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

Author(s)

Geistlinger, Ludwig ^{[1, 2, 3, 4, 5]} ; da Silva, Vinicius Henrique ^{[2, 3]} ; Mello Cesar, Aline Silva ^[2] ; Tizioto, Polyana Cristine ^[2] ; Waldron, Levi ^{[4, 5]} ; Zimmer, Ralf ^[3] ; de Almeida Regitano, Luciana Correia ^[1] ; Coutinho, Luiz Lehmann ^[2]

Affiliation

^[1] Embrapa Pecuaria Sudeste, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Luiz Queiroz Coll Agr ESALQ, Anim Sci Dept, Anim Biotechnol Lab, BR-13418900 Piracicaba - Brazil

^[3] Ludwig Maximilians Univ Munchen LMU, Inst Bioinformat, Dept Informat, D-80333 Munich - Germany

^[4] CUNY, Grad Sch Publ Hlth & Hlth Policy, New York, NY 10027 - USA

^[5] CUNY, Inst Implementat Sci & Populat Hlth, New York, NY 10027 - USA

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, JAN 23 2018.
• Web of Science Citations: 4

Abstract

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. (AU)

• FAPESP's process: 14/01438-2 - Metabolic pathways and meat tenderness: from CNVs to gene expression in Nelore cattle breed
• Grantee: Vinicius Henrique da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 12/23638-8 - Molecular basis of meat quality in Nelore beef cattle
• Grantee: Luciana Correia de Almeida Regitano
• Support Opportunities: Research Projects - Thematic Grants