title: Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas.
abstract: Sheep has successfully adapted to the extreme high-altitude Himalayan region. To identify genes underlying such adaptation, we genotyped genome-wide single nucleotide polymorphisms (SNPs) of four major sheep breeds living at different altitudes in Nepal and downloaded SNP array data from additional Asian and Middle East breeds. Using a di value-based genomic comparison between four high-altitude and eight lowland Asian breeds, we discovered the most differentiated variants at the locus of FGF-7 (Keratinocyte growth factor-7), which was previously reported as a good protective candidate for pulmonary injuries. We further found a SNP upstream of FGF-7 that appears to contribute to the divergence signature. First, the SNP occurred at an extremely conserved site. Second, the SNP showed an increasing allele frequency with the elevated altitude in Nepalese sheep. Third, the electrophoretic mobility shift assays (EMSA) analysis using human lung cancer cells revealed the allele-specific DNA-protein interactions. We thus hypothesized that FGF-7 gene potentially enhances lung function by regulating its expression level in high-altitude sheep through altering its binding of specific transcription factors. Especially, FGF-7 gene was not implicated in previous studies of other high-altitude species, suggesting a potential novel adaptive mechanism to high altitude in sheep at the Himalayas.
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|Animal Breeding Division, National Animal Science Institute, Nepal Agriculture Research Council (NARC), Kathmandu, Nepal.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Neena Amatya
authors.initials: NA
authors.lastname: Gorkhali
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Kunzhe
authors.initials: K
authors.lastname: Dong
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.|Department of Animal Genetics and Breeding, China Agricultural University, Beijing 100094, P. R. China.
authors.forename: Shen
authors.initials: S
authors.lastname: Song
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Adiljian
authors.initials: A
authors.lastname: Kader
authors.affiliation: Animal Breeding Division, National Animal Science Institute, Nepal Agriculture Research Council (NARC), Kathmandu, Nepal.
authors.forename: Bhola Shankar
authors.initials: BS
authors.lastname: Shrestha
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: He
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Qianjun
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Pu
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Xiangchen
authors.initials: X
authors.lastname: Li
authors.affiliation: CSIRO Livestock Industries, St Lucia, Brisbane, Qld, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Kijas
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Guan
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.|International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi 00100, Kenya.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Han
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China.|CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000072283:A549 Cells; D000222:Adaptation, Physiological / Q000235:genetics*; D000531:Altitude; D000818:Animals; D001483:Base Sequence; D001947:Breeding; D051523:Fibroblast Growth Factor 7 / Q000235:genetics; D056426:Genetic Loci; D023281:Genomics; D006801:Humans; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012756:Sheep / Q000235:genetics*; D018609:Tibet
chemical_list: D051523:Fibroblast Growth Factor 7