The impact of the genetic background on gene deletion phenotypes inSaccharomyces cerevisiae

Abstract

AbstractLoss-of-function (LoF) mutations associated with disease don’t manifest equally in different individuals, a phenomenon known as incomplete penetrance. The impact of the genetic background on incomplete penetrance remains poorly characterized. Here, we systematically assessed the changes in gene deletion phenotypes for 3,786 gene knockouts in fourSaccharomyces cerevisiaestrains and 38 conditions. We observed 16% to 42% of deletion phenotypes changing between pairs of strains with a small fraction conserved in all strains. Conditions causing higher WT growth differences and the deletion of pleiotropic genes showed above average changes in phenotypes. We further illustrate how these changes affect the interpretation of the impact of genetic variants across 925 yeast isolates. These results show the high degree of genetic background dependencies for LoF phenotypes.