Differences in the evolutionary history of disease genes affected by dominant or recessive mutations

被引:80
作者
Furney, Simon J.
Alba, M. Mar
Lopez-Bigas, Nuria
机构
[1] Univ Pompeu Fabra, Ctr Genome Regulat, Genome Bioinformat Lab, E-08003 Barcelona, Spain
[2] Univ Pompeu Fabra, ICREA, Inst Municipal Invest Med, E-08003 Barcelona, Spain
[3] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland
关键词
D O I
10.1186/1471-2164-7-165
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Global analyses of human disease genes by computational methods have yielded important advances in the understanding of human diseases. Generally these studies have treated the group of disease genes uniformly, thus ignoring the type of disease-causing mutations ( dominant or recessive). In this report we present a comprehensive study of the evolutionary history of autosomal disease genes separated by mode of inheritance. Results: We examine differences in protein and coding sequence conservation between dominant and recessive human disease genes. Our analysis shows that disease genes affected by dominant mutations are more conserved than those affected by recessive mutations. This could be a consequence of the fact that recessive mutations remain hidden from selection while heterozygous. Furthermore, we employ functional annotation analysis and investigations into disease severity to support this hypothesis. Conclusion: This study elucidates important differences between dominantly- and recessively-acting disease genes in terms of protein and DNA sequence conservation, paralogy and essentiality. We propose that the division of disease genes by mode of inheritance will enhance both understanding of the disease process and prediction of candidate disease genes in the future.
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页数:11
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