The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae
The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae
复制标题
DOI：
10.15252/msb.20198831
复制
发表时间：
2019-12-01
影响因子：
9.9
通讯作者：
Beltrao, Pedro
中科院分区：
文献类型：
--
作者：
Galardini, Marco;Busby, Bede P.;Beltrao, Pedro
与疾病相关的功能丧失（LoF）突变在不同个体中的表现并不相同。遗传背景对LoF突变后果的影响仍不清楚。在这里，我们系统地评估了4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变化。我们观察到18.5%的缺失表型变化对菌株之间的平均一小部分保守在所有四个菌株。条件导致更高的野生型生长差异和多效性基因的删除表现出高于平均水平的表型变化。此外，我们进行了全基因组关联研究（GWAS）的增长在相同的条件下的一组925酵母分离株。来自GWAS的基因-条件关联在相同条件下不富集具有缺失表型的基因。然而，结果一致的病例表明GWAS信号最可能的机制。总的来说，这些结果显示了LoF表型的高度遗传背景依赖性。
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.