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Citation
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HERO ID
2064246
Reference Type
Journal Article
Title
High Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population
Author(s)
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
Year
2013
Is Peer Reviewed?
1
Journal
Genetics
ISSN:
0016-6731
EISSN:
1943-2631
Volume
195
Issue
3
Page Numbers
1141-1155
Language
English
PMID
24037264
DOI
10.1534/genetics.113.155515
Web of Science Id
WOS:000329874100038
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 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.
Keywords
yeast; genetics; quantitative traits; meiotic recombination; artificial selection
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