possible relation to disease states in humans remain unknown. We explored evolutionary conservation of regulatory elements and natural human inter-individual epigenetic variation in Treg cells to identify the core transcriptional control program of lineage specification. Analysis of single nucleotide polymorphisms in core lineage-specific enhancers revealed disease associations, which were further corroborated by high-resolution genotyping to fine map causal polymorphisms in lineage-specific enhancers. Our findings suggest that a small set of regulatory elements specify the Treg lineage and that genetic variation in Treg cell-specific enhancers may alter Treg cell function contributing to polygenic disease. DOI: http://dx.doi.org/10.7554/eLife.07571.001 PMID:26510014

Genetic variation in vitamin B-12 content of bovine milk and its association with SNP along the bovine genome.

PubMed

Rutten, Marc J M; Bouwman, Aniek C; Sprong, R Corinne; van Arendonk, Johan A M; Visker, Marleen H P W

2013-01-01

Vitamin B-12 (also called cobalamin) is essential for human health and current intake levels of vitamin B-12 are considered to be too low. Natural enrichment of the vitamin B-12 content in milk, an important dietary source of vitamin B-12, may help to increase vitamin B-12 intake. Natural enrichment of the milk vitamin B-12 content could be achieved through genetic selection, provided there is genetic variation between cows with respect to the vitamin B-12 content in their milk. A substantial amount of genetic variation in vitamin B-12 content was detected among raw milk samples of 544 first-lactation Dutch Holstein Friesian cows. The presence of genetic variation between animals in vitamin B-12 content in milk indicates that the genotype of the cow affects the amount of vitamin B-12 that ends up in her milk and, consequently, that the average milk vitamin B-12 content of the cow population can be increased by genetic selection. A genome-wide association study revealed significant association between 68 SNP and vitamin B-12 content in raw milk of 487 first-lactation Dutch Holstein Friesian cows. This knowledge facilitates genetic selection for milk vitamin B-12 content. It also contributes to the understanding of the biological mechanism responsible for the observed genetic variation in vitamin B-12 content in milk. None of the 68 significantly associated SNP were in or near known candidate genes involved in transport of vitamin B-12 through the gastrointestinal tract, uptake by ileum epithelial cells, export from ileal cells, transport through the blood, uptake from the blood, intracellular processing, or reabsorption by the kidneys. Probably, associations relate to genes involved in alternative pathways of well-studied processes or to genes involved in less well-studied processes such as ruminal production of vitamin B-12 or secretion of vitamin B-12 by the mammary gland.

Changes in composition of cuticular biochemicals of the facultatively polygynous ant Petalomyrmex phylax during range expansion in Cameroon with respect to social, spatial and genetic variation.

PubMed

Dalecky, Ambroise; Renucci, Marielle; Tirard, Alain; Debout, Gabriel; Roux, Maurice; Kjellberg, Finn; Provost, Erick

2007-09-01

In social insects, biochemicals found at the surface of the cuticle are involved in the recognition process and in protection against desiccation and pathogens. However, the relative contribution of evolutionary forces in shaping diversity of these biochemicals remains largely unresolved in ants. We determined the composition of epicuticular biochemicals for workers sampled in 12 populations of the ant Petalomyrmex phylax from Cameroon. Genetic variation at 12 microsatellite markers was used to infer population history and to provide null expectations under the neutrality hypothesis. Genetic data suggest a recent southward range expansion of this ant species. Furthermore, there is a decline southward in the numbers of queens present in mature colonies. Here, we contrast the pattern of biochemical variation against genetic, social and spatial parameters. We thus provide the first estimates of the relative contribution of neutral and selective processes on variation of ant cuticular profile. Populations in migration-drift disequilibrium showed reduction of within-population variation for genetic markers as well as for cuticular profiles. In these populations, the cuticular profile became biased towards a limited number of high molecular weight molecules. Within- and among-population biochemical variation was explained by both genetic and social variation and by the spatial distribution of populations. We therefore propose that during range expansion of P. phylax, the composition of epicuticular compounds has been affected by a combination of neutral processes - genetic drift and spatially limited dispersal - and spatially varying selection, social organization and environmental effects.

Human genetics and sleep behavior.

PubMed

Shi, Guangsen; Wu, David; Ptáček, Louis J; Fu, Ying-Hui

2017-06-01

Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation

PubMed Central

Nikolaitchik, Olga A.; Burdick, Ryan C.; Gorelick, Robert J.; Keele, Brandon F.; Hu, Wei-Shau; Pathak, Vinay K.

2016-01-01

Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10−5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10−21 and1 × 10−11, respectively) and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic

Genetic variation of Taenia pisiformis collected from Sichuan, China, based on the mitochondrial cytochrome B gene.

PubMed

Yang, Deying; Ren, Yongjun; Fu, Yan; Xie, Yue; Nie, Huaming; Nong, Xiang; Gu, Xiaobin; Wang, Shuxian; Peng, Xuerong; Yang, Guangyou

2013-08-01

Taenia pisiformis is one of the most important parasites of canines and rabbits. T. pisiformis cysticercus (the larval stage) causes severe damage to rabbit breeding, which results in huge economic losses. In this study, the genetic variation of T. pisiformis was determined in Sichuan Province, China. Fragments of the mitochondrial cytochrome b (cytb) (922 bp) gene were amplified in 53 isolates from 8 regions of T. pisiformis. Overall, 12 haplotypes were found in these 53 cytb sequences. Molecular genetic variations showed 98.4% genetic variation derived from intra-region. FST and Nm values suggested that 53 isolates were not genetically differentiated and had low levels of genetic diversity. Neutrality indices of the cytb sequences showed the evolution of T. pisiformis followed a neutral mode. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. These findings indicate that 53 isolates of T. pisiformis keep a low genetic variation, which provide useful knowledge for monitoring changes in parasite populations for future control strategies.

Linking Genetic Variation in Adaptive Plant Traits to Climate in Tetraploid and Octoploid Basin Wildrye [Leymus cinereus (Scribn. & Merr.) A. Love] in the Western U.S.

PubMed

Johnson, R C; Vance-Borland, Ken

2016-01-01

Few studies have assessed how ploidy type within a species affects genetic variation among populations in relation to source climates. Basin wildrye (Leymus cinereus (Scribn. & Merr.) A. Love) is a large bunchgrass common in the intermountain Western U.S. found in both octoploid and tetraploid types. In common gardens at two sites over two years differences in both ploidy type and genetic variation within ploidy were observed in phenology, morphology, and production traits on 57 octoploid and 52 tetraploid basin wildrye from the intermountain Western U.S. (P<0.01). Octoploids had larger leaves, longer culms, and greater crown circumference than tetraploids but the numerical ranges of plant traits and their source climates overlapped between ploidy types. Still, among populations octoploids often had greater genetic variation for traits and occupied more diverse climates than tetraploids. Genetic variation for both ploidy types was linked to source climates in canonical correlation analysis, with the first two variates explaining 70% of the variation. Regression of those canonical variates with seed source climate variables produced models that explained 64% and 38% of the variation, respectively, and were used to map 15 seed zones covering 673,258 km2. Utilization of these seed zones will help ensure restoration with adaptive seed sources for both ploidy types. The link between genetic traits and seed source climates suggests climate driven natural selection and adaptive evolution in basin wildrye. The more diverse climates occupied by octoploids and higher trait variation suggests a higher capacity for ecological differentiation than tetraploids in the intermountain Western U.S.

Genetic Architecture of Flowering-Time Variation in Brachypodium distachyon

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

Woods, Daniel P.; Bednarek, Ryland; Bouché, Frédéric

The transition to reproductive development is a crucial step in the plant life cycle, and the timing of this transition is an important factor in crop yields. Here, we report new insights into the genetic control of natural variation in flowering time in Brachypodium distachyon, a nondomesticated pooid grass closely related to cereals such as wheat (Triticum spp.) and barley (Hordeum vulgare L.). A recombinant inbred line population derived from a cross between the rapid-flowering accession Bd21 and the delayed-flowering accession Bd1-1 were grown in a variety of environmental conditions to enable exploration of the genetic architecture of flowering time.more » A genotyping-by-sequencing approach was used to develop SNP markers for genetic map construction, and quantitative trait loci (QTLs) that control differences in flowering time were identified. Many of the flowering-time QTLs are detected across a range of photoperiod and vernalization conditions, suggesting that the genetic control of flowering within this population is robust. The two major QTLs identified in undomesticated B. distachyon colocalize with VERNALIZATION1/PHYTOCHROME C and VERNALIZATION2, loci identified as flowering regulators in the domesticated crops wheat and barley. This suggests that variation in flowering time is controlled in part by a set of genes broadly conserved within pooid grasses.« less

Genetic Architecture of Flowering-Time Variation in Brachypodium distachyon

DOE PAGES

Woods, Daniel P.; Bednarek, Ryland; Bouché, Frédéric; ...

2016-10-14

The transition to reproductive development is a crucial step in the plant life cycle, and the timing of this transition is an important factor in crop yields. Here, we report new insights into the genetic control of natural variation in flowering time in Brachypodium distachyon, a nondomesticated pooid grass closely related to cereals such as wheat (Triticum spp.) and barley (Hordeum vulgare L.). A recombinant inbred line population derived from a cross between the rapid-flowering accession Bd21 and the delayed-flowering accession Bd1-1 were grown in a variety of environmental conditions to enable exploration of the genetic architecture of flowering time.more » A genotyping-by-sequencing approach was used to develop SNP markers for genetic map construction, and quantitative trait loci (QTLs) that control differences in flowering time were identified. Many of the flowering-time QTLs are detected across a range of photoperiod and vernalization conditions, suggesting that the genetic control of flowering within this population is robust. The two major QTLs identified in undomesticated B. distachyon colocalize with VERNALIZATION1/PHYTOCHROME C and VERNALIZATION2, loci identified as flowering regulators in the domesticated crops wheat and barley. This suggests that variation in flowering time is controlled in part by a set of genes broadly conserved within pooid grasses.« less

Genetic and epigenetic variation in Spartina alterniflora following the Deepwater Horizon oil spill.

PubMed

Robertson, Marta; Schrey, Aaron; Shayter, Ashley; Moss, Christina J; Richards, Christina

2017-09-01

Catastrophic events offer unique opportunities to study rapid population response to stress in natural settings. In concert with genetic variation, epigenetic mechanisms may allow populations to persist through severe environmental challenges. In 2010, the Deepwater Horizon oil spill devastated large portions of the coastline along the Gulf of Mexico. However, the foundational salt marsh grass, Spartina alterniflora , showed high resilience to this strong environmental disturbance. Following the spill, we simultaneously examined the genetic and epigenetic structure of recovering populations of S. alterniflora to oil exposure. We quantified genetic and DNA methylation variation using amplified fragment length polymorphism and methylation sensitive fragment length polymorphism (MS-AFLP) to test the hypothesis that response to oil exposure in S. alterniflora resulted in genetically and epigenetically based population differentiation. We found high genetic and epigenetic variation within and among sites and found significant genetic differentiation between contaminated and uncontaminated sites, which may reflect nonrandom mortality in response to oil exposure. Additionally, despite a lack of genomewide patterns in DNA methylation between contaminated and uncontaminated sites, we found five MS-AFLP loci (12% of polymorphic MS-AFLP loci) that were correlated with oil exposure. Overall, our findings support genetically based differentiation correlated with exposure to the oil spill in this system, but also suggest a potential role for epigenetic mechanisms in population differentiation.

The Genetic Basis of Natural Variation in Caenorhabditis elegans Telomere Length.

PubMed

Cook, Daniel E; Zdraljevic, Stefan; Tanny, Robyn E; Seo, Beomseok; Riccardi, David D; Noble, Luke M; Rockman, Matthew V; Alkema, Mark J; Braendle, Christian; Kammenga, Jan E; Wang, John; Kruglyak, Leonid; Félix, Marie-Anne; Lee, Junho; Andersen, Erik C

2016-09-01

Telomeres are involved in the maintenance of chromosomes and the prevention of genome instability. Despite this central importance, significant variation in telomere length has been observed in a variety of organisms. The genetic determinants of telomere-length variation and their effects on organismal fitness are largely unexplored. Here, we describe natural variation in telomere length across the Caenorhabditis elegans species. We identify a large-effect variant that contributes to differences in telomere length. The variant alters the conserved oligonucleotide/oligosaccharide-binding fold of protection of telomeres 2 (POT-2), a homolog of a human telomere-capping shelterin complex subunit. Mutations within this domain likely reduce the ability of POT-2 to bind telomeric DNA, thereby increasing telomere length. We find that telomere-length variation does not correlate with offspring production or longevity in C. elegans wild isolates, suggesting that naturally long telomeres play a limited role in modifying fitness phenotypes in C. elegans. Copyright © 2016 by the Genetics Society of America.

[Genetic ecological monitoring in human populations: heterozygosity, mtDNA haplotype variation, and genetic load].

PubMed

Balanovskiĭ, O P; Koshel', S M; Zaporozhchenko, V V; Pshenichnov, A S; Frolova, S A; Kuznetsova, M A; Baranova, E E; Teuchezh, I E; Kuznetsova, A A; Romashkina, M V; Utevskaia, O M; Churnosov, M I; Villems, R; Balanovskaia, E V

2011-11-01

Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

Origin of genetic variation: regulation of genetic recombination in the higher organisms - a theory.

PubMed

Pandey, K K

1972-01-01

Recent studies in the fungi, particularly Neurospora and Schizophyllum, have revealed a number of genetic features which, viewed in conjunction with earlier observations on other organisms, form a pattern, or model, which appears to be basic to the control of recombination in all eukaryotes, including higher organisms. It is assumed that the control is exercised on mechanisms that produce new alleles through recombination, as understood in broad terms and including such a likely phenomenon as gene conversion, which may or may not involve crossing-over, as well as equal and unequal crossing-over. The recombination may thus occur between alleles in either the homozygous or heterozygous condition. In the model, regulatory genes and breeding behaviour are integrated into one self-regulatory system controlling the production of new genetic variation.The model is based on the following five general features, largely substantiated by the results in Neurospora and Schizophyllum: 1) The frequency of recombination in a particular chromosomal region is controlled by specific regulatory genes (rec). 2) There may be a number of such specific, regulatory genes responsible for recombination in a given region. 3) A rec. locus may influence recombination in more than one region. 4) The regulatory genes have no specific physical relationship with the region(s) they control, and are usually located at random in the genome. 5) Of the allelic forms of the regulatory genes it is always the dominant gene which suppresses recombination and the recessive gene which increases recombination. The rec system is epistatic to other genetic elements jointly involved in the overall control of recombination in a specific region. It is suggested that usually the control of recombination in a given region is exercised, cumulatively, by the balance of the dominant and recessive genes of the specific rec loci in the organism. Outbreeding, with the associated high heterozygosity of the regulatory rec

Genetic factors affecting dental caries risk.

PubMed

Opal, S; Garg, S; Jain, J; Walia, I

2015-03-01

This article reviews the literature on genetic aspects of dental caries and provides a framework for the rapidly changing disease model of caries. The scope is genetic aspects of various dental factors affecting dental caries. The PubMed database was searched for articles with keywords 'caries', 'genetics', 'taste', 'diet' and 'twins'. This was followed by extensive handsearching using reference lists from relevant articles. The post-genomic era will present many opportunities for improvement in oral health care but will also present a multitude of challenges. We can conclude from the literature that genes have a role to play in dental caries; however, both environmental and genetic factors have been implicated in the aetiology of caries. Additional studies will have to be conducted to replicate the findings in a different population. Identification of genetic risk factors will help screen and identify susceptible patients to better understand the contribution of genes in caries aetiopathogenesis. Information derived from these diverse studies will provide new tools to target individuals and/or populations for a more efficient and effective implementation of newer preventive measures and diagnostic and novel therapeutic approaches in the management of this disease. © 2015 Australian Dental Association.

Female fecundity variation affects reproducibility of experiments on host plant preference and acceptance in a phytophagous insect

PubMed Central

Schäpers, Alexander; Petrén, Hampus; Wheat, Christopher W.; Wiklund, Christer

2017-01-01

Reproducibility is a scientific cornerstone. Many recent studies, however, describe a reproducibility crisis and call for assessments of reproducibility across scientific domains. Here, we explore the reproducibility of a classic ecological experiment—that of assessing female host plant preference and acceptance in phytophagous insects, a group in which host specialization is a key driver of diversification. We exposed multiple cohorts of Pieris napi butterflies from the same population to traditional host acceptance and preference tests on three Brassicaceae host species. Whereas the host plant rank order was highly reproducible, the propensity to oviposit on low-ranked hosts varied significantly even among cohorts exposed to similar conditions. Much variation could be attributed to among-cohort variation in female fecundity, a trait strongly correlated both to female size and to the size of the nuptial gift a female receives during mating. Small males provide small spermatophores, and in our experiment small females that mated with small males had a disproportionally low propensity to oviposit on low-ranked hosts. Hence, our results provide empirical support to the theoretical prediction that female host utilization is strongly affected by non-genetic, environmental variation, and that such variation can affect the reproducibility of ecological experiments even under seemingly identical conditions. PMID:28202813

The Effects of Predator Evolution and Genetic Variation on Predator-Prey Population-Level Dynamics.

PubMed

Cortez, Michael H; Patel, Swati

2017-07-01

This paper explores how predator evolution and the magnitude of predator genetic variation alter the population-level dynamics of predator-prey systems. We do this by analyzing a general eco-evolutionary predator-prey model using four methods: Method 1 identifies how eco-evolutionary feedbacks alter system stability in the fast and slow evolution limits; Method 2 identifies how the amount of standing predator genetic variation alters system stability; Method 3 identifies how the phase lags in predator-prey cycles depend on the amount of genetic variation; and Method 4 determines conditions for different cycle shapes in the fast and slow evolution limits using geometric singular perturbation theory. With these four methods, we identify the conditions under which predator evolution alters system stability and shapes of predator-prey cycles, and how those effect depend on the amount of genetic variation in the predator population. We discuss the advantages and disadvantages of each method and the relations between the four methods. This work shows how the four methods can be used in tandem to make general predictions about eco-evolutionary dynamics and feedbacks.

Genetic variation of piperidine alkaloids in Pinus ponderosa: a common garden study

PubMed Central

Gerson, Elizabeth A.; Kelsey, Rick G.; St Clair, J. Bradley

2009-01-01

Background and Aims Previous measurements of conifer alkaloids have revealed significant variation attributable to many sources, environmental and genetic. The present study takes a complementary and intensive, common garden approach to examine genetic variation in Pinus ponderosa var. ponderosa alkaloid production. Additionally, this study investigates the potential trade-off between seedling growth and alkaloid production, and associations between topographic/climatic variables and alkaloid production. Methods Piperidine alkaloids were quantified in foliage of 501 nursery seedlings grown from seed sources in west-central Washington, Oregon and California, roughly covering the western half of the native range of ponderosa pine. A nested mixed model was used to test differences among broad-scale regions and among families within regions. Alkaloid concentrations were regressed on seedling growth measurements to test metabolite allocation theory. Likewise, climate characteristics at the seed sources were also considered as explanatory variables. Key Results Quantitative variation from seedling to seedling was high, and regional variation exceeded variation among families. Regions along the western margin of the species range exhibited the highest alkaloid concentrations, while those further east had relatively low alkaloid levels. Qualitative variation in alkaloid profiles was low. All measures of seedling growth related negatively to alkaloid concentrations on a natural log scale; however, coefficients of determination were low. At best, annual height increment explained 19·4 % of the variation in ln(total alkaloids). Among the climate variables, temperature range showed a negative, linear association that explained 41·8 % of the variation. Conclusions Given the wide geographic scope of the seed sources and the uniformity of resources in the seedlings' environment, observed differences in alkaloid concentrations are evidence for genetic regulation of alkaloid

Genetic variation of piperidine alkaloids in Pinus ponderosa: a common garden study.

PubMed

Gerson, Elizabeth A; Kelsey, Rick G; St Clair, J Bradley

2009-02-01

Previous measurements of conifer alkaloids have revealed significant variation attributable to many sources, environmental and genetic. The present study takes a complementary and intensive, common garden approach to examine genetic variation in Pinus ponderosa var. ponderosa alkaloid production. Additionally, this study investigates the potential trade-off between seedling growth and alkaloid production, and associations between topographic/climatic variables and alkaloid production. Piperidine alkaloids were quantified in foliage of 501 nursery seedlings grown from seed sources in west-central Washington, Oregon and California, roughly covering the western half of the native range of ponderosa pine. A nested mixed model was used to test differences among broad-scale regions and among families within regions. Alkaloid concentrations were regressed on seedling growth measurements to test metabolite allocation theory. Likewise, climate characteristics at the seed sources were also considered as explanatory variables. Quantitative variation from seedling to seedling was high, and regional variation exceeded variation among families. Regions along the western margin of the species range exhibited the highest alkaloid concentrations, while those further east had relatively low alkaloid levels. Qualitative variation in alkaloid profiles was low. All measures of seedling growth related negatively to alkaloid concentrations on a natural log scale; however, coefficients of determination were low. At best, annual height increment explained 19.4 % of the variation in ln(total alkaloids). Among the climate variables, temperature range showed a negative, linear association that explained 41.8 % of the variation. Given the wide geographic scope of the seed sources and the uniformity of resources in the seedlings' environment, observed differences in alkaloid concentrations are evidence for genetic regulation of alkaloid secondary metabolism in ponderosa pine. The theoretical

Genetic variation and structure in remnant population of critically endangered Melicope zahlbruckneri

USGS Publications Warehouse

Raji, J. A.; Atkinson, Carter T.

