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

Michaela M. Gutacker, Barun Mathema, Hanna Soini, Elena Shashkina, Barry N. Kreiswirth, Edward A. Graviss, James M. Musser

Research output: Contribution to journalArticle

164 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)121-128
Number of pages8
JournalJournal of Infectious Diseases
Volume193
Issue number1
DOIs
StatePublished - Jan 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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