Linking Functionally Related Genes by Sensitive and Quantitative Characterization of Genetic Interaction Profiles

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 bu...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-04, Vol.105 (15), p.5821-5826
Main Authors: Decourty, Laurence, Saveanu, Cosmin, Zemam, Kenza, Hantraye, Florence, Frachon, Emmanuel, Rousselle, Jean-Claude, Fromont-Racine, Micheline, Jacquier, Alain
Format: Article
Language:English
Subjects:
Biological Sciences
Datasets
Gene Library
Gene Regulatory Networks
Genes
Genes, Fungal
Genetic mutation
Genetic screening
Genetics
Genome, Fungal
Genomics
Genotype & phenotype
Haploidy
Libraries
Life Sciences
Messenger RNA
Mutation
Quantitative genetics
RNA stability
Saccharomyces cerevisiae - genetics
Yeast
Yeasts
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0710533105