A genome-wide association study for nutritional indices in Drosophila.
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ABSTRACT:
SUBMITTER: Unckless RL
PROVIDER: S-EPMC4349095 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSleep is a highly conserved behavior, yet its duration and pattern vary extensively among species and between individuals within species. The genetic basis of natural variation in sleep remains unknown.ResultsWe used the Drosophila Genetic Reference Panel (DGRP) to perform a genome-wide association (GWA) study of sleep in D. melanogaster. We identified candidate single nucleotide polymorphisms (SNPs) associated with differences in the mean as well as the environmental sensitivity of sleep traits; these SNPs typically had sex-specific or sex-biased effects, and were generally located in non-coding regions. The majority of SNPs (80.3%) affecting sleep were at low frequency and had moderately large effects. Additive models incorporating multiple SNPs explained as much as 55% of the genetic variance for sleep in males and females. Many of these loci are known to interact physically and/or genetically, enabling us to place them in candidate genetic networks. We confirmed the role of seven novel loci on sleep using insertional mutagenesis and RNA interference.ConclusionsWe identified many SNPs in novel loci that are potentially associated with natural variation in sleep, as well as SNPs within genes previously known to affect Drosophila sleep. Several of the candidate genes have human homologues that were identified in studies of human sleep, suggesting that genes affecting variation in sleep are conserved across species. Our discovery of genetic variants that influence environmental sensitivity to sleep may have a wider application to all GWA studies, because individuals with highly plastic genotypes will not have consistent phenotypes.
| S-EPMC3644253 | biostudies-literature
Project description:Circadian rhythms influence physiological processes from sleep-wake cycles to body temperature and are controlled by highly conserved cycling molecules. Although the mechanistic basis of the circadian clock has been known for decades, the extent to which circadian rhythms vary in nature and the underlying genetic basis for that variation is not well understood. We measured circadian period (?) and rhythmicity index in the Drosophila Genetic Reference Panel (DGRP) and observed extensive genetic variation in both. Seven DGRP lines had sexually dimorphic arrhythmicity and one line had an exceptionally long ?. Genome-wide analyses identified 584 polymorphisms in 268 genes. We observed differences among transcripts for nine genes predicted to interact among themselves and canonical clock genes in the long period line and a control. Mutations/RNAi knockdown targeting these genes also affected circadian behavior. Our observations reveal that complex genetic interactions influence high levels of variation in circadian phenotypes.
| S-EPMC6326971 | biostudies-literature
Project description:Human genome-wide association studies (GWAS) of longevity attempt to identify alleles at different frequencies in the extremely old, relative to a younger control sample. Here, we apply a GWAS approach to "synthetic" populations of Drosophila melanogaster derived from a small number of inbred founders. We used next-generation DNA sequencing to estimate allele and haplotype frequencies in the oldest surviving individuals of an age cohort and compared these frequencies with those of randomly sampled individuals from the same cohort. We used this case-control strategy in four independent cohorts and identified eight significantly differentiated regions of the genome potentially harboring genes with relevance for longevity. By modeling the effects of local haplotypes, we have more power to detect regions enriched for longevity genes than marker-based GWAS. Most significant regions occur near chromosome ends or centromeres where recombination is infrequent, consistent with these regions harboring unconditionally deleterious alleles impacting longevity. Genes in regions of normal recombination are enriched for those relevant to immune function and a gene family involved in oxidative stress response. Genetic differentiation between our experimental cohorts is comparable to that between human populations, suggesting in turn that our results may help explain heterogeneous signals in human association studies of extreme longevity when panels have diverse ancestry.
| S-EPMC3914684 | biostudies-literature
Project description:To increase plumage color uniformity and understand the genetic background of Korean chickens, we performed a genome-wide association study of different plumage color in Korean native chickens. We analyzed 60K SNP chips on 279 chickens with GEMMA methods for GWAS and estimated the genetic heritability for plumage color. The estimated heritability suggests that plumage coloration is a polygenic trait. We found new loci associated with feather pigmentation at the genome-wide level and from the results infer that there are additional genetic effect for plumage color. The results will be used for selecting and breeding chicken for plumage color uniformity.
| S-EPMC4093824 | biostudies-other
Project description:BACKGROUND:The deployment of Genome-wide association studies (GWASs) requires genomic information of a large population to produce reliable results. This raises significant privacy concerns, making people hesitate to contribute their genetic information to such studies. RESULTS:We propose two provably secure solutions to address this challenge: (1) a somewhat homomorphic encryption (HE) approach, and (2) a secure multiparty computation (MPC) approach. Unlike previous work, our approach does not rely on adding noise to the input data, nor does it reveal any information about the patients. Our protocols aim to prevent data breaches by calculating the ?2 statistic in a privacy-preserving manner, without revealing any information other than whether the statistic is significant or not. Specifically, our protocols compute the ?2 statistic, but only return a yes/no answer, indicating significance. By not revealing the statistic value itself but only the significance, our approach thwarts attacks exploiting statistic values. We significantly increased the efficiency of our HE protocols by introducing a new masking technique to perform the secure comparison that is necessary for determining significance. CONCLUSIONS:We show that full-scale privacy-preserving GWAS is practical, as long as the statistics can be computed by low degree polynomials. Our implementations demonstrated that both approaches are efficient. The secure multiparty computation technique completes its execution in approximately 2 ms for data contributed by one million subjects.
