Genome-wide association and transcriptome studies identify candidate genes regulating perirenal fat deposition in sheep

作者：Xiaoyu Fu, Liming Zhao, Huibin Tian, Deyin Zhang, Yukun Zhang, Yuan Zhao, Jiangbo Cheng, Xiaolong Li, Quanzhong Xu, Dan Xu, Xiaobin Yang, Zongwu Ma, Weiwei Wu, Fei Li, Weimin Wang, Xiaoxue Zhang · 发表于：Genomics · 年份：2025 · DOI：10.1016/j.ygeno.2025.111182 · 被引用次数：3 · 研究领域：Genetic and phenotypic traits in livestock、Lipid metabolism and biosynthesis、Fatty Acid Research and Health

Perirenal fat deposition significantly impacts sheep carcass quality and economic efficiency. To elucidate the underlying genetic regulation, we performed a genome-wide association study (GWAS) on 556 Hu sheep and a comparative transcriptome analysis on 24 Hu sheep (12 with high- and 12 with low-perirenal fat deposition), all with accurate phenotypic records. Furthermore, hub genes and tissue-specific genes (TSGs) were discerned through weighted gene co-expression network analysis (WGCNA) and by leveraging RNA-Seq data from 12 tissues, respectively. qRT-PCR is used to validate the accuracy of RNA-Seq data. GWAS identified significant SNPs near genes including SETD4, TIMP2, SOCS3, and DNAH17. Comparative transcriptome analysis of HPF and LPF groups identified 2072 differentially expressed genes (DEGs), which were significantly associated with lipid storage (LPL), fatty acid homeostasis (APOE, GOT1), and biosynthesis (ACACA). A total of 2333 differential alternative splicing events were identified in 1169 genes, with skipped exons (SE, 30.65 %) being the most common. GO analysis of these SEs showed links to RNA splicing and lipid metabolism, with genes like BSCL2, DGAT1, PLIN5, and PNPLA2 involved in lipid droplet organization and triglyceride storage. WGCNA revealed key modules that were positively and negatively correlated with perirenal fat deposition, emphasizing hub genes (SAR1B, THRSP, ACSS2, KIF5B) associated with lipid droplet organization and metabolism. The integrated...