1例中国塔吉克族人全基因组重测序分析及其与高原适应关联的初步研究

龚亮; 阳盛洪; 高亮; 陈郁; 陈兴书; 罗勇军

doi:10.16016/j.1000-5404.201808171

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1例中国塔吉克族人全基因组重测序分析及其与高原适应关联的初步研究

基础医学 | 更新时间：2026-01-09

- 1例中国塔吉克族人全基因组重测序分析及其与高原适应关联的初步研究
- Whole genome resequencing and correlation analysis with high altitude adaptation: a preliminary study of a Tajik male in China
- 第三军医大学学报 2019年41卷第7期页码：665-672
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)：陆军卫勤训练基地军事医学地理学教研室
  2.400038 重庆，陆军军医大学(第三军医大学)：全军战救训练技术与器材研发实验室
  3.859000 西藏阿里，解放军第957医院卫生处
  4.844900 新疆叶城，解放军第950医院新疆军区高山病研究所
- 作者简介：
  
  [ 罗勇军，E-mail:ajun-333333@163.com LUO Yongjun, E-mail:ajun-333333@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81571843);军队创新工程专项(16CXZ014)
- DOI：10.16016/j.1000-5404.201808171
  中图分类号： R339.54;R394-33;R394.5
- 收稿：2018-08-27，
  
  修回：2018-12-06，
  
  纸质出版：2019-04-15
- 稿件说明：
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龚亮, 阳盛洪, 高亮, 等. 1例中国塔吉克族人全基因组重测序分析及其与高原适应关联的初步研究[J]. 第三军医大学学报, 2019,41(7):665-672.

Liang GONG, Shenghong YANG, Liang GAO, et al. Whole genome resequencing and correlation analysis with high altitude adaptation: a preliminary study of a Tajik male in China[J]. Journal of Third Military Medical University, 2019, 41(7): 665-672.
龚亮, 阳盛洪, 高亮, 等. 1例中国塔吉克族人全基因组重测序分析及其与高原适应关联的初步研究[J]. 第三军医大学学报, 2019,41(7):665-672. DOI： 10.16016/j.1000-5404.201808171.

Liang GONG, Shenghong YANG, Liang GAO, et al. Whole genome resequencing and correlation analysis with high altitude adaptation: a preliminary study of a Tajik male in China[J]. Journal of Third Military Medical University, 2019, 41(7): 665-672. DOI： 10.16016/j.1000-5404.201808171.

摘要

目的

通过对1例中国塔吉克族人的全基因组重测序分析，探讨塔吉克族人的遗传特征和高原适应之间的关系。

方法

选取1例健康的中国塔吉克族成年男性(编号为T153)，提取全血DNA后进行全基因组测序和线粒体DNA全长序列比对分析。

结果

在线粒体DNA全长序列分析中发现，T153在线粒体DNA系统进化上的单倍群分型属于K1a12。本次全基因组测序深度为32.17×，通过与hg38千人基因组数据库进行序列比对，共发现了3 351 535个单核苷酸变异(single nucleotide variant，SNV)，845 638个小的缺失插入(insertion-deletion，INDEL)，7 829个染色体结构变异(structure variation，SV)，63 397个拷贝数变异(copy number variation，CNV)。在高原遗传适应相关基因EGLN1和EPAS1的SNV分析中发现，T153EGLN1基因位点rs479200和rs480902的基因型分别是T和C，EPAS1基因位点rs6756667的基因型是G，而由高原原发性高血压相关基因ROCK2的多态性位点rs978906、rs6753921、rs10495582和rs2230774组成的基因单倍型为GAGA，这些均是高原遗传适应不良的影响因素。同时还发现与男性性激素水平变化相关基因DAZ、BPY2、CDY的CNV变化，均表现为拷贝数减少。

结论

DAZ的拷贝数降低是影响中国塔吉克族男性性激素水平变化的一个重要因素，而其SNV分布情况与既往研究发现的常见高原遗传适应位点无关，可能存在其他高原遗传适应机制。

Abstract

Objective

To investigate the correlation between genetic characteristics of Chinese Tajik population and high altitude adaptation by sequencing and analyzing the whole genome of a healthy Chinese Tajik adult male.

Methods

A healthy Chinese Tajik adult male was subjected as participant (named as T153) in this study. His whole blood DNA was extracted for the mitochondrial DNA

and whole genome sequencing and analysis were used to analyze.

Results

In the analysis of the complete nucleotide sequence of the mitochondrial genome

we found that the haplotype of mitochondrial DNA phylogeny of the Tajik male belonged to K1a12. The genome sequencing depth was 32.17×

sequence alignment was with the hg38 human genome database. There were 3 351 535 single nucleotide variant (SNV)

8 456 338 insertion-deletion (INDEL)

7 829 structure variation (SV) and 63 397 copy number variation (CNV) in total. In the analysis on the SNV of genes EGLN1 and EPAS1 (they are related to high altitude genetic adaptation in Tibetan)

the results showed that the genotypes of polymorphic loci rs479200 and rs480902 of gene EGLN1 were T and C

respectively

and the loci rs6756667 genotype of gene EPAS1 was G. The polymorphic loci rs978906

rs6753921

rs10495582 and rs2230774 of gene ROCK2 (related with high altitude essential hypertension) formed the gene haplotype GAGA

which all were the genetic factors that were involved in poor acclimatization at high altitude. What's more

some CNV changes

as copy number reduction

were found in genes DAZ

BPY2 and CDY (related to changes in male sex hormone levels).

Conclusion

The decrease of copy number of DAZ may be an important factor affecting the change of male sex hormone levels in Chinese Tajik. However

there was no correlation between SNV distribution of this male and common high altitude genetic adaptation sites found in previous studies. There may be other mechanisms of genetic adaptation to high altitude.

关键词

Keywords

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