Locus heterogeneity disease genes encode proteins with high interconnectivity in the human protein interaction network.

TitleLocus heterogeneity disease genes encode proteins with high interconnectivity in the human protein interaction network.
Publication TypeJournal Article
Year of Publication2014
AuthorsKeith BP, Robertson DL, Hentges KE
JournalFront Genet
Volume5
Pagination434
Date Published2014
ISSN1664-8021
Abstract

Mutations in genes potentially lead to a number of genetic diseases with differing severity. These disease genes have been the focus of research in recent years showing that the disease gene population as a whole is not homogeneous, and can be categorized according to their interactions. Locus heterogeneity describes a single disorder caused by mutations in different genes each acting individually to cause the same disease. Using datasets of experimentally derived human disease genes and protein interactions, we created a protein interaction network to investigate the relationships between the products of genes associated with a disease displaying locus heterogeneity, and use network parameters to suggest properties that distinguish these disease genes from the overall disease gene population. Through the manual curation of known causative genes of 100 diseases displaying locus heterogeneity and 397 single-gene Mendelian disorders, we use network parameters to show that our locus heterogeneity network displays distinct properties from the global disease network and a Mendelian network. Using the global human proteome, through random simulation of the network we show that heterogeneous genes display significant interconnectivity. Further topological analysis of this network revealed clustering of locus heterogeneity genes that cause identical disorders, indicating that these disease genes are involved in similar biological processes. We then use this information to suggest additional genes that may contribute to diseases with locus heterogeneity.

DOI10.3389/fgene.2014.00434
Alternate JournalFront Genet
Citation Key1573
PubMed ID25538735