新疆隔离人群的遗传多样性研究及流行病学资源数据库建立

As an area of contact between eastern and western Eurasia, Xinjiang has been a complex assembly of peoples, cultures, and habitats. The human populations have been long living in Xinjiang, especially those have been isolated, are valuable resource for studies on human migration history, local adaptation and gene mapping of diseases with high incidence in this area. In this project, we plan to investigate genetic diversity and epidemiological information in three typical isolated populations in Xinjiang. Blood samples and DNA of three isolated groups, Lop, Keriya and Dolan, will be collected. Microarray-based technology will be applied for generating genomic data such as short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) as well as gene expression data in the three population samples. Our aims are (a) to find out population specific genetic variation in the three isolated populations and develop a database of genetic structure and genetic resources in Xinjiang; (b) to investigate genetic diversity of disease susceptibility genes in the three isolated groups, and integrating epidemiological data, analyze the genetic susceptibility of the isolated populations and ethnic groups in Xinjiang. We also plan to explore the human local adaptation in Xinjiang and map disease genes which could be associated with population specific genetic variants. The project will advance our understanding of human evolutionary history and mechanism of high-incidence diseases in Xinjiang. Furthermore, our efforts can promote the preservation, use and sharing of national genetic resources, and provide an important theoretical basis for disease prevention, early diagnosis and treatment of diseases with high incidence in local populations in Xinjiang.

新疆自古以来是联系东西方文明的纽带，世居新疆的人群，尤其是至今仍然很少与外界交流、处于相对隔离生活状态的人群，是研究欧亚大陆人群基因交流历史、环境适应以及地域性高发疾病的宝贵遗传资源。本项目拟对新疆罗布人、克里雅人及刀郎人等3个典型隔离人群进行系统的遗传多样性研究和流行病学调查。通过收集血液样本和流调数据，采用全基因组基因分型和表达谱微阵列技术，基于基因变异和表达数量性状，整合流调数据，建立新疆隔离人群遗传多样性和疾病资源数据库；同时利用基因组数据研究欧亚人群的迁移和融合历史；并充分利用隔离人群的独特优势和建立的数据库资源，开展以新疆典型隔离人群为模型的环境适应和疾病基因定位研究。本项目重视和及时利用我国区域性特有遗传资源，有助于推动民族遗传资源的保存、利用和共享，促进深入了解我国西部人群的起源和迁移历史，也将为新疆地方性和人群高发疾病的预防、早期诊断和治疗等提供重要理论依据。

本研究采用新一代测序法对新疆罗布人、克里雅人、刀郎人三个隔离人群Y染色体和线粒体全基因组遗传结构及其遗传多样性进行分析。研究结果表明：三个人群Y染色体变异位点分别检出27, 41, 145处，分别构建了12, 16, 40个单倍群，主要高频单倍群有J2a1b1(25.64%), R1a1a1b2a(20.51%), R2a(17.95%), R1a1a1b2a2(15.38%)；J2a1(43.75%), J2a2(14.06%), R2(9.38%), L1c(7.81%)，O3a2c (4.69%)；R1b1a1a1(9.21%), R1a1a1b2a1a(7.89%), R1a1a1b2a2b(6.58%), C3c1(6.58%)。三个隔离人群在单倍群类型和频率上与维吾尔族最接近且无显著性差异(f=0.833，p=0.367)。三个人群mtDNA变异位点分别检出256, 315, 735处，其中多态性位点分别为245, 298, 639处，A263G, A750G, A8860G, A15326G 四个位点变异率均为100%, 分别构建20, 27, 100个单倍型，主要高频单倍型分别为M(30.01%), F(28.57%), H(21.43%), U(8.58%), R(5.71%); B(39.03%), H(30.49%), D(15.85%), C(7.32%); D(20.14%), U(13.43%), C(12.86%), H(15.64%)。HD为0.9264, 0.8360, 0.9910, Pi为30.2714, 36.1220, 32.5506, DP为0.9132, 0.8309, 0.9854。三个人群单倍群类型和频率与维吾尔族最接近亲缘关系最密切。三个人群父系和母系遗传结构显示明显的亚欧混合现象。罗布人EH患病率高达37.20%, 年龄、BMI、腰围与EH有显著关联性；线粒体全基因组分析在EH组共发现变异位点235处，未报道过的10处，NT组共发现变异位点253处，未报道过的13处；70个位点变异只在EH组中被发现，这些位点可能与原发性高血压的发生有直接关联，87个位点变异只在对照组中被发现，这些位点可能对原发性高血压的发生有抑制作用。这些研究成果开展以新疆隔离人群为模型的环境适应和疾病基因定位研究具有重要意义。