Individual Loci Radically Alter the Genetic Architecture of Complex Traits
Authors: Gareth Cromie 1; Russell Lo 1; Lauren Ames 1; Trey Morgan 1; Katherine Owens 2; Anne Clark 3; Martin Timour 1; Julee Ashmead 1; Michelle Tang 1; Nathan Kutz 2; Joshua Akey 4,5; Aimee Dudley 1
Affiliations: 1) Pacific Northwest Research Institute; 2) Department of Applied Mathematics, University of Washington, Seattle, Washington, USA ; 3) Department of Genome Sciences, University of Washington, Seattle, Washington, USA ; 4) Lewis Sigler Institute, Princeton University, Princeton, New Jersey, USA ; 5) Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, USA
Keywords: Complex traits
While advances in DNA sequencing technology have greatly increased our ability to map phenotype to genotype, many biomedical, agricultural, and evolutionary phenotypes of interest are complex and remain difficult to genetically dissect. Here, we present a powerful resource for delineating the genetic architecture of complex and quantitative traits in the budding yeast, Saccharomyces cerevisiae. Using an eight-parent funnel cross design that captures a significant proportion of the genetic diversity of the global yeast population, we have generated an unstructured mapping population of ~11,500 genetically diverse strains and determined their genome sequences. Using these data, and accurate individual phenotying of each strain, we investigated the genetic architecture underlying ten quantitative traits.Confirming the remarkable power of the resource and leveraging only standing genetic variation, we demonstrate that we can identify the regulatory and mechanistic components of a complete biological pathway. We also detect genetic heterogeneity underlying strong quantitative trait loci (QTL), and dissect one example down to the level of two closely-linked quantitative trait nucleotides (QTN). Finally, we demonstrate strong effects of genetic stratification, identifying individual alleles defining subpopulations with radically different genetic architectures for the same trait.