The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae
Abstract 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 3,7...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2019-12-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20198831 |
| _version_ | 1797283917212942336 |
|---|---|
| author | Marco Galardini Bede P Busby Cristina Vieitez Alistair S Dunham Athanasios Typas Pedro Beltrao |
| author_facet | Marco Galardini Bede P Busby Cristina Vieitez Alistair S Dunham Athanasios Typas Pedro Beltrao |
| author_sort | Marco Galardini |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T17:38:47Z |
| format | Article |
| id | doaj.art-3343ed5c76554252800c2d2617bd8b76 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:38:47Z |
| publishDate | 2019-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-3343ed5c76554252800c2d2617bd8b762024-03-02T16:10:04ZengSpringer NatureMolecular Systems Biology1744-42922019-12-011512n/an/a10.15252/msb.20198831The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiaeMarco Galardini0Bede P Busby1Cristina Vieitez2Alistair S Dunham3Athanasios Typas4Pedro Beltrao5European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Trust Genome Campus Hinxton, Cambridge UKEuropean Molecular Biology Laboratory European Bioinformatics Institute Wellcome Trust Genome Campus Hinxton, Cambridge UKEuropean Molecular Biology Laboratory European Bioinformatics Institute Wellcome Trust Genome Campus Hinxton, Cambridge UKEuropean Molecular Biology Laboratory European Bioinformatics Institute Wellcome Trust Genome Campus Hinxton, Cambridge UKEuropean Molecular Biology Laboratory Genome Biology Unit Heidelberg GermanyEuropean Molecular Biology Laboratory European Bioinformatics Institute Wellcome Trust Genome Campus Hinxton, Cambridge UKAbstract 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.https://doi.org/10.15252/msb.20198831chemical genomicsgenetic backgroundLoF phenotypesSaccharomyces cerevisiae |
| spellingShingle | Marco Galardini Bede P Busby Cristina Vieitez Alistair S Dunham Athanasios Typas Pedro Beltrao The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae Molecular Systems Biology chemical genomics genetic background LoF phenotypes Saccharomyces cerevisiae |
| title | The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae |
| title_full | The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae |
| title_fullStr | The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae |
| title_full_unstemmed | The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae |
| title_short | The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae |
| title_sort | impact of the genetic background on gene deletion phenotypes in saccharomyces cerevisiae |
| topic | chemical genomics genetic background LoF phenotypes Saccharomyces cerevisiae |
| url | https://doi.org/10.15252/msb.20198831 |
| work_keys_str_mv | AT marcogalardini theimpactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT bedepbusby theimpactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT cristinavieitez theimpactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT alistairsdunham theimpactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT athanasiostypas theimpactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT pedrobeltrao theimpactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT marcogalardini impactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT bedepbusby impactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT cristinavieitez impactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT alistairsdunham impactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT athanasiostypas impactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae AT pedrobeltrao impactofthegeneticbackgroundongenedeletionphenotypesinsaccharomycescerevisiae |