Role of Duplicate Genes in Robustness against Deleterious Human Mutations
avril 6, 2008 par Oldcola
Role of Duplicate Genes in Robustness against Deleterious Human Mutations: ”
by Tzu-Lin Hsiao, Dennis Vitkup
Author Summary
Genetic robustness is the ability of an organism to buffer deleterious genetic mutations. It has been previously demonstrated that the functional compensation by duplicates plays an important role in protection against gene deletions in model organisms. Close duplicates often share similar functions, and loss of one paralog may be buffered by others. In the present work we specifically investigate the contribution of gene duplicates to backup against deleterious human mutations. We find that genes with close homologs are significantly less likely to harbor known disease mutations compared to genes with remote homologs. In addition, close duplicates affect the phenotypic consequences of deleterious mutations by making a decrease in life expectancy less likely. Similarity of expression profiles across tissues increases the likelihood of functional compensation by homologs. Taken together, our analysis demonstrates that functional compensation by close duplicates plays an important role in human genetic disease.