2016-01-01

The distribution and amount of genetic variation within and between populations of plant species are important for their adaptability to future habitat changes and also critical for their restoration and overall management. This study was initiated to assess the genetic status of the remnant population of Melicope zahlbruckneri–a critically endangered species in Hawaii, and determine the extent of genetic variation and diversity in order to propose valuable conservation approaches. Estimated genetic structure of individuals based on molecular marker allele frequencies identified genetic groups with low overall differentiation but identified the most genetically diverse individuals within the population. Analysis of Amplified Fragment Length Polymorphic (AFLP) marker loci in the population based on Bayesian model and multivariate statistics classified the population into four subgroups. We inferred a mixed species population structure based on Bayesian clustering and frequency of unique alleles. The percentage of Polymorphic Fragment (PPF) ranged from 18.8 to 64.6% for all marker loci with an average of 54.9% within the population. Inclusion of all surviving M. zahlbruckneri trees in future restorative planting at new sites are suggested, and approaches for longer term maintenance of genetic variability are discussed. To our knowledge, this study represents the first report of molecular genetic analysis of the remaining population of M. zahlbruckneri and also illustrates the importance of genetic variability for conservation of a small endangered population.

Geographic variation and genetic structure in Spotted Owls

USGS Publications Warehouse

Haig, Susan M.; Wagner, R.S.; Forsman, E.D.; Mullins, Thomas D.

2001-01-01

We examined genetic variation, population structure, and definition of conservation units in Spotted Owls (Strix occidentalis). Spotted Owls are mostly non-migratory, long-lived, socially monogamous birds that have decreased population viability due to their occupation of highly-fragmented late successional forests in western North America. To investigate potential effects of habitat fragmentation on population structure, we used random amplified polymorphic DNA (RAPD) to examine genetic variation hierarchically among local breeding areas, subregional groups, regional groups, and subspecies via sampling of 21 breeding areas (276 individuals) among the three subspecies of Spotted Owls. Data from 11 variable bands suggest a significant relationship between geographic distance among local breeding groups and genetic distance (Mantel r = 0.53, P < 0.02) although multi-dimensional scaling of three significant axes did not identify significant grouping at any hierarchical level. Similarly, neighbor-joining clustering of Manhattan distances indicated geographic structure at all levels and identified Mexican Spotted Owls as a distinct clade. RAPD analyses did not clearly differentiate Northern Spotted Owls from California Spotted Owls. Among Northern Spotted Owls, estimates of population differentiation (FST) ranged from 0.27 among breeding areas to 0.11 among regions. Concordantly, within-group agreement values estimated via multi-response permutation procedures of Jaccarda??s distances ranged from 0.22 among local sites to 0.11 among regions. Pairwise comparisons of FST and geographic distance within regions suggested only the Klamath region was in equilibrium with respect to gene flow and genetic drift. Merging nuclear data with recent mitochondrial data provides support for designation of an Evolutionary Significant Unit for Mexican Spotted Owls and two overlapping Management Units for Northern and California Spotted Owls.

Obesity, hypertension and genetic variation in the TIGER Study

USDA-ARS?s Scientific Manuscript database

Obesity and hypertension are multifactoral conditions in which the onset and severity of the conditions are influenced by the interplay of genetic and environmental factors. We hypothesize that multiple genes and environmental factors account for a significant amount of variation in BMI and blood pr...

Moderate Multiple Parentage and Low Genetic Variation Reduces the Potential for Genetic Incompatibility Avoidance Despite High Risk of Inbreeding

PubMed Central

Tuni, Cristina; Goodacre, Sara; Bechsgaard, Jesper; Bilde, Trine

2012-01-01

Background Polyandry is widespread throughout the animal kingdom. In the absence of direct benefits of mating with different males, the underlying basis for polyandry is enigmatic because it can carry considerable costs such as elevated exposure to sexual diseases, physical injury or other direct fitness costs. Such costs may be balanced by indirect genetic benefits to the offspring of polyandrous females. We investigated polyandry and patterns of parentage in the spider Stegodyphus lineatus. This species experiences relatively high levels of inbreeding as a result of its spatial population structure, philopatry and limited male mating dispersal. Polyandry may provide an opportunity for post mating inbreeding avoidance that reduces the risk of genetic incompatibilities arising from incestuous matings. However, multiple mating carries direct fitness costs to females suggesting that genetic benefits must be substantial to counter direct costs. Methodology/Principal Findings Genetic parentage analyses in two populations from Israel and a Greek island, showed mixed-brood parentage in approximately 50% of the broods. The number of fathers ranged from 1–2 indicating low levels of multiple parentage and there was no evidence for paternity bias in mixed-broods from both populations. Microsatellite loci variation suggested limited genetic variation within populations, especially in the Greek island population. Relatedness estimates among females in the maternal generation and potentially interacting individuals were substantial indicating full-sib and half-sib relationships. Conclusions/Significance Three lines of evidence indicate limited potential to obtain substantial genetic benefits in the form of reduced inbreeding. The relatively low frequency of multiple parentage together with low genetic variation among potential mates and the elevated risk of mating among related individuals as corroborated by our genetic data suggest that there are limited actual outbreeding

Genetic profile for five common variants associated with age-related macular degeneration in densely affected families: a novel analytic approach

PubMed Central

Sobrin, Lucia; Maller, Julian B; Neale, Benjamin M; Reynolds, Robyn C; Fagerness, Jesen A; Daly, Mark J; Seddon, Johanna M

2010-01-01

About 40% of the genetic variance of age-related macular degeneration (AMD) can be explained by a common variation at five common single-nucleotide polymorphisms (SNPs). We evaluated the degree to which these known variants explain the clustering of AMD in a group of densely affected families. We sought to determine whether the actual number of risk alleles at the five variants in densely affected families matched the expected number. Using data from 322 families with AMD, we used a simulation strategy to generate comparison groups of families and determined whether their genetic profile at the known AMD risk loci differed from the observed genetic profile, given the density of disease observed. Overall, the genotypic loads for the five SNPs in the families did not deviate significantly from the genotypic loads predicted by the simulation. However, for a subset of densely affected families, the mean genotypic load in the families was significantly lower than the expected load determined from the simulation. Given that these densely affected families may harbor rare, more penetrant variants for AMD, linkage analyses and resequencing targeting these families may be an effective approach to finding additional implicated genes. PMID:19844262

Genetic Variation in the MAPK/ERK Pathway Affects Contact Hypersensitivity Responses.

PubMed

Legrand, Julien M D; Roy, Edwige; Baz, Batoul; Mukhopadhyay, Pamela; Wong, Ho Yi; Ram, Ramesh; Morahan, Grant; Walker, Graeme; Khosrotehrani, Kiarash

2018-05-10

Using a genetic resource that enables rapid mapping of genes for complex traits, we demonstrate dramatic diversity between murine strains in response to immune challenge. We identified several candidate genes that point to the MAPK/ERK pathway as a key modulator of this process. Copyright © 2018. Published by Elsevier Inc.

Trait variation and genetic diversity in a banana genomic selection training population

PubMed Central

Nyine, Moses; Uwimana, Brigitte; Swennen, Rony; Batte, Michael; Brown, Allan; Christelová, Pavla; Hřibová, Eva; Lorenzen, Jim

2017-01-01

Banana (Musa spp.) is an important crop in the African Great Lakes region in terms of income and food security, with the highest per capita consumption worldwide. Pests, diseases and climate change hamper sustainable production of bananas. New breeding tools with increased crossbreeding efficiency are being investigated to breed for resistant, high yielding hybrids of East African Highland banana (EAHB). These include genomic selection (GS), which will benefit breeding through increased genetic gain per unit time. Understanding trait variation and the correlation among economically important traits is an essential first step in the development and selection of suitable GS models for banana. In this study, we tested the hypothesis that trait variations in bananas are not affected by cross combination, cycle, field management and their interaction with genotype. A training population created using EAHB breeding material and its progeny was phenotyped in two contrasting conditions. A high level of correlation among vegetative and yield related traits was observed. Therefore, genomic selection models could be developed for traits that are easily measured. It is likely that the predictive ability of traits that are difficult to phenotype will be similar to less difficult traits they are highly correlated with. Genotype response to cycle and field management practices varied greatly with respect to traits. Yield related traits accounted for 31–35% of principal component variation under low and high input field management conditions. Resistance to Black Sigatoka was stable across cycles but varied under different field management depending on the genotype. The best cross combination was 1201K-1xSH3217 based on selection response (R) of hybrids. Genotyping using simple sequence repeat (SSR) markers revealed that the training population was genetically diverse, reflecting a complex pedigree background, which was mostly influenced by the male parents. PMID:28586365

Trait variation and genetic diversity in a banana genomic selection training population.

PubMed

Nyine, Moses; Uwimana, Brigitte; Swennen, Rony; Batte, Michael; Brown, Allan; Christelová, Pavla; Hřibová, Eva; Lorenzen, Jim; Doležel, Jaroslav

2017-01-01

Banana (Musa spp.) is an important crop in the African Great Lakes region in terms of income and food security, with the highest per capita consumption worldwide. Pests, diseases and climate change hamper sustainable production of bananas. New breeding tools with increased crossbreeding efficiency are being investigated to breed for resistant, high yielding hybrids of East African Highland banana (EAHB). These include genomic selection (GS), which will benefit breeding through increased genetic gain per unit time. Understanding trait variation and the correlation among economically important traits is an essential first step in the development and selection of suitable GS models for banana. In this study, we tested the hypothesis that trait variations in bananas are not affected by cross combination, cycle, field management and their interaction with genotype. A training population created using EAHB breeding material and its progeny was phenotyped in two contrasting conditions. A high level of correlation among vegetative and yield related traits was observed. Therefore, genomic selection models could be developed for traits that are easily measured. It is likely that the predictive ability of traits that are difficult to phenotype will be similar to less difficult traits they are highly correlated with. Genotype response to cycle and field management practices varied greatly with respect to traits. Yield related traits accounted for 31-35% of principal component variation under low and high input field management conditions. Resistance to Black Sigatoka was stable across cycles but varied under different field management depending on the genotype. The best cross combination was 1201K-1xSH3217 based on selection response (R) of hybrids. Genotyping using simple sequence repeat (SSR) markers revealed that the training population was genetically diverse, reflecting a complex pedigree background, which was mostly influenced by the male parents.

Genetic and phenotypic variation of the malaria vector Anopheles atroparvus in southern Europe.

PubMed

Vicente, José L; Sousa, Carla A; Alten, Bulent; Caglar, Selim S; Falcutá, Elena; Latorre, José M; Toty, Celine; Barré, Hélène; Demirci, Berna; Di Luca, Marco; Toma, Luciano; Alves, Ricardo; Salgueiro, Patrícia; Silva, Teresa L; Bargues, Maria D; Mas-Coma, Santiago; Boccolini, Daniela; Romi, Roberto; Nicolescu, Gabriela; do Rosário, Virgílio E; Ozer, Nurdan; Fontenille, Didier; Pinto, João

2011-01-11

There is a growing concern that global climate change will affect the potential for pathogen transmission by insect species that are vectors of human diseases. One of these species is the former European malaria vector, Anopheles atroparvus. Levels of population differentiation of An. atroparvus from southern Europe were characterized as a first attempt to elucidate patterns of population structure of this former malaria vector. Results are discussed in light of a hypothetical situation of re-establishment of malaria transmission. Genetic and phenotypic variation was analysed in nine mosquito samples collected from five European countries, using eight microsatellite loci and geometric morphometrics on 21 wing landmarks. Levels of genetic diversity were comparable to those reported for tropical malaria vectors. Low levels of genetic (0.004 Genetic differentiation (0.202

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

PubMed Central

Scott, William R.; Zhang, Weihua; Loh, Marie; Tan, Sian-Tsung; Lehne, Benjamin; Afzal, Uzma; Peralta, Juan; Saxena, Richa; Ralhan, Sarju; Wander, Gurpreet S.; Bozaoglu, Kiymet; Sanghera, Dharambir K.; Elliott, Paul; Scott, James; Chambers, John C.; Kooner, Jaspal S.

2016-01-01

South Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10−6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans. PMID:27195708

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians.

PubMed

Scott, William R; Zhang, Weihua; Loh, Marie; Tan, Sian-Tsung; Lehne, Benjamin; Afzal, Uzma; Peralta, Juan; Saxena, Richa; Ralhan, Sarju; Wander, Gurpreet S; Bozaoglu, Kiymet; Sanghera, Dharambir K; Elliott, Paul; Scott, James; Chambers, John C; Kooner, Jaspal S

2016-01-01

South Asians are 1/4 of the world's population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10-6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans.

The African Genome Variation Project shapes medical genetics in Africa

NASA Astrophysics Data System (ADS)

Gurdasani, Deepti; Carstensen, Tommy; Tekola-Ayele, Fasil; Pagani, Luca; Tachmazidou, Ioanna; Hatzikotoulas, Konstantinos; Karthikeyan, Savita; Iles, Louise; Pollard, Martin O.; Choudhury, Ananyo; Ritchie, Graham R. S.; Xue, Yali; Asimit, Jennifer; Nsubuga, Rebecca N.; Young, Elizabeth H.; Pomilla, Cristina; Kivinen, Katja; Rockett, Kirk; Kamali, Anatoli; Doumatey, Ayo P.; Asiki, Gershim; Seeley, Janet; Sisay-Joof, Fatoumatta; Jallow, Muminatou; Tollman, Stephen; Mekonnen, Ephrem; Ekong, Rosemary; Oljira, Tamiru; Bradman, Neil; Bojang, Kalifa; Ramsay, Michele; Adeyemo, Adebowale; Bekele, Endashaw; Motala, Ayesha; Norris, Shane A.; Pirie, Fraser; Kaleebu, Pontiano; Kwiatkowski, Dominic; Tyler-Smith, Chris; Rotimi, Charles; Zeggini, Eleftheria; Sandhu, Manjinder S.

2015-01-01

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

The African Genome Variation Project shapes medical genetics in Africa.

PubMed

Gurdasani, Deepti; Carstensen, Tommy; Tekola-Ayele, Fasil; Pagani, Luca; Tachmazidou, Ioanna; Hatzikotoulas, Konstantinos; Karthikeyan, Savita; Iles, Louise; Pollard, Martin O; Choudhury, Ananyo; Ritchie, Graham R S; Xue, Yali; Asimit, Jennifer; Nsubuga, Rebecca N; Young, Elizabeth H; Pomilla, Cristina; Kivinen, Katja; Rockett, Kirk; Kamali, Anatoli; Doumatey, Ayo P; Asiki, Gershim; Seeley, Janet; Sisay-Joof, Fatoumatta; Jallow, Muminatou; Tollman, Stephen; Mekonnen, Ephrem; Ekong, Rosemary; Oljira, Tamiru; Bradman, Neil; Bojang, Kalifa; Ramsay, Michele; Adeyemo, Adebowale; Bekele, Endashaw; Motala, Ayesha; Norris, Shane A; Pirie, Fraser; Kaleebu, Pontiano; Kwiatkowski, Dominic; Tyler-Smith, Chris; Rotimi, Charles; Zeggini, Eleftheria; Sandhu, Manjinder S

2015-01-15

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

Host-parasite coevolution: genetic variation in a virus population and the interaction with a host gene.

PubMed

Wilfert, L; Jiggins, F M

2010-07-01

Host-parasite coevolution is considered to be an important factor in maintaining genetic variation in resistance to pathogens. Drosophila melanogaster is naturally infected by the sigma virus, a vertically transmitted and host-specific pathogen. In fly populations, there is a large amount of genetic variation in the transmission rate from parent to offspring, much of which is caused by major-effect resistance polymorphisms. We have found that there are similarly high levels of genetic variation in the rate of paternal transmission among 95 different isolates of the virus as in the host. However, when we examined a transmission-blocking gene in the host, we found that it was effective across virus isolates. Therefore, the high levels of genetic variation observed in this system do not appear to be maintained because of coevolution resulting from interactions between this host gene and parasite genes.

Assessment of imprinting- and genetic variation-dependent monoallelic expression using reciprocal allele descendants between human family trios.

PubMed

Chuang, Trees-Juen; Tseng, Yu-Hsiang; Chen, Chia-Ying; Wang, Yi-Da

2017-08-01

Genomic imprinting is an important epigenetic process that silences one of the parentally-inherited alleles of a gene and thereby exhibits allelic-specific expression (ASE). Detection of human imprinting events is hampered by the infeasibility of the reciprocal mating system in humans and the removal of ASE events arising from non-imprinting factors. Here, we describe a pipeline with the pattern of reciprocal allele descendants (RADs) through genotyping and transcriptome sequencing data across independent parent-offspring trios to discriminate between varied types of ASE (e.g., imprinting, genetic variation-dependent ASE, and random monoallelic expression (RME)). We show that the vast majority of ASE events are due to sequence-dependent genetic variant, which are evolutionarily conserved and may themselves play a cis-regulatory role. Particularly, 74% of non-RAD ASE events, even though they exhibit ASE biases toward the same parentally-inherited allele across different individuals, are derived from genetic variation but not imprinting. We further show that the RME effect may affect the effectiveness of the population-based method for detecting imprinting events and our pipeline can help to distinguish between these two ASE types. Taken together, this study provides a good indicator for categorization of different types of ASE, opening up this widespread and complex mechanism for comprehensive characterization.

Empathy in early childhood: genetic, environmental, and affective contributions.

PubMed

Knafo, Ariel; Zahn-Waxler, Carolyn; Davidov, Maayan; Van Hulle, Carol; Robinson, JoAnn L; Rhee, Soo Hyun

2009-06-01

We investigated the genetic and environmental origins of children's empathy toward a distress victim and its correlates with emotional symptoms and affective knowledge. The cognitive (hypothesis testing) and affective (empathic concern) empathy of 122 twin pairs in response to simulated pain by an adult examiner was observed at 3.5 years of age. Moderate (0.19 to 0.44) heritabilities were estimated for individual differences in empathy, and the nonshared environment and error accounted for the rest of the variance. Hypothesis testing and empathic concern were moderately correlated, mainly through overlapping genetic effects. Although children's affective knowledge did not correlate with their empathy, affective knowledge interacted with mother-rated emotional symptoms in predicting empathy; knowledge about emotions was associated with greater empathy in children low in emotional symptoms. In contrast, among children with high degrees of emotional symptoms, those with better affective knowledge tended to show lower empathy.

Hubby and Lewontin on Protein Variation in Natural Populations: When Molecular Genetics Came to the Rescue of Population Genetics.

PubMed

Charlesworth, Brian; Charlesworth, Deborah; Coyne, Jerry A; Langley, Charles H

2016-08-01

The 1966 GENETICS papers by John Hubby and Richard Lewontin were a landmark in the study of genome-wide levels of variability. They used the technique of gel electrophoresis of enzymes and proteins to study variation in natural populations of Drosophila pseudoobscura, at a set of loci that had been chosen purely for technical convenience, without prior knowledge of their levels of variability. Together with the independent study of human populations by Harry Harris, this seminal study provided the first relatively unbiased picture of the extent of genetic variability in protein sequences within populations, revealing that many genes had surprisingly high levels of diversity. These papers stimulated a large research program that found similarly high electrophoretic variability in many different species and led to statistical tools for interpreting the data in terms of population genetics processes such as genetic drift, balancing and purifying selection, and the effects of selection on linked variants. The current use of whole-genome sequences in studies of variation is the direct descendant of this pioneering work. Copyright © 2016 by the Genetics Society of America.

A simple genetic architecture underlies morphological variation in dogs.

PubMed

Boyko, Adam R; Quignon, Pascale; Li, Lin; Schoenebeck, Jeffrey J; Degenhardt, Jeremiah D; Lohmueller, Kirk E; Zhao, Keyan; Brisbin, Abra; Parker, Heidi G; vonHoldt, Bridgett M; Cargill, Michele; Auton, Adam; Reynolds, Andy; Elkahloun, Abdel G; Castelhano, Marta; Mosher, Dana S; Sutter, Nathan B; Johnson, Gary S; Novembre, John; Hubisz, Melissa J; Siepel, Adam; Wayne, Robert K; Bustamante, Carlos D; Ostrander, Elaine A

2010-08-10

Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (< or = 3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.

A Simple Genetic Architecture Underlies Morphological Variation in Dogs

PubMed Central

Schoenebeck, Jeffrey J.; Degenhardt, Jeremiah D.; Lohmueller, Kirk E.; Zhao, Keyan; Brisbin, Abra; Parker, Heidi G.; vonHoldt, Bridgett M.; Cargill, Michele; Auton, Adam; Reynolds, Andy; Elkahloun, Abdel G.; Castelhano, Marta; Mosher, Dana S.; Sutter, Nathan B.; Johnson, Gary S.; Novembre, John; Hubisz, Melissa J.; Siepel, Adam; Wayne, Robert K.; Bustamante, Carlos D.; Ostrander, Elaine A.

2010-01-01

Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (≤3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species. PMID:20711490

Genetic Alterations Affecting Cholesterol Metabolism and Human Fertility1

PubMed Central

DeAngelis, Anthony M.; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

2014-01-01

ABSTRACT Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. PMID:25122065

Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study.

PubMed

Papadimitriou, George N; Dikeos, Dimitris G; Souery, Daniel; Del-Favero, Jurgen; Massat, Isabelle; Avramopoulos, Dimitrios; Blairy, Sylvie; Cichon, Sven; Ivezic, Sladjana; Kaneva, Radka; Karadima, Georgia; Lilli, Roberta; Milanova, Vihra; Nöthen, Markus; Oruc, Lilijana; Rietschel, Marcella; Serretti, Alessandro; Van Broeckhoven, Christine; Stefanis, Costas N; Mendlewicz, Julien

2003-12-01

The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.

Cryptic genetic variation, evolution's hidden substrate

PubMed Central

Paaby, Annalise B.; Rockman, Matthew V.

