title: Genome-wide analysis reveals adaptation to high altitudes in Tibetan sheep.
abstract: Tibetan sheep have lived on the Tibetan Plateau for thousands of years; however, the process and consequences of adaptation to this extreme environment have not been elucidated for important livestock such as sheep. Here, seven sheep breeds, representing both highland and lowland breeds from different areas of China, were genotyped for a genome-wide collection of single-nucleotide polymorphisms (SNPs). The FST and XP-EHH approaches were used to identify regions harbouring local positive selection between these highland and lowland breeds, and 236 genes were identified. We detected selection events spanning genes involved in angiogenesis, energy production and erythropoiesis. In particular, several candidate genes were associated with high-altitude hypoxia, including EPAS1, CRYAA, LONP1, NF1, DPP4, SOD1, PPARG and SOCS2. EPAS1 plays a crucial role in hypoxia adaption; therefore, we investigated the exon sequences of EPAS1 and identified 12 mutations. Analysis of the relationship between blood-related phenotypes and EPAS1 genotypes in additional highland sheep revealed that a homozygous mutation at a relatively conserved site in the EPAS1 3' untranslated region was associated with increased mean corpuscular haemoglobin concentration and mean corpuscular volume. Taken together, our results provide evidence of the genetic diversity of highland sheep and indicate potential high-altitude hypoxia adaptation mechanisms, including the role of EPAS1 in adaptation.
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Wei
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.|National Animal Husbandry Service, National Center of Preservation &Utilization of Animal Genetic Resources, Beijing, People's Republic of China.|Institute of apicultural research, Chinese Academy of Agricultural Sciences, Beijing, People's Republic of China.
authors.forename: Huihua
authors.initials: H
authors.lastname: Wang
authors.affiliation: National Animal Husbandry Service, National Center of Preservation &Utilization of Animal Genetic Resources, Beijing, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Fuping
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Livestock Industries, CSIRO, Brisbane, Australia.
authors.forename: James W
authors.initials: JW
authors.lastname: Kijas
authors.affiliation: College of Animal Science and Technology, Gansu Agriculture University, Lanzhou 730070, People's Republic of China.
authors.forename: Youji
authors.initials: Y
authors.lastname: Ma
authors.affiliation: National Animal Husbandry Service, National Center of Preservation &Utilization of Animal Genetic Resources, Beijing, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Jiaxue
authors.initials: J
authors.lastname: Cao
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Wu
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Guangkai
authors.initials: G
authors.lastname: Wang
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Ruizao
authors.initials: R
authors.lastname: Liu
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: National Animal Husbandry Service, National Center of Preservation &Utilization of Animal Genetic Resources, Beijing, People's Republic of China.
authors.forename: Chousheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, National Center for Molecular Genetics and Breeding of Animal, Beijing, People's Republic of China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Du
mesh_terms: D000064:Acclimatization; D000531:Altitude; D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D016678:Genome; D005838:Genotype; D008297:Male; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D012756:Sheep / Q000235:genetics*