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A major susceptibility locus for leprosy in India maps to chromosome 10p13

Abstract

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur1. A role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex segregation analyses and human leukocyte antigen (HLA) association studies. We report here a genetic linkage scan of the genomes of 224 families from South India, containing 245 independent affected sibpairs with leprosy, mainly of the paucibacillary type. In a two-stage genome screen using 396 microsatellite markers, we found significant linkage (maximum lod score (MLS)=4.09, P<2×10−5) on chromosome 10p13 for a series of neighboring microsatellite markers, providing evidence for a major locus for this prevalent infectious disease. Thus, despite the polygenic nature of infectious disease susceptibility, some major, non-HLA–linked loci exist that may be mapped through obtainable numbers of affected sibling pairs.

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Figure 1: Maximum likelihood multipoint map for 25 microsatellite markers on chromosome 10, including 8 markers flanking D10S548.

References

  1. WHO Elimination of leprosy as a public health problem. Wkly Epidemiol. Rec. 73, 308–312 (1998).

  2. Aredath, S.P. The occurrence of leprosy in an eight-member family—a case report. Lepr. Rev. 55, 47–50 (1984).

    CAS  PubMed  Google Scholar 

  3. Shields, E.D., Russell, D.A. & Pericak-Vance, M.A. Genetic epidemiology of the susceptibility to leprosy. J. Clin. Invest. 79, 1139–1143 (1987).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Chakravartti, M.R. & Vogel, F. A twin study on leprosy. in Topics in Human Genetics (ed. Becker, P.E.) 1–123 (Georg Thieme, Stuttgart, 1973).

    Google Scholar 

  5. Mohammed Ali, P. & Ramanujam, K. Leprosy in twins. Int. J. Lepr. 34, 405–406 (1966).

    Google Scholar 

  6. Abel, L. & Demenais, F. Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island. Am. J. Hum. Genet. 42, 256–266 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Feitosa, M.F., Borecki, I., Krieger, H., Beiguelman, B. & Rao, D.C. The genetic epidemiology of leprosy in a Brazilian population. Am. J. Hum. Genet. 56, 1179–1185 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Todd, J.R., West, B.C. & McDonald, J.C. Human leukocyte antigen and leprosy: study in northern Louisiana and review. Rev. Infect. Dis. 12, 63–74 (1990).

    CAS  Article  PubMed  Google Scholar 

  9. Risch, N. Assessing the role of HLA-linked and unlinked determinants of disease. Am. J. Hum. Genet. 40, 1–14 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Davies, J.L. et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature 371, 130–136 (1994).

    CAS  Article  PubMed  Google Scholar 

  11. Lander, E.S. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 (1995).

    CAS  Article  PubMed  Google Scholar 

  12. Kruglyak, L. & Lander, E.S. Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am. J. Hum. Genet. 57, 439–454 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Abel, L. et al. Susceptibility to leprosy is linked to the human NRAMP1 gene. J. Infect. Dis. 177, 133–145 (1998).

    CAS  Article  PubMed  Google Scholar 

  14. Marquet, S. et al. Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31–q33. Nature Genet. 14, 181–184 (1996).

    CAS  Article  PubMed  Google Scholar 

  15. Marquet, S., Abel, L., Hillaire, D. & Dessein, A. Full results of the genome-wide scan which localises a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31–q33. Eur. J. Hum. Genet. 7, 88–97 (1999).

    CAS  Article  PubMed  Google Scholar 

  16. Rihet, P. et al. Malaria in humans: Plasmodium falciparum blood infection levels are linked to chromosome 5q31–q33. Am. J. Hum. Genet. 63, 498–505 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Bellamy, R. et al. Genetic susceptibility to tuberculosis in Africans: a genome-wide scan. Proc. Natl. Acad. Sci. USA 97, 8005–8009 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Haile, R.W., Iselius, L., Fine, P.E. & Morton, N.E. Segregation and linkage analyses of 72 leprosy pedigrees. Hum. Hered. 35, 43–52 (1985).

    CAS  Article  PubMed  Google Scholar 

  19. Ridley, D.S. & Jopling, W.H. Classification of leprosy according to immunity. A five-group system. Int. J. Lepr. Other Mycobact. Dis. 34, 255–273 (1966).

    CAS  PubMed  Google Scholar 

  20. Dib, C. et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 380, 152–154 (1996).

    CAS  Article  PubMed  Google Scholar 

  21. Satsangi, J. et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nature Genet. 14, 199–202 (1996).

    CAS  Article  PubMed  Google Scholar 

  22. Risch, N. Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. Am. J. Hum. Genet. 46, 242–253 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Risch, N. Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am. J. Hum. Genet. 46, 229–241 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Holmans, P. Asymptotic properties of affected-sib-pair linkage analysis. Am. J. Hum. Genet. 52, 362–374 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the authorities and staff of the Hindu Mission Hospital and the Sacred Heart Leprosy Centre, Kumbakonam, Sakthi sugar factory voluntary health services, Erode, Madurai Kamaraj University, Madurai, and the JALMA Institute, Agra, for assistance, permissions and facilities and support; the families for their cooperation and consent; J.H. Edwards for facilitation; and the field teams for assistance. S.M. is an MRC clinical research fellow. A.V.S.H. is a Wellcome Trust Principal Research Fellow.

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Correspondence to Adrian V.S. Hill.

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Siddiqui, M., Meisner, S., Tosh, K. et al. A major susceptibility locus for leprosy in India maps to chromosome 10p13. Nat Genet 27, 439–441 (2001). https://doi.org/10.1038/86958

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