Loss-of-function (LoF) mutations associated with disease do not manifest equally in different individuals. The impact of the genetic background on the consequences of LoF mutations remains poorly characterized. Here, we systematically assessed the changes in gene deletion phenotypes for 3,786 gene knockouts in four Saccharomyces cerevisiae strains and 38 conditions. We observed 18.5% of deletion phenotypes changing between pairs of strains on average with a small fraction conserved in all four strains. Conditions causing higher wild-type growth differences and the deletion of pleiotropic genes showed above-average changes in phenotypes. In addition, we performed a genome-wide association study (GWAS) for growth under the same conditions for a panel of 925 yeast isolates. Gene-condition associations derived from GWAS were not enriched for genes with deletion phenotypes under the same conditions. However, cases where the results were congruent indicate the most likely mechanism underlying the GWAS signal. Overall, these results show a high degree of genetic background dependencies for LoF phenotypes.

中文翻译：

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遗传背景对酿酒酵母基因缺失表型的影响。

与疾病相关的功能丧失（LoF）突变在不同个体中的表现不同。遗传背景对LoF突变后果的影响仍然不明确。在这里，我们系统地评估了四种酿酒酵母菌株和38种条件下3,786个基因敲除的基因缺失表型的变化。我们观察到平均缺失对表型之间有18.5％的缺失表型发生变化，在所有四个菌株中都有一小部分保守。导致较高的野生型生长差异和多效性基因缺失的条件表明表型变化高于平均水平。此外，我们对一组925个酵母菌在相同条件下进行了全基因组关联研究（GWAS）。来自GWAS的基因条件关联在相同条件下未富集具有缺失表型的基因。但是，结果一致的情况表明GWAS信号最可能的机制。总体而言，这些结果表明LoF表型具有高度的遗传背景依赖性。