A Functional Regulatory Variant of FGF9 Gene Affected the Body Weight in Hu Sheep

Body weight (BW) is a critical economic trait closely linked to livestock meat production performance and producer profitability. In the present study, we measured individual BW of 1070 male Hu sheep at six growth stages (80, 100, 120, 140, 160, and 180 days of age) and conducted descriptive statistical analyses. Results showed that the coefficient of variation (CV) for BW at each stage was higher than 13%. Additionally, we investigated the expression patterns of the FGF9 gene and its associations with single nucleotide polymorphisms (SNPs) and BW. Quantitative real-time PCR (qRT-PCR) revealed FGF9 is significantly higher expressed in the hypophysis tissues that in the other tested tissues. Association analyses indicated that the SNP FGF9:c.382-1264C>T was significantly associated with BW across different measurement periods. Finally, we performed assay for transposase-accessible chromatin using sequencing (ATAC-seq) and cleavage under targets and tagmentation (CUT&Tag) techniques to identify the OCRs (open chromatin regions) and regulatory regions in the hypophysis tissues of Hu sheep, and we obtained an average of 221243, 52692, and 20957.5 peaks in the ATAC-seq, H3K27ac, and H3K4me3 data per sample. Simultaneously, by integrating the SNPs of FGF9 and hypophysis tissue's epigenomic data, we found that the SNP FGF9:c.382-1264C>T was located in the adjacent OCR- and H3K27ac-modified peaks. Therefore, we propose that the SNP FGF9:c.382-1264C>T plays an important role in regulating body weight in sheep. Overall, this study generated a valuable epigenetic dataset (ATAC-seq, H3K27ac, and H3K4me3) in sheep hypophysis tissue and identified a novel functional regulatory variant for improving body weight in sheep.