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The dominant Tibetan EGLN1 haplotype at sites D4E and C127S reduces the interaction of the EGLN1 protein with p23, an HSP cochaperone important in HIF-α hydroxylation. This suggests that the adaptive Tibetan EGLN1 allele results in a loss of function that leads to impaired downregulation of the HIF pathway to facilitate adaptation to high altitude.
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36•• Song, D., Li, L.S., Arsenault, P.R., Tan, Q., Bigham, A.W., Heaton-Johnson, K.J., Master, S.R., Lee, F.S., Defective Tibetan PHD2 binding to p23 links high altitude adaptation to altered oxygen sensing. J Biol Chem 289 (2014), 14656–14665 The dominant Tibetan EGLN1 haplotype at sites D4E and C127S reduces the interaction of the EGLN1 protein with p23, an HSP cochaperone important in HIF-α hydroxylation. This suggests that the adaptive Tibetan EGLN1 allele results in a loss of function that leads to impaired downregulation of the HIF pathway to facilitate adaptation to high altitude.
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39 Yang, D., Peng, Y., Ouzhuluobu, Bianbazhuoma, Cui, C., Bianba, Wang, L., Xiang, K., He, Y., Zhang, H., et al. HMOX2 functions as a modifier gene for high-altitude adaptation in Tibetans. Hum Mutat 37 (2016), 216–223.
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40 Hanaoka, M., Droma, Y., Basnyat, B., Ito, M., Kobayashi, N., Katsuyama, Y., Kubo, K., Ota, M., Genetic variants in EPAS1 contribute to adaptation to high-altitude hypoxia in Sherpas. PLoS ONE, 7, 2012, e50566.
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41 Kang, L., Zheng, H.X., Chen, F., Yan, S., Liu, K., Qin, Z., Liu, L., Zhao, Z., Li, L., Wang, X., et al. mtDNA lineage expansions in Sherpa population suggest adaptive evolution in Tibetan highlands. Mol Biol Evol 30 (2013), 2579–2587.
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42 Aggarwal, S., Negi, S., Jha, P., Singh, P.K., Stobdan, T., Pasha, M.A., Ghosh, S., Agrawal, A., Prasher, B., Mukerji, M., EGLN1 involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda. Proc Natl Acad Sci U S A 107 (2010), 18961–18966.
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This research identifies a novel mechanism, admixture-mediated adaptation, of adaptation. The modern Tibetan population is an admixed population comprised of ancestral groups related to present day Nepalese Sherpa and Han Chinese. The results indicate that admixture-mediated adaptation has been an important mechanism beyond selection through which Tibetans have adapted to hypoxia.
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44• Jeong, C., Alkorta-Aranburu, G., Basnyat, B., Neupane, M., Witonsky, D.B., Pritchard, J.K., Beall, C.M., Di Rienzo, A., Admixture facilitates genetic adaptations to high altitude in Tibet. Nat Commun, 5, 2014, 3281 This research identifies a novel mechanism, admixture-mediated adaptation, of adaptation. The modern Tibetan population is an admixed population comprised of ancestral groups related to present day Nepalese Sherpa and Han Chinese. The results indicate that admixture-mediated adaptation has been an important mechanism beyond selection through which Tibetans have adapted to hypoxia.
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45 Alkorta-Aranburu, G., Beall, C.M., Witonsky, D.B., Gebremedhin, A., Pritchard, J.K., Di Rienzo, A., The genetic architecture of adaptations to high altitude in Ethiopia. PLoS Genet, 8, 2012, e1003110.
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46 Scheinfeldt, L.B., Soi, S., Thompson, S., Ranciaro, A., Woldemeskel, D., Beggs, W., Lambert, C., Jarvis, J.P., Abate, D., Belay, G., et al. Genetic adaptation to high altitude in the Ethiopian highlands. Genome Biol, 13, 2012, R1.
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47 Huerta-Sanchez, E., Degiorgio, M., Pagani, L., Tarekegn, A., Ekong, R., Antao, T., Cardona, A., Montgomery, H.E., Cavalleri, G.L., Robbins, P.A., et al. Genetic signatures reveal high-altitude adaptation in a set of Ethiopian populations. Mol Biol Evol 30 (2013), 1877–1888.
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50 Kiyamu, M., Bigham, A., Parra, E., Leon-Velarde, F., Rivera-Chira, M., Brutsaert, T.D., Developmental and genetic components explain enhanced pulmonary volumes of female Peruvian Quechua. Am J Phys Anthropol 148 (2012), 534–542.
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Elevated arterial oxygen saturation has been previously identified as an Andean high-altitude adaptive trait. This study demonstrates compelling evidence for a developmental component to their adaptive higher arterial oxygen saturation phenotype.
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51• Kiyamu, M., Leon-Velarde, F., Rivera-Chira, M., Elias, G., Brutsaert, T.D., Developmental Effects determine submaximal arterial oxygen saturation in Peruvian Quechua. High Alt Med Biol 16 (2015), 138–146 Elevated arterial oxygen saturation has been previously identified as an Andean high-altitude adaptive trait. This study demonstrates compelling evidence for a developmental component to their adaptive higher arterial oxygen saturation phenotype.
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