Single-nucleotide polymorphism-based population genetic analysis of Mycobacterium tuberculosis strains from 4 geographic sites

J Infect Dis. 2006 Jan 1;193(1):121-8. doi: 10.1086/498574. Epub 2005 Nov 28.

Abstract

We studied genetic relationships among 5069 Mycobacterium tuberculosis strains recovered from patients enrolled in 4 population-based studies in the United States and Europe, by analysis of 36 synonymous single-nucleotide polymorphisms (SNPs). All strains were assigned to 1 of 9 major genetic clusters based on sSNP profile. The same 9 genetic clusters were revealed by analysis of 227 nonsynonymous SNPs, 121 intergenic SNPs, and concatenated profiles of 578 SNPs available for a subset of 48 representative strains. IS6110 profiles, spoligotypes, and mycobacterial interspersed repetitive unit patterns were nonrandomly associated with SNP-based phylogenetic lineages, together indicating a strongly clonal population structure. Isolates of the 9 genetic clusters were not distributed with equal frequency in all localities, reflecting geographic subdivision. The SNP-based phylogenetic framework provides new insight into the worldwide evolution of M. tuberculosis and a gateway for investigating genotype-disease phenotype relationships in large samples of strains.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Bacterial Typing Techniques
  • DNA Transposable Elements
  • Europe / epidemiology
  • Humans
  • Mycobacterium tuberculosis / classification*
  • Mycobacterium tuberculosis / genetics*
  • Oligonucleotides / analysis
  • Phylogeny
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics*
  • Tuberculosis, Pulmonary / epidemiology*
  • Tuberculosis, Pulmonary / microbiology
  • United States / epidemiology

Substances

  • DNA Transposable Elements
  • Oligonucleotides