柯尔克孜族PPARG基因重组热点遗传定位及其与维吾尔族人群的比较分析  

A comparative study on characterizations of genetic recombination hotspots in PPARG gene between Kirgiz and Uyghur ethnic groups in Xinjiang

作　　者：祖克拉·肉孜[1] 宋曼殳[2] 伊力哈木·乃扎木[1] 多力坤·买买提玉素甫[1] 

机构地区：[1]新疆大学生命科学与技术学院,乌鲁木齐830046 [2]首都医科大学公共卫生学院

出　　处：《中华医学杂志》2016年第31期2487-2492,共6页National Medical Journal of China

基　　金：新疆维吾尔自治区自然科学基金（2013211A016）

摘　　要：目的分析探讨柯尔克孜族和维吾尔族两个人群过氧化物酶体增殖物激活受体叫（PPARG）基因重组热点特征及连锁不平衡（LD）模式。方法采用基质辅助激光解吸电离飞行时间质谱（MALDI—TOF—MS）方法对2013年8月采自新疆克孜勒苏柯尔克孜自治州阿图什市哈拉峻乡柯尔克孜族50例2型糖尿病患者（糖尿病组）、50名健康对照居民（健康对照组）和2012年5月采自新疆南疆和田地区的50名维吾尔族健康对照居民（维吾尔健康对照组）血液样品进行PPARG基因的31个标签单核苷酸多态性（taqSNP）位点的基因分型，采用HotspotFisher和Haploview软件推断该两个族群的PPARG基因重组热点特征及其LD模式。结果柯尔克孜糖尿病组、健康对照组和维吾尔健康对照组均有18个tagSNP相同（rs1151999、rs1175540、rs1875796、rs1899951、rs2292101、rs2921190、rs29383977、29592727、rs29592737、rs29721627、rs38568067 rs41352477、rs41352757、rs7091517 rs41353547、rs6805419、rs17036700、rs4135304），并在组间各个位点具有较高的重组率。LD分析结果显示，柯尔克孜健康对照组5个单体域的连锁不平衡系数（D’）=1，处于完全的连锁不平衡状态，不发生重组。柯尔克孜糖尿病组5个单体域的连锁不平衡系数D’0．91，D’〈1，说明两个位点间发生过重组。维吾尔健康对照组各4个单体域的连锁不平衡系数D’1，处于完全的连锁不平衡状态，也说明此区域无重组热点。柯尔克孜族、维吾尔族PPARG重组热点图谱与HapMap图比较发现存在明显差异，在HapMap重组热点谱图中有6个重组热点，柯尔克孜族PPARG重组热点图谱最后5个SNP显示较低的重组率，而维吾尔族PPARG基因重组热点图谱中未发现重组热点。结论在同一种族的糖尿病组与健康对照组或不同人群中在染色体某些区域的重组率变化可能存在很大差异，可能存在种群特异性的重组�Objective To investigate the characterizations of genetic recombination hotspots and linkage disequilibrium （LD） patterns in peroxisome proliferative activated receptor gamma （PPARG） gene in Kirgiz and Uyghur ethnic groups. Methods Blood samples were collected from 100 Kirgiz （50 healthy controls and 50 patients with type 2 diabetes mellitus） residents in Halajun County, Artux City, Kizilsu Kirgiz Autonomous Prefecture, Xinjiang in August 2013, and 50 healthy Uyghur residents in Hotan Prefecture of Xinjiang Uygur Autonomous Region in May 2012. Thirty-one tagSNPs in PPARG gene were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry （MALDI- TOF-MS） method. The recombination hotspots and LD patterns within the PPARG gene were estimated by analyzing the SNP genotying data using the Hotspot Fisher program and Haploview software, respectively. Results Eighteen tagSNPs （rs1151999, rs1175540, rs1875796, rs1899951, rs2292101, rs2921190, rs2938397, rs2959272, rs2959273, rs2972162, rs3856806, rs4135247, rs4135275,rs709151, rs4135354, rs6805419, rs17036700 and rs4135304） were same with relatively higher recombination rates between the patients with type 2 diabetes mellitus （T2DM） and healthy controls of Kirgiz ethnic group, and healthy controls of Uyghur ethnic group. Five haplotype blocks with LD coefficient D＇ value of 1, indicating no genetic recombination occurred within the region, were observed in the healthy controls of Kirgiz ethnic groups, whereas five haplotype blocks with LD coefficient D＇ value less than 1 were observed in the Kirgiz patients with T2DM, indicating historical recombination events occurred within the region. Four haplotype blocks with LD coefficient D＇ value of 1 were observed in the Uyghur healthy controls, indicating no genetic recombination occurred within the region. There were significantly different recombination hotspot profiles between the Kirgiz, Uyghur, Utah residents with Northern and Western European ancestry （CEU

关 键 词：过氧化物酶体增殖物激活受体 多态性 单核苷酸 连锁不平衡 重组热点 

分 类 号：R394[医药卫生—医学遗传学]