title: 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.
abstract: 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.
authors.affiliation: Pathogen Evolution Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500 076, India.
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmed
authors.forename: Mahfooz
authors.initials: M
authors.lastname: Alam
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Rao
authors.forename: Farhana
authors.initials: F
authors.lastname: Kauser
authors.forename: N Ashok
authors.initials: NA
authors.lastname: Kumar
authors.forename: Nazia N
authors.initials: NN
authors.lastname: Qazi
authors.forename: Vartul
authors.initials: V
authors.lastname: Sangal
authors.forename: V D
authors.initials: VD
authors.lastname: Sharma
authors.forename: Ram
authors.initials: R
authors.lastname: Das
authors.forename: V M
authors.initials: VM
authors.lastname: Katoch
authors.forename: K J R
authors.initials: KJ
authors.lastname: Murthy
authors.forename: Sujai
authors.initials: S
authors.lastname: Suneetha
authors.forename: S K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Sechi
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Seyed E
authors.initials: SE
authors.lastname: Hasnain
mesh_terms: D004251:DNA Transposable Elements; D016680:Genome, Bacterial; D005838:Genotype; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D011110:Polymorphism, Genetic
chemical_list: D004251:DNA Transposable Elements