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Vol. 11, Issue 4, 547-554, April 2001

LETTER
Comparing Genomes within the Species Mycobacterium tuberculosis

Midori Kato-Maeda,1 Jeanne T. Rhee,2 Thomas R. Gingeras,3 Hugh Salamon,1,4 Jorg Drenkow,3 Nat Smittipat,1 and Peter M. Small1,5,6

1 Division of Infectious Diseases and Geographic Medicine, Department of Medicine and 2 Department of Epidemiology, Stanford Medical School University, Stanford, California 94305, USA; 3 Affymetrix, Santa Clara, California 95051, USA

The study of genetic variability within natural populations of pathogens may provide insight into their evolution and pathogenesis. We used a Mycobacterium tuberculosis high-density oligonucleotide microarray to detect small-scale genomic deletions among 19 clinically and epidemiologically well-characterized isolates of M. tuberculosis. The pattern of deletions detected was identical within mycobacterial clones but differed between different clones, suggesting that this is a suitable genotyping system for epidemiologic studies. An analysis of genomic deletions among an extant population of pathogenic bacteria provided a novel perspective on genomic organization and evolution. Deletions are likely to contain ancestral genes whose functions are no longer essential for the organism's survival, whereas genes that are never deleted constitute the minimal mycobacterial genome. As the amount of genomic deletion increased, the likelihood that the bacteria will cause pulmonary cavitation decreased, suggesting that the accumulation of mutations tends to diminish their pathogenicity. Array-based comparative genomics is a promising approach to exploring molecular epidemiology, microbial evolution, and pathogenesis.


Present addresses: 4Berlex Biosciences, 15049 San Pablo Avenue, Richmond, CA 94804, USA; 5300 Pasteur Drive, Grant Building S-143, Medical Center, Stanford University, Stanford, CA 94305, USA.

6 Corresponding author.


11:547-554 ©2001 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/01 $5.00

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