Cargando…

Broker Genes in Human Disease

Genes that underlie human disease are important subjects of systems biology research. In the present study, we demonstrate that Mendelian and complex disease genes have distinct and consistent protein–protein interaction (PPI) properties. We show that five different network properties can be reduced...

Descripción completa

Detalles Bibliográficos
Autores principales: Cai, James J., Borenstein, Elhanan, Petrov, Dmitri A.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988523/
https://www.ncbi.nlm.nih.gov/pubmed/20937604
http://dx.doi.org/10.1093/gbe/evq064
_version_ 1782192254945853440
author Cai, James J.
Borenstein, Elhanan
Petrov, Dmitri A.
author_facet Cai, James J.
Borenstein, Elhanan
Petrov, Dmitri A.
author_sort Cai, James J.
collection PubMed
description Genes that underlie human disease are important subjects of systems biology research. In the present study, we demonstrate that Mendelian and complex disease genes have distinct and consistent protein–protein interaction (PPI) properties. We show that five different network properties can be reduced to two independent metrics when applied to the human PPI network. These two metrics largely coincide with the degree (number of connections) and the clustering coefficient (the number of connections among the neighbors of a particular protein). We demonstrate that disease genes have simultaneously unusually high degree and unusually low clustering coefficient. Such genes can be described as brokers in that they connect many proteins that would not be connected otherwise. We show that these results are robust to the effect of gene age and inspection bias variation. Notably, genes identified in genome-wide association study (GWAS) have network patterns that are almost indistinguishable from the network patterns of nondisease genes and significantly different from the network patterns of complex disease genes identified through non-GWAS means. This suggests either that GWAS focused on a distinct set of diseases associated with an unusual set of genes or that mapping of GWAS-identified single nucleotide polymorphisms onto the causally affected neighboring genes is error prone.
format Text
id pubmed-2988523
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-29885232010-11-19 Broker Genes in Human Disease Cai, James J. Borenstein, Elhanan Petrov, Dmitri A. Genome Biol Evol Research Articles Genes that underlie human disease are important subjects of systems biology research. In the present study, we demonstrate that Mendelian and complex disease genes have distinct and consistent protein–protein interaction (PPI) properties. We show that five different network properties can be reduced to two independent metrics when applied to the human PPI network. These two metrics largely coincide with the degree (number of connections) and the clustering coefficient (the number of connections among the neighbors of a particular protein). We demonstrate that disease genes have simultaneously unusually high degree and unusually low clustering coefficient. Such genes can be described as brokers in that they connect many proteins that would not be connected otherwise. We show that these results are robust to the effect of gene age and inspection bias variation. Notably, genes identified in genome-wide association study (GWAS) have network patterns that are almost indistinguishable from the network patterns of nondisease genes and significantly different from the network patterns of complex disease genes identified through non-GWAS means. This suggests either that GWAS focused on a distinct set of diseases associated with an unusual set of genes or that mapping of GWAS-identified single nucleotide polymorphisms onto the causally affected neighboring genes is error prone. Oxford University Press 2010 2010-10-11 /pmc/articles/PMC2988523/ /pubmed/20937604 http://dx.doi.org/10.1093/gbe/evq064 Text en © The Author(s) 2010. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Cai, James J.
Borenstein, Elhanan
Petrov, Dmitri A.
Broker Genes in Human Disease
title Broker Genes in Human Disease
title_full Broker Genes in Human Disease
title_fullStr Broker Genes in Human Disease
title_full_unstemmed Broker Genes in Human Disease
title_short Broker Genes in Human Disease
title_sort broker genes in human disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988523/
https://www.ncbi.nlm.nih.gov/pubmed/20937604
http://dx.doi.org/10.1093/gbe/evq064
work_keys_str_mv AT caijamesj brokergenesinhumandisease
AT borensteinelhanan brokergenesinhumandisease
AT petrovdmitria brokergenesinhumandisease