Quantitative analysis of fitness and genetic interactions in yeast on a genome scale.
Document Type
Article
Publication Date
2010
Keywords
Gene-Expression-Regulation-Fungal, Genetic-Fitness, Genome-Fungal, Genome-Wide-Association-Study, Mutagenesis, Mutation, Oligonucleotide-Array-Sequence-Analysis, Ultraviolet-Rays, Yeasts
First Page
1017
Last Page
1024
JAX Source
Nat Methods 2010 Dec; 7(12):1017-24.
Abstract
Global quantitative analysis of genetic interactions is a powerful approach for deciphering the roles of genes and mapping functional relationships among pathways. Using colony size as a proxy for fitness, we developed a method for measuring fitness-based genetic interactions from high-density arrays of yeast double mutants generated by synthetic genetic array (SGA) analysis. We identified several experimental sources of systematic variation and developed normalization strategies to obtain accurate single- and double-mutant fitness measurements, which rival the accuracy of other high-resolution studies. We applied the SGA score to examine the relationship between physical and genetic interaction networks, and we found that positive genetic interactions connect across functionally distinct protein complexes revealing a network of genetic suppression among loss-of-function alleles.
Recommended Citation
Baryshnikova A,
Costanzo M,
Koh J,
Toufighi K,
Youn JY,
Hibbs M,
Hess D,
Gingras AC,
et a.
Quantitative analysis of fitness and genetic interactions in yeast on a genome scale. Nat Methods 2010 Dec; 7(12):1017-24.