Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Fudan University, Shanghai, China.
J Clin Microbiol. 2012 Mar;50(3):633-9. doi: 10.1128/JCM.05539-11. Epub 2012 Jan 11.
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.
标准的 15 位和 24 位可变数目串联重复（VNTR）基因分型方法已经证明了足够的区分能力和较小的同型性效应，可用于追踪结核病（TB）的传播并预测欧洲和北美国家的结核分枝杆菌谱系。然而，其在具有高结核病负担的同质结核分枝杆菌人群中定义传播的有效性受到了质疑。在这里，我们基于标准的 15 位 VNTR（VNTR-15）和 8 个单核苷酸多态性（SNP）对中国上海的一个基于人群的 191 株北京菌株进行了基因分型。在进化上“现代”的北京菌株同质人群中，观察到有限的区分能力和高 VNTR 同型性率。对 VNTR-15 为基础的聚类进行了三个高变区（VNTR3820、VNTR4120 和 VNTR3232）的额外分型。在 SNP 亚谱系不一致的聚类中观察到高变的高变等位基因。我们得出结论，SNP 和高变 VNTR 位点有助于提高区分能力和降低 VNTR 同型性效应，以定义聚类。我们建议将标准的 VNTR-15 和 SNP 组合作为一线分型方法，并将高变位点用于聚类菌株的二线分型，用于同质结核分枝杆菌人群的分子流行病学研究。
