ResearchPad - genetics-of-complex-traits https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Genetic Associations in Four Decades of Multienvironment Trials Reveal Agronomic Trait Evolution in Common Bean]]> https://www.researchpad.co/article/N6d8101b5-f616-4a7e-9374-895be39b490c Multienvironment trials (METs) are widely used to assess the performance of promising crop germplasm. Though seldom designed to elucidate genetic mechanisms, MET data sets are often much larger than could be duplicated for genetic research and, given proper interpretation, may offer valuable insights into the genetics of adaptation across time and space. The Cooperative Dry Bean Nursery (CDBN) is a MET for common bean (Phaseolus vulgaris) grown for > 70 years in the United States and Canada, consisting of 20–50 entries each year at 10–20 locations. The CDBN provides a rich source of phenotypic data across entries, years, and locations that is amenable to genetic analysis. To study stable genetic effects segregating in this MET, we conducted genome-wide association studies (GWAS) using best linear unbiased predictions derived across years and locations for 21 CDBN phenotypes and genotypic data (1.2 million SNPs) for 327 CDBN genotypes. The value of this approach was confirmed by the discovery of three candidate genes and genomic regions previously identified in balanced GWAS. Multivariate adaptive shrinkage (mash) analysis, which increased our power to detect significant correlated effects, found significant effects for all phenotypes. Mash found two large genomic regions with effects on multiple phenotypes, supporting a hypothesis of pleiotropic or linked effects that were likely selected on in pursuit of a crop ideotype. Overall, our results demonstrate that statistical genomics approaches can be used on MET phenotypic data to discover significant genetic effects and to define genomic regions associated with crop improvement.

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<![CDATA[Deciphering Sex-Specific Genetic Architectures Using Local Bayesian Regressions]]> https://www.researchpad.co/article/N68148aac-d687-487e-92e5-890c4a4ea7d6 Many complex human traits exhibit differences between sexes. While numerous factors likely contribute to this phenomenon, growing evidence from genome-wide studies suggest a partial explanation: that males and females from the same population possess differing genetic architectures. Despite this, mapping gene-by-sex (G×S) interactions remains a challenge likely because the magnitude of such an interaction is typically and exceedingly small; traditional genome-wide association techniques may be underpowered to detect such events, due partly to the burden of multiple test correction. Here, we developed a local Bayesian regression (LBR) method to estimate sex-specific SNP marker effects after fully accounting for local linkage-disequilibrium (LD) patterns. This enabled us to infer sex-specific effects and G×S interactions either at the single SNP level, or by aggregating the effects of multiple SNPs to make inferences at the level of small LD-based regions. Using simulations in which there was imperfect LD between SNPs and causal variants, we showed that aggregating sex-specific marker effects with LBR provides improved power and resolution to detect G×S interactions over traditional single-SNP-based tests. When using LBR to analyze traits from the UK Biobank, we detected a relatively large G×S interaction impacting bone mineral density within ABO, and replicated many previously detected large-magnitude G×S interactions impacting waist-to-hip ratio. We also discovered many new G×S interactions impacting such traits as height and body mass index (BMI) within regions of the genome where both male- and female-specific effects explain a small proportion of phenotypic variance (R2 < 1 × 10−4), but are enriched in known expression quantitative trait loci.

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<![CDATA[A Microbe Associated with Sleep Revealed by a Novel Systems Genetic Analysis of the Microbiome in Collaborative Cross Mice]]> https://www.researchpad.co/article/Ned935595-f49f-4db4-a938-54dd5fb9548a

Host genetic diversity provides a variable selection environment and physiological context for microbiota and their interaction with host physiology. Using a highly diverse mouse population, Bubier et al. identified that Odoribacter abundance influences sleep archi-tecture in a manner...

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<![CDATA[Deleterious Mutation Burden and Its Association with Complex Traits in Sorghum (Sorghum bicolor)]]> https://www.researchpad.co/article/N3617b511-46e9-462b-8906-86aec6d4d1ec

Sorghum (Sorghum bicolor (L.) Moench) is a major staple food cereal for millions of people worldwide. Valluru et al. identify putative deleterious mutations among ∼5.5M segregating variants of 229 diverse sorghum...

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<![CDATA[Shared Genomic Regions Underlie Natural Variation in Diverse Toxin Responses]]> https://www.researchpad.co/article/5c22c6f1d5eed0c484aa2ccd

Phenotypic complexity is caused by the contributions of environmental factors and multiple genetic loci, interacting or acting independently. Studies of yeast and Arabidopsis often find that the majority of natural variation across phenotypes is attributable to independent additive quantitative trait loci (QTL). Detected loci in these organisms explain most of the estimated heritable variation. By contrast, many heritable components underlying phenotypic variation in metazoan models remain undetected. Before the relative impacts of additive and interactive variance components on metazoan phenotypic variation can be dissected, high replication and precise phenotypic measurements are required to obtain sufficient statistical power to detect loci contributing to this missing heritability. Here, we used a panel of 296 recombinant inbred advanced intercross lines of Caenorhabditis elegans and a high-throughput fitness assay to detect loci underlying responses to 16 different toxins, including heavy metals, chemotherapeutic drugs, pesticides, and neuropharmaceuticals. Using linkage mapping, we identified 82 QTL that underlie variation in responses to these toxins, and predicted the relative contributions of additive loci and genetic interactions across various growth parameters. Additionally, we identified three genomic regions that impact responses to multiple classes of toxins. These QTL hotspots could represent common factors impacting toxin responses. We went further to generate near-isogenic lines and chromosome substitution strains, and then experimentally validated these QTL hotspots, implicating additive and interactive loci that underlie toxin-response variation.

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