Rare and common regulatory variation in population-scale sequenced human genomes.

Population-scale genome sequencing allows the characterization of functional effects of a broad spectrum of genetic variants underlying human phenotypic variation. Here, we investigate the influence of rare and common genetic variants on gene expression patterns, using variants identified from seque...

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Autores principales:	Stephen B Montgomery, Tuuli Lappalainen, Maria Gutierrez-Arcelus, Emmanouil T Dermitzakis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/30da82ecc5444f778ec209abb4815dbe
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spelling	oai:doaj.org-article:30da82ecc5444f778ec209abb4815dbe2021-11-18T06:17:13ZRare and common regulatory variation in population-scale sequenced human genomes.1553-73901553-740410.1371/journal.pgen.1002144https://doaj.org/article/30da82ecc5444f778ec209abb4815dbe2011-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21811411/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Population-scale genome sequencing allows the characterization of functional effects of a broad spectrum of genetic variants underlying human phenotypic variation. Here, we investigate the influence of rare and common genetic variants on gene expression patterns, using variants identified from sequencing data from the 1000 genomes project in an African and European population sample and gene expression data from lymphoblastoid cell lines. We detect comparable numbers of expression quantitative trait loci (eQTLs) when compared to genotypes obtained from HapMap 3, but as many as 80% of the top expression quantitative trait variants (eQTVs) discovered from 1000 genomes data are novel. The properties of the newly discovered variants suggest that mapping common causal regulatory variants is challenging even with full resequencing data; however, we observe significant enrichment of regulatory effects in splice-site and nonsense variants. Using RNA sequencing data, we show that 46.2% of nonsynonymous variants are differentially expressed in at least one individual in our sample, creating widespread potential for interactions between functional protein-coding and regulatory variants. We also use allele-specific expression to identify putative rare causal regulatory variants. Furthermore, we demonstrate that outlier expression values can be due to rare variant effects, and we approximate the number of such effects harboured in an individual by effect size. Our results demonstrate that integration of genomic and RNA sequencing analyses allows for the joint assessment of genome sequence and genome function.Stephen B MontgomeryTuuli LappalainenMaria Gutierrez-ArcelusEmmanouil T DermitzakisPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 7, p e1002144 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Stephen B Montgomery Tuuli Lappalainen Maria Gutierrez-Arcelus Emmanouil T Dermitzakis Rare and common regulatory variation in population-scale sequenced human genomes.
description	Population-scale genome sequencing allows the characterization of functional effects of a broad spectrum of genetic variants underlying human phenotypic variation. Here, we investigate the influence of rare and common genetic variants on gene expression patterns, using variants identified from sequencing data from the 1000 genomes project in an African and European population sample and gene expression data from lymphoblastoid cell lines. We detect comparable numbers of expression quantitative trait loci (eQTLs) when compared to genotypes obtained from HapMap 3, but as many as 80% of the top expression quantitative trait variants (eQTVs) discovered from 1000 genomes data are novel. The properties of the newly discovered variants suggest that mapping common causal regulatory variants is challenging even with full resequencing data; however, we observe significant enrichment of regulatory effects in splice-site and nonsense variants. Using RNA sequencing data, we show that 46.2% of nonsynonymous variants are differentially expressed in at least one individual in our sample, creating widespread potential for interactions between functional protein-coding and regulatory variants. We also use allele-specific expression to identify putative rare causal regulatory variants. Furthermore, we demonstrate that outlier expression values can be due to rare variant effects, and we approximate the number of such effects harboured in an individual by effect size. Our results demonstrate that integration of genomic and RNA sequencing analyses allows for the joint assessment of genome sequence and genome function.
format	article
author	Stephen B Montgomery Tuuli Lappalainen Maria Gutierrez-Arcelus Emmanouil T Dermitzakis
author_facet	Stephen B Montgomery Tuuli Lappalainen Maria Gutierrez-Arcelus Emmanouil T Dermitzakis
author_sort	Stephen B Montgomery
title	Rare and common regulatory variation in population-scale sequenced human genomes.
title_short	Rare and common regulatory variation in population-scale sequenced human genomes.
title_full	Rare and common regulatory variation in population-scale sequenced human genomes.
title_fullStr	Rare and common regulatory variation in population-scale sequenced human genomes.
title_full_unstemmed	Rare and common regulatory variation in population-scale sequenced human genomes.
title_sort	rare and common regulatory variation in population-scale sequenced human genomes.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/30da82ecc5444f778ec209abb4815dbe
work_keys_str_mv	AT stephenbmontgomery rareandcommonregulatoryvariationinpopulationscalesequencedhumangenomes AT tuulilappalainen rareandcommonregulatoryvariationinpopulationscalesequencedhumangenomes AT mariagutierrezarcelus rareandcommonregulatoryvariationinpopulationscalesequencedhumangenomes AT emmanouiltdermitzakis rareandcommonregulatoryvariationinpopulationscalesequencedhumangenomes
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Rare and common regulatory variation in population-scale sequenced human genomes.

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