2016-01-01

Cryptic genetic variation is invisible under normal conditions but fuel for evolution when circumstances change. In theory, CGV can represent a massive cache of adaptive potential or a pool of deleterious alleles in need of constant suppression. CGV emerges from both neutral and selective processes and it may inform how human populations respond to change. In experimental settings, CGV facilitates adaptation, but does it play an important role in the real world? We review the empirical support for widespread CGV in natural populations, including its potential role in emerging human diseases and the growing evidence of its contribution to evolution. PMID:24614309

Patterns of genetic variation across inversions: geographic variation in the In(2L)t inversion in populations of Drosophila melanogaster from eastern Australia.

PubMed

Kennington, W Jason; Hoffmann, Ary A

2013-05-20

Chromosomal inversions are increasingly being recognized as important in adaptive shifts and are expected to influence patterns of genetic variation, but few studies have examined genetic patterns in inversion polymorphisms across and within populations. Here, we examine genetic variation at 20 microsatellite loci and the alcohol dehydrogenase gene (Adh) located within and near the In(2L)t inversion of Drosophila melanogaster at three different sites along a latitudinal cline on the east coast of Australia. We found significant genetic differentiation between the standard and inverted chromosomal arrangements at each site as well as significant, but smaller differences among sites in the same arrangement. Genetic differentiation between pairs of sites was higher for inverted chromosomes than standard chromosomes, while inverted chromosomes had lower levels of genetic variation even well away from inversion breakpoints. Bayesian clustering analysis provided evidence of genetic exchange between chromosomal arrangements at each site. The strong differentiation between arrangements and reduced variation in the inverted chromosomes are likely to reflect ongoing selection at multiple loci within the inverted region. They may also reflect lower effective population sizes of In(2L)t chromosomes and colonization of Australia, although there was no consistent evidence of a recent bottleneck and simulations suggest that differences between arrangements would not persist unless rates of gene exchange between them were low. Genetic patterns therefore support the notion of selection and linkage disequilibrium contributing to inversion polymorphisms, although more work is needed to determine whether there are spatially varying targets of selection within this inversion. They also support the idea that the allelic content within an inversion can vary between geographic locations.

The distribution of nuclear genetic variation and historical demography of sea otters

USGS Publications Warehouse

Aguilar, A.; Jessup, David A.; Estes, J.; Garza, J.C.

2008-01-01

The amount and distribution of population genetic variation is crucial information for the design of effective conservation strategies for endangered species and can also be used to provide inference about demographic processes and patterns of migration. Here, we describe variation at a large number of nuclear genes in sea otters Enhydra lutris ssp. We surveyed 14 variable microsatellite loci and two genes of the major histocompatibility complex (MHC) in up to 350 California sea otters Enhydra lutris nereis, which represents ∼10% of the subspecies' population, and 46 otters from two Alaskan sites. We utilized methods for detecting past reductions in effective population size to examine the effects of near extinction from the fur trade. Summary statistic tests largely failed to find a signal of a recent population size reduction (within the past 200 years), but a Bayesian method found a signal of a strong reduction over a longer time scale (up to 500 years ago). These results indicate that the reduction in size began long enough ago that much genetic variation was lost before the 19th century fur trade. A comparison of geographic distance and pairwise relatedness for individual otters found no evidence of kin-based spatial clustering for either gender. This indicates that there is no population structure, due to extended family groups, within the California population. A survey of population genetic variation found that two of the MHC genes, DQB and DRB, had two alleles present and one of the genes, DRA, was monomorphic in otters. This contrasts with other mammals, where they are often the most variable coding genes known. Genetic variation in the sea otter is among the lowest observed for a mammal and raises concerns about the long-term viability of the species, particularly in the face of future environmental changes.

GENETIC STRUCTURE OF NORWAY SPRUCE (PICEA ABIES): CONCORDANCE OF MORPHOLOGICAL AND ALLOZYMIC VARIATION.

PubMed

Lagercrantz, Ulf; Ryman, Nils

1990-02-01

This study describes the population structure of Norway spruce (Picea abies) as revealed by protein polymorphisms and morphological variation. Electrophoretically detectable genetic variability was examined at 22 protein loci in 70 populations from the natural range of the species in Europe. Like other conifers, Norway spruce exhibits a relatively large amount of genetic variability and little differentiation among populations. Sixteen polymorphic loci (73%) segregate for a total of 51 alleles, and average heterozygosity per population is 0.115. Approximately 5% of the total genetic diversity is explained by differences between populations (G ST = 0.052), and Nei's standard genetic distance is less than 0.04 in all cases. We suggest that the population structure largely reflects relatively recent historical events related to the last glaciation and that Norway spruce is still in a process of adaptation and differentiation. There is a clear geographic pattern in the variation of allele frequencies. A major part of the allelefrequency variation can be accounted for by a few synthetic variables (principal components), and 80% of the variation of the first principal component is "explained" by latitude and longitude. The central European populations are consistently depauperate of genetic variability, most likely as an effect of severe restrictions of population size during the last glaciation. The pattern of differentiation at protein loci is very similar to that observed for seven morphological traits examined. This similarity suggests that the same evolutionary forces have acted upon both sets of characters. © 1990 The Society for the Study of Evolution.

Genetic variation, multiple paternity, and measures of reproductive success in the critically endangered hawksbill turtle (Eretmochelys imbricata).

PubMed

González-Garza, Blanca Idalia; Stow, Adam; Sánchez-Teyer, Lorenzo Felipe; Zapata-Pérez, Omar

2015-12-01

The Yucatán Peninsula in Mexico contains some of the largest breeding groups of the globally distributed and critically endangered hawksbill turtle (Eretmochelys imbricata). An improved understanding of the breeding system of this species and how its genetic variation is structured among nesting areas is required before the threats to its survival can be properly evaluated. Here, we genotype 1195 hatchlings and 41 nesting females at 12 microsatellite loci to assess levels of multiple paternity, genetic variation and whether individual levels of homozygosity are associated with reproductive success. Of the 50 clutches analyzed, only 6% have multiple paternity. The distribution of pairwise relatedness among nesting localities (rookeries) was not random with elevated within-rookery relatedness, and declining relatedness with geographic distance indicating some natal philopatry. Although there was no strong evidence that particular rookeries had lost allelic variation via drift, younger turtles had significantly lower levels of genetic variation than older turtles, suggesting some loss of genetic variation. At present there is no indication that levels of genetic variation are associated with measures of reproductive success such as clutch size, hatching success, and frequency of infertile eggs.

Epigenetic and genetic variation among three separate introductions of the house sparrow (Passer domesticus) into Australia

PubMed Central

Schrey, A.; Ragsdale, A.; Griffith, S. C.

2018-01-01

Invasive populations are often associated with low levels of genetic diversity owing to population bottlenecks at the initial stages of invasion. Despite this, the ability of invasive species to adapt rapidly in response to novel environments is well documented. Epigenetic mechanisms have recently been proposed to facilitate the success of invasive species by compensating for reduced levels of genetic variation. Here, we use methylation sensitive-amplification fragment length polymorphism and microsatellite analyses to compare levels of epigenetic and genetic diversity and differentiation across 15 sites in the introduced Australian house sparrow population. We find patterns of epigenetic and genetic differentiation that are consistent with historical descriptions of three distinct, introductions events. However unlike genetic differentiation, epigenetic differentiation was higher among sample sites than among invasion clusters, suggesting that patterns of epigenetic variation are more strongly influenced by local environmental stimuli or sequential founder events than the initial diversity in the introduction population. Interestingly, we fail to detect correlations between pairwise site comparisons of epigenetic and genetic differentiation, suggesting that some of the observed epigenetic variation has arisen independently of genetic variation. We also fail to detect the potentially compensatory relationship between epigenetic and genetic diversity that has been detected in a more recent house sparrow invasion in Africa. We discuss the potential for this relationship to be obscured by recovered genetic diversity in more established populations, and highlight the importance of incorporating introduction history into population-wide epigenetic analyses. PMID:29765671

A comparison of worldwide phonemic and genetic variation in human populations

PubMed Central

Creanza, Nicole; Ruhlen, Merritt; Pemberton, Trevor J.; Rosenberg, Noah A.; Feldman, Marcus W.; Ramachandran, Sohini

2015-01-01

Worldwide patterns of genetic variation are driven by human demographic history. Here, we test whether this demographic history has left similar signatures on phonemes—sound units that distinguish meaning between words in languages—to those it has left on genes. We analyze, jointly and in parallel, phoneme inventories from 2,082 worldwide languages and microsatellite polymorphisms from 246 worldwide populations. On a global scale, both genetic distance and phonemic distance between populations are significantly correlated with geographic distance. Geographically close language pairs share significantly more phonemes than distant language pairs, whether or not the languages are closely related. The regional geographic axes of greatest phonemic differentiation correspond to axes of genetic differentiation, suggesting that there is a relationship between human dispersal and linguistic variation. However, the geographic distribution of phoneme inventory sizes does not follow the predictions of a serial founder effect during human expansion out of Africa. Furthermore, although geographically isolated populations lose genetic diversity via genetic drift, phonemes are not subject to drift in the same way: within a given geographic radius, languages that are relatively isolated exhibit more variance in number of phonemes than languages with many neighbors. This finding suggests that relatively isolated languages are more susceptible to phonemic change than languages with many neighbors. Within a language family, phoneme evolution along genetic, geographic, or cognate-based linguistic trees predicts similar ancestral phoneme states to those predicted from ancient sources. More genetic sampling could further elucidate the relative roles of vertical and horizontal transmission in phoneme evolution. PMID:25605893

MetaRanker 2.0: a web server for prioritization of genetic variation data.

PubMed

Pers, Tune H; Dworzyński, Piotr; Thomas, Cecilia Engel; Lage, Kasper; Brunak, Søren

2013-07-01

MetaRanker 2.0 is a web server for prioritization of common and rare frequency genetic variation data. Based on heterogeneous data sets including genetic association data, protein-protein interactions, large-scale text-mining data, copy number variation data and gene expression experiments, MetaRanker 2.0 prioritizes the protein-coding part of the human genome to shortlist candidate genes for targeted follow-up studies. MetaRanker 2.0 is made freely available at www.cbs.dtu.dk/services/MetaRanker-2.0.

Genetic interactions contribute less than additive effects to quantitative trait variation in yeast

PubMed Central

Bloom, Joshua S.; Kotenko, Iulia; Sadhu, Meru J.; Treusch, Sebastian; Albert, Frank W.; Kruglyak, Leonid

2015-01-01

Genetic mapping studies of quantitative traits typically focus on detecting loci that contribute additively to trait variation. Genetic interactions are often proposed as a contributing factor to trait variation, but the relative contribution of interactions to trait variation is a subject of debate. Here we use a very large cross between two yeast strains to accurately estimate the fraction of phenotypic variance due to pairwise QTL–QTL interactions for 20 quantitative traits. We find that this fraction is 9% on average, substantially less than the contribution of additive QTL (43%). Statistically significant QTL–QTL pairs typically have small individual effect sizes, but collectively explain 40% of the pairwise interaction variance. We show that pairwise interaction variance is largely explained by pairs of loci at least one of which has a significant additive effect. These results refine our understanding of the genetic architecture of quantitative traits and help guide future mapping studies. PMID:26537231

Mutation Is a Sufficient and Robust Predictor of Genetic Variation for Mitotic Spindle Traits in Caenorhabditis elegans

PubMed Central

Farhadifar, Reza; Ponciano, José Miguel; Andersen, Erik C.; Needleman, Daniel J.; Baer, Charles F.

2016-01-01

Different types of phenotypic traits consistently exhibit different levels of genetic variation in natural populations. There are two potential explanations: Either mutation produces genetic variation at different rates or natural selection removes or promotes genetic variation at different rates. Whether mutation or selection is of greater general importance is a longstanding unresolved question in evolutionary genetics. We report mutational variances (VM) for 19 traits related to the first mitotic cell division in Caenorhabditis elegans and compare them to the standing genetic variances (VG) for the same suite of traits in a worldwide collection C. elegans. Two robust conclusions emerge. First, the mutational process is highly repeatable: The correlation between VM in two independent sets of mutation accumulation lines is ∼0.9. Second, VM for a trait is a good predictor of VG for that trait: The correlation between VM and VG is ∼0.9. This result is predicted for a population at mutation–selection balance; it is not predicted if balancing selection plays a primary role in maintaining genetic variation. PMID:27334268

Climate variables explain neutral and adaptive variation within salmonid metapopulations: The importance of replication in landscape genetics

USGS Publications Warehouse

Hand, Brian K.; Muhlfeld, Clint C.; Wade, Alisa A.; Kovach, Ryan; Whited, Diane C.; Narum, Shawn R.; Matala, Andrew P.; Ackerman, Michael W.; Garner, B. A.; Kimball, John S; Stanford, Jack A.; Luikart, Gordon

2016-01-01

Understanding how environmental variation influences population genetic structure is important for conservation management because it can reveal how human stressors influence population connectivity, genetic diversity and persistence. We used riverscape genetics modelling to assess whether climatic and habitat variables were related to neutral and adaptive patterns of genetic differentiation (population-specific and pairwise FST) within five metapopulations (79 populations, 4583 individuals) of steelhead trout (Oncorhynchus mykiss) in the Columbia River Basin, USA. Using 151 putatively neutral and 29 candidate adaptive SNP loci, we found that climate-related variables (winter precipitation, summer maximum temperature, winter highest 5% flow events and summer mean flow) best explained neutral and adaptive patterns of genetic differentiation within metapopulations, suggesting that climatic variation likely influences both demography (neutral variation) and local adaptation (adaptive variation). However, we did not observe consistent relationships between climate variables and FST across all metapopulations, underscoring the need for replication when extrapolating results from one scale to another (e.g. basin-wide to the metapopulation scale). Sensitivity analysis (leave-one-population-out) revealed consistent relationships between climate variables and FST within three metapopulations; however, these patterns were not consistent in two metapopulations likely due to small sample sizes (N = 10). These results provide correlative evidence that climatic variation has shaped the genetic structure of steelhead populations and highlight the need for replication and sensitivity analyses in land and riverscape genetics.

Genetic variation in Southern USA rice genotypes for seedling salinity tolerance

PubMed Central

De Leon, Teresa B.; Linscombe, Steven; Gregorio, Glenn; Subudhi, Prasanta K.

2015-01-01

The success of a rice breeding program in developing salt tolerant varieties depends on genetic variation and the salt stress response of adapted and donor rice germplasm. In this study, we used a combination of morphological and physiological traits in multivariate analyses to elucidate the phenotypic and genetic variation in salinity tolerance of 30 Southern USA rice genotypes, along with 19 donor genotypes with varying degree of tolerance. Significant genotypic variation and correlations were found among the salt injury score (SIS), ion leakage, chlorophyll reduction, shoot length reduction, shoot K+ concentration, and shoot Na+/K+ ratio. Using these parameters, the combined methods of cluster analysis and discriminant analysis validated the salinity response of known genotypes and classified most of the USA varieties into sensitive groups, except for three and seven varieties placed in the tolerant and moderately tolerant groups, respectively. Discriminant function and MANOVA delineated the differences in tolerance and suggested no differences between sensitive and highly sensitive (HS) groups. DNA profiling using simple sequence repeat markers showed narrow genetic diversity among USA genotypes. However, the overall genetic clustering was mostly due to subspecies and grain type differentiation and not by varietal grouping based on salinity tolerance. Among the donor genotypes, Nona Bokra, Pokkali, and its derived breeding lines remained the donors of choice for improving salinity tolerance during the seedling stage. However, due to undesirable agronomic attributes and photosensitivity of these donors, alternative genotypes such as TCCP266, Geumgangbyeo, and R609 are recommended as useful and novel sources of salinity tolerance for USA rice breeding programs. PMID:26074937

MetaRanker 2.0: a web server for prioritization of genetic variation data

PubMed Central

Pers, Tune H.; Dworzyński, Piotr; Thomas, Cecilia Engel; Lage, Kasper; Brunak, Søren

2013-01-01

MetaRanker 2.0 is a web server for prioritization of common and rare frequency genetic variation data. Based on heterogeneous data sets including genetic association data, protein–protein interactions, large-scale text-mining data, copy number variation data and gene expression experiments, MetaRanker 2.0 prioritizes the protein-coding part of the human genome to shortlist candidate genes for targeted follow-up studies. MetaRanker 2.0 is made freely available at www.cbs.dtu.dk/services/MetaRanker-2.0. PMID:23703204

Population genetic variation in the tree fern Alsophila spinulosa (Cyatheaceae): effects of reproductive strategy.

PubMed

Wang, Ting; Su, Yingjuan; Li, Yuan

2012-01-01

Essentially all ferns can perform both sexual and asexual reproduction. Their populations represent suitable study objects to test the population genetic effects of different reproductive systems. Using the diploid homosporous fern Alsophila spinulosa as an example species, the main purpose of this study was to assess the relative impact of sexual and asexual reproduction on the level and structure of population genetic variation. Inter-simple sequence repeats analysis was conducted on 140 individuals collected from seven populations (HSG, LCH, BPC, MPG, GX, LD, and ZHG) in China. Seventy-four polymorphic bands discriminated a total of 127 multilocus genotypes. Character compatibility analysis revealed that 50.0 to 70.0% of the genotypes had to be deleted in order to obtain a tree-like structure in the data set from populations HSG, LCH, MPG, BPC, GX, and LD; and there was a gradual decrease of conflict in the data set when genotypes with the highest incompatibility counts were successively deleted. In contrast, in population ZHG, only 33.3% of genotypes had to be removed to achieve complete compatibility in the data set, which showed a sharp decline in incompatibility upon the deletion of those genotypes. All populations examined possessed similar levels of genetic variation. Population ZHG was not found to be more differentiated than the other populations. Sexual recombination is the predominant source of genetic variation in most of the examined populations of A. spinulosa. However, somatic mutation contributes most to the genetic variation in population ZHG. This change of the primary mode of reproduction does not cause a significant difference in the population genetic composition. Character compatibility analysis represents an effective approach to separate the role of sexual and asexual components in shaping the genetic pattern of fern populations.

Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation

PubMed Central

Porto, Arthur; Sebastião, Harley; Pavan, Silvia Eliza; VandeBerg, John L.; Marroig, Gabriel; Cheverud, James M.

2015-01-01

We tested the hypothesis that the rate of marsupial cranial evolution is dependent on the distribution of genetic variation in multivariate space. To do so, we carried out a genetic analysis of cranial morphological variation in laboratory strains of Monodelphis domestica and used estimates of genetic covariation to analyze the morphological diversification of the Monodelphis brevicaudata species group. We found that within-species genetic variation is concentrated in only a few axes of the morphospace and that this strong genetic covariation influenced the rate of morphological diversification of the brevicaudata group, with between-species divergence occurring fastest when occurring along the genetic line of least resistance. Accounting for the geometric distribution of genetic variation also increased our ability to detect the selective regimen underlying species diversification, with several instances of selection only being detected when genetic covariances were taken into account. Therefore, this work directly links patterns of genetic covariation among traits to macroevolutionary patterns of morphological divergence. Our findings also suggest that the limited distribution of Monodelphis species in morphospace is the result of a complex interplay between the limited dimensionality of available genetic variation and strong stabilizing selection along two major axes of genetic variation. PMID:25818173

Genetic variation in CD38 and breastfeeding experience interact to impact infants’ attention to social eye cues

PubMed Central

Krol, Kathleen M.; Monakhov, Mikhail; Lai, Poh San; Ebstein, Richard P.; Grossmann, Tobias

2015-01-01

Attending to emotional information conveyed by the eyes is an important social skill in humans. The current study examined this skill in early development by measuring attention to eyes while viewing emotional faces in 7-mo-old infants. In particular, we investigated individual differences in infant attention to eyes in the context of genetic variation (CD38 rs3796863 polymorphism) and experiential variation (exclusive breastfeeding duration) related to the oxytocin system. Our results revealed that, whereas infants at this age show a robust fear bias (increased attention to fearful eyes), their attention to angry and happy eyes varies as a function of exclusive breastfeeding experience and genetic variation in CD38. Specifically, extended exclusive breastfeeding duration selectively enhanced looking preference to happy eyes and decreased looking to angry eyes. Importantly, however, this interaction was impacted by CD38 variation, such that only the looking preferences of infants homozygous for the C allele of rs3796863 were affected by breastfeeding experience. This genotype has been associated with reduced release of oxytocin and higher rates of autism. In contrast, infants with the CA/AA genotype showed similar looking preferences regardless of breastfeeding exposure. Thus, differences in the sensitivity to emotional eyes may be linked to an interaction between the endogenous (CD38) and exogenous (breastfeeding) availability of oxytocin. These findings underline the importance of maternal care and the oxytocin system in contributing to the early development of responding to social eye cues. PMID:26371313

The Genetics of Mexico Recapitulates Native American Substructure and Affects Biomedical Traits

PubMed Central

Moreno-Estrada, Andrés; Gignoux, Christopher R.; Fernández-López, Juan Carlos; Zakharia, Fouad; Sikora, Martin; Contreras, Alejandra V.; Acuña-Alonzo, Victor; Sandoval, Karla; Eng, Celeste; Romero-Hidalgo, Sandra; Ortiz-Tello, Patricia; Robles, Victoria; Kenny, Eimear E.; Nuño-Arana, Ismael; Barquera-Lozano, Rodrigo; Macín-Pérez, Gastón; Granados-Arriola, Julio; Huntsman, Scott; Galanter, Joshua M.; Via, Marc; Ford, Jean G.; Chapela, Rocío; Rodriguez-Cintron, William; Rodríguez-Santana, Jose R.; Romieu, Isabelle; Sienra-Monge, Juan José; Navarro, Blanca del Rio; London, Stephanie J.; Ruiz-Linares, Andrés; Garcia-Herrera, Rodrigo; Estrada, Karol; Hidalgo-Miranda, Alfredo; Jimenez-Sanchez, Gerardo; Carnevale, Alessandra; Soberón, Xavier; Canizales-Quinteros, Samuel; Rangel-Villalobos, Héctor; Silva-Zolezzi, Irma; Burchard, Esteban Gonzalez; Bustamante, Carlos D.

