Novel SNP of EPAS1 gene associated with higher hemoglobin concentration revealed the hypoxia adaptation of yak (Bos grunniens)

Endothelial PAS domain protein 1 gene (EPAS1) is a key transcription factor that activates the expression of oxygen-regulated genes. In this study, in order to better understand the effects of EPAS1 gene on hematologic parameters in yak, we firstly quantified the tissue expression patterns for EPAS1 mRNA of yak, identified polymorphism in this gene and evaluated its association with hematologic parameters. Expression of EPAS1 mRNA was detected in all eight tissues (heart, liver, lung, spleen, pancreas, kidney, muscles and ovary). The expressions of EPAS1 in lung and pancreas were extremely higher than other tissues examined. Three novel single nucleotide polymorphisms (SNPs) (g.83052 C>T, g.83065 G>A and g.83067 C>A) within the EPAS1 were identified and genotyped in Pali (PL), Gannan (GN) and Tianzhu White (TZW) yak breeds. Significant higher frequencies of the AA and GA genotypes and A allele of the g.83065 G>A were observed in the PL and GN breeds than that in the TZW breed (P<0.01). Association analysis of the PL breed indicated that the g.83065 G>A polymorphism was significantly associated with hemoglobin (HGB) concentration in yaks (P<0.05). Individuals with genotype AA had significantly higher HGB concentration (P<0.05) than those with genotype GA and GG. All these results will help our further understanding of biological functional of yak EPAS1 gene in responding to hypoxia and also indicate EPAS1 might contribute to the hypoxia adaptation of the yak.