Genomic and transcriptomic analyses enable the identification of important genes associated with subcutaneous fat deposition in Holstein cows.

Subcutaneous fat deposition has many important roles in dairy cattle, including immunological defense and mechanical protection. The main objectives of this study are to identify key candidate genes regulating subcutaneous fat deposition in high-producing dairy cows by integrating genomic and transcriptomic datasets. A total of 1654 genotyped Holstein cows are used to perform a genome-wide association study (GWAS) aiming to identify genes associated with subcutaneous fat deposition. Subsequently, weighted gene co-expression network analyses (WGCNA) are conducted based on RNA-sequencing data of 34 cows and cow yield deviations of subcutaneous fat deposition. Lastly, differentially expressed (DE) mRNA, lncRNA, and differentially alternative splicing genes are obtained for 12 Holstein cows with extreme and divergent phenotypes for subcutaneous fat deposition. Forty-six protein-coding genes are identified as candidate genes regulating subcutaneous fat deposition in Holstein cattle based on GWAS. Eleven overlapping genes are identified based on the analyses of DE genes and WGCNA. Furthermore, the candidate genes identified based on GWAS, WGCNA, and analyses of DE genes are significantly enriched for pathways involved in metabolism, oxidative phosphorylation, thermogenesis, fatty acid degradation, and glycolysis/gluconeogenesis pathways. Integrating all findings, the NID2, STARD3, UFC1, DEDD, PPP1R1B, and USP21 genes are considered to be the most important candidate genes influencing subcutaneous fat deposition traits in Holstein cows. This study provides novel insights into the regulation mechanism underlying fat deposition in high-producing dairy cows, which will be useful when designing management and breeding strategies.