Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways

被引：361

作者：

Lehner, Ben ^{[1
]}

Crombie, Catriona ^{[1
]}

Tischler, Julia ^{[1
]}

Fortunato, Angelo ^{[1
]}

Fraser, Andrew G. ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England

来源：

NATURE GENETICS | 2006年 / 38卷 / 08期

基金：

英国惠康基金;

关键词：

D O I：

10.1038/ng1844

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学]; 090102 [作物遗传育种];

摘要：

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 similar to 65,000 pairs of genes for their ability to interact genetically. We identify similar to 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.

引用

页码：896 / 903

页数：8

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