Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Sci Rep. 2017 May 3;7(1):1425. doi: 10.1038/s41598-017-01580-z.
Tuberculosis (TB) is a severe infectious disease worldwide. Genetic variation of the causative agent, Mycobacterium tuberculosis (MTB), determines the outcomes of infection and anti-TB treatment. Until recently, there has been no effective and convenient way for classifying clinical isolates based on the DNA sequences of the divergent lineages of MTB infecting human populations. Here, we identified single nucleotide polymorphisms (SNPs) of six representative strains from Taiwan by whole-genome sequencing and comparing the results to the sequence of the H37Rv reference strain. One hundred and ten SNPs, each unique to one of the six strains, were used to genotype 150 additional isolates by applying DNA mass spectrometry. Lineage-specific SNPs were identified that could distinguish the major lineages of the clinical isolates. A subset including 32 SNPs was found to be sufficient to type four major groups of MTB isolates in Taiwan (ancient Beijing, modern Beijing, East African-Indian, and Latin-American Mediterranean). However, there was high genetic homozygosity within the Euro-American lineage, which included spoligotype-classified Haarlem and T strains. By whole-genome sequencing of 12 representative Euro-American isolates, we identified multiple subtype-specific SNPs which allowed us to distinguish two major branches within the Euro-American lineage.
结核病（TB）是一种严重的传染病，在全球范围内流行。致病微生物结核分枝杆菌（MTB）的遗传变异决定了感染和抗结核治疗的结果。直到最近，还没有一种有效且方便的方法可以根据感染人类的 MTB 分歧谱系的 DNA 序列对临床分离株进行分类。在这里，我们通过全基因组测序鉴定了来自台湾的 6 个代表性菌株的单核苷酸多态性（SNP），并将结果与 H37Rv 参考菌株的序列进行比较。通过应用 DNA 质谱，将 110 个独特的 SNP 用于对 150 个额外的分离株进行基因分型。鉴定出了具有种系特异性的 SNP，这些 SNP 可以区分临床分离株的主要谱系。发现包括 32 个 SNP 的子集足以对台湾的 4 个主要 MTB 分离株组（古老的北京、现代的北京、东非-印度和拉丁美洲地中海）进行分型。然而，在包括 spoligotype 分类的 Haarlem 和 T 株在内的欧洲-美洲谱系中存在高度遗传同质性。通过对 12 个代表性欧洲-美洲分离株的全基因组测序，我们鉴定出了多个亚型特异性 SNP，这些 SNP 允许我们区分欧洲-美洲谱系内的两个主要分支。
