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Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.
Proc Natl Acad Sci U S A. 2000 Jul 05; 97(14):8005-9.PN

Abstract

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

Authors+Show Affiliations

Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10859364

Citation

Bellamy, R, et al. "Genetic Susceptibility to Tuberculosis in Africans: a Genome-wide Scan." Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 14, 2000, pp. 8005-9.
Bellamy R, Beyers N, McAdam KP, et al. Genetic susceptibility to tuberculosis in Africans: a genome-wide scan. Proc Natl Acad Sci USA. 2000;97(14):8005-9.
Bellamy, R., Beyers, N., McAdam, K. P., Ruwende, C., Gie, R., Samaai, P., Bester, D., Meyer, M., Corrah, T., Collin, M., Camidge, D. R., Wilkinson, D., Hoal-Van Helden, E., Whittle, H. C., Amos, W., van Helden, P., & Hill, A. V. (2000). Genetic susceptibility to tuberculosis in Africans: a genome-wide scan. Proceedings of the National Academy of Sciences of the United States of America, 97(14), 8005-9.
Bellamy R, et al. Genetic Susceptibility to Tuberculosis in Africans: a Genome-wide Scan. Proc Natl Acad Sci USA. 2000 Jul 5;97(14):8005-9. PubMed PMID: 10859364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic susceptibility to tuberculosis in Africans: a genome-wide scan. AU - Bellamy,R, AU - Beyers,N, AU - McAdam,K P, AU - Ruwende,C, AU - Gie,R, AU - Samaai,P, AU - Bester,D, AU - Meyer,M, AU - Corrah,T, AU - Collin,M, AU - Camidge,D R, AU - Wilkinson,D, AU - Hoal-Van Helden,E, AU - Whittle,H C, AU - Amos,W, AU - van Helden,P, AU - Hill,A V, PY - 2000/6/22/pubmed PY - 2000/8/12/medline PY - 2000/6/22/entrez SP - 8005 EP - 9 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 97 IS - 14 N2 - Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/10859364/Genetic_susceptibility_to_tuberculosis_in_Africans:_a_genome_wide_scan_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10859364 DB - PRIME DP - Unbound Medicine ER -