Modeling epistasis in mice and yeast using the proportion of two or more distinct genetic backgrounds: Evidence for “polygenic epistasis”

English version

Autoři: Christoph D. Rau ^aff001; Natalia M. Gonzales ^aff002; Joshua S. Bloom ^aff003; Danny Park ^aff004; Julien Ayroles ^aff005; Abraham A. Palmer ^aff006; Aldons J. Lusis ^aff003; Noah Zaitlen ^aff007
Působiště autorů: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America ^aff001; Department of Human Genetics, University of Chicago, Chicago, IL, United States of America ^aff002; Department of Human Genetics, UCLA, Los Angeles, CA, United States of America ^aff003; Department of Medicine, UCSF, San Francisco, CA, United States of America ^aff004; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, United States of America ^aff005; Department of Psychiatry, and Institute for Genomic Medicine, UCSD, San Diego, CA, United States of America ^aff006; Department of Neurology, UCLA, Los Angeles, CA, United States of America ^aff007
Vyšlo v časopise: Modeling epistasis in mice and yeast using the proportion of two or more distinct genetic backgrounds: Evidence for “polygenic epistasis”. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009165
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009165

Souhrn

Background

The majority of quantitative genetic models used to map complex traits assume that alleles have similar effects across all individuals. Significant evidence suggests, however, that epistatic interactions modulate the impact of many alleles. Nevertheless, identifying epistatic interactions remains computationally and statistically challenging. In this work, we address some of these challenges by developing a statistical test for polygenic epistasis that determines whether the effect of an allele is altered by the global genetic ancestry proportion from distinct progenitors.

Results

We applied our method to data from mice and yeast. For the mice, we observed 49 significant genotype-by-ancestry interaction associations across 14 phenotypes as well as over 1,400 Bonferroni-corrected genotype-by-ancestry interaction associations for mouse gene expression data. For the yeast, we observed 92 significant genotype-by-ancestry interactions across 38 phenotypes. Given this evidence of epistasis, we test for and observe evidence of rapid selection pressure on ancestry specific polymorphisms within one of the cohorts, consistent with epistatic selection.

Conclusions

Unlike our prior work in human populations, we observe widespread evidence of ancestry-modified SNP effects, perhaps reflecting the greater divergence present in crosses using mice and yeast.

Klíčová slova:

Epistasis – Genetic loci – Inbred strains – Mammalian genomics – Mouse models – Phenotypes – Single nucleotide polymorphisms – Yeast

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