Role of duplicate genes in robustness against deleterious human mutations.

Abstract:

:It is now widely recognized that robustness is an inherent property of biological systems [1],[2],[3]. The contribution of close sequence homologs to genetic robustness against null mutations has been previously demonstrated in simple organisms [4],[5]. In this paper we investigate in detail the contribution of gene duplicates to back-up against deleterious human mutations. Our analysis demonstrates that the functional compensation by close homologs may play an important role in human genetic disease. Genes with a 90% sequence identity homolog are about 3 times less likely to harbor known disease mutations compared to genes with remote homologs. Moreover, close duplicates affect the phenotypic consequences of deleterious mutations by making a decrease in life expectancy significantly less likely. We also demonstrate that similarity of expression profiles across tissues significantly increases the likelihood of functional compensation by homologs.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Hsiao TL,Vitkup D

doi

10.1371/journal.pgen.1000014

subject

Has Abstract

pub_date

2008-03-14 00:00:00

pages

e1000014

issue

3

eissn

1553-7390

issn

1553-7404

journal_volume

4

pub_type

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