2014-01-01

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1,000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between sub-continental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide. PMID:24926019

Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors.

PubMed

Figueroa, Jonine D; Sakoda, Lori C; Graubard, Barry I; Chanock, Stephen; Rubertone, Mark V; Erickson, R Loren; McGlynn, Katherine A

2008-11-01

Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54-1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12-1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51-0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42-1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma.

Cryptic genetic variation: evolution's hidden substrate.

PubMed

Paaby, Annalise B; Rockman, Matthew V

2014-04-01

Cryptic genetic variation (CGV) is invisible under normal conditions, but it can fuel evolution when circumstances change. In theory, CGV can represent a massive cache of adaptive potential or a pool of deleterious alleles that are in need of constant suppression. CGV emerges from both neutral and selective processes, and it may inform about how human populations respond to change. CGV facilitates adaptation in experimental settings, but does it have an important role in the real world? Here, we review the empirical support for widespread CGV in natural populations, including its potential role in emerging human diseases and the growing evidence of its contribution to evolution.

Genetic variation in Northern Thailand Hill Tribes: origins and relationships with social structure and linguistic differences.

PubMed

Besaggio, Davide; Fuselli, Silvia; Srikummool, Metawee; Kampuansai, Jatupol; Castrì, Loredana; Tyler-Smith, Chris; Seielstad, Mark; Kangwanpong, Daoroong; Bertorelle, Giorgio

2007-08-16

Ethnic minorities in Northern Thailand, often referred to as Hill Tribes, are considered an ideal model to study the different genetic impact of sex-specific migration rates expected in matrilocal (women remain in their natal villages after the marriage and men move to their wife's village) and patrilocal societies (the opposite is true). Previous studies identified such differences, but little is known about the possible interaction with another cultural factor that may potentially affect genetic diversity, i.e. linguistic differences. In addition, Hill Tribes started to migrate to Thailand in the last centuries from different Northern areas, but the history of these migrations, the level of genetic legacy with their places of origin, and the possible confounding effects related to this migration history in the patterns of genetic diversity, have not been analysed yet. Using both original and published data on the Hill Tribes and several other Asian populations, we focused on all these aspects. Genetic variation within population at mtDNA is lower in matrilocal, compared to patrilocal, tribes. The opposite is true for Y-chromosome microsatellites within the Sino-Tibetan linguistic family, but Hmong-Mien speaking patrilocal groups have a genetic diversity very similar to the matrilocal samples. Population divergence ranges between 5% and 14% at mtDNA sequences, and between 5% and 36% at Y-chromosomes STRs, and follows the sex-specific differences expected in patrilocal and matrilocal tribes. On the average, about 2 men and 14 women, and 4 men and 4 women, are exchanged in patrilocal and matrilocal tribes every generation, respectively. Most of the Hill Tribes in Thailand seem to preserve a genetic legacy with their likely geographic origin, with children adoption probably affecting this pattern in one tribe. Overall, the sex specific genetic signature of different postmarital habits of residence in the Hill Tribes is robust. However, specific perturbations related

Population-genetic properties of differentiated copy number variations in cattle

USDA-ARS?s Scientific Manuscript database

Copy number variations (CNVs) have been shown to be both common in mammals and important for understanding the relationship between genotype and phenotype. However, CNV differentiation, selection and its population genetic properties are not well understood across diverse populations. We performed a...

Genetic variation and relationship among and within Withania species as revealed by AFLP markers.

PubMed

Negi, M S; Singh, A; Lakshmikumaran, M

2000-12-01

Withania somnifera is an important medicinal plant, and its anticancerous properties have been attributed to various classes of withanolide compounds. The objective of the present study was to investigate the inter- and intraspecific genetic variation present in 35 individuals of W. somnifera and 5 individuals of W. coagulans using AFLP (amplified fragment length polymorphism) marker technique. The information about genetic variation determined from AFLP data for 40 individuals was employed to estimate similarity matrix value based on Jaccard's coefficient. The similarity values were further used to construct a phenetic dendrogram revealing the genetic relationships. The dendrogram generated by UPGMA (unweighted pair group method of arithmetic averages) distinguished W. somnifera from W. coagulans and formed two major clusters. These two main clusters shared a similarity coefficient of 0.3, correlating with the high level of polymorphism detected. The dendrogram further separated W. somnifera into three subclasses corresponding to Kashmiri and Nagori groups and an intermediate type. The AFLP profile of Kashmiri individuals was distinct from that of the Nagori group of plants. The intermediate genotype was distinct as it shared bands with both the Kashmiri and Nagori individuals, even though it was identified as a Kashmiri morphotype. Furthermore, the intermediate type shared a similarity coefficient of 0.8 with the Kashmiri individuals. The present work revealed low levels of variation within a population though high levels of polymorphism were detected between Nagori and Kashmiri populations. The ability of AFLP markers for efficient and rapid detection of genetic variations at the species as well as intraspecific level qualifies it as an efficient tool for estimating genetic similarity in plant species and effective management of genetic resources.

Genetic variation in aggregation behaviour and interacting phenotypes in Drosophila.

PubMed

Philippe, Anne-Sophie; Jeanson, Raphael; Pasquaretta, Cristian; Rebaudo, Francois; Sueur, Cedric; Mery, Frederic

2016-03-30

Aggregation behaviour is the tendency for animals to group together, which may have important consequences on individual fitness. We used a combination of experimental and simulation approaches to study how genetic variation and social environment interact to influence aggregation dynamics in Drosophila To do this, we used two different natural lines of Drosophila that arise from a polymorphism in the foraging gene (rovers and sitters). We placed groups of flies in a heated arena. Flies could freely move towards one of two small, cooler refuge areas. In groups of the same strain, sitters had a greater tendency to aggregate. The observed behavioural variation was based on only two parameters: the probability of entering a refuge and the likelihood of choosing a refuge based on the number of individuals present. We then directly addressed how different strains interact by mixing rovers and sitters within a group. Aggregation behaviour of each line was strongly affected by the presence of the other strain, without changing the decision rules used by each. Individuals obeying local rules shaped complex group dynamics via a constant feedback loop between the individual and the group. This study could help to identify the circumstances under which particular group compositions may improve individual fitness through underlying aggregation mechanisms under specific environmental conditions. © 2016 The Author(s).

Living in isolation - population structure, reproduction, and genetic variation of the endangered plant species Dianthus gratianopolitanus (Cheddar pink).

PubMed

Putz, Christina M; Schmid, Christoph; Reisch, Christoph

2015-09-01

The endangered plant species Dianthus gratianopolitanus exhibits a highly fragmented distribution range comprising many isolated populations. Based upon this pattern of distribution, we selected a study region in Switzerland with a lower magnitude of isolation (Swiss Jura) and another study region in Germany with a higher degree of isolation (Franconian Jura). In each region, we chose ten populations to analyze population structure, reproduction, and genetic variation in a comparative approach. Therefore, we determined population density, cushion size, and cushion density to analyze population structure, investigated reproductive traits, including number of flowers, capsules, and germination rate, and analyzed amplified fragment length polymorphisms to study genetic variation. Population and cushion density were credibly higher in German than in Swiss populations, whereas reproductive traits and genetic variation within populations were similar in both study regions. However, genetic variation among populations and isolation by distance were stronger in Germany than in Switzerland. Generally, cushion size and density as well as flower and capsule production increased with population size and density, whereas genetic variation decreased with population density. In contrast to our assumptions, we observed denser populations and cushions in the region with the higher magnitude of isolation, whereas reproductive traits and genetic variation within populations were comparable in both regions. This corroborates the assumption that stronger isolation must not necessarily result in the loss of fitness and genetic variation. Furthermore, it supports our conclusion that the protection of strongly isolated populations contributes essentially to the conservation of a species' full evolutionary potential.

Progressive erosion of genetic and epigenetic variation in callus-derived cocoa (Theobroma cacao) plants.

PubMed

Rodríguez López, Carlos M; Wetten, Andrew C; Wilkinson, Michael J

2010-06-01

*Relatively little is known about the timing of genetic and epigenetic forms of somaclonal variation arising from callus growth. We surveyed for both types of change in cocoa (Theobroma cacao) plants regenerated from calli of various ages, and also between tissues from the source trees. *For genetic change, we used 15 single sequence repeat (SSR) markers from four source trees and from 233 regenerated plants. For epigenetic change, we used 386 methylation-sensitive amplified polymorphism (MSAP) markers on leaf and explant (staminode) DNA from two source trees and on leaf DNA from 114 regenerants. *Genetic variation within source trees was limited to one slippage mutation in one leaf. Regenerants were far more variable, with 35% exhibiting at least one mutation. Genetic variation initially accumulated with culture age but subsequently declined. MSAP (epigenetic) profiles diverged between leaf and staminode samples from source trees. Multivariate analysis revealed that leaves from regenerants occupied intermediate eigenspace between leaves and staminodes of source plants but became progressively more similar to source tree leaves with culture age. *Statistical analysis confirmed this rather counterintuitive finding that leaves of 'late regenerants' exhibited significantly less genetic and epigenetic divergence from source leaves than those exposed to short periods of callus growth.

Large copy-number variations in patients with statin-associated myopathy affecting statin myopathy-related loci.

PubMed

Stránecký, V; Neřoldová, M; Hodaňová, K; Hartmannová, H; Piherová, L; Zemánková, P; Přistoupilová, A; Vrablík, M; Adámková, V; Kmoch, S; Jirsa, M

2016-12-13

Some patients are susceptible to statin-associated myopathy (SAM) either because of genetic variations affecting statin uptake and metabolism, or because they predispose their carriers to muscular diseases. Among the frequent variants examined using the genome-wide association study approach, SLCO1B1 c.521T>C represents the only validated predictor of SAM in patients treated with high-dose simvastatin. Our aim was to ascertain the overall contribution of large copy-number variations (CNVs) to SAM diagnosed in 86 patients. CNVs were detected by whole genome genotyping using Illumina HumanOmni2.5 Exome BeadChips. Exome sequence data were used for validation of CNVs in SAM-related loci. In addition, we performed a specific search for CNVs in the SLCO1B region detected recently in Rotor syndrome subjects. Rare deletions possibly contributing to genetic predisposition to SAM were found in two patients: one removed EYS associated previously with SAM, the other was present in LARGE associated with congenital muscular dystrophy. Another two patients carried deletions in CYP2C19, which may predispose to clopidogrel-statin interactions. We found no common large CNVs potentially associated with SAM and no CNVs in the SLCO1B locus. Our findings suggest that large CNVs do not play a substantial role in the etiology of SAM.

Adaptive genetic variation mediates bottom-up and top-down control in an aquatic ecosystem

PubMed Central

Rudman, Seth M.; Rodriguez-Cabal, Mariano A.; Stier, Adrian; Sato, Takuya; Heavyside, Julian; El-Sabaawi, Rana W.; Crutsinger, Gregory M.

2015-01-01

Research in eco-evolutionary dynamics and community genetics has demonstrated that variation within a species can have strong impacts on associated communities and ecosystem processes. Yet, these studies have centred around individual focal species and at single trophic levels, ignoring the role of phenotypic variation in multiple taxa within an ecosystem. Given the ubiquitous nature of local adaptation, and thus intraspecific variation, we sought to understand how combinations of intraspecific variation in multiple species within an ecosystem impacts its ecology. Using two species that co-occur and demonstrate adaptation to their natal environments, black cottonwood (Populus trichocarpa) and three-spined stickleback (Gasterosteus aculeatus), we investigated the effects of intraspecific phenotypic variation on both top-down and bottom-up forces using a large-scale aquatic mesocosm experiment. Black cottonwood genotypes exhibit genetic variation in their productivity and consequently their leaf litter subsidies to the aquatic system, which mediates the strength of top-down effects from stickleback on prey abundances. Abundances of four common invertebrate prey species and available phosphorous, the most critically limiting nutrient in freshwater systems, are dictated by the interaction between genetic variation in cottonwood productivity and stickleback morphology. These interactive effects fit with ecological theory on the relationship between productivity and top-down control and are comparable in strength to the effects of predator addition. Our results illustrate that intraspecific variation, which can evolve rapidly, is an under-appreciated driver of community structure and ecosystem function, demonstrating that a multi-trophic perspective is essential to understanding the role of evolution in structuring ecological patterns. PMID:26203004

Adaptive genetic variation mediates bottom-up and top-down control in an aquatic ecosystem.

PubMed

Rudman, Seth M; Rodriguez-Cabal, Mariano A; Stier, Adrian; Sato, Takuya; Heavyside, Julian; El-Sabaawi, Rana W; Crutsinger, Gregory M

2015-08-07

Research in eco-evolutionary dynamics and community genetics has demonstrated that variation within a species can have strong impacts on associated communities and ecosystem processes. Yet, these studies have centred around individual focal species and at single trophic levels, ignoring the role of phenotypic variation in multiple taxa within an ecosystem. Given the ubiquitous nature of local adaptation, and thus intraspecific variation, we sought to understand how combinations of intraspecific variation in multiple species within an ecosystem impacts its ecology. Using two species that co-occur and demonstrate adaptation to their natal environments, black cottonwood (Populus trichocarpa) and three-spined stickleback (Gasterosteus aculeatus), we investigated the effects of intraspecific phenotypic variation on both top-down and bottom-up forces using a large-scale aquatic mesocosm experiment. Black cottonwood genotypes exhibit genetic variation in their productivity and consequently their leaf litter subsidies to the aquatic system, which mediates the strength of top-down effects from stickleback on prey abundances. Abundances of four common invertebrate prey species and available phosphorous, the most critically limiting nutrient in freshwater systems, are dictated by the interaction between genetic variation in cottonwood productivity and stickleback morphology. These interactive effects fit with ecological theory on the relationship between productivity and top-down control and are comparable in strength to the effects of predator addition. Our results illustrate that intraspecific variation, which can evolve rapidly, is an under-appreciated driver of community structure and ecosystem function, demonstrating that a multi-trophic perspective is essential to understanding the role of evolution in structuring ecological patterns. © 2015 The Author(s).

Comparative RNA sequencing reveals substantial genetic variation in endangered primates

PubMed Central

Perry, George H.; Melsted, Páll; Marioni, John C.; Wang, Ying; Bainer, Russell; Pickrell, Joseph K.; Michelini, Katelyn; Zehr, Sarah; Yoder, Anne D.; Stephens, Matthew; Pritchard, Jonathan K.; Gilad, Yoav

2012-01-01

Comparative genomic studies in primates have yielded important insights into the evolutionary forces that shape genetic diversity and revealed the likely genetic basis for certain species-specific adaptations. To date, however, these studies have focused on only a small number of species. For the majority of nonhuman primates, including some of the most critically endangered, genome-level data are not yet available. In this study, we have taken the first steps toward addressing this gap by sequencing RNA from the livers of multiple individuals from each of 16 mammalian species, including humans and 11 nonhuman primates. Of the nonhuman primate species, five are lemurs and two are lorisoids, for which little or no genomic data were previously available. To analyze these data, we developed a method for de novo assembly and alignment of orthologous gene sequences across species. We assembled an average of 5721 gene sequences per species and characterized diversity and divergence of both gene sequences and gene expression levels. We identified patterns of variation that are consistent with the action of positive or directional selection, including an 18-fold enrichment of peroxisomal genes among genes whose regulation likely evolved under directional selection in the ancestral primate lineage. Importantly, we found no relationship between genetic diversity and endangered status, with the two most endangered species in our study, the black and white ruffed lemur and the Coquerel's sifaka, having the highest genetic diversity among all primates. Our observations imply that many endangered lemur populations still harbor considerable genetic variation. Timely efforts to conserve these species alongside their habitats have, therefore, strong potential to achieve long-term success. PMID:22207615

Copy Number Variation in Fungi and Its Implications for Wine Yeast Genetic Diversity and Adaptation

PubMed Central

Steenwyk, Jacob L.; Rokas, Antonis

2018-01-01

In recent years, copy number (CN) variation has emerged as a new and significant source of genetic polymorphisms contributing to the phenotypic diversity of populations. CN variants are defined as genetic loci that, due to duplication and deletion, vary in their number of copies across individuals in a population. CN variants range in size from 50 base pairs to whole chromosomes, can influence gene activity, and are associated with a wide range of phenotypes in diverse organisms, including the budding yeast Saccharomyces cerevisiae. In this review, we introduce CN variation, discuss the genetic and molecular mechanisms implicated in its generation, how they can contribute to genetic and phenotypic diversity in fungal populations, and consider how CN variants may influence wine yeast adaptation in fermentation-related processes. In particular, we focus on reviewing recent work investigating the contribution of changes in CN of fermentation-related genes in yeast wine strains and offer notable illustrations of such changes, including the high levels of CN variation among the CUP genes, which confer resistance to copper, a metal with fungicidal properties, and the preferential deletion and duplication of the MAL1 and MAL3 loci, respectively, which are responsible for metabolizing maltose and sucrose. Based on the available data, we propose that CN variation is a substantial dimension of yeast genetic diversity that occurs largely independent of single nucleotide polymorphisms. As such, CN variation harbors considerable potential for understanding and manipulating yeast strains in the wine fermentation environment and beyond. PMID:29520259

Classification and Reporting of Potentially Proarrhythmic Common Genetic Variation in Long QT Syndrome Genetic Testing.

PubMed

Giudicessi, John R; Roden, Dan M; Wilde, Arthur A M; Ackerman, Michael J

2018-02-06

The acquired and congenital forms of long QT syndrome represent 2 distinct but clinically and genetically intertwined disorders of cardiac repolarization characterized by the shared final common pathway of QT interval prolongation and risk of potentially life-threatening arrhythmias. Over the past 2 decades, our understanding of the spectrum of genetic variation that (1) perturbs the function of cardiac ion channel macromolecular complexes and intracellular calcium-handling proteins, (2) underlies acquired/congenital long QT syndrome susceptibility, and (3) serves as a determinant of QT interval duration in the general population has grown exponentially. In turn, these molecular insights led to the development and increased utilization of clinically impactful genetic testing for congenital long QT syndrome. However, the widespread adoption and potential misinterpretation of the 2015 American College of Medical Genetics and Genomics variant classification and reporting guidelines may have contributed unintentionally to the reduced reporting of common genetic variants, with compelling epidemiological and functional evidence to support a potentially proarrhythmic role in patients with congenital and acquired long QT syndrome. As a result, some genetic testing reports may fail to convey the full extent of a patient's genetic susceptibility for a potentially life-threatening arrhythmia to the ordering healthcare professional. In this white paper, we examine the current classification and reporting (or lack thereof) of potentially proarrhythmic common genetic variants and investigate potential mechanisms to facilitate the reporting of these genetic variants without increasing the risk of diagnostic miscues. © 2018 American Heart Association, Inc.

Patterns of genetic variation in the endangered European mink (Mustela lutreola L., 1761).

PubMed

Cabria, Maria Teresa; Gonzalez, Elena G; Gomez-Moliner, Benjamin J; Michaux, Johan R; Skumatov, Dimitry; Kranz, Andreas; Fournier, Pascal; Palazon, Santiago; Zardoya, Rafael

2015-07-17

The European mink (Mustela lutreola, L. 1761) is a critically endangered mustelid, which inhabits several main river drainages in Europe. Here, we assess the genetic variation of existing populations of this species, including new sampling sites and additional molecular markers (newly developed microsatellite loci specific to European mink) as compared to previous studies. Probabilistic analyses were used to examine genetic structure within and between existing populations, and to infer phylogeographic processes and past demography. According to both mitochondrial and nuclear microsatellite markers, Northeastern (Russia, Estonia and Belarus) and Southeastern (Romania) European populations showed the highest intraspecific diversity. In contrast, Western European (France and Spain) populations were the least polymorphic, featuring a unique mitochondrial DNA haplotype. The high differentiation values detected between Eastern and Western European populations could be the result of genetic drift in the latter due to population isolation and reduction. Genetic differences among populations were further supported by Bayesian clustering and two main groups were confirmed (Eastern vs. Western Europe) along with two contained subgroups at a more local scale (Northeastern vs. Southeastern Europe; France vs. Spain). Genetic data and performed analyses support a historical scenario of stable European mink populations, not affected by Quaternary climate oscillations in the Late Pleistocene, and posterior expansion events following river connections in both North- and Southeastern European populations. This suggests an eastern refuge during glacial maxima (as already proposed for boreal and continental species). In contrast, Western Europe was colonised more recently following either natural expansions or putative human introductions. Low levels of genetic diversity observed within each studied population suggest recent bottleneck events and stress the urgent need for

Allozyme variation of Port-Orford-Cedar (Chamaecyparis lawsoniana): implications for genetic conservation

Treesearch

Constance I. Millar; Kimberly A. Marshall

1991-01-01

Variation at 32 allozyme loci in nine disjunct populations of Part-Orford-cedar (POC) from the California floristic region was measured to estimate the amount and pattern of genetic variability in natural stands. Variation in electrophoretically detectable loci was moderately high, with mean number of alleles per locus = 1.9, 64.9% polymorphic loci, and observed...

Population size is weakly related to quantitative genetic variation and trait differentiation in a stream fish.

