TY - JOUR KW - Chromosome Mapping KW - Chromosomes, Human, Pair 10 KW - Genetic Markers KW - Genetic Predisposition to Disease KW - HLA Antigens KW - Humans KW - India KW - leprosy KW - Prevalence AU - Siddiqui M R AU - Meisner S AU - Tosh K AU - Balakrishnan K AU - Ghei S AU - Fisher S E AU - Golding M AU - Shanker Narayan N P AU - Sitaraman T AU - Sengupta U AU - Pitchappan R AU - Hill A V AB -

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur. 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 < 2x10-5) 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.

BT - Nature genetics C1 - http://www.ncbi.nlm.nih.gov/pubmed/11279529?dopt=Abstract DA - 2001 Apr DO - 10.1038/86958 IS - 4 J2 - Nat. Genet. LA - eng N2 -

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur. 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 < 2x10-5) 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.

PY - 2001 SP - 439 EP - 41 T2 - Nature genetics TI - A major susceptibility locus for leprosy in India maps to chromosome 10p13. VL - 27 SN - 1061-4036 ER -