Mapping Causal Variants with Single-Nucleotide Resolution Reveals Biochemical Drivers of Phenotypic Change.

ABSTRACT: Understanding the sequence determinants that give rise to diversity among individuals and species is the central challenge of genetics. However, despite ever greater numbers of sequenced genomes, most genome-wide association studies cannot distinguish causal variants from linked passenger mutations spanning many genes. We report that this inherent challenge can be overcome in model organisms. By pushing the advantages of inbred crossing to its practical limit in Saccharomyces cerevisiae, we improved the statistical resolution of linkage analysis to single nucleotides. This "super-resolution" approach allowed us to map 370 causal variants across 26 quantitative traits. Missense, synonymous, and cis-regulatory mutations collectively gave rise to phenotypic diversity, providing mechanistic in

SUBMITTER: She R 

PROVIDER: S-EPMC5788306 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature