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| Genetic Variation of EPAS1 Gene in Tibetan Pigs and Three Low-Altitude Pig Breeds in China |
| DONG Kun-zhe, KANG Ye, YAO Na, SHU Guo-tao, ZUO Qing-qing, ZHAO Qian-jun , MA Yue-hui |
1、Key Laboratory of Farm Animal Genetic Resources and Utilization, Ministry of Agriculture/Institute of Animal Science, Chinese Academy of
Agricultural Sciences, Beijing 100193, P.R.China
2、College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, P.R.China |
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摘要 Endothelial PAS domain protein 1 (EPAS1), also called hypoxia-inducible factor-2, is a key regulatory factor of hypoxic responses and plays an essential role in high-altitude adaptation in mammalian species. In this study, polymorphisms of EPAS1 were detected in 217 individuals from 2 Tibetan pig populations and 3 low-altitude pig breeds by DNA pooling, PCR-SSCP, PCR-RFLP and DNA sequencing methods. A total of 14 synonymous polymorphisms were identified in the coding region. The analysis suggested that SNP1 (G963A), SNP7 (C1632T), SNP10 (G1929A) and SNP11 (G1947A) showed potential association with high-altitude environment because of their particular variation patterns in Tibetan pigs. Linkage disequilibrium (LD) of these SNPs was analyzed. One common LD block including 5 SNPs clustering in exon 12 was identified in all studied pig populations. Haplotype H1 (AGGTC) in LD block was dominant in Tibetan pigs (76.6 and 74.2% in Linzhi (LZ) and Chayu (CY) pigs, respectively) and segregated at higher frequency than that in low-altitude pig breeds (52.3, 58.7 and 56.2% in Wuzhishan (WZS), Min (M) and Laiwu (LW) pigs, respectively), indicating that H1 may relate to adaptation to high altitude in Tibetan pigs. These findings raise hope that EPAS1 gene can be a candidate gene that involved in adaptation of high altitude in Tibetan pigs.
Abstract Endothelial PAS domain protein 1 (EPAS1), also called hypoxia-inducible factor-2, is a key regulatory factor of hypoxic responses and plays an essential role in high-altitude adaptation in mammalian species. In this study, polymorphisms of EPAS1 were detected in 217 individuals from 2 Tibetan pig populations and 3 low-altitude pig breeds by DNA pooling, PCR-SSCP, PCR-RFLP and DNA sequencing methods. A total of 14 synonymous polymorphisms were identified in the coding region. The analysis suggested that SNP1 (G963A), SNP7 (C1632T), SNP10 (G1929A) and SNP11 (G1947A) showed potential association with high-altitude environment because of their particular variation patterns in Tibetan pigs. Linkage disequilibrium (LD) of these SNPs was analyzed. One common LD block including 5 SNPs clustering in exon 12 was identified in all studied pig populations. Haplotype H1 (AGGTC) in LD block was dominant in Tibetan pigs (76.6 and 74.2% in Linzhi (LZ) and Chayu (CY) pigs, respectively) and segregated at higher frequency than that in low-altitude pig breeds (52.3, 58.7 and 56.2% in Wuzhishan (WZS), Min (M) and Laiwu (LW) pigs, respectively), indicating that H1 may relate to adaptation to high altitude in Tibetan pigs. These findings raise hope that EPAS1 gene can be a candidate gene that involved in adaptation of high altitude in Tibetan pigs.
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Received: 17 May 2013
Accepted: 24 September 2014
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| Fund: This work was supported by the National Natural Science Foundation of China (31272403), the Determination of Molecular Characterization for Genetically Modified Organism, China (2013ZX08012-002), and the Livestock and Poultry Sharing Platform in China (2013). |
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Corresponding Authors:
MA Yue-hui, Tel/Fax: +86-10-62813463, E-mail: yuehui_ma@263.net
E-mail: yuehui_ma@263.net
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| About author: DONG Kun-zhe, Mobile: 13811208140, E-mail: dkzhe1987@163.com |
Cite this article:
DONG Kun-zhe, KANG Ye, YAO Na, SHU Guo-tao, ZUO Qing-qing, ZHAO Qian-jun , MA Yue-hui.
2014.
Genetic Variation of EPAS1 Gene in Tibetan Pigs and Three Low-Altitude Pig Breeds in China. Journal of Integrative Agriculture, 13(9): 1990-1998.