PubMed

Wood, Jacquelyn L A; Tezel, Defne; Joyal, Destin; Fraser, Dylan J

2015-09-01

How population size influences quantitative genetic variation and differentiation among natural, fragmented populations remains unresolved. Small, isolated populations might occupy poor quality habitats and lose genetic variation more rapidly due to genetic drift than large populations. Genetic drift might furthermore overcome selection as population size decreases. Collectively, this might result in directional changes in additive genetic variation (VA ) and trait differentiation (QST ) from small to large population size. Alternatively, small populations might exhibit larger variation in VA and QST if habitat fragmentation increases variability in habitat types. We explored these alternatives by investigating VA and QST using nine fragmented populations of brook trout varying 50-fold in census size N (179-8416) and 10-fold in effective number of breeders, Nb (18-135). Across 15 traits, no evidence was found for consistent differences in VA and QST with population size and almost no evidence for increased variability of VA or QST estimates at small population size. This suggests that (i) small populations of some species may retain adaptive potential according to commonly adopted quantitative genetic measures and (ii) populations of varying sizes experience a variety of environmental conditions in nature, however extremely large studies are likely required before any firm conclusions can be made. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Community Involvement in Developing Policies for Genetic Testing: Assessing the Interests and Experiences of Individuals Affected by Genetic Conditions

PubMed Central

Gollust, Sarah E.; Apse, Kira; Fuller, Barbara P.; Miller, Paul Steven; Biesecker, Barbara B.

2005-01-01

Because the introduction of genetic testing into clinical medicine and public health creates concerns for the welfare of individuals affected with genetic conditions, those individuals should have a role in policy decisions about testing. Mechanisms for promoting participation range from membership on advisory committees to community dialogues to surveys that provide evidence for supporting practice guidelines. Surveys can assess the attitudes and the experiences of members of an affected group and thus inform discussions about that community’s concerns regarding the appropriate use of a genetic test. Results of a survey of individuals affected with inherited dwarfism show how data can be used in policy and clinical-practice contexts. Future research of affected communities’ interests should be pursued so that underrepresented voices can be heard. PMID:15623855

A Drosophila model for toxicogenomics: Genetic variation in susceptibility to heavy metal exposure

PubMed Central

Luoma, Sarah E.; St. Armour, Genevieve E.; Thakkar, Esha

2017-01-01

The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag. Drosophila melanogaster is a powerful model that enables genome-wide studies for the identification of allelic variants that contribute to variation in susceptibility to environmental toxins, since the genetic background, environmental rearing conditions and toxic exposure can be precisely controlled. Here, we used extreme QTL mapping in an outbred population derived from the D. melanogaster Genetic Reference Panel to identify alleles associated with resistance to lead and/or cadmium, two ubiquitous environmental toxins that present serious health risks. We identified single nucleotide polymorphisms (SNPs) associated with variation in resistance to both heavy metals as well as SNPs associated with resistance specific to each of them. The effects of these SNPs were largely sex-specific. We applied mutational and RNAi analyses to 33 candidate genes and functionally validated 28 of them. We constructed networks of candidate genes as blueprints for orthologous networks of human genes. The latter not only provided functional contexts for known human targets of heavy metal toxicity, but also implicated novel candidate susceptibility genes. These studies validate Drosophila as a translational toxicogenomics gene discovery system. PMID:28732062

Variation and evolution of male sex combs in Drosophila: nature of selection response and theories of genetic variation for sexual traits.

PubMed

Ahuja, Abha; Singh, Rama S

2008-05-01

We investigated the genetic architecture of variation in male sex comb bristle number, a rapidly evolving secondary sexual character of Drosophila. Twenty-four generations of divergent artificial selection for sex comb bristle number in a heterogeneous population of Drosophila melanogaster resulted in a significant response that was more pronounced in the direction of low bristle numbers. We observed a strong positive correlated response to selection in the corresponding female transverse bristle row. The correlated response in male abdominal and sternopleural bristle numbers, on the other hand, did not follow the same pattern as sex comb bristle number differences between selection lines. Relaxation-of-selection experiments along with mate choice and fecundity assays using the selection lines developed demonstrated the action of stabilizing selection on sex comb bristle number. Our results show (1) substantial genetic variation underlying sex comb bristle number variation; (2) a weak relationship between the sex comb and developmentally related, non-sex bristle systems; and (3) that sexual selection may be a driving force in sex comb evolution, indicating the potential of sex combs to diversify rapidly during population differentiation and speciation. We discuss the implications of these results for theories of genetic variation in display and nondisplay male sex traits.

No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival.

PubMed

Sucheston-Campbell, Lara E; Cannioto, Rikki; Clay, Alyssa I; Etter, John Lewis; Eng, Kevin H; Liu, Song; Battaglia, Sebastiano; Hu, Qiang; Szender, J Brian; Minlikeeva, Albina; Joseph, Janine M; Mayor, Paul; Abrams, Scott I; Segal, Brahm H; Wallace, Paul K; Soh, Kah Teong; Zsiros, Emese; Anton-Culver, Hoda; Bandera, Elisa V; Beckmann, Matthias W; Berchuck, Andrew; Bjorge, Line; Bruegl, Amanda; Campbell, Ian G; Campbell, Shawn Patrice; Chenevix-Trench, Georgia; Cramer, Daniel W; Dansonka-Mieszkowska, Agnieszka; Dao, Fanny; Diergaarde, Brenda; Doerk, Thilo; Doherty, Jennifer A; du Bois, Andreas; Eccles, Diana; Engelholm, Svend Aage; Fasching, Peter A; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Glasspool, Rosalind M; Goodman, Marc T; Gronwald, Jacek; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hillemmanns, Peter; Høgdall, Claus; Høgdall, Estrid V S; Huzarski, Tomasz; Jensen, Allan; Johnatty, Sharon E; Jung, Audrey; Karlan, Beth Y; Klapdor, Reudiger; Kluz, Tomasz; Konopka, Bożena; Kjær, Susanne Krüger; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lester, Jenny; Lubiński, Jan; Levine, Douglas A; Lundvall, Lene; McGuire, Valerie; McNeish, Iain A; Menon, Usha; Modugno, Francesmary; Ness, Roberta B; Orsulic, Sandra; Paul, James; Pearce, Celeste Leigh; Pejovic, Tanja; Pharoah, Paul; Ramus, Susan J; Rothstein, Joseph; Rossing, Mary Anne; Rübner, Matthias; Schildkraut, Joellen M; Schmalfeldt, Barbara; Schwaab, Ira; Siddiqui, Nadeem; Sieh, Weiva; Sobiczewski, Piotr; Song, Honglin; Terry, Kathryn L; Van Nieuwenhuysen, Els; Vanderstichele, Adriaan; Vergote, Ignace; Walsh, Christine S; Webb, Penelope M; Wentzensen, Nicolas; Whittemore, Alice S; Wu, Anna H; Ziogas, Argyrios; Odunsi, Kunle; Chang-Claude, Jenny; Goode, Ellen L; Moysich, Kirsten B

2017-03-01

Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing ( P < 3.5 × 10 -5 ), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. ©2016 AACR . ©2016 American Association for Cancer Research.

Genetic variation in domestic reindeer and wild caribou in Alaska

USGS Publications Warehouse

Cronin, M.; Renecker, L.; Pierson, Barbara J.; Patton, J.C.

1995-01-01

Reindeer were introduced into Alaska 100 years ago and have been maintained as semidomestic livestock. They have had contact with wild caribou herds, including deliberate cross-breeding and mixing in the wild. Reindeer have considerable potential as a domestic animal for meat or velvet antler production, and wild caribou are important to subsistence and sport hunters. Our objective was to quantify the genetic relationships of reindeer and caribou in Alaska. We identified allelic variation among five herds of wild caribou and three herds of reindeer with DNA sequencing and restriction enzymes for three loci: a DQA locus of the major histocompatibility complex (Rata-DQA1), k-casein and the D-loop of mitochondrial DNA. These loci are of interest because of their potential influence on domestic animal performance and the fitness of wild populations. There is considerable genetic variation in reindeer and caribou for all three loci, including five, three and six alleles for DQA, k-casein and D-loop respectively. Most alleles occur in both reindeer and caribou, which may be the result of recent common ancestry or genetic introgression in either direction. However, allele frequencies differ considerably between reindeer and caribou, which suggests that gene flow has been limited.

Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden.

PubMed

Rainey-Smith, Stephanie R; Mazzucchelli, Gavin N; Villemagne, Victor L; Brown, Belinda M; Porter, Tenielle; Weinborn, Michael; Bucks, Romola S; Milicic, Lidija; Sohrabi, Hamid R; Taddei, Kevin; Ames, David; Maruff, Paul; Masters, Colin L; Rowe, Christopher C; Salvado, Olivier; Martins, Ralph N; Laws, Simon M

2018-02-26

The glymphatic system is postulated to be a mechanism of brain Aβ-amyloid clearance and to be most effective during sleep. Ablation of the astrocytic end-feet expressed water-channel protein, Aquaporin-4, in mice, results in impairment of this clearance mechanism and increased brain Aβ-amyloid deposition, suggesting that Aquaporin-4 plays a pivotal role in glymphatic function. Currently there is a paucity of literature regarding the impact of AQP4 genetic variation on sleep, brain Aβ-amyloid burden and their relationship to each other in humans. To address this a cross-sectional observational study was undertaken in cognitively normal older adults from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Genetic variants in AQP4 were investigated with respect to self-reported Pittsburgh Sleep Quality Index sleep parameters, positron emission tomography derived brain Aβ-amyloid burden and whether these genetic variants moderated the sleep-Aβ-amyloid burden relationship. One AQP4 variant, rs72878776, was associated with poorer overall sleep quality, while several SNPs moderated the effect of sleep latency (rs491148, rs9951307, rs7135406, rs3875089, rs151246) and duration (rs72878776, rs491148 and rs2339214) on brain Aβ-amyloid burden. This study suggests that AQP4 genetic variation moderates the relationship between sleep and brain Aβ-amyloid burden, which adds weight to the proposed glymphatic system being a potential Aβ-amyloid clearance mechanism and suggests that AQP4 genetic variation may impair this function. Further, AQP4 genetic variation should be considered when interpreting sleep-Aβ relationships.

The African Genome Variation Project shapes medical genetics in Africa

PubMed Central

Gurdasani, Deepti; Carstensen, Tommy; Tekola-Ayele, Fasil; Pagani, Luca; Tachmazidou, Ioanna; Hatzikotoulas, Konstantinos; Karthikeyan, Savita; Iles, Louise; Pollard, Martin O.; Choudhury, Ananyo; Ritchie, Graham R. S.; Xue, Yali; Asimit, Jennifer; Nsubuga, Rebecca N.; Young, Elizabeth H.; Pomilla, Cristina; Kivinen, Katja; Rockett, Kirk; Kamali, Anatoli; Doumatey, Ayo P.; Asiki, Gershim; Seeley, Janet; Sisay-Joof, Fatoumatta; Jallow, Muminatou; Tollman, Stephen; Mekonnen, Ephrem; Ekong, Rosemary; Oljira, Tamiru; Bradman, Neil; Bojang, Kalifa; Ramsay, Michele; Adeyemo, Adebowale; Bekele, Endashaw; Motala, Ayesha; Norris, Shane A.; Pirie, Fraser; Kaleebu, Pontiano; Kwiatkowski, Dominic; Tyler-Smith, Chris; Rotimi, Charles; Zeggini, Eleftheria; Sandhu, Manjinder S.

2014-01-01

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterisation of African genetic diversity is needed. The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across SSA. We identify new loci under selection, including for malaria and hypertension. We show that modern imputation panels can identify association signals at highly differentiated loci across populations in SSA. Using WGS, we show further improvement in imputation accuracy supporting efforts for large-scale sequencing of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa, showing for the first time that such designs are feasible. PMID:25470054

Global and disease-associated genetic variation in the human Fanconi anemia gene family

PubMed Central

Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.

2014-01-01

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57 240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. PMID:25104853

Temperature-Related Divergence in Experimental Populations of DROSOPHILA MELANOGASTER. I. Genetic and Developmental Basis of Wing Size and Shape Variation

PubMed Central

Cavicchi, Sandro; Guerra, Daniela; Giorgi, Gianfranco; Pezzoli, Cristina

1985-01-01

The effects of environmental temperature on wing size and shape of Drosophila melanogaster were analyzed in populations derived from an Oregon laboratory strain kept at three temperatures (18°, 25°, 28°) for 4 yr. Temperature-directed selection was identified for both wing size and shape. The length of the four longitudinal veins, used as a test for wing size variations in the different populations, appears to be affected by both genetic and maternal influences. Vein expression appears to be dependent upon developmental pattern of the wing: veins belonging to the same compartment are coordinated in their expression and relative position, whereas veins belonging to different compartments are not. Both wing and cell areas show genetic divergence, particularly in the posterior compartment. Cell number seems to compensate for cell size variations. Such compensation is carried out both at the level of single organisms and at the level of population as a whole. The two compartments behave as individual units of selection. PMID:17246257

Genetic sex determination and extinction.

PubMed

Hedrick, Philip W; Gadau, Jürgen; Page, Robert E

2006-02-01

Genetic factors can affect the probability of extinction either by increasing the effect of detrimental variants or by decreasing the potential for future adaptive responses. In a recent paper, Zayed and Packer demonstrate that low variation at a specific locus, the complementary sex determination (csd) locus in Hymenoptera (ants, bees and wasps), can result in a sharply increased probability of extinction. Their findings illustrate situations in which there is a feedback process between decreased genetic variation at the csd locus owing to genetic drift and decreased population growth, resulting in an extreme type of extinction vortex for these ecologically important organisms.

Conservation genetics and geographic patterns of genetic variation of the endangered officinal herb Fritillaria pallidiflora

Treesearch

Zhihao Su; Borong Pan; Stewart C. Sanderson; Xiaolong Jiang; Mingli Zhang

2015-01-01

Fritillaria pallidiflora is an endangered officinal herb distributed in the Tianshan Mountains of northwestern China. We examined its phylogeography to study evolutionary processes and suggest implications for conservation. Six haplotypes were detected based on three chloroplast non-coding spacers (psbA-trnH, rps16, and trnS-trnG); genetic variation mainly occurred...

The Moroccan Genetic Disease Database (MGDD): a database for DNA variations related to inherited disorders and disease susceptibility.

PubMed

Charoute, Hicham; Nahili, Halima; Abidi, Omar; Gabi, Khalid; Rouba, Hassan; Fakiri, Malika; Barakat, Abdelhamid

2014-03-01

National and ethnic mutation databases provide comprehensive information about genetic variations reported in a population or an ethnic group. In this paper, we present the Moroccan Genetic Disease Database (MGDD), a catalogue of genetic data related to diseases identified in the Moroccan population. We used the PubMed, Web of Science and Google Scholar databases to identify available articles published until April 2013. The Database is designed and implemented on a three-tier model using Mysql relational database and the PHP programming language. To date, the database contains 425 mutations and 208 polymorphisms found in 301 genes and 259 diseases. Most Mendelian diseases in the Moroccan population follow autosomal recessive mode of inheritance (74.17%) and affect endocrine, nutritional and metabolic physiology. The MGDD database provides reference information for researchers, clinicians and health professionals through a user-friendly Web interface. Its content should be useful to improve researches in human molecular genetics, disease diagnoses and design of association studies. MGDD can be publicly accessed at http://mgdd.pasteur.ma.

Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

PubMed Central

Barman, Adriana; Assmann, Anne; Richter, Sylvia; Soch, Joram; Schütze, Hartmut; Wüstenberg, Torsten; Deibele, Anna; Klein, Marieke; Richter, Anni; Behnisch, Gusalija; Düzel, Emrah; Zenker, Martin; Seidenbecher, Constanze I.; Schott, Björn H.

2014-01-01

The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans. PMID:24808846

Allozyme and RAPD Analysis of the Genetic Diversity and Geographic Variation in Wild Populations of the American Chestnut (Fagaceae)

Treesearch

Hongwen Huang; Fenny Dane; Thomas L. Kubisiak

1998-01-01

Genetic variation among 12 populations of the American chestnut (Custanea dentata) was investigated. Population genetic parameters estimated from allozyme variation suggest that C. dentata at both the population and species level has narrow genetic diversity as compared to other species in the genus. Average expected heterozygosity...

Molecular identification and genetic variation of varieties of Styphnolobium japonicum (Fabaceae) using SRAP markers.

PubMed

Sun, R X; Zhang, C H; Zheng, Y Q; Zong, Y C; Yu, X D; Huang, P

2016-05-06

Thirty-four Styphnolobium japonicum varieties were analyzed using sequence-related amplified polymorphism (SRAP) markers, to investigate genetic variation and test the effectiveness of SRAP markers in DNA fingerprint establishment. Twelve primer pairs were selected from 120 primer combinations for their reproducibility and high polymorphism. We found a total of 430 amplified fragments, of which 415 fragments were considered polymorphic with an average of 34.58 polymorphic fragments for each primer combination. The percentage of polymorphic fragments was 96.60%, and four primer pairs showed 100% polymorphism. Moreover, simple matched coefficients ranged between 0.68 and 0.89, with an average of 0.785, indicating that the genetic variation among varieties was relatively low. This could be because of the narrow genetic basis of the selected breeding material. Based on the similarity coefficient value of 0.76, the varieties were divided into four major groups. In addition, abundant and clear SRAP fingerprints were obtained and could be used to establish DNA fingerprints. In the DNA fingerprints, each variety had its unique pattern that could be easily distinguished from others. The results demonstrated that 34 varieties of S. japonicum had a relatively narrow genetic variation. Hence, a broadening of the genetic basis of breeding material is necessary. We conclude that establishment of DNA fingerprint is feasible by means of SRAP markers.

Evolving Landscapes: the Effect of Genetic Variation on Salt Marsh Erosion

NASA Astrophysics Data System (ADS)

Bernik, B. M.; Blum, M. J.

2014-12-01

Ecogeomorphic studies have demonstrated that biota can exert influence over geomorphic processes, such as sediment transport, which in turn have biotic consequences and generate complex feedbacks. However, little attention has been paid to the potential for feedback to arise from evolutionary processes as population genetic composition changes in response to changing physical landscapes. In coastal ecosystems experiencing land loss, for example, shoreline erosion entails reduced plant survival and reproduction, and thereby represents a geomorphic response with inherent consequences for evolutionary fitness. To get at this topic, we examined the effect of genetic variation in the saltmarsh grass Spartina alterniflora, a renowned ecosystem engineer, on rates of shoreline erosion. Field transplantation studies and controlled greenhouse experiments were conducted to compare different genotypes from both wild and cultivated populations. Plant traits, soil properties, accretion/subsidence, and rates of land loss were measured. We found significant differences in rates of erosion between field plots occupied by different genotypes. Differences in erosion corresponded to variation in soil properties including critical shear stress and subsidence. Plant traits that differed across genotypes included belowground biomass, root tensile strength, and C:N ratios. Our results demonstrate the importance of genetic variation to salt marsh functioning, elucidating the relationship between evolutionary processes and ecogeomorphic dynamics in these systems. Because evolutionary processes can occur on ecological timescales, the direction and strength of ecogeomorphic feedbacks may be more dynamic than previously accounted for.

MAINTENANCE OF ECOLOGICALLY SIGNIFICANT GENETIC VARIATION IN THE TIGER SWALLOWTAIL BUTTERFLY THROUGH DIFFERENTIAL SELECTION AND GENE FLOW.

PubMed

Bossart, J L; Scriber, J M

1995-12-01

Differential selection in a heterogeneous environment is thought to promote the maintenance of ecologically significant genetic variation. Variation is maintained when selection is counterbalanced by the homogenizing effects of gene flow and random mating. In this study, we examine the relative importance of differential selection and gene flow in maintaining genetic variation in Papilio glaucus. Differential selection on traits contributing to successful use of host plants (oviposition preference and larval performance) was assessed by comparing the responses of southern Ohio, north central Georgia, and southern Florida populations of P. glaucus to three hosts: Liriodendron tulipifera, Magnolia virginiana, and Prunus serotina. Gene flow among populations was estimated using allozyme frequencies from nine polymorphic loci. Significant genetic differentiation was observed among populations for both oviposition preference and larval performance. This differentiation was interpreted to be the result of selection acting on Florida P. glaucus for enhanced use of Magnolia, the prevalent host in Florida. In contrast, no evidence of population differentiation was revealed by allozyme frequencies. F ST -values were very small and Nm, an estimate of the relative strengths of gene flow and genetic drift, was large, indicating that genetic exchange among P. glaucus populations is relatively unrestricted. The contrasting patterns of spatial differentiation for host-use traits and lack of differentiation for electrophoretically detectable variation implies that differential selection among populations will be counterbalanced by gene flow, thereby maintaining genetic variation for host-use traits. © 1995 The Society for the Study of Evolution.

Genetic variation, phenotypic stability, and repeatability of drought response in European larch throughout 50 years in a common garden experiment

PubMed Central

George, Jan-Peter; Grabner, Michael; Karanitsch-Ackerl, Sandra; Mayer, Konrad; Weißenbacher, Lambert; Schueler, Silvio

2017-01-01

Abstract Assessing intra-specific variation in drought stress response is required to mitigate the consequences of climate change on forest ecosystems. Previous studies suggest that European larch (Larix decidua Mill.), an important European conifer in mountainous and alpine forests, is highly vulnerable to drought. In light of this, we estimated the genetic variation in drought sensitivity and its degree of genetic determination in a 50-year-old common garden experiment in the drought-prone northeastern Austria. Tree ring data from larch provenances originating from across the species' natural range were used to estimate the drought reaction in four consecutive drought events (1977, 1981, 1990–1994, and 2003) with extremely low standardized precipitation- and evapotranspiration-index values that affected growth in all provenances. We found significant differences among provenances across the four drought periods for the trees’ capacity to withstand drought (resistance) and for their capacity to reach pre-drought growth levels after drought (resilience). Provenances from the species' northern distribution limit in the Polish lowlands were found to be more drought resistant and showed higher stability across all drought periods than provenances from mountainous habitats at the southern fringe. The degree of genetic determination, as estimated by the repeatability, ranged up to 0.39, but significantly differed among provenances, indicating varying degrees of natural selection at the provenance origin. Generally, the relationship between the provenances’ source climate and drought behavior was weak, suggesting that the contrasting patterns of drought response are a result of both genetic divergence out of different refugial lineages and local adaptation to summer or winter drought conditions. Our analysis suggests that European larch posseses high genetic variation among and within provenances that can be used for assisted migration and breeding programs. PMID

Natural genetic variation in social environment choice: context-dependent gene-environment correlation in Drosophila melanogaster.

