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首页> 外文期刊>BMC Genomics >Genetic heterogeneity revealed by sequence analysis of Mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients
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Genetic heterogeneity revealed by sequence analysis of Mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients

机译：肺结核分枝杆菌患者结核分枝杆菌分离株序列分析揭示了遗传异质性

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Background Tuberculosis remains a major public health problem. Clinical tuberculosis manifests often as pulmonary and occasionally as extra-pulmonary tuberculosis. The emergence of drug resistant tubercle bacilli and its association with HIV is a formidable challenge to curb the spread of tuberculosis. There have been concerted efforts by whole genome sequencing and bioinformatics analysis to identify genomic patterns and to establish a relationship between the genotype of the organism and clinical manifestation of tuberculosis. Extra-pulmonary TB constitutes 15–20 percent of the total clinical cases of tuberculosis reported among immunocompetent patients, whereas among HIV patients the incidence is more than 50 percent. Genomic analysis of M. tuberculosis isolates from extra pulmonary patients has not been explored. Results The genomic DNA of 5 extra-pulmonary clinical isolates of M. tuberculosis derived from cerebrospinal fluid, lymph node fine needle aspirates (FNAC) / biopsies, were sequenced. Next generation sequencing approach (NGS) was employed to identify Single Nucleotide Variations (SNVs) and computational methods used to predict their consequence on functional genes. Analysis of distribution of SNVs led to the finding that there are mixed genotypes in patient isolates and that many SNVs are likely to influence either gene function or their expression. Phylogenetic relationship between the isolates correlated with the origin of the isolates. In addition, insertion sites of IS elements were identified and their distribution revealed a variation in number and position of the element in the 5 extra-pulmonary isolates compared to the reference M. tuberculosis H37Rv strain. Conclusions The results suggest that NGS sequencing is able to identify small variations in genomes of M. tuberculosis isolates including changes in IS element insertion sites. Moreover, variations in isolates of M. tuberculosis from non-pulmonary sites were documented. The analysis of our results indicates genomic heterogeneity in the clinical isolates.
机译：背景结核病仍然是主要的公共卫生问题。临床肺结核的表现通常与肺外结核一样，偶尔也与肺外结核一样。耐药结核杆菌的出现及其与艾滋病毒的结合是遏制结核病传播的巨大挑战。通过全基因组测序和生物信息学分析已经做出了一致的努力，以鉴定基因组模式并建立生物体的基因型与结核病临床表现之间的关系。在免疫能力强的患者中，肺外结核占结核病临床病例总数的15％至20％，而在HIV患者中，这一比例超过50％。尚未探索来自额外肺部患者的结核分枝杆菌的基因组分析。结果对5份来源于脑脊液的结核分枝杆菌肺外临床分离株，淋巴结细针抽吸物（FNAC）/活检组织的基因组DNA进行了测序。下一代测序方法（NGS）用于鉴定单核苷酸变异（SNV），以及用于预测其对功能基因后果的计算方法。对SNV分布的分析导致发现患者分离株中存在混合基因型，并且许多SNV可能影响基因功能或其表达。分离株之间的亲缘关系与分离株的起源有关。另外，鉴定出IS元件的插入位点，并且它们的分布揭示了与参考结核分枝杆菌H37Rv菌株相比，在5个肺外分离物中该元件的数目和位置的变化。结论结果表明，NGS测序能够鉴定结核分枝杆菌分离株基因组的微小变化，包括IS元件插入位点的变化。此外，从非肺部位分离出的结核分枝杆菌也有变异。我们的结果分析表明临床分离物中的基因组异质性。

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