Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.

MYH9 was recently identified as renal susceptibility gene (OR 3-8, p < 10(-8)) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (> or = 60%) than in European Americans...

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Autores principales:	Taras K Oleksyk, George W Nelson, Ping An, Jeffrey B Kopp, Cheryl A Winkler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/57d2f38def5749fe9eb360abaf0c34ab
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spelling	oai:doaj.org-article:57d2f38def5749fe9eb360abaf0c34ab2021-12-02T20:20:13ZWorldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.1932-620310.1371/journal.pone.0011474https://doaj.org/article/57d2f38def5749fe9eb360abaf0c34ab2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20634883/?tool=EBIhttps://doaj.org/toc/1932-6203MYH9 was recently identified as renal susceptibility gene (OR 3-8, p < 10(-8)) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (> or = 60%) than in European Americans (< 4%), revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1 risk haplotype and the demographic and selective forces acting on the MYH9 region are not well explored. We reconstructed MYH9 haplotypes from 4 tagging single nucleotide polymorphisms (SNPs) spanning introns 12-23 using available data from HapMap Phase II, and by genotyping 938 DNAs from the Human Genome Diversity Panel (HGDP). The E-1 risk haplotype followed a cline, being most frequent within sub-Saharan African populations (range 50-80%), less frequent in populations from the Middle East (9-27%) and Europe (0-9%), and rare or absent in Asia, the Americas, and Oceania. The fixation indexes (F(ST)) for pairwise comparisons between the risk haplotypes for continental populations were calculated for MYH9 haplotypes; F(ST) ranged from 0.27-0.40 for Africa compared to other continental populations, possibly due to selection. Uniquely in Africa, the Yoruba population showed high frequency extended haplotype length around the core risk allele (C) compared to the alternative allele (T) at the same locus (rs4821481, iHs = 2.67), as well as high population differentiation (F(ST(CEU vs. YRI)) = 0.51) in HapMap Phase II data, also observable only in the Yoruba population from HGDP (F(ST) = 0.49), pointing to an instance of recent selection in the genomic region. The population-specific divergence in MYH9 risk allele frequencies among the world's populations may prove important in risk assessment and public health policies to mitigate the burden of kidney disease in vulnerable populations.Taras K OleksykGeorge W NelsonPing AnJeffrey B KoppCheryl A WinklerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11474 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Taras K Oleksyk George W Nelson Ping An Jeffrey B Kopp Cheryl A Winkler Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.
description	MYH9 was recently identified as renal susceptibility gene (OR 3-8, p < 10(-8)) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (> or = 60%) than in European Americans (< 4%), revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1 risk haplotype and the demographic and selective forces acting on the MYH9 region are not well explored. We reconstructed MYH9 haplotypes from 4 tagging single nucleotide polymorphisms (SNPs) spanning introns 12-23 using available data from HapMap Phase II, and by genotyping 938 DNAs from the Human Genome Diversity Panel (HGDP). The E-1 risk haplotype followed a cline, being most frequent within sub-Saharan African populations (range 50-80%), less frequent in populations from the Middle East (9-27%) and Europe (0-9%), and rare or absent in Asia, the Americas, and Oceania. The fixation indexes (F(ST)) for pairwise comparisons between the risk haplotypes for continental populations were calculated for MYH9 haplotypes; F(ST) ranged from 0.27-0.40 for Africa compared to other continental populations, possibly due to selection. Uniquely in Africa, the Yoruba population showed high frequency extended haplotype length around the core risk allele (C) compared to the alternative allele (T) at the same locus (rs4821481, iHs = 2.67), as well as high population differentiation (F(ST(CEU vs. YRI)) = 0.51) in HapMap Phase II data, also observable only in the Yoruba population from HGDP (F(ST) = 0.49), pointing to an instance of recent selection in the genomic region. The population-specific divergence in MYH9 risk allele frequencies among the world's populations may prove important in risk assessment and public health policies to mitigate the burden of kidney disease in vulnerable populations.
format	article
author	Taras K Oleksyk George W Nelson Ping An Jeffrey B Kopp Cheryl A Winkler
author_facet	Taras K Oleksyk George W Nelson Ping An Jeffrey B Kopp Cheryl A Winkler
author_sort	Taras K Oleksyk
title	Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.
title_short	Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.
title_full	Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.
title_fullStr	Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.
title_full_unstemmed	Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.
title_sort	worldwide distribution of the myh9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in africa.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/57d2f38def5749fe9eb360abaf0c34ab
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Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa.

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