PubMed

Saltz, Julia B

2011-08-01

Gene-environment correlation (rGE) occurs when an individual's genotype determines its choice of environment, generating a correlation between environment and genotype frequency. In particular, social rGE, caused by genetic variation in social environment choice, can critically determine both individual development and the course of social selection. Despite its foundational role in social evolution and developmental psychology theory, natural genetic variation in social environment choice has scarcely been examined empirically. Drosophila melanogaster provides an ideal system for investigating social rGE. Flies live socially in nature and have many opportunities to make social decisions; and natural, heterozygous genotypes may be replicated, enabling comparisons between genotypes across environments. Using this approach, I show that all aspects of social environment choice vary among natural genotypes, demonstrating pervasive social rGE. Surprisingly, genetic variation in group-size preference was density dependent, indicating that the behavioral and evolutionary consequences of rGE may depend on the context in which social decisions are made. These results provide the first detailed investigation of social rGE, and illustrate that that genetic variation may influence organismal performance by specifying the environment in which traits are expressed. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Genetic variation associated with cardiovascular risk in autoimmune diseases

PubMed Central

Perrotti, Pedro P.; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P.; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L.; Lasanta, María L.; Marsal, Sara; Julià, Antonio

2017-01-01

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity. PMID:28982122

Genetic variation of the weaning weight of beef cattle as a function of accumulated heat stress.

PubMed

Santana, M L; Bignardi, A B; Eler, J P; Ferraz, J B S

2016-04-01

The objective of this study was to identify the genetic variation in the weaning weight (WW) of beef cattle as a function of heat stress. The WWs were recorded at approximately 205 days of age in three Brazilian beef cattle populations: Nelore (93,616), Brangus (18,906) and Tropical Composite (62,679). In view of the cumulative nature of WW, the effect of heat stress was considered as the accumulation of temperature and humidity index units (ACTHI) from the animal's birth to weaning. A reaction norm model was used to estimate the (co)variance components of WW across the ACTHI scale. The accumulation of THI units from birth to weaning negatively affected the WW. The definition of accumulated THI units as an environmental descriptor permitted to identify important genetic variation in the WW as a function of heat stress. As evidence of genotype by environment interaction, substantial heterogeneity was observed in the (co)variance components for WW across the environmental gradient. In this respect, the best animals in less stressful environments are not necessarily the best animals in more stressful environments. Furthermore, the response to selection for WW is expected to be lower in more stressful environments. © 2015 Blackwell Verlag GmbH.

Genetic Variation in the Acorn Barnacle from Allozymes to Population Genomics

PubMed Central

Flight, Patrick A.; Rand, David M.

2012-01-01

Understanding the patterns of genetic variation within and among populations is a central problem in population and evolutionary genetics. We examine this question in the acorn barnacle, Semibalanus balanoides, in which the allozyme loci Mpi and Gpi have been implicated in balancing selection due to varying selective pressures at different spatial scales. We review the patterns of genetic variation at the Mpi locus, compare this to levels of population differentiation at mtDNA and microsatellites, and place these data in the context of genome-wide variation from high-throughput sequencing of population samples spanning the North Atlantic. Despite considerable geographic variation in the patterns of selection at the Mpi allozyme, this locus shows rather low levels of population differentiation at ecological and trans-oceanic scales (FST ∼ 5%). Pooled population sequencing was performed on samples from Rhode Island (RI), Maine (ME), and Southwold, England (UK). Analysis of more than 650 million reads identified approximately 335,000 high-quality SNPs in 19 million base pairs of the S. balanoides genome. Much variation is shared across the Atlantic, but there are significant examples of strong population differentiation among samples from RI, ME, and UK. An FST outlier screen of more than 22,000 contigs provided a genome-wide context for interpretation of earlier studies on allozymes, mtDNA, and microsatellites. FST values for allozymes, mtDNA and microsatellites are close to the genome-wide average for random SNPs, with the exception of the trans-Atlantic FST for mtDNA. The majority of FST outliers were unique between individual pairs of populations, but some genes show shared patterns of excess differentiation. These data indicate that gene flow is high, that selection is strong on a subset of genes, and that a variety of genes are experiencing diversifying selection at large spatial scales. This survey of polymorphism in S. balanoides provides a number of

Female guppies agree to differ: phenotypic and genetic variation in mate-choice behavior and the consequences for sexual selection.

PubMed

Brooks, R; Endler, J A

2001-08-01

Variation among females in mate choice may influence evolution by sexual selection. The genetic basis of this variation is of interest because the elaboration of mating preferences requires additive genetic variation in these traits. Here we measure the repeatability and heritability of two components of female choosiness (responsiveness and discrimination) and of female preference functions for the multiple ornaments borne by male guppies (Poecilia reticulata). We show that there is significant repeatable variation in both components of choosiness and in some preference functions but not in others. There appear to be several male ornaments that females find uniformly attractive and others for which females differ in preference. One consequence is that there is no universally attractive male phenotype. Only responsiveness shows significant additive genetic variation. Variation in responsiveness appears to mask variation in discrimination and some preference functions and may be the most biologically relevant source of phenotypic and genetic variation in mate-choice behavior. To test the potential evolutionary importance of the phenotypic variation in mate choice that we report, we estimated the opportunity for and the intensity of sexual selection under models of mate choice that excluded and that incorporated individual female variation. We then compared these estimates with estimates based on measured mating success. Incorporating individual variation in mate choice generally did not predict the outcome of sexual selection any better than models that ignored such variation.

Evolutionary genetics of maternal effects

PubMed Central

Wolf, Jason B.; Wade, Michael J.

2016-01-01

Maternal genetic effects (MGEs), where genes expressed by mothers affect the phenotype of their offspring, are important sources of phenotypic diversity in a myriad of organisms. We use a single‐locus model to examine how MGEs contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations. We elucidate the influence of MGEs by examining the offspring genotype‐phenotype relationship, which determines how MGEs affect evolutionary dynamics in response to selection on offspring phenotypes. This approach reveals important results that are not apparent from classic quantitative genetic treatments of MGEs. We show that additive and dominance MGEs make different contributions to evolutionary dynamics and patterns of variation, which are differentially affected by inbreeding. Dominance MGEs make the offspring genotype‐phenotype relationship frequency dependent, resulting in the appearance of negative frequency‐dependent selection, while additive MGEs contribute a component of parent‐of‐origin dependent variation. Inbreeding amplifies the contribution of MGEs to the additive genetic variance and, therefore enhances their evolutionary response. Considering evolutionary dynamics of allele frequency change on an adaptive landscape, we show that this landscape differs from the mean fitness surface, and therefore, under some condition, fitness peaks can exist but not be “available” to the evolving population. PMID:26969266

Global and disease-associated genetic variation in the human Fanconi anemia gene family.

PubMed

Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J

2014-12-20

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetic variation in Dip5, an amino acid permease, and Pdr5, a multiple drug transporter, regulates glyphosate resistance in S. cerevisiae.

PubMed

Rong-Mullins, Xiaoqing; Ravishankar, Apoorva; McNeal, Kirsten A; Lonergan, Zachery R; Biega, Audrey C; Creamer, J Philip; Gallagher, Jennifer E G

2017-01-01

S. cerevisiae from different environments are subject to a wide range of selective pressures, whether intentional or by happenstance. Chemicals classified by their application, such as herbicides, fungicides and antibiotics, can affect non-target organisms. First marketed as RoundUp™, glyphosate is the most widely used herbicide. In plants, glyphosate inhibits EPSPS, of the shikimate pathway, which is present in many organisms but lacking in mammals. The shikimate pathway produces chorismate which is the precursor to all the aromatic amino acids, para-aminobenzoic acid, and Coenzyme Q10. Crops engineered to be resistant to glyphosate contain a homolog of EPSPS that is not bound by glyphosate. Here, we show that S. cerevisiae has a wide-range of glyphosate resistance. Sequence comparison between the target proteins, i.e., the plant EPSPS and the yeast orthologous protein Aro1, predicted that yeast would be resistant to glyphosate. However, the growth variation seen in the subset of yeast tested was not due to polymorphisms within Aro1, instead, it was caused by genetic variation in an ABC multiple drug transporter, Pdr5, and an amino acid permease, Dip5. Using genetic variation as a probe into glyphosate response, we uncovered mechanisms that contribute to the transportation of glyphosate in and out of the cell. Taking advantage of the natural genetic variation within yeast and measuring growth under different conditions that would change the use of the shikimate pathway, we uncovered a general transport mechanism of glyphosate into eukaryotic cells.

Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome

PubMed Central

Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O’Connor, Timothy D.; Abecasis, Gonçalo R.; Wojcik, Genevieve L; Gignoux, Christopher R.; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E.; Bustamante, Carlos; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Qin, Zhaohui S.; Preethi Boorgula, Meher; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Ruczinski, Ingo; Scott, Alan F.; Taub, Margaret A.; Vergara, Candelaria; Levin, Albert M.; Padhukasahasram, Badri; Williams, L. Keoki; Dunston, Georgia M.; Faruque, Mezbah U.; Gietzen, Kimberly; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-Youn A.; Kumar, Rajesh; Schleimer, Robert; De La Vega, Francisco M.; Shringarpure, Suyash S.; Musharoff, Shaila; Burchard, Esteban G.; Eng, Celeste; Hernandez, Ryan D.; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Maul, Pissamai; Maul, Trevor; Watson, Harold; Ilma Araujo, Maria; Riccio Oliveira, Ricardo; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Francisco Herrera-Paz, Edwin; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Marina Vasquez, Olga; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria

2017-01-01

A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an ‘African Diaspora Power Chip’ (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry. PMID:28429804

Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics.

PubMed

Sirugo, Giorgio; Hennig, Branwen J; Adeyemo, Adebowale A; Matimba, Alice; Newport, Melanie J; Ibrahim, Muntaser E; Ryckman, Kelli K; Tacconelli, Alessandra; Mariani-Costantini, Renato; Novelli, Giuseppe; Soodyall, Himla; Rotimi, Charles N; Ramesar, Raj S; Tishkoff, Sarah A; Williams, Scott M

2008-07-01

Africa is the ultimate source of modern humans and as such harbors more genetic variation than any other continent. For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease.

The Genetics Underlying Natural Variation in the Biotic Interactions of Arabidopsis thaliana: The Challenges of Linking Evolutionary Genetics and Community Ecology.

PubMed

Roux, F; Bergelson, J

2016-01-01

In the context of global change, predicting the responses of plant communities in an ever-changing biotic environment calls for a multipronged approach at the interface of evolutionary genetics and community ecology. However, our understanding of the genetic basis of natural variation involved in mediating biotic interactions, and associated adaptive dynamics of focal plants in their natural communities, is still in its infancy. Here, we review the genetic and molecular bases of natural variation in the response to biotic interactions (viruses, bacteria, fungi, oomycetes, herbivores, and plants) in the model plant Arabidopsis thaliana as well as the adaptive value of these bases. Among the 60 identified genes are a number that encode nucleotide-binding site leucine-rich repeat (NBS-LRR)-type proteins, consistent with early examples of plant defense genes. However, recent studies have revealed an extensive diversity in the molecular mechanisms of defense. Many types of genetic variants associate with phenotypic variation in biotic interactions, even among the genes of large effect that tend to be identified. In general, we found that (i) balancing selection rather than directional selection explains the observed patterns of genetic diversity within A. thaliana and (ii) the cost/benefit tradeoffs of adaptive alleles can be strongly dependent on both genomic and environmental contexts. Finally, because A. thaliana rarely interacts with only one biotic partner in nature, we highlight the benefit of exploring diffuse biotic interactions rather than tightly associated host-enemy pairs. This challenge would help to improve our understanding of coevolutionary quantitative genetics within the context of realistic community complexity. © 2016 Elsevier Inc. All rights reserved.

Geographic variation in genetic and demographic performance: new insights from an old biogeographical paradigm.

PubMed

Pironon, Samuel; Papuga, Guillaume; Villellas, Jesús; Angert, Amy L; García, María B; Thompson, John D

2017-11-01

The 'centre-periphery hypothesis' (CPH) is a long-standing postulate in ecology that states that genetic variation and demographic performance of a species decrease from the centre to the edge of its geographic range. This hypothesis is based on an assumed concordance between geographical peripherality and ecological marginality such that environmental conditions become harsher towards the limits of a species range. In this way, the CPH sets the stage for understanding the causes of distribution limits. To date, no study has examined conjointly the consistency of these postulates. In an extensive literature review we discuss the birth and development of the CPH and provide an assessment of the CPH by reviewing 248 empirical studies in the context of three main themes. First, a decrease in species occurrence towards their range limits was observed in 81% of studies, while only 51% demonstrated reduced abundance of individuals. A decline in genetic variation, increased differentiation among populations and higher rates of inbreeding were demonstrated by roughly one in two studies (47, 45 and 48%, respectively). However, demographic rates, size and population performance less often followed CPH expectations (20-30% of studies). We highlight the impact of important methodological, taxonomic, and biogeographical biases on such validation rates. Second, we found that geographic and ecological marginality gradients are not systematically concordant, which casts doubt on the reliability of a main assumption of the CPH. Finally, we attempt to disentangle the relative contribution of geographical, ecological and historical processes on the spatial distribution of genetic and demographic parameters. While ecological marginality gradients explain variation in species' demographic performance better than geographic gradients, contemporary and historical factors may contribute interactively to spatial patterns of genetic variation. We thereby propose a framework that integrates

The Genetic Basis of Natural Variation in Kernel Size and Related Traits Using a Four-Way Cross Population in Maize.

PubMed

Chen, Jiafa; Zhang, Luyan; Liu, Songtao; Li, Zhimin; Huang, Rongrong; Li, Yongming; Cheng, Hongliang; Li, Xiantang; Zhou, Bo; Wu, Suowei; Chen, Wei; Wu, Jianyu; Ding, Junqiang

2016-01-01

Kernel size is an important component of grain yield in maize breeding programs. To extend the understanding on the genetic basis of kernel size traits (i.e., kernel length, kernel width and kernel thickness), we developed a set of four-way cross mapping population derived from four maize inbred lines with varied kernel sizes. In the present study, we investigated the genetic basis of natural variation in seed size and other components of maize yield (e.g., hundred kernel weight, number of rows per ear, number of kernels per row). In total, ten QTL affecting kernel size were identified, three of which (two for kernel length and one for kernel width) had stable expression in other components of maize yield. The possible genetic mechanism behind the trade-off of kernel size and yield components was discussed.

The Genetic Basis of Natural Variation in Kernel Size and Related Traits Using a Four-Way Cross Population in Maize

PubMed Central

Liu, Songtao; Li, Zhimin; Huang, Rongrong; Li, Yongming; Cheng, Hongliang; Li, Xiantang; Zhou, Bo; Wu, Suowei; Chen, Wei; Wu, Jianyu; Ding, Junqiang

2016-01-01

Kernel size is an important component of grain yield in maize breeding programs. To extend the understanding on the genetic basis of kernel size traits (i.e., kernel length, kernel width and kernel thickness), we developed a set of four-way cross mapping population derived from four maize inbred lines with varied kernel sizes. In the present study, we investigated the genetic basis of natural variation in seed size and other components of maize yield (e.g., hundred kernel weight, number of rows per ear, number of kernels per row). In total, ten QTL affecting kernel size were identified, three of which (two for kernel length and one for kernel width) had stable expression in other components of maize yield. The possible genetic mechanism behind the trade-off of kernel size and yield components was discussed. PMID:27070143

Increased genetic variation and evolutionary potential drive the success of an invasive grass

PubMed Central

Lavergne, Sébastien; Molofsky, Jane

2007-01-01

Despite the increasing biological and economic impacts of invasive species, little is known about the evolutionary mechanisms that favor geographic range expansion and evolution of invasiveness in introduced species. Here, we focus on the invasive wetland grass Phalaris arundinacea L. and document the evolutionary consequences that resulted from multiple and uncontrolled introductions into North America of genetic material native to different European regions. Continental-scale genetic variation occurring in reed canarygrass' European range has been reshuffled and recombined within North American introduced populations, giving rise to a number of novel genotypes. This process alleviated genetic bottlenecks throughout reed canarygrass' introduced range, including in peripheral populations, where depletion of genetic diversity is expected and is observed in the native range. Moreover, reed canarygrass had higher genetic diversity and heritable phenotypic variation in its invasive range relative to its native range. The resulting high evolutionary potential of invasive populations allowed for rapid selection of genotypes with higher vegetative colonization ability and phenotypic plasticity. Our results show that repeated introductions of a single species may inadvertently create harmful invaders with high adaptive potential. Such invasive species may be able to evolve in response to changing climate, allowing them to have increasing impact on native communities and ecosystems in the future. More generally, multiple immigration events may thus trigger future adaptation and geographic spread of a species population by preventing genetic bottlenecks and generating genetic novelties through recombination. PMID:17360447

Increased genetic variation and evolutionary potential drive the success of an invasive grass.

PubMed

Lavergne, Sébastien; Molofsky, Jane

2007-03-06

Despite the increasing biological and economic impacts of invasive species, little is known about the evolutionary mechanisms that favor geographic range expansion and evolution of invasiveness in introduced species. Here, we focus on the invasive wetland grass Phalaris arundinacea L. and document the evolutionary consequences that resulted from multiple and uncontrolled introductions into North America of genetic material native to different European regions. Continental-scale genetic variation occurring in reed canarygrass' European range has been reshuffled and recombined within North American introduced populations, giving rise to a number of novel genotypes. This process alleviated genetic bottlenecks throughout reed canarygrass' introduced range, including in peripheral populations, where depletion of genetic diversity is expected and is observed in the native range. Moreover, reed canarygrass had higher genetic diversity and heritable phenotypic variation in its invasive range relative to its native range. The resulting high evolutionary potential of invasive populations allowed for rapid selection of genotypes with higher vegetative colonization ability and phenotypic plasticity. Our results show that repeated introductions of a single species may inadvertently create harmful invaders with high adaptive potential. Such invasive species may be able to evolve in response to changing climate, allowing them to have increasing impact on native communities and ecosystems in the future. More generally, multiple immigration events may thus trigger future adaptation and geographic spread of a species population by preventing genetic bottlenecks and generating genetic novelties through recombination.

Genetic variation in Northern Thailand Hill Tribes: origins and relationships with social structure and linguistic differences

PubMed Central

Besaggio, Davide; Fuselli, Silvia; Srikummool, Metawee; Kampuansai, Jatupol; Castrì, Loredana; Tyler-Smith, Chris; Seielstad, Mark; Kangwanpong, Daoroong; Bertorelle, Giorgio

2007-01-01

Background Ethnic minorities in Northern Thailand, often referred to as Hill Tribes, are considered an ideal model to study the different genetic impact of sex-specific migration rates expected in matrilocal (women remain in their natal villages after the marriage and men move to their wife's village) and patrilocal societies (the opposite is true). Previous studies identified such differences, but little is known about the possible interaction with another cultural factor that may potentially affect genetic diversity, i.e. linguistic differences. In addition, Hill Tribes started to migrate to Thailand in the last centuries from different Northern areas, but the history of these migrations, the level of genetic legacy with their places of origin, and the possible confounding effects related to this migration history in the patterns of genetic diversity, have not been analysed yet. Using both original and published data on the Hill Tribes and several other Asian populations, we focused on all these aspects. Results Genetic variation within population at mtDNA is lower in matrilocal, compared to patrilocal, tribes. The opposite is true for Y-chromosome microsatellites within the Sino-Tibetan linguistic family, but Hmong-Mien speaking patrilocal groups have a genetic diversity very similar to the matrilocal samples. Population divergence ranges between 5% and 14% at mtDNA sequences, and between 5% and 36% at Y- chromosomes STRs, and follows the sex-specific differences expected in patrilocal and matrilocal tribes. On the average, about 2 men and 14 women, and 4 men and 4 women, are exchanged in patrilocal and matrilocal tribes every generation, respectively. Most of the Hill Tribes in Thailand seem to preserve a genetic legacy with their likely geographic origin, with children adoption probably affecting this pattern in one tribe. Conclusion Overall, the sex specific genetic signature of different postmarital habits of residence in the Hill Tribes is robust. However

Incorporating latitudinal and central–marginal trends in assessing genetic variation across species ranges

Treesearch

Qinfeng Guo

2012-01-01

The genetic variation across a species’ range is an important factor in speciation and conservation, yet searching for general patterns and underlying causes remains challenging. While the majority of comparisons between central and marginal populations have revealed a general central–marginal (C-M) decline in genetic diversity, others show no clear pattern. Similarly...

Genetic and environmental causes of variation in gestation length of Jersey crossbred cattle.

