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Differences in the evolutionary history of disease genes affected by dominant or recessive mutations
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)....
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1534034/ https://www.ncbi.nlm.nih.gov/pubmed/16817963 http://dx.doi.org/10.1186/1471-2164-7-165 |
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author | Furney, Simon J Albà, M Mar López-Bigas, Núria |
author_facet | Furney, Simon J Albà, M Mar López-Bigas, Núria |
author_sort | Furney, Simon J |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-1534034 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-15340342006-08-09 Differences in the evolutionary history of disease genes affected by dominant or recessive mutations Furney, Simon J Albà, M Mar López-Bigas, Núria BMC Genomics Research Article 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. BioMed Central 2006-07-03 /pmc/articles/PMC1534034/ /pubmed/16817963 http://dx.doi.org/10.1186/1471-2164-7-165 Text en Copyright © 2006 Furney et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Furney, Simon J Albà, M Mar López-Bigas, Núria Differences in the evolutionary history of disease genes affected by dominant or recessive mutations |
title | Differences in the evolutionary history of disease genes affected by dominant or recessive mutations |
title_full | Differences in the evolutionary history of disease genes affected by dominant or recessive mutations |
title_fullStr | Differences in the evolutionary history of disease genes affected by dominant or recessive mutations |
title_full_unstemmed | Differences in the evolutionary history of disease genes affected by dominant or recessive mutations |
title_short | Differences in the evolutionary history of disease genes affected by dominant or recessive mutations |
title_sort | differences in the evolutionary history of disease genes affected by dominant or recessive mutations |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1534034/ https://www.ncbi.nlm.nih.gov/pubmed/16817963 http://dx.doi.org/10.1186/1471-2164-7-165 |
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