Combination of Single Nucleotide Polymorphism and Variable-Number Tandem Repeats for Genotyping a Homogenous Population of Mycobacterium tuberculosis Beijing Strains in China
Combination of Single Nucleotide Polymorphism and Variable-Number Tandem Repeats for Genotyping a Homogenous Population of Mycobacterium tuberculosis Beijing Strains in China
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DOI：
10.1128/jcm.05539-11
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发表时间：
2012-03-01
影响因子：
9.4
通讯作者：
Gao, Qian
中科院分区：
文献类型：
--
作者：
Luo, Tao;Yang, Chongguang;Gao, Qian
标准的15-和24-位点可变数目串联重复序列（VNTR）基因分型方法已被证明有足够的区分能力和小的同源性效应，用于追踪结核病（TB）传播和预测欧洲和北美国家的结核分枝杆菌谱系。然而，它的有效性的定义的传输在齐次M。结核病高负担环境中的结核病人群受到质疑。在这里，我们基因型的191个北京菌株的基础上，标准的15个位点的VNTR（VNTR-15）和8个单核苷酸多态性（SNPs）在上海，中国人群为基础的收集。在进化上的“现代”北京菌株的同质群体中观察到有限的区分能力和高比率的VNTR同源性。对基于VNTR-15的簇进行三个高变基因座（VNTR 3820、VNTR 4120和VNTR 3232）的额外分型。在具有不一致SNP亚系的簇中观察到高变等位基因的高度变异。我们认为，SNPs和高变VNTR位点有助于提高区分能力，降低VNTR的同源性效应，以确定集群。我们建议将标准VNTR-15和SNPs作为一线分型方法，高变位点作为二线分型方法，用于同质性M.肺结核人群。
The standard 15- and 24-locus variable-number tandem repeat (VNTR) genotyping methods have demonstrated adequate discriminatory power and a small homoplasy effect for tracing tuberculosis (TB) transmission and predicting Mycobacterium tuberculosis lineages in European and North American countries. However, its validity for the definition of transmission in homogenous M. tuberculosis populations in settings with high TB burdens has been questioned. Here, we genotyped a population-based collection of 191 Beijing strains based on standard 15-locus VNTR (VNTR-15) and 8 single nucleotide polymorphisms (SNPs) in Shanghai, China. Limited discriminatory power and high rates of VNTR homoplasy were observed in the homogenous population of evolutionarily "modern" Beijing strains. Additional typing of three hypervariable loci (VNTR3820, VNTR4120, and VNTR3232) was performed for VNTR-15-based clusters. High variations of hypervariable alleles were observed in clusters with inconsistent SNP sublineages. We concluded that SNPs and hypervariable VNTR loci are helpful to enhance the discriminatory power and decrease the VNTR homoplasy effect for defining clusters. We recommend the combination of standard VNTR-15 and SNPs as first-line typing methods and the hypervariable loci for second-line typing of clustered strains for molecular epidemiology studies of homogenous M. tuberculosis populations.