Institute for Molecular Bioscience, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia;
The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, China National Engineering Research Center of Ophthalmology and Optometry, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou 325027, China.
Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):4189-4194. doi: 10.1073/pnas.1617042114. Epub 2017 Apr 3.
Indigenous Tibetan people have lived on the Tibetan Plateau for millennia. There is a long-standing question about the genetic basis of high-altitude adaptation in Tibetans. We conduct a genome-wide study of 7.3 million genotyped and imputed SNPs of 3,008 Tibetans and 7,287 non-Tibetan individuals of Eastern Asian ancestry. Using this large dataset, we detect signals of high-altitude adaptation at nine genomic loci, of which seven are unique. The alleles under natural selection at two of these loci [methylenetetrahydrofolate reductase () and ] are strongly associated with blood-related phenotypes, such as hemoglobin, homocysteine, and folate in Tibetans. The folate-increasing allele of rs1801133 at the locus has an increased frequency in Tibetans more than expected under a drift model, which is probably a consequence of adaptation to high UV radiation. These findings provide important insights into understanding the genomic consequences of high-altitude adaptation in Tibetans.
藏族人在青藏高原上生活了数千年。长期以来，人们一直对藏族人适应高海拔的遗传基础存在疑问。我们对 3008 名藏族人和 7287 名东亚血统的非藏族个体的 730 万个已分型和推断的 SNP 进行了全基因组研究。利用这个大型数据集，我们在 9 个基因组位点检测到了适应高海拔的信号，其中 7 个是独特的。这两个位点（亚甲基四氢叶酸还原酶 () 和 ）中自然选择的等位基因与血红蛋白、同型半胱氨酸和叶酸等血液相关表型强烈相关。位于 位点的 rs1801133 的叶酸增加等位基因在藏族人中的频率高于漂移模型所预期的频率，这可能是对高紫外线辐射适应的结果。这些发现为理解藏族人适应高海拔的基因组后果提供了重要的见解。
