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Widespread modulation of gene expression by copy number variation in skeletal muscle

Copy number variation (CNV) is a frequently observed deviation from the diploid state due to duplication or deletion of genomic regions. Although intensively analyzed for association with diseases and production traits, the specific mechanisms and extent by which such variations affect the phenotype...

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Autores principales: Geistlinger, Ludwig, da Silva, Vinicius Henrique, Cesar, Aline Silva Mello, Tizioto, Polyana Cristine, Waldron, Levi, Zimmer, Ralf, Regitano, Luciana Correia de Almeida, Coutinho, Luiz Lehmann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780461/
https://www.ncbi.nlm.nih.gov/pubmed/29362391
http://dx.doi.org/10.1038/s41598-018-19782-4
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author Geistlinger, Ludwig
da Silva, Vinicius Henrique
Cesar, Aline Silva Mello
Tizioto, Polyana Cristine
Waldron, Levi
Zimmer, Ralf
Regitano, Luciana Correia de Almeida
Coutinho, Luiz Lehmann
author_facet Geistlinger, Ludwig
da Silva, Vinicius Henrique
Cesar, Aline Silva Mello
Tizioto, Polyana Cristine
Waldron, Levi
Zimmer, Ralf
Regitano, Luciana Correia de Almeida
Coutinho, Luiz Lehmann
author_sort Geistlinger, Ludwig
collection PubMed
description Copy number variation (CNV) is a frequently observed deviation from the diploid state due to duplication or deletion of genomic regions. Although intensively analyzed for association with diseases and production traits, the specific mechanisms and extent by which such variations affect the phenotype are incompletely understood. We present an integrative study on CNV and genome-wide gene expression in Brazilian Bos indicus cattle. We analyzed CNVs inferred from SNP-chip data for effects on gene expression measured with RNA-seq in skeletal muscle samples of 183 steers. Local effects, where expression changes coincided with CNVs in the respective genes, were restricted to immune genes. Distal effects were attributable to several high-impact CNVs that modulated remote expression in an orchestrated and intertwined fashion. These CNVs were located in the vicinity of major skeletal muscle pathway regulators and associated genes were enriched for proteolysis, autophagy, and muscle structure development. From association analysis between CNVs and several meat quality and production traits, we found CNV-associated expression effects to also manifest at the phenotype level. Based on genome sequences of the population founders, we further demonstrate that CNVs with impact on expression and phenotype are passed on from one generation to another.
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spelling pubmed-57804612018-02-06 Widespread modulation of gene expression by copy number variation in skeletal muscle Geistlinger, Ludwig da Silva, Vinicius Henrique Cesar, Aline Silva Mello Tizioto, Polyana Cristine Waldron, Levi Zimmer, Ralf Regitano, Luciana Correia de Almeida Coutinho, Luiz Lehmann Sci Rep Article Copy number variation (CNV) is a frequently observed deviation from the diploid state due to duplication or deletion of genomic regions. Although intensively analyzed for association with diseases and production traits, the specific mechanisms and extent by which such variations affect the phenotype are incompletely understood. We present an integrative study on CNV and genome-wide gene expression in Brazilian Bos indicus cattle. We analyzed CNVs inferred from SNP-chip data for effects on gene expression measured with RNA-seq in skeletal muscle samples of 183 steers. Local effects, where expression changes coincided with CNVs in the respective genes, were restricted to immune genes. Distal effects were attributable to several high-impact CNVs that modulated remote expression in an orchestrated and intertwined fashion. These CNVs were located in the vicinity of major skeletal muscle pathway regulators and associated genes were enriched for proteolysis, autophagy, and muscle structure development. From association analysis between CNVs and several meat quality and production traits, we found CNV-associated expression effects to also manifest at the phenotype level. Based on genome sequences of the population founders, we further demonstrate that CNVs with impact on expression and phenotype are passed on from one generation to another. Nature Publishing Group UK 2018-01-23 /pmc/articles/PMC5780461/ /pubmed/29362391 http://dx.doi.org/10.1038/s41598-018-19782-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Geistlinger, Ludwig
da Silva, Vinicius Henrique
Cesar, Aline Silva Mello
Tizioto, Polyana Cristine
Waldron, Levi
Zimmer, Ralf
Regitano, Luciana Correia de Almeida
Coutinho, Luiz Lehmann
Widespread modulation of gene expression by copy number variation in skeletal muscle
title Widespread modulation of gene expression by copy number variation in skeletal muscle
title_full Widespread modulation of gene expression by copy number variation in skeletal muscle
title_fullStr Widespread modulation of gene expression by copy number variation in skeletal muscle
title_full_unstemmed Widespread modulation of gene expression by copy number variation in skeletal muscle
title_short Widespread modulation of gene expression by copy number variation in skeletal muscle
title_sort widespread modulation of gene expression by copy number variation in skeletal muscle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780461/
https://www.ncbi.nlm.nih.gov/pubmed/29362391
http://dx.doi.org/10.1038/s41598-018-19782-4
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