High-Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population

被引:91
作者
Cubillos, Francisco A. [1 ,2 ,3 ]
Parts, Leopold [4 ,5 ]
Salinas, Francisco [7 ]
Bergstroem, Anders [7 ]
Scovacricchi, Eugenio [1 ]
Zia, Amin [6 ]
Illingworth, Christopher J. R. [4 ]
Mustonen, Ville [4 ]
Ibstedt, Sebastian [8 ]
Warringer, Jonas [8 ]
Louis, Edward J. [1 ,9 ]
Durbin, Richard [4 ]
Liti, Gianni [7 ]
机构
[1] Univ Nottingham, Queens Med Ctr, Ctr Genet & Genom, Nottingham NG7 2UH, England
[2] Univ Santiago Chile, Dept Ciencia & Tecnol Alimentos, Santiago 9170201, Chile
[3] Univ Santiago Chile, Ctr Estudios Ciencia & Tecnol Alimentos, Santiago 9170201, Chile
[4] Wellcome Trust Sanger Inst, Hinxton CB10 1HH, England
[5] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3B2, Canada
[6] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 3B2, Canada
[7] Univ Nice Sophia Antipolis, Fac Med, INSERM, CNRS,Inst Res Canc & Ageing Nice,UMR 7284,U1081, F-06107 Nice 2, France
[8] Univ Gothenburg, Dept Chem & Mol Biol, S-40530 Gothenburg, Sweden
[9] Univ Leicester, Ctr Genet Architecture Complex Traits, Leicester LE1 7RH, Leics, England
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
yeast; genetics; quantitative traits; meiotic recombination; artificial selection; GENETIC ARCHITECTURE; COLLABORATIVE CROSS; MISSING HERITABILITY; QUANTITATIVE TRAITS; SACCHAROMYCES; DISSECTION; CHALLENGES; EVOLUTION; GROWTH; LOCUS;
D O I
10.1534/genetics.113.155515
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:1141 / +
页数:47
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