The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae.
Saccharomyces cerevisiae
LoF phenotypes
chemical genomics
genetic background
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
17
01
2019
revised:
13
11
2019
accepted:
14
11
2019
entrez:
31
12
2019
pubmed:
31
12
2019
medline:
25
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31885205
doi: 10.15252/msb.20198831
pmc: PMC6901017
doi:
Substances chimiques
Saccharomyces cerevisiae Proteins
0
Banques de données
GEO
['GSE123118']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e8831Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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