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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.

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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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