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利用额外的可变数目串联重复序列位点改进英格兰北部结核分枝杆菌分离株的鉴别

Improved differentiation of Mycobacterium tuberculosis isolates in the north of England using additional variable number tandem repeat loci.

作者信息

Gaukrodger N, Thompson D, Sarginson S J, Magee J G, Sails A D

机构信息

Health Protection Agency, Institute of Pathology, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK.

出版信息

Br J Biomed Sci. 2011;68(1):23-8. doi: 10.1080/09674845.2011.11732837.

DOI:10.1080/09674845.2011.11732837
PMID:21473258
Abstract

Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) genotyping of over 3300 Mycobacterium tuberculosis isolates from the north of England has identified large clusters of strains which share common profiles. However, many apparent clusters identified when typed using the existing 15 loci lack clear epidemiological links. This study seeks to discover whether or not six additional VNTR loci can increasethe discriminatory power of the existing MIRU-VNTR 15-loci technique. Two hundred and six M. tuberculosis isolates were genotyped, including 57 isolates from 20 epidemiologically linked clusters and 149 from unlinked patients belonging to six large MIRU-VNTR-defined clusters. The discriminatory power of the six additional loci was high (Hunter Gaston Discriminatory Index [HGDI]: 0.952). Five of the six loci were highly discriminative (h > 0.6); however, locus 2401 was less discriminative (h = 0.5). The additional VNTR loci were able to subtype all six unlinked common MIRU-VNTR clusters into 56 subclusters, significantly differentiating unrelated strains in a set previously incorrectly clustered using 15 MIRU-VNTR loci. The largest cluster size was 14 (9.3%) when typed using the six additional VNTR loci, compared to 30 (20%) when typed using the original 15 MIRU-VNTR loci. The same loci were also found to be stable as a result of their inability to subdivide any of the epidemiologically linked clusters. This study has demonstrated that expanding the MIRU-VNTR panel beyond the 15 previously used loci significantly increases the discriminatory power of the technique and thus provides a valuable tool in the epidemiological monitoring of this disease.

摘要

对来自英格兰北部的3300多株结核分枝杆菌分离株进行的分枝杆菌散布重复单位-可变数目串联重复序列(MIRU-VNTR)基因分型,已识别出具有共同图谱的大量菌株簇。然而,使用现有的15个位点进行分型时所识别出的许多明显簇缺乏明确的流行病学联系。本研究旨在探究另外六个VNTR位点是否能够提高现有MIRU-VNTR 15位点技术的鉴别力。对206株结核分枝杆菌分离株进行了基因分型,其中包括来自20个有流行病学联系的簇的57株分离株,以及来自属于六个由MIRU-VNTR定义的大簇的无联系患者的149株分离株。另外六个位点的鉴别力很高(亨特·加斯顿鉴别指数[HGDI]:0.952)。六个位点中的五个具有高度鉴别力(h>0.6);然而,位点2401的鉴别力较低(h = 0.5)。额外的VNTR位点能够将所有六个无联系的常见MIRU-VNTR簇进一步细分为56个亚簇,显著区分了一组先前使用15个MIRU-VNTR位点错误聚类的无关菌株。使用另外六个VNTR位点进行分型时,最大簇大小为14(9.3%),而使用原始的15个MIRU-VNTR位点进行分型时为30(20%)。由于这些位点无法细分任何有流行病学联系的簇,因此还发现它们具有稳定性。本研究表明,将MIRU-VNTR检测板扩展到先前使用的15个位点之外,可显著提高该技术的鉴别力,从而为该疾病的流行病学监测提供了一个有价值的工具。

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