Wada Takayuki, Iwamoto Tomotada, Tamaru Aki, Seto Junji, Ahiko Tadayuki, Yamamoto Kaori, Hase Atushi, Maeda Shinji, Yamamoto Taro
Department of International Health, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Department of Microbiology, Kobe Institute of Health, Kobe, Japan.
PLoS One. 2015 Mar 3;10(3):e0118495. doi: 10.1371/journal.pone.0118495. eCollection 2015.
Mycobacterium tuberculosis transmission routes can be estimated from genotypic analysis of clinical isolates from patients. In Japan, still a middle-incidence country of TB, a unique genotype strain designated as 'M-strain' has been isolated nationwide recently. To ascertain the history of the wide spread of the strain, 10 clinical isolates from different areas were subjected to genome-wide analysis based on deep sequencers. Results show that all isolates possessed common mutations to those of referential strains. The greatest number of accumulated single nucleotide variants (SNVs) from the oldest coalescence was 13 nucleotides, indicating high clonality of these isolates. When an SNV common to the isolates was used as a surrogate marker of the clone, authentic clonal isolates with variation in a reliable subset of variable number of tandem repeat (VNTR) genotyping method can be selected successfully from clinical isolates populations of M. tuberculosis. When the authentic clones can also be assigned to sub-clonal groups by SNVs derived from the genomic comparison, they are classifiable into three sub-clonal groups with a bias of geographical origins. Feedback from genomic analysis of clinical isolates of M. tuberculosis to genotypic markers will be an efficient strategy for the big data in various settings for public health actions against TB.
结核分枝杆菌的传播途径可通过对患者临床分离株进行基因型分析来估计。在日本这个结核病中等发病率的国家，最近在全国范围内分离出了一种名为“M株”的独特基因型菌株。为了确定该菌株广泛传播的历史，对来自不同地区的10株临床分离株进行了基于深度测序仪的全基因组分析。结果显示，所有分离株与参考菌株都有共同的突变。从最古老的合并事件开始积累的单核苷酸变异（SNV）数量最多为13个核苷酸，表明这些分离株具有高度的克隆性。当将分离株共有的一个SNV用作克隆的替代标记时，就可以从结核分枝杆菌的临床分离株群体中成功筛选出在可变数目串联重复序列（VNTR）基因分型方法的可靠子集中存在变异的真实克隆分离株。当通过基因组比较得到的SNV也能将真实克隆归入亚克隆组时，它们可被分为三个亚克隆组，且存在地理起源偏向。对结核分枝杆菌临床分离株进行基因组分析并反馈给基因标记，将是在各种环境下针对结核病采取公共卫生行动时处理大数据的有效策略。
