@article{Gou01082014,
author = {Gou, Xiao and Wang, Zhen and Li, Ning and Qiu, Feng and Xu, Ze and Yan, Dawei and Yang, Shuli and Jia, Jia and Kong, Xiaoyan and Wei, Zehui and Lu, Shaoxiong and Lian, Linsheng and Wu, Changxin and Wang, Xueyan and Li, Guozhi and Ma, Teng and Jiang, Qiang and Zhao, Xue and Yang, Jiaqiang and Liu, Baohong and Wei, Dongkai and Li, Hong and Yang, Jianfa and Yan, Yulin and Zhao, Guiying and Dong, Xinxing and Li, Mingli and Deng, Weidong and Leng, Jing and Wei, Chaochun and Wang, Chuan and Mao, Huaming and Zhang, Hao and Ding, Guohui and Li, Yixue}, 
title = {Whole-genome sequencing of six dog breeds from continuous altitudes reveals adaptation to high-altitude hypoxia},
volume = {24}, 
number = {8}, 
pages = {1308-1315}, 
year = {2014}, 
doi = {10.1101/gr.171876.113}, 
abstract ={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.}, 
URL = {http://genome.cshlp.org/content/24/8/1308.abstract}, 
eprint = {http://genome.cshlp.org/content/24/8/1308.full.pdf+html}, 
journal = {Genome Research} 
}