PubMed

Kumar, Anshuman; Mandal, Ajoy; Gupta, A K; Ratwan, Poonam

2016-04-01

The objective of this study was to investigate the effect of genetic and non-genetic factors and estimate the genetic parameter for gestation length (GL) of Jersey crossbred cattle. The data included the 986 parturition records on Jersey crossbred cattle maintained at the Eastern Regional Station of ICAR-National Dairy Research Institute, Kalyani, West Bengal, India during 36 years (1978-2013). The data were analyzed applying mixed model least square technique considering the fixed effects of genetic group, season of calving, period of calving, parity of animal, birth weight, and sex of calf born from animal. The effect of sire was included as a random effect in the model. The genetic group of animal, season of calving, parity of animal, and birth weight of calf born were found to be a significant source of variation in the GL, whereas the period of calving and sex of calf did not affect this trait. Cows with <50% and >62.5% Jersey inheritance had the shortest and longest GLs, respectively. Cows calved in summer and rainy season had shorter GL than those calved in the winter season. Older cows in 4(th) parity carried calves for longer days than the cows in 1(st) parity. The increase in calf birth weight significantly (p<0.01) contributed to a linear increase in GL value in this study. The heritability estimate of GL was 0.24±0.08. It can be concluded that selection for lower GL without distressing future growth of calf can be used to reduce calving difficulty, but a very small standard deviation of GL limits the benefit. Moreover, more accurate prediction of calving date will help in better management and health care of pregnant animals.

Sex-dependent selection differentially shapes genetic variation on and off the guppy Y chromosome.

PubMed

Postma, Erik; Spyrou, Nicolle; Rollins, Lee Ann; Brooks, Robert C

2011-08-01

Because selection is often sex-dependent, alleles can have positive effects on fitness in one sex and negative effects in the other, resulting in intralocus sexual conflict. Evolutionary theory predicts that intralocus sexual conflict can drive the evolution of sex limitation, sex-linkage, and sex chromosome differentiation. However, evidence that sex-dependent selection results in sex-linkage is limited. Here, we formally partition the contribution of Y-linked and non-Y-linked quantitative genetic variation in coloration, tail, and body size of male guppies (Poecilia reticulata)-traits previously implicated as sexually antagonistic. We show that these traits are strongly genetically correlated, both on and off the Y chromosome, but that these correlations differ in sign and magnitude between both parts of the genome. As predicted, variation in attractiveness was found to be associated with the Y-linked, rather than with the non-Y-linked component of genetic variation in male ornamentation. These findings show how the evolution of Y-linkage may be able to resolve sexual conflict. More generally, they provide unique insight into how sex-specific selection has the potential to differentially shape the genetic architecture of fitness traits across different parts of the genome. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Genetic Variation in Dopamine Pathways Differentially Associated with Smoking Progression in Adolescence

ERIC Educational Resources Information Center

Laucht, Manfred; Becker, Katja; Frank, Josef; Schmidt, Martin H.; Esser, Gunter; Treutlein, Jens; Skowronek, Markus H.; Schumann, Gunter

2008-01-01

A study examines whether genetic variation in dopamine pathways differentially associate with smoking progression in adolescence. Results indicate the influence of specific dopamine genes in different stages of smoking progression in adolescents.

Landscape genetics and limiting factors

Treesearch

Samuel A. Cushman; Andrew J. Shirk; Erin L. Landguth

2013-01-01

Population connectivity is mediated by the movement of organisms or propagules through landscapes. However, little is known about how variation in the pattern of landscape mosaics affects the detectability of landscape genetic relationships. The goal of this paper is to explore the impacts of limiting factors on landscape genetic processes using simulation...

Indirect Genetic Effects and the Spread of Infectious Disease: Are We Capturing the Full Heritable Variation Underlying Disease Prevalence?

PubMed Central

Lipschutz-Powell, Debby; Woolliams, John A.; Bijma, Piter; Doeschl-Wilson, Andrea B.

2012-01-01

Reducing disease prevalence through selection for host resistance offers a desirable alternative to chemical treatment. Selection for host resistance has proven difficult, however, due to low heritability estimates. These low estimates may be caused by a failure to capture all the relevant genetic variance in disease resistance, as genetic analysis currently is not taylored to estimate genetic variation in infectivity. Host infectivity is the propensity of transmitting infection upon contact with a susceptible individual, and can be regarded as an indirect effect to disease status. It may be caused by a combination of physiological and behavioural traits. Though genetic variation in infectivity is difficult to measure directly, Indirect Genetic Effect (IGE) models, also referred to as associative effects or social interaction models, allow the estimation of this variance from more readily available binary disease data (infected/non-infected). We therefore generated binary disease data from simulated populations with known amounts of variation in susceptibility and infectivity to test the adequacy of traditional and IGE models. Our results show that a conventional model fails to capture the genetic variation in infectivity inherent in populations with simulated infectivity. An IGE model, on the other hand, does capture some of the variation in infectivity. Comparison with expected genetic variance suggests that there is scope for further methodological improvement, and that potential responses to selection may be greater than values presented here. Nonetheless, selection using an index of estimated direct and indirect breeding values was shown to have a greater genetic selection differential and reduced future disease risk than traditional selection for resistance only. These findings suggest that if genetic variation in infectivity substantially contributes to disease transmission, then breeding designs which explicitly incorporate IGEs might help reduce disease

Genetic regulation of the variation of circulating insulin-like growth factors and leptin in human pedigrees.

PubMed

Pantsulaia, Ia; Pantsulaia, I; Trofimov, Svetlana; Kobyliansky, Eugene; Livshits, Gregory

2005-07-01

Recent literature has shown that circulating levels of insulin-like growth factor I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk assessment of several chronic diseases including cancer, cardiovascular disease, diabetes mellitus and so on. The present study examined the extent of genetic and environmental influences on the populational variation of circulating IGF-I and IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative genetic analysis showed that the IGF-I variation was appreciably attributable to genetic effects (47.1% +/- 9.0%), whereas for IGF-BP-1, only 23.3% +/- 7.8% of the interindividual variation was explained by genetic determinants. Common familial environment factors contributed significantly only to IGF-BP-1 variation (23.3% +/- 7.8%). In addition, we examined the covariations between these molecules and between them and IGF-BP-3 and leptin that were previously studied in the same sample. The analysis revealed that the pleiotropic genetic effects were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 +/- 0.04 and 0.15 +/- 0.05. The common environmental factors were consistently a significant source of correlation between all pairs (barring IGF-I and leptin) of the studied molecules; they were the sole predictors of correlation between IGF-I and IGF-BP-1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of specific and common genetic pathways that in combination determine a substantial proportion of the circulating variation of these molecules.

A mutational approach for the detection of genetic factors affecting seed size in maize.

PubMed

Sangiorgio, Stefano; Carabelli, Laura; Gabotti, Damiano; Manzotti, Priscilla Sofia; Persico, Martina; Consonni, Gabriella; Gavazzi, Giuseppe

2016-12-01

Genes influencing seed size. The designation emp (empty pericarp) refers to a group of defective kernel mutants that exhibit a drastic reduction in endosperm tissue production. They allow the isolation of genes controlling seed development and affecting seed size. Nine independently isolated emp mutants have been analyzed in this study and in all cases longitudinal sections of mature seeds revealed the absence of morphogenesis in the embryo proper, an observation that correlates with their failure to germinate. Complementation tests with the nine emp mutants, crossed inter se in all pairwise combinations, identified complementing and non-complementing pairs in the F 1 progenies. Data were then validated in the F 2 /F 3 generations. Mutant chromosomal location was also established. Overall our study has identified two novel emp genes and a novel allele at the previously identified emp4 gene. The introgression of single emp mutants in a different genetic background revealed the existence of a cryptic genetic variation (CGV) recognizable as a variable increase in the endosperm tissue. The unmasking of CGV by introducing single mutants in different genetic backgrounds is the result of the interaction of the emp mutants with a suppressor that has no obvious phenotype of its own and is present in the genetic background of the inbred lines into which the emp mutants were transferred. On the basis of these results, emp mutants could be used as tools for the detection of genetic factors that enhance the amount of endosperm tissue in the maize kernel and which could thus become valuable targets to exploit in future breeding programs.

Ecology has contrasting effects on genetic variation within species versus rates of molecular evolution across species in water beetles.

PubMed

Fujisawa, Tomochika; Vogler, Alfried P; Barraclough, Timothy G

2015-01-22

Comparative analysis is a potentially powerful approach to study the effects of ecological traits on genetic variation and rate of evolution across species. However, the lack of suitable datasets means that comparative studies of correlates of genetic traits across an entire clade have been rare. Here, we use a large DNA-barcode dataset (5062 sequences) of water beetles to test the effects of species ecology and geographical distribution on genetic variation within species and rates of molecular evolution across species. We investigated species traits predicted to influence their genetic characteristics, such as surrogate measures of species population size, latitudinal distribution and habitat types, taking phylogeny into account. Genetic variation of cytochrome oxidase I in water beetles was positively correlated with occupancy (numbers of sites of species presence) and negatively with latitude, whereas substitution rates across species depended mainly on habitat types, and running water specialists had the highest rate. These results are consistent with theoretical predictions from nearly-neutral theories of evolution, and suggest that the comparative analysis using large databases can give insights into correlates of genetic variation and molecular evolution.

Genetic variation in bison (bison bison) subspecies and cattle (Bos taurus) breeds and subspecies

USDA-ARS?s Scientific Manuscript database

Genetic variation was quantified at 29 polymorphic microsatellite DNA loci in nine herds of plains bison (Bison bison bison), three herds of wood bison (B.b. athabascae), fourteen breeds of taurine cattle (Bos Taurus Taurus), and two breeds of indicine cattle (Bos Taurus indicus). Genetic distances,...

Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans.

PubMed

Rodrigues, Sarina M; Saslow, Laura R; Garcia, Natalia; John, Oliver P; Keltner, Dacher

2009-12-15

Oxytocin, a peptide that functions as both a hormone and neurotransmitter, has broad influences on social and emotional processing throughout the body and the brain. In this study, we tested how a polymorphism (rs53576) of the oxytocin receptor relates to two key social processes related to oxytocin: empathy and stress reactivity. Compared with individuals homozygous for the G allele of rs53576 (GG), individuals with one or two copies of the A allele (AG/AA) exhibited lower behavioral and dispositional empathy, as measured by the "Reading the Mind in the Eyes" Test and an other-oriented empathy scale. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals, as determined by heart rate response during a startle anticipation task and an affective reactivity scale. Our results provide evidence of how a naturally occurring genetic variation of the oxytocin receptor relates to both empathy and stress profiles.

Genetic variation patterns of American chestnut populations at EST-SSRs

Treesearch

Oliver Gailing; C. Dana Nelson

2017-01-01

The objective of this study is to analyze patterns of genetic variation at genic expressed sequence tag - simple sequence repeats (EST-SSRs) and at chloroplast DNA markers in populations of American chestnut (Castanea dentata Borkh.) to assist in conservation and breeding efforts. Allelic diversity at EST-SSRs decreased significantly from southwest to northeast along...

Integrating common and rare genetic variation in diverse human populations.

PubMed

Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E

2010-09-02

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.

Low Genetic Variation of Red-Crowned Cranes on Hokkaido Island, Japan, Over the Hundred Years.

PubMed

Akiyama, Takuya; Momose, Kunikazu; Onuma, Manabu; Matsumoto, Fumio; Masuda, Ryuichi

2017-06-01

The red-crowned crane (Grus japonensis) is recognized internationally as an endangered species. Migratory populations breed in eastern Russia and northeastern China, whereas the resident population inhabits the island of Hokkaido, Japan. Although the population inhabiting Hokkaido had experienced a severe bottleneck by the end of the 19th century, the population size has recovered to about 1500 and continues to increase now thanks to conservation efforts. A previous study reported that no marked genetic differences were seen in the island population, and that the genetic variation of the whole population on Hokkaido was lower than that of the continental population. However, the precise genetic structure of the island population in the past or near present remains unclear. To better understand the spatiotemporal changes in the genetic structure of the island population, we performed mitochondrial DNA (mtDNA) analyses using stuffed specimens (years 1878-2001) and tissue or blood samples (years 1970-2014). We found three haplotypes in the island population, one of which was a novel mtDNA haplotype in 1997 and 2007 samples. In addition, there was no clear difference in the haplotype frequency through the time span. These results suggest that the low genetic variation of the island population persisted for the last hundred years. It is thus nearly impossible for the island population to recover its genetic variation in isolation. Conservation plans for this species should therefore include the promotion of genetic exchanges between the continental and island populations, such as through artificial introduction to Hokkaido.

Functional and genetic analysis of haplotypic sequence variation at the nicastrin genomic locus

PubMed Central

Hamilton, Gillian; Killick, Richard; Lambert, Jean-Charles; Amouyel, Philippe; Carrasquillo, Minerva M.; Pankratz, V. Shane; Graff-Radford, Neill R.; Dickson, Dennis W.; Petersen, Ronald C.; Younkin, Steven G.; Powell, John F.; Wade-Martins, Richard

2013-01-01

Nicastrin (NCSTN) is a component of the γ-secretase complex and therefore potentially a candidate risk gene for Alzheimer's disease. Here, we have developed a novel functional genomics methodology to express common locus haplotypes to assess functional differences. DNA recombination was used to engineer 5 bacterial artificial chromosomes (BACs) to each express a different haplotype of the NCSTN locus. Each NCSTN-BAC was delivered to knockout nicastrin (Ncstn−/−) cells and clonal NCSTN-BAC+/Ncstn−/− cell lines were created for functional analyses. We showed that all NCSTN-BAC haplotypes expressed nicastrin protein and rescued γ-secretase activity and amyloid beta (Aβ) production in NCSTN-BAC+/Ncstn−/− lines. We then showed that genetic variation at the NCSTN locus affected alternative splicing in human postmortem brain tissue. However, there was no robust functional difference between clonal cell lines rescued by each of the 5 different haplotypes. Finally, there was no statistically significant association of NCSTN with disease risk in the 4 cohorts. We therefore conclude that it is unlikely that common variation at the NCSTN locus is a risk factor for Alzheimer's disease. PMID:22405046

Genetic variation maintained in multilocus models of additive quantitative traits under stabilizing selection.

PubMed Central

Bürger, R; Gimelfarb, A

1999-01-01

Stabilizing selection for an intermediate optimum is generally considered to deplete genetic variation in quantitative traits. However, conflicting results from various types of models have been obtained. While classical analyses assuming a large number of independent additive loci with individually small effects indicated that no genetic variation is preserved under stabilizing selection, several analyses of two-locus models showed the contrary. We perform a complete analysis of a generalization of Wright's two-locus quadratic-optimum model and investigate numerically the ability of quadratic stabilizing selection to maintain genetic variation in additive quantitative traits controlled by up to five loci. A statistical approach is employed by choosing randomly 4000 parameter sets (allelic effects, recombination rates, and strength of selection) for a given number of loci. For each parameter set we iterate the recursion equations that describe the dynamics of gamete frequencies starting from 20 randomly chosen initial conditions until an equilibrium is reached, record the quantities of interest, and calculate their corresponding mean values. As the number of loci increases from two to five, the fraction of the genome expected to be polymorphic declines surprisingly rapidly, and the loci that are polymorphic increasingly are those with small effects on the trait. As a result, the genetic variance expected to be maintained under stabilizing selection decreases very rapidly with increased number of loci. The equilibrium structure expected under stabilizing selection on an additive trait differs markedly from that expected under selection with no constraints on genotypic fitness values. The expected genetic variance, the expected polymorphic fraction of the genome, as well as other quantities of interest, are only weakly dependent on the selection intensity and the level of recombination. PMID:10353920

Genetic variation in caribou and reindeer (Rangifer tarandus).

PubMed

Cronin, M A; Patton, J C; Balmysheva, N; MacNeil, M D

2003-02-01

Genetic variation at seven microsatellite DNA loci was quantified in 19 herds of wild caribou and domestic reindeer (Rangifer tarandus) from North America, Scandinavia and Russia. There is an average of 2.0-6.6 alleles per locus and observed individual heterozygosity of 0.33-0.50 in most herds. A herd on Svalbard Island, Scandinavia, is an exception, with relatively few alleles and low heterozygosity. The Central Arctic, Western Arctic and Porcupine River caribou herds in Alaska have similar allele frequencies and comprise one breeding population. Domestic reindeer in Alaska originated from transplants from Siberia, Russia, more than 100 years ago. Reindeer in Alaska and Siberia have different allele frequencies at several loci, but a relatively low level of genetic differentiation. Wild caribou and domestic reindeer in Alaska have significantly different allele frequencies at the seven loci, indicating that gene flow between reindeer and caribou in Alaska has been limited.

Genetic variation and differentiation in parent-descendant cattle and bison populations

USDA-ARS?s Scientific Manuscript database

Genetic variation and differentiation at 32 microsatellite DNA loci is quantified for parent-descendant cattle populations and parent-descendant bison (Bison bison) populations. Heterozygosity (Ho) and numbers of alleles/locus (AR) are less in the Line 1 Hereford inbred cattle population than in t...

Conservation genetics and geographic patterns of genetic variation of the vulnerable officinal herb Fritillaria walujewii (Liliaceae)

Treesearch

Zhihao Su; Borong Pan; Stewart C. Sanderson; Xiaojun Shi; Xiaolong Jiang

2015-01-01

The Chinese herb Fritillaria walujewii Regel is an important officinal species that is vulnerable because of over-harvesting. Here, we examined the geographic pattern of genetic variation across the species entire range, to study its evolution process and give implication needed for the conservation. Nine haplotypes were detected on the basis of three chloroplast...

Do island plant populations really have lower genetic variation than mainland populations? Effects of selection and distribution range on genetic diversity estimates.

PubMed

García-Verdugo, C; Sajeva, M; La Mantia, T; Harrouni, C; Msanda, F; Caujapé-Castells, J

2015-02-01

Ecological and evolutionary studies largely assume that island populations display low levels of neutral genetic variation. However, this notion has only been formally tested in a few cases involving plant taxa, and the confounding effect of selection on genetic diversity (GD) estimates based on putatively neutral markers has typically been overlooked. Here, we generated nuclear microsatellite and plastid DNA sequence data in Periploca laevigata, a plant taxon with an island-mainland distribution area, to (i) investigate whether selection affects GD estimates of populations across contrasting habitats; and (ii) test the long-standing idea that island populations have lower GD than their mainland counterparts. Plastid data showed that colonization of the Canary Islands promoted strong lineage divergence within P. laevigata, which was accompanied by selective sweeps at several nuclear microsatellite loci. Inclusion of loci affected by strong divergent selection produced a significant downward bias in the GD estimates of the mainland lineage, but such underestimates were substantial (>14%) only when more than one loci under selection were included in the computations. When loci affected by selection were removed, we did not find evidence that insular Periploca populations have less GD than their mainland counterparts. The analysis of data obtained from a comprehensive literature survey reinforced this result, as overall comparisons of GD estimates between island and mainland populations were not significant across plant taxa (N = 66), with the only exception of island endemics with narrow distributions. This study suggests that identification and removal of markers potentially affected by selection should be routinely implemented in estimates of GD, particularly if different lineages are compared. Furthermore, it provides compelling evidence that the expectation of low GD cannot be generalized to island plant populations. © 2015 John Wiley & Sons Ltd.

Update on Genetic Conditions Affecting the Skin and the Kidneys

PubMed Central

Reimer, Antonia; He, Yinghong; Has, Cristina

2018-01-01

Genetic conditions affecting the skin and kidney are clinically and genetically heterogeneous, and target molecular components present in both organs. The molecular pathology involves defects of cell–matrix adhesion, metabolic or signaling pathways, as well as tumor suppressor genes. This article gives a clinically oriented overview of this group of disorders, highlighting entities which have been recently described, as well as the progress made in understanding well-known entities. The genetic bases as well as molecular cell biological mechanisms are described, with therapeutic applications. PMID:29552546

Geologic events coupled with Pleistocene climatic oscillations drove genetic variation of Omei treefrog (Rhacophorus omeimontis) in southern China.

PubMed

Li, Jun; Zhao, Mian; Wei, Shichao; Luo, Zhenhua; Wu, Hua

2015-12-21

Pleistocene climatic oscillations and historical geological events may both influence current patterns of genetic variation, and the species in southern China that faced unique climatic and topographical events have complex evolutionary histories. However, the relative contributions of climatic oscillations and geographical events to the genetic variation of these species remain undetermined. To investigate patterns of genetic variation and to test the hypotheses about the factors that shaped the distribution of this genetic variation in species of southern China, mitochondrial genes (cytochrome b and NADH dehydrogenase subunit 2) and nine microsatellite loci of the Omei tree frog (Rhacophorus omeimontis) were amplified in this study. The genetic diversity in the populations of R. omeimontis was high. The phylogenetic trees reconstructed from the mitochondrial DNA (mtDNA) haplotypes and the Bayesian genetic clustering analysis based on microsatellite data both revealed that all populations were divided into three lineages (SC, HG and YN). The two most recent splitting events among the lineages coincided with recent geological events (including the intense uplift of the Qinghai-Tibet Plateau, QTP and the subsequent movements of the Yun-Gui Plateau, YGP) and the Pleistocene glaciations. Significant expansion signals were not detected in mismatch analyses or neutrality tests. And the effective population size of each lineage was stable during the Pleistocene. Based on the results of this study, complex geological events (the recent dramatic uplift of the QTP and the subsequent movements of the YGP) and the Pleistocene glaciations were apparent drivers of the rapid divergence of the R. omeimontis lineages. Each diverged lineages survived in situ with limited gene exchanges, and the stable demographics of lineages indicate that the Pleistocene climatic oscillations were inconsequential for this species. The analysis of genetic variation in populations of R. omeimontis

Natural allelic variations of xenobiotic-metabolizing enzymes affect sexual dimorphism in Oryzias latipes.

