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Comparative Study
. 2006 Jul 3:7:165.
doi: 10.1186/1471-2164-7-165.

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

Simon J Furney  1 , M Mar Albà, Núria López-Bigas
Affiliations
Comparative Study

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

Simon J Furney et al. BMC Genomics. .

Abstract

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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Figures

Figure 1
Figure 1
Conservation of dominant and recessive disease genes at protein level. Distribution of conservation score in mouse of dominant and recessive disease genes versus the rest of genes.
Figure 2
Figure 2
Conservation of paralogues of dominant and recessive disease genes at protein level. Distribution of conservation score in paralogues of dominant and recessive disease genes versus the rest of genes.
Figure 3
Figure 3
Evolutionary rates between human and chimpanzee genes of dominant and recessive disease genes at DNA level. (A) Distribution of KA for disease genes versus the rest of genes. (B) Distribution of KS for disease genes versus the rest of genes. (C) Distribution of KA/KS ratio of disease genes versus the rest of genes.
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