Genetic susceptibility to tuberculosis in Africans: A genome-wide scan
Genetic susceptibility to tuberculosis in Africans: A genome-wide scan
复制标题
DOI：
10.1073/pnas.140201897
复制
发表时间：
2000-07-05
影响因子：
11.1
通讯作者：
Hill, AVS
中科院分区：
文献类型：
--
作者：
Bellamy, R;Beyers, N;Hill, AVS
人类遗传变异是结核分枝杆菌感染结果的重要决定因素。我们进行了两阶段的全基因组连锁研究，以寻找人类基因组中含有结核病易感基因的区域。这种方法使用包含两个全同胞的同胞家庭，他们都受到临床结核病的影响。对于任何含有主要结核病易感基因的染色体区域，受影响的同胞继承相同的父母等位基因的几率比预期的要高。在第一轮筛选中，对来自冈比亚和南非的92对同胞进行了299个高度信息化的遗传标记的分型，这些标记跨越了整个人类基因组。七个染色体区域，显示与临床结核病共遗传的临时证据进行了鉴定。为了确定这些区域是否含有潜在的结核病易感基因，在来自相同国家的第二组81对同胞中对来自这些区域的22个标记进行了基因分型，染色体15q和Xq上的标记显示了连锁的暗示性证据（lod分别为2.00和1.77）与结核病、利用微卫星定位的一个独立的分析指定的共同祖先的支持，在染色体15q和Xq的易感位点的潜在识别。这些结果表明，全基因组连锁分析有助于定位和鉴定人类多因素传染病的主基因。X染色体易感基因可能导致在许多不同人群中观察到的男性结核病患者过多。
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.