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Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways
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Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways
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Journal Article
Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways
2006
Overview
Most heritable traits, including disease susceptibility, are affected by interactions between multiple genes. However, we understand little about how genes interact because very few possible genetic interactions have been explored experimentally. We have used RNA interference in
Caenorhabditis elegans
to systematically test ∼65,000 pairs of genes for their ability to interact genetically. We identify ∼350 genetic interactions between genes functioning in signaling pathways that are mutated in human diseases, including components of the EGF/Ras, Notch and Wnt pathways. Most notably, we identify a class of highly connected 'hub' genes: inactivation of these genes can enhance the phenotypic consequences of mutation of many different genes. These hub genes all encode chromatin regulators, and their activity as genetic hubs seems to be conserved across animals. We propose that these genes function as general buffers of genetic variation and that these hub genes may act as modifier genes in multiple, mechanistically unrelated genetic diseases in humans.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Animals
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Buffers
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans - metabolism
/ Classical genetics, quantitative genetics, hybrids
/ Disease
/ Epidermal Growth Factor - genetics
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Genetics of eukaryotes. Biological and molecular evolution
/ Genomics
/ Humans
/ Methods, theories and miscellaneous
/ Molecular and cellular biology
/ Mutation
/ Vulva - growth & development
/ Worms
