High-resolution mapping of complex traits with a four-parent advanced intercross yeast population

Cubillos, F. A. et al. (2013) High-resolution mapping of complex traits with a four-parent advanced intercross yeast population. Genetics, 195(3), pp. 1141-1155. (doi: 10.1534/genetics.113.155515) (PMID:24037264) (PMCID:PMC3813843)

Abstract

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 multiparent 12th generation intercross. We selected four representative founder strains to produce the Saccharomyces Genome Resequencing Project (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 characterized 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.

• Item Type: Articles
• Additional Information: This work was funded by grants from Atip-Avenir, Association pour la Recherche Contre le Cancer (SFI20111203947) (to G.L.), and The Wellcome Trust (grant WT077192/Z/05/Z) (to R.D.). We further acknowledge the Wellcome Trust for support under grant 098051. This work was also supported in part by Region Midi Pyrénées (France) under grant 09005247 and was carried out in the frame of the European Cooperation in Science and Technology Action (FA0907-Bioflavour) under the European Union’s Seventh Framework Programme for Research (FP7). F.A.C. is supported by Conicyt–Programa de Atracción e Inserción/Concurso Nacional de Apoyo al retorno de investigadores/as desde el extranjero grant 82130010. L.P. is supported by a fellowship from the Canadian Institute for Advanced Research and a Marie Curie International Outgoing Fellowship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Illingworth, Dr Chris
• Authors: Cubillos, F. A., Parts, L., Salinas, F., Bergström, A., Scovacricchi, E., Zia, A., Illingworth, C. J.R., Mustonen, V., Ibstedt, S., Warringer, J., Louis, E. J., Durbin, R., and Liti, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Genetics
• Publisher: Oxford University Press
• ISSN: 0016-6731
• ISSN (Online): 1943-2631