title: Exome sequencing reveals genetic differentiation due to high-altitude adaptation in the Tibetan cashmere goat (Capra hircus).
abstract: BACKGROUND
  The Tibetan cashmere goat (Capra hircus), one of the most ancient breeds in China, has historically been a critical source of meat and cashmere production for local farmers. To adapt to the high-altitude area, extremely harsh climate, and hypoxic environment that the Tibetan cashmere goat lives in, this goat has developed distinct phenotypic traits compared to lowland breeds. However, the genetic components underlying this phenotypic adaptation remain largely unknown.
  
  
  RESULTS
  We obtained 118,700 autosomal SNPs through exome sequencing of 330 cashmere goats located at a wide geographic range, including the Tibetan Plateau and low-altitude regions in China. The great majority of SNPs showed low genetic differentiation among populations; however, approximately 2-3% of the loci showed more genetic differentiation than expected under a selectively neutral model. Together with a combined analysis of high- and low-altitude breeds, we revealed 339 genes potentially under high-altitude selection. Genes associated with cardiovascular system development were significantly enriched in our study. Among these genes, the most evident one was endothelial PAS domain protein 1 (EPAS1), which has been previously reported to be involved in complex oxygen sensing and significantly associated with high-altitude adaptation of human, dog, and grey wolf. The missense mutation Q579L that we identified in EPAS1, which occurs next to the Hypoxia-Inducible Factor-1 (HIF-1) domain, was exclusively enriched in the high-altitude populations.
  
  
  CONCLUSIONS
  Our study provides insights concerning the population variation in six different cashmere goat populations in China. The variants in cardiovascular system-related genes may explain the observed phenotypic adaptation of the Tibetan cashmere goat.
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. songs_193@163.com.|Department of Animal Genetics and Breeding, China Agricultural University, Beijing, 100094, China. songs_193@163.com.
authors.forename: Shen
authors.initials: S
authors.lastname: Song
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. yaona820226@126.com.
authors.forename: Na
authors.initials: N
authors.lastname: Yao
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. yangmindk@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. lxx_caas@163.com.
authors.forename: Xuexue
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. dkzhe1987@163.com.
authors.forename: Kunzhe
authors.initials: K
authors.lastname: Dong
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. zhaoqianjun@caas.cn.
authors.forename: Qianjun
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. pyb@iascaas.net.cn.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Pu
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. hexiaohong@caas.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: He
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. wjguan86@iascaas.net.cn.
authors.forename: Weijun
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of Animal Genetics and Breeding, China Agricultural University, Beijing, 100094, China. nyang@cau.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. yuehui.ma@263.net.
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Ma
authors.affiliation: The Key Laboratory for Farm Animal Genetic Resources and Utilization of Ministry of Agriculture of China, Institute of Animal Science (IAS), Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. jianglin@caas.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000531:Altitude; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002681:China; D059472:Exome; D005828:Genetics, Population; D006041:Goats / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1