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Quantifying Dominance and Deleterious Effect on Human Disease Genes

Naoki Osada, Shuhei Mano, Jun Gojobori and Tomoko Ohta
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 3 (Jan. 20, 2009), pp. 841-846
Stable URL: http://www.jstor.org/stable/40254759
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Quantifying Dominance and Deleterious Effect on Human Disease Genes
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Abstract

Human genes responsible for inherited diseases are important for the understanding of human disease. We investigated the degree of polymorphism and divergence in the human disease genes to elucidate the effect of natural selection on human disease genes. In particular, the effect of disease dominance was incorporated into the analysis. Both dominant disease genes (DDG) and recessive disease genes (RDG) had a higher mutation rate per site and encoded longer proteins than the nondisease genes, which exposed the disease genes to a faster flux of new mutations. Using an unbiased polymorphism dataset, we found that proportionally, RDG harbor more nonsynonymous polymorphisms compared with DDG. We estimated the selection intensity on the disease genes using polymorphism and divergence data and determined whether the different patterns of polymorphism and divergence between DDG and RDG could be explained by the difference in only dominance. Even after the dominance effect was considered, the selection intensity on RDG was significantly different from DDG, suggesting that the deleterious effect of the dominant and recessive disease mutations re fundamentally different.

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