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| Barrett J C, Fry B, Maller J, Daly M J. 2005. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics, 21, 263-265 Beall C M, Cavalleri G L, Deng L, Elston R C, Gao Y, Knight J, Li C, Li J C, Liang Y, McCormack M, Montgomery H E, Pan H, Robbins P A, Shianna K V, Tam S C, Tsering N, Veeramah K R, Wang W, Wangdui P, Weale M E, et al. 2010. Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders. Proceedings of the National Academy of Sciences of the United States of America, 107, 11459-11464 Bigham A, Bauchet M, Pinto D, Mao X Y, Akey J M, Mei R, Scherer S W, Julian C G, Wilson M J, Herráez D, Brutsaert T, Parra E J, Moore L G, Shriver M D. 2010. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data. PLoS Gentics, 6, e1001116. Brusselmans K, Bono F, Maxwell P, Dor Y, Dewerchin M, Collen D, Herbert J M, Carmeliet P. 2001. Hypoxia-inducible factor-2α (HIF-2α) is involved in the apoptotic response to hypoglycemia but not to hypoxia The Journal of Biological Chemistry, 276, 39192-39196. Chun S, Fay J C. 2011. Evidence for hitchhiking of deleterious mutations within the human genome. PLoS Genetics, 7, e1002240. Conrad D F, Jakobsson M, Coop G, Wen X, Wall J D, Rosenberg N A, Pritchard J K. 2006. A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Natural Genetics, 38, 1251-1260 Girard P, Angers B. 2011. The functional gene diversity in natural populations over postglacial areas: The shaping mechanisms behind genetic composition of longnose dace (Rhinichthys cataractae) in northeastern North America. Journal of Molecular Evolution, 73, 45-57 Holmquist-Mengelbier L, Fredlund E, Lofstedt T, Noguera R, Navarro S, Nilsson H, Pietras A, Vallon-Christersson J, Borg A, Gradin K, Poellinger L, Pahlman S. 2006. Recruitment of HIF-1α and HIF-2α to common target genes is differentially regulated in neuroblastoma: HIF- 2α promotes an aggressive phenotype Cancer Cell, 10, 413-423. Monge C, Leon-Velarde F. 1991. Physiological adaptation to high altitude: Oxygen transport in mammals and birds. Physiological Reviews, 71, 1135-1172 Mullenbach R, Lagoda P J, Welter C. 1989. An efficient salt- chloroform extraction of DNA from blood and tissues. Trends in Genetics, 5, 391. Nielsen R. 2005. Molecular signatures of natural selection. Annual Review of Genetics, 39, 197-218 Nordborg M, Tavare S. 2002. Linkage disequilibrium: What history has to tell us. Trends in Genetics, 18, 83-90 Patel S A, Simon M C. 2008. Biology of hypoxia-inducible factor-2α in development and disease Cell Death and Differentiation, 15, 628-634 Peng Y, Yang Z, Zhang H, Cui C, Qi X, Luo X, Tao X, Wu T, Ouzhuluobu, Basang, Ciwangsangbu, Danzengduojie, Chen H, Shi H, Su B. 2011. Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas. Molecular Biology and Evolution, 28, 1075-1081 Ruan Z, Koizumi T, Sakai A, Ishizaki T, Wang Z, Chen Q, Wang X. 2004. Comparison of pulmonary vascular response to endogenous nitric oxide inhibition in sheep and pigs living at 2,300 m. Journal of Comparative Physiology (B), 174, 549-554 Sakai A, Matsumoto T, Saitoh M, Matsuzaki T, Koizumi T, Ishizaki T, Ruan Z H, Wang Z G, Chen Q H, Wang X Q. 2003. Cardiopulmonary hemodynamics of blue-sheep, Pseudois nayaur, as high-altitude adapted mammals. The Japanese Journal of Physiology, 53, 377-384 Sun J, Zhang C, Lan X, Lei C, Chen H. 2012. Exploring polymorphisms and associations of the bovine MOGAT3 gene with growth traits. Genome, 55, 56-62 Wang B B, Zhang Y B, Zhang F, Lin H B, Wang X M, Wan N, Ye Z Q, Weng H Y, Zhang L L, Li X, Yan J W, Wang P P, Wu T T, Cheng L F, Wang J, Wang D M, Ma X, Yu J. 2011. On the origin of tibetans and their genetic basis in adapting high-altitude environments. PLoS ONE, 6, e17002. Warnecke C, Zaborowska Z, Kurreck J, Erdmann V A, Frei U, Wiesener M, Eckardt K U. 2004. Differentiating the functional role of hypoxia-inducible factor (HIF)-1α and HIF-2α (EPAS-1) by the use of RNA interference: Erythropoietin is a HIF-2α target gene in Hep3B and Kelly cells The Journal of the Federation of American Societies for Experimental Biology, 18, 1462-1464 Wiesener M S, Jurgensen J S, Rosenberger C, Scholze C K, Horstrup J H, Warnecke C, Mandriota S, Bechmann I, Frei U A, Pugh C W, Ratcliffe P J, Bachmann S, Maxwell P H, Eckardt K U. 2003. Widespread hypoxia- inducible expression of HIF-2α in distinct cell populations of different organs The Journal of the Federation of American Societies for Experimental Biology, 17, 271-273 Xu S, Li S, Yang Y, Tan J, Lou H, Jin W, Yang L, Pan X, Wang J, Shen Y, Wu B, Wang H, Jin L. 2011. A genome-wide search for signals of high-altitude adaptation in Tibetans. Molecular Biology and Evolution, 28, 1003-1011 Yang S, Zhang H, Mao H, Yan D, Lu S, Lian L, Zhao G, Yan Y, Deng W, Shi X, Han S, Li S, Wang X, Gou X. 2011. The local origin of the Tibetan pig and additional insights into the origin of Asian pigs. PLoS ONE, 6, e28215. Yi X, Liang Y, Huerta-Sanchez E, Jin X, Cuo Z X, Pool J E, Xu X, Jiang H, Vinckenbosch N, Korneliussen T S, Zheng H, Liu T, He W, Li K, Luo R, Nie X, Wu H, Zhao M, Cao H, Zou J, et al. 2010. Sequencing of 50 human exomes reveals adaptation to high altitude. Science, 329, 75-78 Zhang C, Wang Y, Chen H, Lan X, Lei C. 2007. Enhance the efficiency of single-strand conformation polymorphism analysis by short polyacrylamide gel and modified silver staining. Analytical Biochemistry, 365, 286-287 Zhang Z G, Li B D, Chen X H. 1986. Pig Breeds in China. Shanghai Scientific and Technical Publishers, Shanghai. pp. 175-178. (in Chinese) |
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