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PLoS Genet

Title:		Use of pleiotropy to model genetic interactions in a population
Author(s):		Carter GW; Hays M; Sherman A; Galitski T;
Address:		"The Jackson Laboratory, Bar Harbor, Maine, USA. Greg.Carter@jax.org"
Journal Title:		PLoS Genet
Year:		2012
Volume:		20121011
Issue:		10
Page Number:		e1003010 -
DOI:		10.1371/journal.pgen.1003010
ISSN/ISBN:		1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking)
Abstract:		"Systems-level genetic studies in humans and model systems increasingly involve both high-resolution genotyping and multi-dimensional quantitative phenotyping. We present a novel method to infer and interpret genetic interactions that exploits the complementary information in multiple phenotypes. We applied this approach to a population of yeast strains with randomly assorted perturbations of five genes involved in mating. We quantified pheromone response at the molecular level and overall mating efficiency. These phenotypes were jointly analyzed to derive a network of genetic interactions that mapped mating-pathway relationships. To determine the distinct biological processes driving the phenotypic complementarity, we analyzed patterns of gene expression to find that the pheromone response phenotype is specific to cellular fusion, whereas mating efficiency was a combined measure of cellular fusion, cell cycle arrest, and modifications in cellular metabolism. We applied our novel method to global gene expression patterns to derive an expression-specific interaction network and demonstrate applicability to global transcript data. Our approach provides a basis for interpretation of genetic interactions and the generation of specific hypotheses from populations assayed for multiple phenotypes"
Keywords:		"Algorithms *Epistasis, Genetic Gene Expression Regulation, Fungal Gene Regulatory Networks *Genetic Pleiotropy *Models, Genetic Mutation Phenotype Transcription Factors/metabolism Yeasts/genetics/metabolism;"
Notes:		"MedlineCarter, Gregory W Hays, Michelle Sherman, Amir Galitski, Timothy eng K25 GM079404/GM/NIGMS NIH HHS/ P50 GM076468/GM/NIGMS NIH HHS/ P50 GM076547/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2012/10/17 PLoS Genet. 2012; 8(10):e1003010. doi: 10.1371/journal.pgen.1003010. Epub 2012 Oct 11"