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

• Published in: Scientific reports Vol. 8; no. 1; pp. 1399 - 11
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.01.2018; Nature Publishing Group
• Subjects: 38/23; 38/39; 38/43; 38/47; 38/61; 631/114/2401; 631/208/199; 631/208/8; 631/61/17; Animals; Association analysis; Autophagy; Bos taurus indicus; Cattle; Copy number; DNA Copy Number Variations; Gene expression; Gene Expression Profiling - veterinary; Gene Expression Regulation; Gene Regulatory Networks; Genomes; Humanities and Social Sciences; Meat; multidisciplinary; Muscle, Skeletal - chemistry; Musculoskeletal system; Phagocytosis; Phenotype; Phenotypic variations; Proteolysis; Quantitative Trait Loci; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sequence Analysis, RNA - methods; Single-nucleotide polymorphism; Skeletal muscle
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-19782-4

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.