Genetic analysis of PMEL in Sibu yaks: a candidate gene for black and brown coat color

Coat color is an important trait in Sibu yak, which includes black and brown phenotypes. Genome-wide association studies combined with multi-omics approaches were conducted to investigate the genetic mechanisms underlying the brown coat color of Sibu yak. A total of eleven SNPs (P-adjust<4.47×10–⁹) on CHR5 were significantly associated with the brown coat. The top SNP (CHR5: g.47487664 A>G, P-adjust=2.38×10–10) was located in an intron of PMEL. PMEL expression was also found to be significantly lower in brown yak fibroblasts. Multi-omics analyses showed that PMEL overexpression significantly altered the expression of 1 088 genes, 444 proteins, and 57 metabolites. These molecular changes were enriched in the melanogenesis-related pathways, including cAMP (e.g., ADCY7, EDNRA, and epinephrine), PI3K-Akt (e.g., FGF5, PIK3CG, and FGF7), and MAPK (e.g., MAP2K6, FGFR3, and ERBB4) signaling. Our results suggested that the intronic PMEL variant may regulate gene expression and affect pigmentation through these pathways, contributing to coat color variation in Sibu yak. This study provides insights into the genetic mechanisms underlying Sibu yak pigmentation and identifies PMEL as a key candidate gene in coat color differentiation of Sibu yak.