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Journal of Clinical Microbiology, April 2009, p. 1119-1128, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.02142-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Major Mycobacterium tuberculosis Lineages Associate with Patient Country of Origin ^,

Michael B. Reed,^1* Victoria K. Pichler,¹ Fiona McIntosh,¹ Alicia Mattia,¹ Ashley Fallow,¹ Speranza Masala,¹ Pilar Domenech,¹ Alice Zwerling,² Louise Thibert,³ Dick Menzies,² Kevin Schwartzman,² and Marcel A. Behr¹

Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada,¹ Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, Quebec, Canada,² Laboratoire de Santé Publique du Québec, Sainte-Anne-de-Bellevue, Quebec, Canada³

Received 8 November 2008/ Returned for modification 25 November 2008/ Accepted 30 January 2009

Over recent years, there has been an increasing acknowledgment of the diversity that exists among Mycobacterium tuberculosis clinical isolates. To facilitate comparative studies aimed at deciphering the relevance of this diversity to human disease, an unambiguous and easily interpretable method of strain classification is required. Presently, the most effective means of assigning isolates into a series of unambiguous lineages is the method of Gagneux et al. (S. Gagneux et al., Proc. Natl. Acad. Sci. USA 103:2869-2873, 2006) that involves the PCR-based detection of large sequence polymorphisms (LSPs). In this manner, isolates are classified into six major lineages, the majority of which display a high degree of geographic restriction. Here we describe an independent replicate of the Gagneux study carried out on 798 isolates collected over a 6-year period from mostly foreign-born patients resident on the island of Montreal, Canada. The original trends in terms of bacterial genotype and patient ethnicity are remarkably conserved within this Montreal cohort, even though the patient distributions between the two populations are quite distinct. In parallel with the LSP analysis, we also demonstrate that "clustered" tuberculosis (TB) cases defined through restriction fragment length polymorphism (RFLP) analysis (for isolates with 6 IS6110 copies) or RFLP in combination with spoligotyping (for isolates with <6 IS6110 copies) do not stray across the LSP-defined lineage boundaries. However, our data also demonstrate the poor discriminatory power of either RFLP or spoligotyping alone for these low-IS6110-copy-number isolates. We believe that this independent validation of the LSP method should encourage researchers to adopt this system in investigations aimed at elucidating the role of strain variation in TB.

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* Corresponding author. Mailing address: Research Institute—McGill University Health Centre, Room Rs1-133, 1625 Pine Ave. West, Montreal, Quebec, Canada H3G 1A4. Phone: (514) 934-1934. Fax: (514) 934-8261. E-mail: michael.reed{at}mcgill.ca

Published ahead of print on 11 February 2009.

Supplemental material for this article may be found at http://jcm.asm.org/.

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Journal of Clinical Microbiology, April 2009, p. 1119-1128, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.02142-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.