International Journal of Legal Medicine

, Volume 132, Issue 6, pp 1527–1535 | Cite as

Differentiation analysis for estimating individual ancestry from the Tibetan Plateau by an archaic altitude adaptation EPAS1 haplotype among East Asian populations

  • Li Jiang
  • Jianxiong Peng
  • Meisha Huang
  • Jing Liu
  • Ling Wang
  • Quan Ma
  • Hui Zhao
  • Xin Yang
  • Anquan Ji
  • Caixia LiEmail author
Original Article


Tibetans have adapted to the extreme environment of high altitude for hundreds of generations. A highly differentiated 5-SNP (Single Nucleotide Polymorphism) haplotype motif (AGGAA) on a hypoxic pathway gene, EPAS1, is observed in Tibetans and lowlanders. To evaluate the potential usage of the 5-SNP haplotype in ancestry inference for Tibetan or Tibetan-related populations, we analyzed this haplotype in 1053 individuals of 12 Chinese populations residing on the Tibetan Plateau, peripheral regions of Tibet, and plain regions. These data were integrated with the genotypes from the 1000 Genome populations and populations in a previously reported paper for population structure analyses. We found that populations representing highland and lowland groups have different dominant ancestry components. The core Denisovan haplotype (AGGAA) was observed at a frequency of 72.32% in the Tibetan Plateau, with a frequency range from 9.48 to 21.05% in the peripheral regions and < 2.5% in the plains area. From the individual perspective, 87.57% of the individuals from the Tibetan Plateau carried the archaic haplotype, while < 5% of the Chinese Han people carried the haplotype. Our findings indicate that the 5-SNP haplotype has a special distribution pattern in populations of Tibet and peripheral regions and could be integrated into AISNP (Ancestry Informative Single Nucleotide Polymorphism) panels to enhance ancestry resolution.


Tibetans Highland adaption Archaic haplotype SNP East Asian 



We would like to thank all of the collaborators who helped to collect the samples. Special thanks are due to the hundreds of individuals who volunteered to give blood samples for studies of genetic diversity.

Author contributions

LJ planned the study, oversaw study data collection and analysis, and wrote the manuscript. JP and XY collected the blood samples. MH, LW, QM, and HZ designed and performed the experiments. JL assisted in statistical analysis. AJ supervised the project. CL supervised the project, provided financial support, and prepared the manuscript.

All authors approved the final manuscript.


This work was funded in part by the National Key Research and Development Program of China (2017YFC0803501) and the basic research project (2016JB039 and 2017JB027). Biological samples from the Caixia laboratory were funded by the National Infrastructure of Chinese Genetic Resources (NICGR: YCZYPT [2017]01–3) and the basic research project (2017JB025).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

414_2018_1789_Fig7_ESM.jpg (145 kb)
Figure S1

Pair-wised Fst value between CTT and the other 91 populations. The Fst values for the five SNPs are each represented by lines, and the combined Fst value for all five SNPs is shown in bars. (JPEG 144 kb)

414_2018_1789_MOESM1_ESM.eps (1.3 mb)
High resolution image (EPS 1352 kb)
414_2018_1789_MOESM2_ESM.ppt (278 kb)
Figure S2 The location of the five SNPs in the EPAS1 gene on chromosome 2. The location is based on GRCh37.p13 in Ensembl (;g = ENSG00000116016;r = 2:46,520,806-46,613,836). (PPT 278 kb)
414_2018_1789_MOESM3_ESM.docx (49 kb)
ESM 1 (DOCX 49 kb)
414_2018_1789_MOESM4_ESM.xlsx (12 kb)
ESM 2 (XLSX 12 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory of Forensic Genetics, Beijing Engineering Research Center of Crime Scene Evidence Examination, National Engineering Laboratory for Forensic ScienceInstitute of Forensic ScienceBeijingPeople’s Republic of China
  2. 2.Institute of Forensic ScienceShanxi Medical UniversityTaiyuanChina
  3. 3.Lanzhou Public Security BureauInstitute of Criminal Science and TechnologyLanzhouChina

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