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Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5821-6. doi: 10.1073/pnas.0710533105. Epub 2008 Apr 11.

Linking functionally related genes by sensitive and quantitative characterization of genetic interaction profiles.

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  • 1Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2171, Paris Cedex 15, France.

Abstract

Describing at a genomic scale how mutations in different genes influence one another is essential to the understanding of how genotype correlates with phenotype and remains a major challenge in biology. Previous studies pointed out the need for accurate measurements of not only synthetic but also buffering interactions in the characterization of genetic networks and functional modules. We developed a sensitive and efficient method that allows such measurements at a genomic scale in yeast. In a pilot experiment (41 genome-wide screens), we quantified the fitness of 140,000 double deletion strains relative to the corresponding single mutants and identified many genetic interactions. In addition to synthetic growth defects (validated experimentally with factors newly identified as genetically interfering with mRNA degradation), most of the identified genetic interactions measured weak epistatic effects. These weak effects, rarely meaningful when considered individually, were crucial to defining specific signatures for many gene deletions and had a major contribution in defining clusters of functionally related genes.

PMID:
18408161
[PubMed - indexed for MEDLINE]
PMCID:
PMC2311358
Free PMC Article
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