title: Linking functionally related genes by sensitive and quantitative characterization of genetic interaction profiles.
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.
authors.affiliation: Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2171, Paris Cedex 15, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Decourty
authors.forename: Cosmin
authors.initials: C
authors.lastname: Saveanu
authors.forename: Kenza
authors.initials: K
authors.lastname: Zemam
authors.forename: Florence
authors.initials: F
authors.lastname: Hantraye
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Frachon
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Rousselle
authors.forename: Micheline
authors.initials: M
authors.lastname: Fromont-Racine
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquier
mesh_terms: D015723:Gene Library; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D016681:Genome, Fungal; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015003:Yeasts