| S-EPMC6302495 | biostudies-other
Project description:Due to the complexity of genotype-phenotype relationships, simultaneous analyses of genomic associations with multiple traits will be more powerful and informative than a series of univariate analyses. However, in most cases, studies of genotype-phenotype relationships have been analyzed only one trait at a time. Here, we report the results of a fully integrated multivariate genome-wide association analysis of the shape of the Drosophila melanogaster wing in the Drosophila Genetic Reference Panel. Genotypic effects on wing shape were highly correlated between two different laboratories. We found 2396 significant SNPs using a 5% false discovery rate cutoff in the multivariate analyses, but just four significant SNPs in univariate analyses of scores on the first 20 principal component axes. One quarter of these initially significant SNPs retain their effects in regularized models that take into account population structure and linkage disequilibrium. A key advantage of multivariate analysis is that the direction of the estimated phenotypic effect is much more informative than a univariate one. We exploit this fact to show that the effects of knockdowns of genes implicated in the initial screen were on average more similar than expected under a null model. A subset of SNP effects were replicable in an unrelated panel of inbred lines. Association studies that take a phenomic approach, considering many traits simultaneously, are an important complement to the power of genomics.
| S-EPMC6456314 | biostudies-literature
Project description:Water availability is a major environmental challenge to a variety of terrestrial organisms. In insects, desiccation tolerance varies predictably over spatial and temporal scales and is an important physiological determinant of fitness in natural populations. Here, we examine the dynamics of desiccation tolerance in North American populations of Drosophila melanogaster using: (a) natural populations sampled across latitudes and seasons; (b) experimental evolution in field mesocosms over seasonal time; (c) genome-wide associations to identify SNPs/genes associated with variation for desiccation tolerance; and (d) subsequent analysis of patterns of clinal/seasonal enrichment in existing pooled sequencing data of populations sampled in both North America and Australia. A cline in desiccation tolerance was observed, for which tolerance exhibited a positive association with latitude; tolerance also varied predictably with culture temperature, demonstrating a significant degree of thermal plasticity. Desiccation tolerance evolved rapidly in field mesocosms, although only males showed differences in desiccation tolerance between spring and autumn collections from natural populations. Water loss rates did not vary significantly among latitudinal or seasonal populations; however, changes in metabolic rates during prolonged exposure to dry conditions are consistent with increased tolerance in higher latitude populations. Genome-wide associations in a panel of inbred lines identified twenty-five SNPs in twenty-one loci associated with sex-averaged desiccation tolerance, but there is no robust signal of spatially varying selection on genes associated with desiccation tolerance. Together, our results suggest that desiccation tolerance is a complex and important fitness component that evolves rapidly and predictably in natural populations.
| S-EPMC6129450 | biostudies-literature
Project description:Male genital morphology of animals with internal fertilization and promiscuous mating systems have been one of the most diverse and rapidly evolving morphological traits. The male genital morphology in general is known to have low phenotypic and genetic variations, but the genetic basis of the male genital variation remains unclear. Drosophila melanogaster and its closely related species are morphologically very similar, but the shapes of the posterior lobe, a cuticular projection on the male genital arch are distinct from each other, representing a model system for studying the genetic basis of male genital morphology. In this study, we used highly inbred whole genome sequenced strains of D. melanogaster to perform genome wide association analysis on posterior lobe morphology. We quantified the outline shape of posterior lobes with Fourier coefficients obtained from elliptic Fourier analysis and performed principal component analysis, and posterior lobe size. The first and second principal components (PC1 and PC2) explained approximately 88% of the total variation of the posterior lobe shape. We then examined the association between the principal component scores and posterior lobe size and 1902142 single nucleotide polymorphisms (SNPs). As a result, we obtained 15, 14 and 15 SNPs for PC1, PC2 and posterior lobe size with P-values smaller than 10(-5). Based on the location of the SNPs, 13, 13 and six protein coding genes were identified as potential candidates for PC1, PC2 and posterior lobe size, respectively. In addition to the previous findings showing that the intraspecific posterior shape variation are regulated by multiple QTL with strong effects, the present study suggests that the intraspecific variation may be under polygenic regulation with a number of loci with small effects. Further studies are required for investigating whether these candidate genes are responsible for the intraspecific posterior lobe shape variation.
| S-EPMC4504508 | biostudies-literature
Project description:Genome Wide Association Study of Asthma
| PRJNA75657 | ENA
Project description:Genome-wide Association Study of Neuroblastoma
| PRJNA75825 | ENA