PubMed

Katsumura, Takafumi; Oda, Shoji; Nakagome, Shigeki; Hanihara, Tsunehiko; Kataoka, Hiroshi; Mitani, Hiroshi; Kawamura, Shoji; Oota, Hiroki

2014-12-22

Sexual dimorphisms, which are phenotypic differences between males and females, are driven by sexual selection. Interestingly, sexually selected traits show geographical variations within species despite strong directional selective pressures. This paradox has eluded many evolutionary biologists for some time, and several models have been proposed (e.g. 'indicator model' and 'trade-off model'). However, disentangling which of these theories explains empirical patterns remains difficult, because genetic polymorphisms that cause variation in sexual differences are still unknown. In this study, we show that polymorphisms in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolizing enzyme, are associated with geographical differences in sexual dimorphism in the anal fin morphology of medaka fish (Oryzias latipes). Biochemical assays and genetic cross experiments show that high- and low-activity CYP1B1 alleles enhanced and declined sex differences in anal fin shapes, respectively. Behavioural and phylogenetic analyses suggest maintenance of the high-activity allele by sexual selection, whereas the low-activity allele possibly has experienced positive selection due to by-product effects of CYP1B1 in inferred ancestral populations. The present data can elucidate evolutionary mechanisms behind genetic variations in sexual dimorphism and indicate trade-off interactions between two distinct mechanisms acting on the two alleles with pleiotropic effects of xenobiotic-metabolizing enzymes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Response of predatory mites to a herbivore-induced plant volatile: genetic variation for context-dependent behaviour.

PubMed

Sznajder, Beata; Sabelis, Maurice W; Egas, Martijn

2010-07-01

Plants infested with herbivores release specific volatile compounds that are known to recruit natural enemies. The response of natural enemies to these volatiles may be either learned or genetically determined. We asked whether there is genetic variation in the response of the predatory mite Phytoseiulus persimilis to methyl salicylate (MeSa). MeSa is a volatile compound consistently produced by plants being attacked by the two-spotted spider mite, the prey of P. persimilis. We predicted that predators express genetically determined responses during long-distance migration where previously learned associations may have less value. Additionally, we asked whether these responses depend on odors from uninfested plants as a background to MeSa. To infer a genetic basis, we analyzed the variation in response to MeSa among iso-female lines of P. persimilis by using choice-tests that involved either (1) MeSa presented as a single compound or (2) MeSa with background-odor from uninfested lima bean plants. These tests were conducted for starved and satiated predators, i.e., two physiological states, one that approximates migration and another that mimics local patch exploration. We found variation among iso-female lines in the responses to MeSa, thus showing genetic variation for this behavior. The variation was more pronounced in the starved predators, thus indicating that P. persimilis relies on innate preferences when migrating. Background volatiles of uninfested plants changed the predators' responses to MeSa in a manner that depended on physiological state and iso-female line. Thus, it is possible to select for context-dependent behavioral responses of natural enemies to plant volatiles.

Response of Predatory Mites to a Herbivore-Induced Plant Volatile: Genetic Variation for Context-Dependent Behaviour

PubMed Central

Sabelis, Maurice W.; Egas, Martijn

2010-01-01

Plants infested with herbivores release specific volatile compounds that are known to recruit natural enemies. The response of natural enemies to these volatiles may be either learned or genetically determined. We asked whether there is genetic variation in the response of the predatory mite Phytoseiulus persimilis to methyl salicylate (MeSa). MeSa is a volatile compound consistently produced by plants being attacked by the two-spotted spider mite, the prey of P. persimilis. We predicted that predators express genetically determined responses during long-distance migration where previously learned associations may have less value. Additionally, we asked whether these responses depend on odors from uninfested plants as a background to MeSa. To infer a genetic basis, we analyzed the variation in response to MeSa among iso-female lines of P. persimilis by using choice-tests that involved either (1) MeSa presented as a single compound or (2) MeSa with background-odor from uninfested lima bean plants. These tests were conducted for starved and satiated predators, i.e., two physiological states, one that approximates migration and another that mimics local patch exploration. We found variation among iso-female lines in the responses to MeSa, thus showing genetic variation for this behavior. The variation was more pronounced in the starved predators, thus indicating that P. persimilis relies on innate preferences when migrating. Background volatiles of uninfested plants changed the predators’ responses to MeSa in a manner that depended on physiological state and iso-female line. Thus, it is possible to select for context-dependent behavioral responses of natural enemies to plant volatiles. PMID:20574785

An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.

PubMed

Bidwell, L C; McGeary, J E; Gray, J C; Palmer, R H C; Knopik, V S; MacKillop, J

2015-11-01

Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND. However, no studies have examined PDM as an intermediate phenotype in African American smokers, an ethnic population that displays unique patterns of smoking and genetic variation. In the current study, 268 African American daily smokers completed a phenotypic assessment and provided a sample of DNA. Associations among haplotypes in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, a dopamine-related gene region associated with ND, PDM intermediate phenotypes, and ND were examined. Dopamine-related genetic variation in the DBH and COMT genes was also considered on an exploratory basis. Mediational analysis was used to test the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region variation was significantly associated with the Automaticity subscale and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and ND. DBH was also significantly associated with Automaticity, Craving, and Tolerance; Automaticity and Tolerance also served as mediators of the DBH-ND relationship. These results suggest that PDM, Automaticity in particular, may be a viable intermediate phenotype for understanding dopamine-related genetic influences on ND in African American smokers. Findings support a model in which putatively dopaminergic variants exert influence on ND through an effect on patterns of automatic routinized smoking. Copyright �

Genetic Variations of Physiological Responses Following Heat Stress in Laying Hens

USDA-ARS?s Scientific Manuscript database

Heat stress (HS), also known as hyperthermia, is a major problem experienced by poultry during high-temperature conditions. The ability to manage the detrimental effects of HS can be attributed to many factors, including genetics. The objective of the present study was to determine the variation of ...

Genes Contributing to Genetic Variation of Muscling in Sheep

PubMed Central

Tellam, Ross L.; Cockett, Noelle E.; Vuocolo, Tony; Bidwell, Christopher A.

2012-01-01

Selective breeding programs aiming to increase the productivity and profitability of the sheep meat industry use elite, progeny tested sires. The broad genetic traits of primary interest in the progeny of these sires include skeletal muscle yield, fat content, eating quality, and reproductive efficiency. Natural mutations in sheep that enhance muscling have been identified, while a number of genome scans have identified and confirmed quantitative trait loci (QTL) for skeletal muscle traits. The detailed phenotypic characteristics of sheep carrying these mutations or QTL affecting skeletal muscle show a number of common biological themes, particularly changes in developmental growth trajectories, alterations of whole animal morphology, and a shift toward fast twitch glycolytic fibers. The genetic, developmental, and biochemical mechanisms underpinning the actions of some of these genetic variants are described. This review critically assesses this research area, identifies gaps in knowledge, and highlights mechanistic linkages between genetic polymorphisms and skeletal muscle phenotypic changes. This knowledge may aid the discovery of new causal genetic variants and in some cases lead to the development of biochemical and immunological strategies aimed at enhancing skeletal muscle. PMID:22952470

Compatibility of breeding for increased wood production and longterm sustainability: the genetic variation of seed orchard seed and associated risks.

Treesearch

R Johnson; S. Lipow

2002-01-01

Because breeding imposes strong artificial selection for a narrow suite of economically important traits, genetic variation is reduced in seedlings derived from operational seed orchards. Both quantitative genetics theory and studies of allozyme variation show that seed orchards contain most of the genetic diversity found in natural populations, although low-frequency...

Genetics of canid skeletal variation: size and shape of the pelvis.

PubMed

Carrier, David R; Chase, Kevin; Lark, Karl G

2005-12-01

The mammalian skeleton presents an ideal system in which to study the genetic architecture of a set of related polygenic traits and the skeleton of the domestic dog (Canis familiaris) is arguably the best system in which to address the relationship between genes and anatomy. We have analyzed the genetic basis for skeletal variation in a population of >450 Portuguese Water Dogs. At this stage of this ongoing project, we have identified >40 putative quantitative trait loci (QTLs) for heritable skeletal phenotypes located on 22 different chromosomes, including the "X." A striking aspect of these is the regulation of suites of traits representing bones located in different parts of the skeleton but related by function. Here we illustrate this by describing genetic variation in postcranial morphology. Two suites of traits are involved. One regulates the size of the pelvis relative to dimensions of the limb bones. The other regulates the shape of the pelvis. Both are examples of trade-offs that may be prototypical of different breeds. For the size of the pelvis relative to limb bones, we describe four QTLs located on autosome CFA 12, 30, 31, and X. For pelvic shape we describe QTLs on autosome CFA 2, 3, 22, and 36. The relation of these polygenic systems to musculoskeletal function is discussed.

Global Genetic Variations Predict Brain Response to Faces

PubMed Central

Dickie, Erin W.; Tahmasebi, Amir; French, Leon; Kovacevic, Natasa; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun; Büchel, Christian; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Gallinat, Juergen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Nichols, Thomas; Lathrop, Mark; Loth, Eva; Pausova, Zdenka; Rietschel, Marcela; Smolka, Michal N.; Ströhle, Andreas; Toro, Roberto; Schumann, Gunter; Paus, Tomáš

2014-01-01

Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40–50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R2 = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R2 = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network. PMID:25122193

RAPD variation and population genetic structure of Physalaemus cuvieri (Anura: Leptodactylidae) in Central Brazil.

PubMed

Telles, Mariana Pires de Campos; Bastos, Rogério Pereira; Soares, Thannya Nascimento; Resende, Lucileide Vilela; Diniz-Filho, José Alexandre Felizola

2006-01-01

Studies about the organization of the genetic variability and population structure in natural populations are used either to understand microevolutionary processes or the effects of isolation by human-inducted landscape modifications. In this paper, we analyzed patterns of genetic population structure using 126 RAPD loci scored for 214 individuals of Physalaemus cuvieri, sampled from 18 local populations. Around 97% of these loci were polymorphic. The among-population variation component (Phi(ST)) obtained by AMOVA was equal to 0.101 and theta B obtained using a Bayesian approach for dominant markers was 0.103. Genetic divergence, analyzed by Mantel spatial correlogram, revealed only a short-distance significant correlation between genetic and geographic distances. This is expected if low levels of population differentiation, due to high abundance buffering the effect of stochastic processes, are combined with low spatially restricted gene flow. Although this may be consistent with the current knowledge of species' biology, the spatial distribution of local populations observed in this study also suggest that, at least in part, recent human occupation and habitat fragmentation may also explain part of the interpopulational component of the genetic variation.

Microsatellite variation reveals weak genetic structure and retention of genetic variability in threatened Chinook salmon (Oncorhynchus tshawytcha) within a Snake River watershed

Treesearch

Helen Neville; Daniel Isaak; Russell Thurow; Jason Dunham; Bruce Rieman

2007-01-01

Pacific salmon (Oncorhynchus spp.) have been central to the development of management concepts associated with evolutionarily significant units (ESUs), yet there are still relatively few studies of genetic diversity within threatened and endangered ESUs for salmon or other species. We analyzed genetic variation at 10 microsatellite loci to evaluate...

HSP90 Shapes the Consequences of Human Genetic Variation.

PubMed

Karras, Georgios I; Yi, Song; Sahni, Nidhi; Fischer, Máté; Xie, Jenny; Vidal, Marc; D'Andrea, Alan D; Whitesell, Luke; Lindquist, Susan

2017-02-23

HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic variation in Dip5, an amino acid permease, and Pdr5, a multiple drug transporter, regulates glyphosate resistance in S. cerevisiae

PubMed Central

McNeal, Kirsten A.; Lonergan, Zachery R.; Biega, Audrey C.; Creamer, J. Philip

2017-01-01

S. cerevisiae from different environments are subject to a wide range of selective pressures, whether intentional or by happenstance. Chemicals classified by their application, such as herbicides, fungicides and antibiotics, can affect non-target organisms. First marketed as RoundUp™, glyphosate is the most widely used herbicide. In plants, glyphosate inhibits EPSPS, of the shikimate pathway, which is present in many organisms but lacking in mammals. The shikimate pathway produces chorismate which is the precursor to all the aromatic amino acids, para-aminobenzoic acid, and Coenzyme Q10. Crops engineered to be resistant to glyphosate contain a homolog of EPSPS that is not bound by glyphosate. Here, we show that S. cerevisiae has a wide-range of glyphosate resistance. Sequence comparison between the target proteins, i.e., the plant EPSPS and the yeast orthologous protein Aro1, predicted that yeast would be resistant to glyphosate. However, the growth variation seen in the subset of yeast tested was not due to polymorphisms within Aro1, instead, it was caused by genetic variation in an ABC multiple drug transporter, Pdr5, and an amino acid permease, Dip5. Using genetic variation as a probe into glyphosate response, we uncovered mechanisms that contribute to the transportation of glyphosate in and out of the cell. Taking advantage of the natural genetic variation within yeast and measuring growth under different conditions that would change the use of the shikimate pathway, we uncovered a general transport mechanism of glyphosate into eukaryotic cells. PMID:29155836

Genetic variation for pseudo-self-compatibility in self-incompatible populations of Leavenworthia alabamica (Brassicaceae).

PubMed

Baldwin, Sarah J; Schoen, Daniel J

2017-01-01

Self-incompatibility (SI) promotes outcrossing, but transitions to self-compatibility (SC) are frequent. Population genetic theory describing the breakdown of SI to SC suggests that, under most conditions, populations should be composed of either SI or SC individuals. Under a narrow range of conditions, theory suggests that SI may persist alongside reduced expression of SI (pseudo-SI, PSI) in mixed-mating populations. We studied genetic variation for PSI segregating in four SI populations of Leavenworthia alabamica by measurement of the heritability of pollen tube number after self-pollination. We tested for the role of the S-locus in this variation by sequencing seven S-alleles from plants with high pseudo-SC (PSC) and testing for the co-segregation of these alleles with PSC. We found a continuous distribution of PSC in all populations and 90% of plants exhibited PSC. The heritability ranged from 0.39 to 0.57. All seven S-alleles from plants with high PSC exhibited trans-specific polymorphism, and no stop codons were observed within the c. 600-bp region sequenced. One of these S-alleles was directly associated with the inheritance of PSC. We conclude that heritable variation in PSC is largely a result of genetic variation in the signaling cascade downstream of the S-locus reaction, together with the presence of one leaky S-allele. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Using induced pluripotent stem cells to explore genetic and epigenetic variation associated with Alzheimer's disease.

PubMed

Imm, Jennifer; Kerrigan, Talitha L; Jeffries, Aaron; Lunnon, Katie

2017-11-01

It is thought that both genetic and epigenetic variation play a role in Alzheimer's disease initiation and progression. With the advent of somatic cell reprogramming into induced pluripotent stem cells it is now possible to generate patient-derived cells that are able to more accurately model and recapitulate disease. Furthermore, by combining this with recent advances in (epi)genome editing technologies, it is possible to begin to examine the functional consequence of previously nominated genetic variants and infer epigenetic causality from recently identified epigenetic variants. In this review, we explore the role of genetic and epigenetic variation in Alzheimer's disease and how the functional relevance of nominated loci can be investigated using induced pluripotent stem cells and (epi)genome editing techniques.

Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans

PubMed Central

Rodrigues, Sarina M.; Saslow, Laura R.; Garcia, Natalia; John, Oliver P.; Keltner, Dacher

2009-01-01

Oxytocin, a peptide that functions as both a hormone and neurotransmitter, has broad influences on social and emotional processing throughout the body and the brain. In this study, we tested how a polymorphism (rs53576) of the oxytocin receptor relates to two key social processes related to oxytocin: empathy and stress reactivity. Compared with individuals homozygous for the G allele of rs53576 (GG), individuals with one or two copies of the A allele (AG/AA) exhibited lower behavioral and dispositional empathy, as measured by the “Reading the Mind in the Eyes” Test and an other-oriented empathy scale. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals, as determined by heart rate response during a startle anticipation task and an affective reactivity scale. Our results provide evidence of how a naturally occurring genetic variation of the oxytocin receptor relates to both empathy and stress profiles. PMID:19934046

Molecular and genetic analyses of geographic variation in isolates of Phoma macrostoma used for biological weed control.

PubMed

Zhou, Lecong; Bailey, K L; Chen, C Y; Keri, Mario

2005-01-01

Molecular and genetic approaches were used to evaluate the genetic relatedness among isolates of the fungus Phoma macrostoma Montagne originating from Canada and Europe and to other species in the genus Phoma. Distinct differences were observed in genetic variation among nine species of the genus Phoma. Randomly amplified polymorphic DNA (RAPD) revealed the presence of intraspecific genetic variation among the isolates of P. macrostoma, with the isolates being used for biological weed control being distributed in a distinct phylogenetic cluster. Additional variation within the biocontrol isolate cluster in P. macrostoma was revealed by pulsed field gel electrophoresis (PFGE), which showed that biocontrol isolates generated two different chromosomal profiles, however the profiles did not relate to their Canadian ecozone origin. Mating studies showed that biocontrol isolates of P. macrostoma from Canada did not produce sexual reproductive structures and were incapable of crossing. These studies also confirmed that no obvious differentiation exists among the biocontrol isolates of P. macrostoma from Canadian Ecozones 3 and 4.

Genetic variation in transmission success of the Lyme borreliosis pathogen Borrelia afzelii.

PubMed

Tonetti, Nicolas; Voordouw, Maarten J; Durand, Jonas; Monnier, Séverine; Gern, Lise

2015-04-01

The vector-to-host and host-to-vector transmission steps are the two critical events that define the life cycle of any vector-borne pathogen. We expect negative genetic correlations between these two transmission phenotypes, if parasite genotypes specialized at invading the vector are less effective at infecting the vertebrate host and vice versa. We used the tick-borne bacterium Borrelia afzelii, a causative agent of Lyme borreliosis in Europe, to test whether genetic trade-offs exist between tick-to-host, systemic (host-to-tick), and a third mode of co-feeding (tick-to-tick) transmission. We worked with six strains of B. afzelii that were differentiated according to their ospC gene. We compared the three components of transmission among the B. afzelii strains using laboratory rodents as the vertebrate host and a laboratory colony of Ixodes ricinus as the tick vector. We used next generation matrix models to combine these transmission components into a single estimate of the reproductive number (R0) for each B. afzelii strain. We also tested whether these strain-specific estimates of R0 were correlated with the strain-specific frequencies in the field. We found significant genetic variation in the three transmission components among the B. afzelii strains. This is the first study to document genetic variation in co-feeding transmission for any tick-borne pathogen. We found no evidence of trade-offs as the three pairwise correlations of the transmission rates were all positive. The R0 values from our laboratory study explained 45% of the variation in the frequencies of the B. afzelii ospC strains in the field. Our study suggests that laboratory estimates of pathogen fitness can predict the distribution of pathogen strains in nature. Copyright © 2015 Elsevier GmbH. All rights reserved.

Assessment of genetic variation for pathogen-specific mastitis resistance in Valle del Belice dairy sheep.

PubMed

Tolone, Marco; Larrondo, Cristian; Yáñez, José M; Newman, Scott; Sardina, Maria Teresa; Portolano, Baldassare

2016-07-28

Mastitis resistance is a complex and multifactorial trait, and its expression depends on both genetic and environmental factors, including infection pressure. The objective of this research was to determine the genetic basis of mastitis resistance to specific pathogens using a repeatability threshold probit animal model. The most prevalent isolated pathogens were coagulase-negative staphylococci (CNS); 39 % of records and 77 % of the animals infected at least one time in the whole period of study. There was significant genetic variation only for Streptococci (STR). In addition, there was a positive genetic correlation between STR and all pathogens together (ALL) (0.36 ± 0.22), and CNS and ALL (0.92 ± 0.04). The results of our study support the presence of significant genetic variation for mastitis caused by Streptococci and suggest the importance of discriminating between different pathogens causing mastitis due to the fact that they most likely influence different genetic traits. Low heritabilities for pathogen specific-mastitis resistance may be considered when including bacteriological status as a measure of mastitis presence to implement breeding strategies for improving udder health in dairy ewes.

Genetic diversity and variation of mitochondrial DNA in native and introduced bighead carp

USGS Publications Warehouse

Li, Si-Fa; Yang, Qin-Ling; Xu, Jia-Wei; Wang, Cheng-Hui; Chapman, Duane C.; Lu, Guoping

2010-01-01

The bighead carp Hypophthalmichthys nobilis is native to China but has been introduced to over 70 countries and is established in many large river systems. Genetic diversity and variation in introduced bighead carp have not previously been evaluated, and a systematic comparison among fish from different river systems was unavailable. In this study, 190 bighead carp specimens were sampled from five river systems in three countries (Yangtze, Pearl, and Amur rivers, China; Danube River, Hungary; Mississippi River basin, USA) and their mitochondrial 16S ribosomal RNA gene and D-loop region were sequenced (around 1,345 base pairs). Moderate genetic diversity was found in bighead carp, ranging from 0.0014 to 0.0043 for nucleotide diversity and from 0.6879 to 0.9333 for haplotype diversity. Haplotype analysis provided evidence that (1) multiple haplotype groups might be present among bighead carp, (2) bighead carp probably originated from the Yangtze River, and (3) bighead carp in the Mississippi River basin may have some genetic ancestry in the Danube River. The analysis of molecular variance showed significant genetic differentiation among these five populations but also revealed limited differentiation between the Yangtze and Amur River bighead carp. This large-scale study of bighead carp genetic diversity and variation provides the first global perspective of bighead carp in the context of biodiversity conservation as well as invasive species control and management.

Attitudes toward prenatal genetic testing for Treacher Collins syndrome among affected individuals and families.

PubMed

Wu, Rebecca L; Lawson, Cathleen S; Jabs, Ethylin Wang; Sanderson, Saskia C