High Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population
Authors: Cubillos, FA; Parts, L; Salinas, F; Bergström, A; Scovacricchi, E; Zia, A; Illingworth, CJ; Mustonen, V; Ibstedt, S; Warringer, J; Louis, EJ; Durbin, R; Liti, G
HERO ID: 2064246
A large fraction of human complex trait heritability is due to a high number of variants with small . . .
A large fraction of human complex trait heritability is due to a high number of variants with small marginal effects, and their interactions with genotype and environment. Such alleles are more easily studied in model organisms, where environment, genetic makeup and allele frequencies can be controlled. Here, we examine the effect of natural genetic variation on heritable traits in a very large pool of baker's yeast from a multi-parent 12(th) generation intercross. We selected four representative founder strains to produce the SGRP-4X mapping population, and sequenced 192 segregants to generate an accurate genetic map. Using these individuals, we mapped 25 loci linked to growth traits under heat stress, arsenite and paraquat, the majority of which were best explained by a diverging phenotype caused by a single allele in one condition. By sequencing pooled DNA from millions of segregants grown under heat stress, we further identified 34 and 39 regions selected in haploid and diploid pools respectively, with most of the selection against a single allele. While the most parsimonious model for the majority of loci mapped using either approach was the effect of an allele private to one founder, we could validate examples of pleiotropic effects, and complex allelic series at a locus. SGRP-4X is a deeply characterised resource that provides a framework for powerful and high-resolution genetic analysis of yeast phenotypes, and serves as a test bed for testing avenues to attack human complex traits.