Jun 12, 2010

Predicting genetic modifier loci using functional gene networks

Genome Research
Insuk LeeEdward M Marcotte

Abstract

Most phenotypes are genetically complex, with contributions from mutations in many different genes. Mutations in more than one gene can combine synergistically to cause phenotypic change, and systematic studies in model organisms show that these genetic interactions are pervasive. However, in human association studies such nonadditive genetic interactions are very difficult to identify because of a lack of statistical power--simply put, the number of potential interactions is too vast. One approach to resolve this is to predict candidate modifier interactions between loci, and then to specifically test these for associations with the phenotype. Here, we describe a general method for predicting genetic interactions based on the use of integrated functional gene networks. We show that in both Saccharomyces cerevisiae and Caenorhabditis elegans a single high-coverage, high-quality functional network can successfully predict genetic modifiers for the majority of genes. For C. elegans we also describe the construction of a new, improved, and expanded functional network, WormNet 2. Using this network we demonstrate how it is possible to rapidly expand the number of modifier loci known for a gene, predicting and validating new genetic...Continue Reading

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  • Citations42

Mentioned in this Paper

Calcinus elegans
Cyartonema elegans
Coleonyx elegans
Cestrum elegans
Clarkia unguiculata
Clathrulina elegans
Cardioglossa elegans
Cymbella elegans
Cyrenella elegans
Chaetophora elegans

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