Human monogenic disease genes have frequently functionally redundant paralogs.

Mendelian disorders are often caused by mutations in genes that are not lethal but induce functional distortions leading to diseases. Here we study the extent of gene duplicates that might compensate genes causing monogenic diseases. We provide evidence for pervasive functional redundancy of human m...

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Autores principales:	Wei-Hua Chen, Xing-Ming Zhao, Vera van Noort, Peer Bork
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/96b5ccdd8f404f21a35804cc1104783f
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spelling	oai:doaj.org-article:96b5ccdd8f404f21a35804cc1104783f2021-11-18T05:52:08ZHuman monogenic disease genes have frequently functionally redundant paralogs.1553-734X1553-735810.1371/journal.pcbi.1003073https://doaj.org/article/96b5ccdd8f404f21a35804cc1104783f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23696728/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Mendelian disorders are often caused by mutations in genes that are not lethal but induce functional distortions leading to diseases. Here we study the extent of gene duplicates that might compensate genes causing monogenic diseases. We provide evidence for pervasive functional redundancy of human monogenic disease genes (MDs) by duplicates by manifesting 1) genes involved in human genetic disorders are enriched in duplicates and 2) duplicated disease genes tend to have higher functional similarities with their closest paralogs in contrast to duplicated non-disease genes of similar age. We propose that functional compensation by duplication of genes masks the phenotypic effects of deleterious mutations and reduces the probability of purging the defective genes from the human population; this functional compensation could be further enhanced by higher purification selection between disease genes and their duplicates as well as their orthologous counterpart compared to non-disease genes. However, due to the intrinsic expression stochasticity among individuals, the deleterious mutations could still be present as genetic diseases in some subpopulations where the duplicate copies are expressed at low abundances. Consequently the defective genes are linked to genetic disorders while they continue propagating within the population. Our results provide insight into the molecular basis underlying the spreading of duplicated disease genes.Wei-Hua ChenXing-Ming ZhaoVera van NoortPeer BorkPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 5, p e1003073 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Wei-Hua Chen Xing-Ming Zhao Vera van Noort Peer Bork Human monogenic disease genes have frequently functionally redundant paralogs.
description	Mendelian disorders are often caused by mutations in genes that are not lethal but induce functional distortions leading to diseases. Here we study the extent of gene duplicates that might compensate genes causing monogenic diseases. We provide evidence for pervasive functional redundancy of human monogenic disease genes (MDs) by duplicates by manifesting 1) genes involved in human genetic disorders are enriched in duplicates and 2) duplicated disease genes tend to have higher functional similarities with their closest paralogs in contrast to duplicated non-disease genes of similar age. We propose that functional compensation by duplication of genes masks the phenotypic effects of deleterious mutations and reduces the probability of purging the defective genes from the human population; this functional compensation could be further enhanced by higher purification selection between disease genes and their duplicates as well as their orthologous counterpart compared to non-disease genes. However, due to the intrinsic expression stochasticity among individuals, the deleterious mutations could still be present as genetic diseases in some subpopulations where the duplicate copies are expressed at low abundances. Consequently the defective genes are linked to genetic disorders while they continue propagating within the population. Our results provide insight into the molecular basis underlying the spreading of duplicated disease genes.
format	article
author	Wei-Hua Chen Xing-Ming Zhao Vera van Noort Peer Bork
author_facet	Wei-Hua Chen Xing-Ming Zhao Vera van Noort Peer Bork
author_sort	Wei-Hua Chen
title	Human monogenic disease genes have frequently functionally redundant paralogs.
title_short	Human monogenic disease genes have frequently functionally redundant paralogs.
title_full	Human monogenic disease genes have frequently functionally redundant paralogs.
title_fullStr	Human monogenic disease genes have frequently functionally redundant paralogs.
title_full_unstemmed	Human monogenic disease genes have frequently functionally redundant paralogs.
title_sort	human monogenic disease genes have frequently functionally redundant paralogs.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/96b5ccdd8f404f21a35804cc1104783f
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_version_	1718424744533950464

Human monogenic disease genes have frequently functionally redundant paralogs.

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