Siddiqui M R, Meisner S, Tosh K, Balakrishnan K, Ghei S, Fisher S E, Golding M, Shanker Narayan N P, Sitaraman T, Sengupta U, Pitchappan R, Hill A V
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Nat Genet. 2001 Apr;27(4):439-41. doi: 10.1038/86958.
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.
麻风病是一种由麻风分枝杆菌引起的慢性传染病，在印度流行，全球约80万例估计病例中约有一半发生在印度。家族聚集性、双胞胎研究、复杂分离分析和人类白细胞抗原（HLA）关联研究表明，宿主基因在麻风易感性差异中起作用。我们在此报告对来自印度南部的224个家庭的基因组进行的遗传连锁扫描，这些家庭中有245对患麻风病的独立患病同胞对，主要是少菌型。在使用396个微卫星标记的两阶段基因组筛选中，我们发现10号染色体p13上一系列相邻微卫星标记存在显著连锁（最大对数优势分数（MLS）=4.09，P<2×10^-5），为这种常见传染病的一个主要基因座提供了证据。因此，尽管传染病易感性具有多基因性质，但仍存在一些主要的、与HLA无关的基因座，可通过可获得数量的患病同胞对进行定位。
