Quantifying dominance and deleterious effect on human disease genes Export

@article{citeulike:3892160, abstract = {10.1073/pnas.0810433106 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 are fundamentally different.}, author = {Osada, Naoki and Mano, Shuhei and Gojobori, Jun}, citeulike-article-id = {3892160}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0810433106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/3/841.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/3/841.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19139396}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19139396}, day = {20}, doi = {10.1073/pnas.0810433106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {dominance}, month = {January}, number = {3}, pages = {841--846}, posted-at = {2009-01-16 16:45:23}, priority = {2}, title = {Quantifying dominance and deleterious effect on human disease genes}, url = {http://dx.doi.org/10.1073/pnas.0810433106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:3892160 L3 - citeulike-article-id:3892160 N2 - 10.1073/pnas.0810433106 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 are fundamentally different. IS - 3 JF - Proceedings of the National Academy of Sciences SN - 1091-6490 EP - 846 TI - Quantifying dominance and deleterious effect on human disease genes VL - 106 SP - 841 KW - dominance AU - Osada, Naoki AU - Mano, Shuhei AU - Gojobori, Jun PY - 2009/01/20/ UR - http://dx.doi.org/10.1073/pnas.0810433106 ER -