Author:
Gamba Alessio,Salmona Mario,Bazzoni Gianfranco
Abstract
AbstractIt is still largely unknown how mutations in different genes cause similar diseases – a condition known as locus heterogeneity. A likely explanation is that the different proteins encoded by the locus heterogeneity genes participate in the same biological function and, specifically, that they belong to the same protein complex. Here we report that, in up to 30% of the instances of locus heterogeneity, the disease-causing proteins are indeed members of the same protein complex. Moreover, we observed that, in many instances, the diseases and protein complexes only partially intersect. Among the possible explanations, we surmised that some genes that encode proteins in the complex have not yet been reported as causing disease and are therefore candidate disease genes. Mutations of known human disease genes and murine orthologs of candidate disease genes that encode proteins in the same protein complex do in fact often cause similar phenotypes in humans and mice. Furthermore, we found that the disease-complex intersection is not only incomplete but also non-univocal, with many examples of one disease intersecting more than one protein complex or one protein complex intersecting more than one disease. These limits notwithstanding, this study shows that action on proteins in the same complex is a widespread pathogenic mechanism underlying numerous instances of locus heterogeneity.
Publisher
Springer Science and Business Media LLC
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献