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Nat Methods. 2010 Dec;7(12):1017-24. doi: 10.1038/nmeth.1534. Epub 2010 Nov 14.

Quantitative analysis of fitness and genetic interactions in yeast on a genome scale.

Author information

  • 1Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada. brenda.andrews@utoronto.ca

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.

PMID:
21076421
[PubMed - indexed for MEDLINE]
PMCID:
PMC3117325
Free PMC Article

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