Analysis of the population structure of Mycobacterium tuberculosis strains from the People's Republic of China showed that the vast majority belong to a genetically closely related group. These strains shared the majority of their IS6110 DNA-containing restriction fragments, and also, the DNA polymorphism associated with other repetitive DNA elements, like the polymorphic GC-rich sequence and the direct repeat, was very limited. Because the majority of these strains originated from the province of Beijing, we designated this grouping the ''Beijing family'' of M. tuberculosis strains. Strains of this family were also found to dominate in neighboring countries such as Mongolia, South Korea, and Thailand, whereas a low prevalence of such strains was observed in countries on other continents. These data indicate that strains of the Beijing family recently expanded from a single ancestor which had a selective advantage. It is speculated that long-term Mycobacterium bovis BCG vaccination may be one of the selective forces implicated in the successful spread of the Beijing genotype.

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The 81-bp region of the rpoB gene in 66 Rif r Mycobacterium tuberculosis isolates from China, Japan, Korea, and Taiwan was analyzed. Twelve single-nucleotide substitutions in the rpoB gene were detected. The most prevalent mutations were at Ser-531 (52%), Asp-516 (17%), and His-526 (11%). Mutations were not found in seven (11%) of the isolates. Higher mutation rates in 50 Beijing family isolates were found than in other isolates for mutations at Asp-516 (18 and 12.5%, respectively) and His-526 (12 and 6.3%, respectively). The different rates of mutation may reflect the choice of rifamycin analogs.

Forty-eight Mycobacterium tuberculosis strains were obtained from patients living in metropolitan Manila, Republic of the Philippines. Three molecular typing methods, IS6110 restriction fragment length polymorphism, spoligotyping, and DNA sequencing of the oxyR, gyrA, and katG loci, established that these strains have restricted diversity and are members of a related genetic group of organisms. Comparison of the DNA fingerprint patterns with those in international databases confirmed the uniqueness of this group of isolates, which we designate the Manila family of M. tuberculosis.The advent of IS6110-based restriction fragment length polymorphism (RFLP) typing of Mycobacterium tuberculosis has led to fingerprinting studies throughout the world (13, 16). These studies have provided insight on the transmission of tuberculosis within and among different geographical areas of the world (10, 16). One finding of IS6110 DNA fingerprinting is that the population structure of M. tuberculosis differs in regions in that some geographical areas are associated with families or groups of related isolates, such as the Beijing, Haarlem, and African genotype families (2,5,7,8,15 Microbiol. 1995Microbiol. , abstr. U-4, p. 117, 1995. Additional DNA typing technologies, such as spoligotyping (6), analysis of the pseudogene oxyR (12), polymorphic GC-rich sequence RFLP (9), and typing of variable numbers of tandem repeats (1) confirmed these family groupings of M. tuberculosis.Since we noticed that tuberculosis isolates from Filipinos, which account for 50% of the M. tuberculosis isolates from foreign-borne patients in Hawaii (State of Hawaii Department of Health data, www.hawaiistate/health/tuberculosis, 2001), had related spoligotyping patterns, we decided to directly investigate isolates from Manila, Republic of the Phillipines (J. T. Douglas, L. Qian, J. C. Montoya, S. Sreevatsan, J. M. Musser, and J. D. A. van Embden, Abstr. 97th Gen. Meet. Am. Soc. Microbiol., abstr. U-166, p. 572, 1997). Manila is the largest city in the Philippines (about 10 million people); it has a high population density and socioeconomic problems, and tuberculosis is highly endemic. Manila is also geographically isolated within an island nation, which could be a fertile ground for clonal expansion of M. tuberculosis. Because little is known about the population structure of tuberculosis in the Philippines, we subjected a random sample of M. tuberculosis isolates originating in Manila to various molecular typing techniques to search for genetic markers that might be useful in studying M. tuberculosis isolates recovered from immigrant populations within Hawaii.The Tuberculosis Study Group at the Research Institute for Tropical Medicine and the Philippine General Hospital provided 48 M. tuberculosis isolates from separate individuals in the metropolitan Manila area. Initially 18 isolates were collected in December 1995, followed by 30 isolates 8 months later. Of these, 35 came with some demographic data. These isolates were from 18 males and 17 females. Th...

Direct repeat spoligotyping of 85 paraffin-embedded lung biopsies was used to investigated the occurrence around Beijing of the Beijing family of Mycobacterium tuberculosis. Samples ranged in time from 1956 to 1990. Hybridization patterns were found with 49 (58%) samples, and 45 (92%) produced typical Beijing family patterns extending over the 34-year period.