Daniels S E, Bhattacharrya S, James A, Leaves N I, Young A, Hill M R, Faux J A, Ryan G F, le Söuef P N, Lathrop G M, Musk A W, Cookson W O
Wellcome Trust Centre for Human Genetic Disease, University of Oxford, UK.
Nature. 1996 Sep 19;383(6597):247-50. doi: 10.1038/383247a0.
Asthma now affects one child in seven in the United Kingdom. Most cases (95%) of childhood asthma are associated with atopy, the immunoglobulin E (IgE)-mediated familial syndrome of allergic asthma, eczema and rhinitis. Segregation analysis has consistently suggested the presence of major genes influencing atopy and IgE levels, with the expectation that these genes may be identified by positional cloning or the examination of candidate genes. Here we report the results of a genome-wide search for linkage to one qualitative and four quantitative traits associated with allergic (atopic) asthma. We have identified six potential linkages (P<0.001), five of which are to quantitative traits. Monte Carlo simulations show that 1.6 false-positive linkages at this level of significance would be expected from the data. One linkage, to chromosome 11q13, has been established previously. Three of the new loci show evidence of linkage to a second panel of families, in which maternal effects and pleiotropy of linked phenotypes are seen. The results demonstrate the extent and the complexity of the genetic predisposition to asthma.
在英国，目前每七个孩子中就有一个患有哮喘。大多数儿童哮喘病例（95%）与特应性有关，特应性是一种由免疫球蛋白E（IgE）介导的过敏性哮喘、湿疹和鼻炎的家族综合征。分离分析一直表明存在影响特应性和IgE水平的主要基因，预计这些基因可通过定位克隆或对候选基因的检测来识别。在此，我们报告了一项全基因组搜索结果，该搜索针对与过敏性（特应性）哮喘相关的一个定性性状和四个定量性状进行连锁分析。我们已经确定了六个潜在的连锁关系（P<0.001），其中五个与定量性状有关。蒙特卡罗模拟表明，从这些数据来看，在这个显著水平上预计会有1.6个假阳性连锁关系。此前已确定11号染色体q13区域存在一个连锁关系。其中三个新位点显示出与另一组家庭存在连锁关系的证据，在这组家庭中观察到了母体效应和连锁表型的多效性。这些结果证明了哮喘遗传易感性的程度和复杂性。
