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-regu- lated 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 EPASl 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.

Genetic Variation of EPAS1 Gene in Tibetan Pigs and Three Low-Altitude Pig Breeds in China

Endothelial PAS domain protein 1（EPAS1）, also called hypoxia-inducible factor-2, is a key regulatory factor of hypoxic responses and plays an essential role in high-altitude adaptation in mammalian species. In this study, polymorphisms of EPAS1 were detected in 217 individuals from 2 Tibetan pig populations and 3 low-altitude pig breeds by DNA pooling, PCR-SSCP, PCR-RFLP and DNA sequencing methods. A total of 14 synonymous polymorphisms were identified in the coding region. The analysis suggested that SNP1（G963A）, SNP7（C1632T）, SNP10（G1929A） and SNP11（G1947A） showed potential association with high-altitude environment because of their particular variation patterns in Tibetan pigs. Linkage disequilibrium（LD） of these SNPs was analyzed. One common LD block including 5 SNPs clustering in exon 12 was identified in all studied pig populations. Haplotype H1（AGGTC） in LD block was dominant in Tibetan pigs（76.6 and 74.2% in Linzhi（LZ） and Chayu（CY） pigs, respectively） and segregated at higher frequency than that in low-altitude pig breeds（52.3, 58.7 and 56.2% in Wuzhishan（WZS）, Min（M） and Laiwu（LW） pigs, respectively）, indicating that H1 may relate to adaptation to high altitude in Tibetan pigs. These findings raise hope that EPAS1 gene can be a candidate gene that involved in adaptation of high altitude in Tibetan pigs.