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J. Clin. Microbiol. doi:10.1128/JCM.00770-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Discordance between MIRU-VNTR and IS6110 RFLP genotyping when analyzing Mycobacterium tuberculosis Beijing strains in a high incidence setting

DST/NRF Centre of Excellence for Biomedical Tuberculosis Research/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Division of Anatomy and Histology, Faculty of Health Sciences, Stellenbosch University, South Africa

^* To whom correspondence should be addressed. Email: rw1{at}sun.ac.za.

	Abstract

IS6110-Restriction Fragment Length Polymorphism (RFLP) genotyping is the most widely used genotyping method to study the epidemiology of Mycobacterium tuberculosis. However, due to the complexity of the IS6110-RFLP genotyping technique, and the interpretation of RFLP data, Mycobacterial Interspersed Repetitive-Unit–Variable-Number Tandem-Repeat (MIRU-VNTR) genotyping has been proposed as the new genotyping standard. This study aimed to determine the discriminatory power of different MIRU-VNTR locus combinations relative to IS6110-RFLP genotyping, using a collection of Beijing genotype M. tuberculosis strains with a well established phylogenetic history. Clustering, diversity index, clustering concordance, concordance among unique genotypes, divergent and convergent evolution were calculated for 7 combinations of 27 different MIRU-VNTR loci and compared to IS6110-RFLP. Our results confirmed previous findings that MIRU-VNTR genotyping could be used to estimate the extent of recent or ongoing transmission. However, molecular epidemiological linking of cases varied significantly depending on the genotyping method used. We conclude that IS6110-RFLP and MIRU-VNTR loci evolve independently and at different rates which leads to discordance between transmission chains predicted by the respective genotyping methods. Concordance between the two genotyping methods could be improved by the inclusion of genetic distance into the clustering formula for some of the MIRU-VNTR loci combinations. In summary, our findings differ from previous reports, which may be explained by the fact that in low incidence settings, the genetic distance between epidemiologically unrelated isolates was sufficient to define a strain using either marker, whereas in high incidence settings, continuous evolution and persistence of strains reveal the weaknesses inherent to these markers.