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Journal of Bacteriology, May 2003, p. 2856-2866, Vol. 185, No. 9
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.9.2856-2866.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

IS6110-Mediated Deletion Polymorphism in the Direct Repeat Region of Clinical Isolates of Mycobacterium tuberculosis

S. L. Sampson, R. M. Warren, M. Richardson, T. C. Victor, A. M. Jordaan, G. D. van der Spuy, and P. D. van Helden*

MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa

Received 23 September 2002/ Accepted 17 January 2003

This study investigates the phenomenon of IS6110-mediated deletion polymorphism in the direct repeat (DR) region of the genome of Mycobacterium tuberculosis. Clinical isolates and their putative predecessors were compared using a combination of DR region restriction fragment length polymorphism, IS6110 DNA fingerprinting, spoligotyping, and DNA sequencing, which allowed the mapping of chromosome structure and deletion junctions. The data suggest that adjacently situated IS6110 elements mediate genome deletion. However, in contrast to previous reports, deletions appear to be mediated by inversely oriented IS6110 elements. This suggests that these events may occur via mechanisms other than RecA-mediated homologous recombination. The results underscore the important role of IS6110-associated deletion hypervariability in driving M. tuberculosis genome evolution.


* Corresponding author. Mailing address: MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa. Phone: 27-21-9389401. Fax: 27-21-9317810. E-mail: PVH{at}SUN.AC.ZA.


Journal of Bacteriology, May 2003, p. 2856-2866, Vol. 185, No. 9
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.9.2856-2866.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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