Intronic CNVs and gene expression variation in human populations
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- dc.contributor.author Rigau, Maria
- dc.contributor.author Juan Sopeña, David Alejandro, 1975-
- dc.contributor.author Valencia, Alfonso
- dc.contributor.author Rico, Daniel
- dc.date.accessioned 2020-07-16T08:01:25Z
- dc.date.available 2020-07-16T08:01:25Z
- dc.date.issued 2019
- dc.description.abstract Introns can be extraordinarily large and they account for the majority of the DNA sequence in human genes. However, little is known about their population patterns of structural variation and their functional implication. By combining the most extensive maps of CNVs in human populations, we have found that intronic losses are the most frequent copy number variants (CNVs) in protein-coding genes in human, with 12,986 intronic deletions, affecting 4,147 genes (including 1,154 essential genes and 1,638 disease-related genes). This intronic length variation results in dozens of genes showing extreme population variability in size, with 40 genes with 10 or more different sizes and up to 150 allelic sizes. Intronic losses are frequent in evolutionarily ancient genes that are highly conserved at the protein sequence level. This result contrasts with losses overlapping exons, which are observed less often than expected by chance and almost exclusively affect primate-specific genes. An integrated analysis of CNVs and RNA-seq data showed that intronic loss can be associated with significant differences in gene expression levels in the population (CNV-eQTLs). These intronic CNV-eQTLs regions are enriched for intronic enhancers and can be associated with expression differences of other genes showing long distance intron-promoter 3D interactions. Our data suggests that intronic structural variation of protein-coding genes makes an important contribution to the variability of gene expression and splicing in human populations.
- dc.description.sponsorship This work was supported by Project Retos BFU2015-71241-R Spanish Ministry of Economy, Industry and Competitiveness (MEIC, http://www.mineco.gob.es), co-funded by European Regional Development Fund (ERDF) to A.V. and Wellcome Trust (https://wellcome.ac.uk) Seed Award in Science (206103/Z/17/Z) to D.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- dc.format.mimetype application/pdf
- dc.identifier.citation Rigau M, Juan D, Valencia A, Rico D. Intronic CNVs and gene expression variation in human populations. PLoS Genet. 2019; 15(1):e1007902. DOI: 10.1371/journal.pgen.1007902
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1007902
- dc.identifier.issn 1553-7390
- dc.identifier.uri http://hdl.handle.net/10230/45121
- dc.language.iso eng
- dc.publisher Public Library of Science (PLoS)
- dc.relation.ispartof PLoS Genet. 2019; 15(1):e1007902
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-71241-R
- dc.rights © 2019 Rigau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Introns
- dc.subject.keyword Gene expression
- dc.subject.keyword Evolutionary genetics
- dc.subject.keyword Permutation
- dc.subject.keyword Gene mapping
- dc.subject.keyword Gene regulation
- dc.subject.keyword Copy number variation
- dc.subject.keyword Mammalian genomics
- dc.title Intronic CNVs and gene expression variation in human populations
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion