RT Journal
A1 Gou, Xiao
A1 Wang, Zhen
A1 Li, Ning
A1 Qiu, Feng
A1 Xu, Ze
A1 Yan, Dawei
A1 Yang, Shuli
A1 Jia, Jia
A1 Kong, Xiaoyan
A1 Wei, Zehui
A1 Lu, Shaoxiong
A1 Lian, Linsheng
A1 Wu, Changxin
A1 Wang, Xueyan
A1 Li, Guozhi
A1 Ma, Teng
A1 Jiang, Qiang
A1 Zhao, Xue
A1 Yang, Jiaqiang
A1 Liu, Baohong
A1 Wei, Dongkai
A1 Li, Hong
A1 Yang, Jianfa
A1 Yan, Yulin
A1 Zhao, Guiying
A1 Dong, Xinxing
A1 Li, Mingli
A1 Deng, Weidong
A1 Leng, Jing
A1 Wei, Chaochun
A1 Wang, Chuan
A1 Mao, Huaming
A1 Zhang, Hao
A1 Ding, Guohui
A1 Li, Yixue
T1 Whole-genome sequencing of six dog breeds from continuous altitudes reveals adaptation to high-altitude hypoxia
JF Genome Research 
JO Genome Research 
YR 2014 
FD August 01 
VO 24 
IS 8 
SP 1308 
OP 1315 
DO 10.1101/gr.171876.113 
UL http://genome.cshlp.org/content/24/8/1308.abstract 
AB The hypoxic environment imposes severe selective pressure on species living at high altitude. To understand the genetic bases of adaptation to high altitude in dogs, we performed whole-genome sequencing of 60 dogs including five breeds living at continuous altitudes along the Tibetan Plateau from 800 to 5100 m as well as one European breed. More than 150× sequencing coverage for each breed provides us with a comprehensive assessment of the genetic polymorphisms of the dogs, including Tibetan Mastiffs. Comparison of the breeds from different altitudes reveals strong signals of population differentiation at the locus of hypoxia-related genes including endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) and beta hemoglobin cluster. Notably, four novel nonsynonymous mutations specific to high-altitude dogs are identified at EPAS1, one of which occurred at a quite conserved site in the PAS domain. The association testing between EPAS1 genotypes and blood-related phenotypes on additional high-altitude dogs reveals that the homozygous mutation is associated with decreased blood flow resistance, which may help to improve hemorheologic fitness. Interestingly, EPAS1 was also identified as a selective target in Tibetan highlanders, though no amino acid changes were found. Thus, our results not only indicate parallel evolution of humans and dogs in adaptation to high-altitude hypoxia, but also provide a new opportunity to study the role of EPAS1 in the adaptive processes.