Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping

Abstract We performed a whole-genome scan of genetic variants in splicing regulatory elements (SREs) and evaluated the extent to which natural selection has shaped extant patterns of variation in SREs. We investigated the degree of differentiation of single nucleotide polymorphisms (SNPs) in SREs am...

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Autores principales:	Eric R. Gamazon, Anuar Konkashbaev, Eske M. Derks, Nancy J. Cox, Younghee Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12fc5fba7bf3435dbf229f585abdd9e0
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spelling	oai:doaj.org-article:12fc5fba7bf3435dbf229f585abdd9e02021-12-02T12:32:26ZEvidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping10.1038/s41598-017-05744-92045-2322https://doaj.org/article/12fc5fba7bf3435dbf229f585abdd9e02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05744-9https://doaj.org/toc/2045-2322Abstract We performed a whole-genome scan of genetic variants in splicing regulatory elements (SREs) and evaluated the extent to which natural selection has shaped extant patterns of variation in SREs. We investigated the degree of differentiation of single nucleotide polymorphisms (SNPs) in SREs among human populations and applied long-range haplotype- and multilocus allelic differentiation-based methods to detect selection signatures. We describe an approach, sampling a large number of loci across the genome from functional classes and using the consensus from multiple tests, for identifying candidates for selection signals. SRE SNPs in various SNP functional classes show different patterns of population differentiation compared with their non-SRE counterparts. Intronic regions display a greater enrichment for extreme population differentiation among the potentially tissue-dependent transcript ratio quantitative trait loci (trQTLs) than SRE SNPs in general and includ outlier trQTLs for cross-population composite likelihood ratio, suggesting that incorporation of context annotation for regulatory variation may lead to improved detection of signature of selection on these loci. The proportion of extremely rare SNPs disrupting SREs is significantly higher in European than in African samples. The approach developed here will be broadly useful for studies of function and disease-associated variation in the human genome.Eric R. GamazonAnuar KonkashbaevEske M. DerksNancy J. CoxYounghee LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eric R. Gamazon Anuar Konkashbaev Eske M. Derks Nancy J. Cox Younghee Lee Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
description	Abstract We performed a whole-genome scan of genetic variants in splicing regulatory elements (SREs) and evaluated the extent to which natural selection has shaped extant patterns of variation in SREs. We investigated the degree of differentiation of single nucleotide polymorphisms (SNPs) in SREs among human populations and applied long-range haplotype- and multilocus allelic differentiation-based methods to detect selection signatures. We describe an approach, sampling a large number of loci across the genome from functional classes and using the consensus from multiple tests, for identifying candidates for selection signals. SRE SNPs in various SNP functional classes show different patterns of population differentiation compared with their non-SRE counterparts. Intronic regions display a greater enrichment for extreme population differentiation among the potentially tissue-dependent transcript ratio quantitative trait loci (trQTLs) than SRE SNPs in general and includ outlier trQTLs for cross-population composite likelihood ratio, suggesting that incorporation of context annotation for regulatory variation may lead to improved detection of signature of selection on these loci. The proportion of extremely rare SNPs disrupting SREs is significantly higher in European than in African samples. The approach developed here will be broadly useful for studies of function and disease-associated variation in the human genome.
format	article
author	Eric R. Gamazon Anuar Konkashbaev Eske M. Derks Nancy J. Cox Younghee Lee
author_facet	Eric R. Gamazon Anuar Konkashbaev Eske M. Derks Nancy J. Cox Younghee Lee
author_sort	Eric R. Gamazon
title	Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
title_short	Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
title_full	Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
title_fullStr	Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
title_full_unstemmed	Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
title_sort	evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/12fc5fba7bf3435dbf229f585abdd9e0
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_version_	1718394080981942272

Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping

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