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Journal of Clinical Microbiology, July 2004, p. 3240-3247, Vol. 42, No. 7
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.7.3240-3247.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Molecular Genotyping of a Large, Multicentric Collection of Tubercle Bacilli Indicates Geographical Partitioning of Strain Variation and Has Implications for Global Epidemiology of Mycobacterium tuberculosis

Niyaz Ahmed,¹ Mahfooz Alam,¹ K. Rajender Rao,¹ Farhana Kauser,¹ N. Ashok Kumar,¹ Nazia N. Qazi,¹ Vartul Sangal,¹ V. D. Sharma,² Ram Das,² V. M. Katoch,² K. J. R. Murthy,³ Sujai Suneetha,⁴ S. K. Sharma,⁵ Leonardo A. Sechi,⁶ Robert H. Gilman,⁷ and Seyed E. Hasnain^1,8*

Pathogen Evolution Group, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500 076,¹ Central JALMA Institute for Leprosy, Tajgunj, Agra 282001,² Mahavir Hospital and Research Centre, Mahavir Marg, Hyderabad 500 004,³ Blue Peter Research Centre, Lepra India, Cherlapally, Hyderabad 501 301,⁴ Department of Medicine, A.I.I.M.S., New Delhi 110029,⁵ Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur 560 064, India,⁸ Dipartimento di Scienze Biomediche, University of Sassari, B07100 Sassari, Sardinia, Italy,⁶ Johns Hopkins University School of Public Health, Baltimore, Maryland 21205⁷

Received 9 February 2004/ Returned for modification 15 March 2004/ Accepted 25 March 2004

Tuberculosis continues to be a major killer disease, despite an all-out effort launched against it in the postgenomic era. We describe here the population structure of Mycobacterium tuberculosis strains, as revealed by a chromosome-wide scan of fluorescent amplified fragment length polymorphisms (FAFLPs), for more than 1,100 independent isolates from 11 different countries. The bacterial strains were genotyped based on a total of 136 ± 1 different FAFLP markers at the genome sequence interface, with details on IS6110 profiles, drug resistance status, clinicopathological observations, and host status integrated into the analysis process. The strains were found to cluster with possible geographic affinities, including the parameters of host species type, IS6110 profile, and drug susceptibility status. Of the five most commonly amplified fragment sets (or amplitypes), type A predominated in strains of mixed origin, deposited in The Netherlands; type B was exclusively observed for Indian isolates; type C was found mainly in strains from Peru and Australia; and types D and E predominated in European strains from France and Italy. The amplitypes were independent of certain large sequence polymorphisms representing two important deletions, TbD1 and Rd9. It appears that M. tuberculosis has a high genomic diversity with a possible geographic evolution. This may have occurred due to specific genomic deletions and synonymous substitutions selected rigorously against host defenses and environmental stresses on an evolutionary timescale. The genotypic data reported here are additionally significant for genotype-phenotype correlations and for determining whether pathogen diversity is a reflection f the host population diversity.

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* Corresponding author. Mailing address: Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500 076, India. Phone: 91 40 2715 5604. Fax: 91 40 2715 5610. E-mail: hasnain{at}cdfd.org.in.

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Journal of Clinical Microbiology, July 2004, p. 3240-3247, Vol. 42, No. 7
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.7.3240-3247.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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