四川盆地结核分枝杆菌群体遗传学特征研究  

Study on the population-genetics of Mycobacterium tuberculosis from Sichuan Basin in China

作　　者：李颖[1] 付育红[2] 原梅[1] 董玲玲[2] 黄海荣[2] 李卫民[2] 高基民[1] 

机构地区：[1]温州医科大学检验医学院生命科学学院浙江省模式生物技术与应用重点实验室,325035 [2]首都医科大学附属北京胸科医院北京市结核病胸部肿瘤研究所国家结核病临床实验室

出　　处：《中华流行病学杂志》2015年第4期374-378,共5页Chinese Journal of Epidemiology

基　　金：国家自然科学基金（81273144）;北京市卫生系统高层次卫生技术人才培养计划项目（20133041）

摘　　要：目的探讨四川盆地（重庆、四川地区）流行的结核分枝杆菌（MTB）群体遗传学特征。方法对413株源自四川盆地的MTB进行长序列多态性（LSP）谱系鉴定，采用3（2检验分析不同谱系MTB在人群中的分布差异。对菌株进行15位点数目可变串联重复序列基因分型，评价各位点的分辨力。构建N—J树分析其系统进化；构建最小跨度树以模拟群体菌株的遗传结构；采用分子方差分析不同谱系MTB的群体问遗传分化；采用贝叶斯模型计算菌株最近共祖年代。结果通过LSP可将413株MTB分为两大谱系，其中北京谱系占56．2％（232／413），欧美谱系占43．8％（181／413）。两谱系MTB在人群中的分布（性别、年龄、民族以及菌株耐药性）差异无统计学意义（P〉0．05）。北京谱系MTB的N—J树呈放射状分布，最小跨度树中有72．4％（168／232）的菌株被划分到同一“克隆复合群”；欧美谱系MTB的N—J树呈枝状分布，最小跨度树中呈现出多个“克隆复合群”。北京谱系MTB在该地区有显著的群体间遗传分化（F ST=0．01891，P〈0．05），而欧美谱系MTB群体间遗传分化不显著（F ST=0．00519，P〉0．05）。欧美谱系MTB中最大菌株复合群的最近共祖年代为723（95％CI：517-946）年。结论北京谱系和欧美谱系MTB在四川盆地以“互相对抗”形式流行；两谱系MTB的群体间遗传分化存在差异；欧美谱系MTB的侵入可能与一次历史事件（约720年前的战争）有关。Objective To explore the population-genetics characteristics of Mycobacterium tuberculosis （MTB） prevailing at the Sichuan basin of China. Methods A total of 413 MTB strains collected from Sichuan basin were genotyped by large sequence polymorphism （LSP） and 15 loci variable number tandem repeat （VNTR）. Difference between the distribution of lineage population was analyzed by x 2-test and the discriminatory ability of each VNTR locus was evaluated under the Hunter-Gaston Discriminatory Index （HGI）. Both phylogeny on population level and genetic structure were demonstrated through N-J tree and the Minimal Spanning Tree （MST）. Genetic differentiation of different lineage strains was analyzed by Analysis of Molecular Variance （AMOVA）. Time of the Most Recent Common Ancestor （TMRCA） was calculated based on the Bayesian model. Results Four hundred and thirteen MTBs were divided into two major lineages, in which the Beijing lineage accounted for 56.2% （232/413） and the Euro-American lineage for 43.8% （181/413）. There was no significant difference of population distribution between the two lineages （P〉0.05）. The N-J tree of Beijing lineage MTB presented distinctly ＂star-like＂ and 72.4% strains were grouped to one clonal complex in MST. The Euro-American lineages MTB presented ＂branch-like＂ in N-J tree and were grouped into multiple clonal complexes in MST. There was significant genetic differentiation in Beijing lineage MTBs between Chongqing and Sichuan （F ST=0.018 91, P〈0.05） , but not in the Euro-American lineage MTB （F ST=0.005 19, P〉0.05）. TMRCA of the largest clonal complex in Euro-American lineage MTB appeared to be 723 （95% CI： 517-946） years. Conclusion Both Beijing lineage and Euro-American lineage MTBs were competitively prevalent in the Sichuan basin. There was some difference noticed between the two lineages referring to genetic differentiation. The invasion of Euro-American lineages MTB to the basin area might be associated with a war occu

关 键 词：结核分枝杆菌 长序列多态性 欧美谱系 群体遗传学 

分 类 号：R378.911[医药卫生—病原生物学]