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J Clin Microbiol. 2018 Jan 24;56(2). pii: e00761-17. doi: 10.1128/JCM.00761-17. Print 2018 Feb.

Occurrence and Nature of Double Alleles in Variable-Number Tandem-Repeat Patterns of More than 8,000 Mycobacterium tuberculosis Complex Isolates in The Netherlands.

Author information

1
National Tuberculosis Reference Laboratory, Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands rana.jajou@rivm.nl.
2
National Tuberculosis Reference Laboratory, Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
3
KNCV Tuberculosis Foundation, The Hague, The Netherlands.
4
University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019, UMR 8204, CIIL, Centre d'Infection et d'Immunité de Lille, Lille, France.
5
Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands.

Abstract

Since 2004, variable-number tandem-repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates has been applied on a structural basis in The Netherlands to study the epidemiology of tuberculosis (TB). Although this technique is faster and technically less demanding than the previously used restriction fragment length polymorphism (RFLP) typing, reproducibility remains a concern. In the period from 2004 to 2015, 8,532 isolates were subjected to VNTR typing in The Netherlands, with 186 (2.2%) of these exhibiting double alleles at one locus. Double alleles were most common in loci 4052 and 2163b. The variables significantly associated with double alleles were urban living (odds ratio [OR], 1.503; 95% confidence interval [CI], 1.084 to 2.084; P = 0.014) and pulmonary TB (OR, 1.703; 95% CI, 1.216 to 2.386; P = 0.002). Single-colony cultures of double-allele strains were produced and revealed single-allele profiles; a maximum of five single nucleotide polymorphisms (SNPs) was observed between the single- and double-allele isolates from the same patient when whole-genome sequencing (WGS) was applied. This indicates the presence of two bacterial populations with slightly different VNTR profiles in the parental population, related to genetic drift. This observation is confirmed by the fact that secondary cases from TB source cases with double-allele isolates sometimes display only one of the two alleles present in the source case. Double alleles occur at a frequency of 2.2% in VNTR patterns in The Netherlands. They are caused by biological variation rather than by technical aberrations and can be transmitted either as single- or double-allele variants.

KEYWORDS:

Mycobacterium tuberculosis; The Netherlands; VNTR; double alleles

PMID:
29142049
PMCID:
PMC5786718
DOI:
10.1128/JCM.00761-17
[Indexed for MEDLINE]
Free PMC Article

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