TY  - JOUR
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
Y1  - 2014/08/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1308 
EP  - 1315 
DO  - 10.1101/gr.171876.113 
VL  - 24 
IS  - 8 
UR  - http://genome.cshlp.org/content/24/8/1308.abstract 
N2  - 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. 
ER  -