中国防痨杂志 ›› 2022, Vol. 44 ›› Issue (11): 1199-1204.doi: 10.19982/j.issn.1000-6621.20220250
收稿日期:
2022-07-07
出版日期:
2022-11-10
发布日期:
2022-11-03
基金资助:
Zhang Rui, Liu Yanping, Qian Jun, Fang Qianglin, Yang Chongguang()
Received:
2022-07-07
Online:
2022-11-10
Published:
2022-11-03
Supported by:
摘要:
结核分枝杆菌(Mycobacterium tuberculosis,MTB)作为引发结核病的主要病原体,其遗传多态性相对保守,随着二代全基因组测序技术的发展和普及,在不同宿主甚至同一宿主内都可观察到MTB菌株丰富的遗传异质性。宿主内异质性的成因包括不同菌株的多重(混合)感染和同一菌株的微进化。宿主内异质性的发生机制及其对MTB耐药、传播和诊疗等方面的影响及应用尚未完全清楚。本文综述了MTB宿主内遗传异质性的鉴定及相关研究进展,以期为结核病防控工作提供更多新思路。
中图分类号:
张睿, 刘艳萍, 钱军, 方强林, 杨崇广. 基于全基因组测序结核分枝杆菌宿主内异质性的鉴定及其研究进展[J]. 中国防痨杂志, 2022, 44(11): 1199-1204. doi: 10.19982/j.issn.1000-6621.20220250
Zhang Rui, Liu Yanping, Qian Jun, Fang Qianglin, Yang Chongguang. Updates on the application of whole-genome sequencing for within-host heterogeneity of Mycobacterium tuberculosis[J]. Chinese Journal of Antituberculosis, 2022, 44(11): 1199-1204. doi: 10.19982/j.issn.1000-6621.20220250
表1
鉴定多重感染及微进化方法[3]
方法 | 分析对象 | 结果识别 | 微进化 | 多重/混合感染 | 参考文献 |
---|---|---|---|---|---|
噬菌体分型 | 噬菌体菌落裂解 | 对特定结核分枝杆菌噬菌体的易感性 | 否 | 对多个不同的结核分枝杆菌噬菌体具有易感性 | [ |
IS6110限制性片段长度多态性分型 | 特异性的插入序列 | 限制性内切酶带杂交指纹图谱 | 1~2个条带差异 | > 2个条带 | [ |
1~3个条带差异 | > 3个条带 | [ | |||
间隔区寡核苷酸分型 | 直接重复区 | 直接重复区序列杂交指纹图谱 | 否 | 多个基因型认定为混合感染 | [ |
结核分枝杆菌散在重复单元-可变数目串联重复序列 | 特异性重复序列 | 基于PCR的拷贝数的差异 | <2个位点出现多个条带 | ≥2个位点出现多个条带 | [5, 29-32] |
二代测序 | 全基因组多态性 | 异质性SNP | 否 | ≥20个SNP或11~19个SNP且异质性SNP占比>1.5% | [ |
≤80个SNP | >80个SNP | [ | |||
≤140个SNP | >140个SNP | [ | |||
0~5个SNP | 757~833个SNP | [ | |||
2~15个SNP | 否 | [ | |||
每个基因组0.5个SNP/年 | 否 | [ | |||
生物信息软件/统计算法 | 否 | 不同进化路径等 | [ |
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