Dizier M-H, Quesneville H, Besse-Schmittler C, Guilloud-Bataille M, Selinger-Leneman H, Clerget-Darpoux F, Demenais F
INSERM U535, Villejuif, France.
Eur J Hum Genet. 2003 Aug;11(8):590-6. doi: 10.1038/sj.ejhg.5201014.
Using the sample of 107 families with at least two asthmatic siblings, as part of the EGEA study, we have investigated linkage to asthma (or atopy) and genetic heterogeneity according to the presence/absence of atopy (or asthma) using two approaches: (1) the triangle test statistic (TTS), which considers the identical by descent (IBD) distribution among affected sib-pairs discordant for another associated phenotype (eg asthmatic sib-pairs discordant for atopy) and (2) the predivided sample test (PST), which compares the IBD distribution of marker alleles between affected sib-pairs concordant and discordant for the associated phenotype. Two regions, 8p and 12q, already reported to be linked to both asthma and atopy, were examined here. A total of 20 asthmatic sib-pairs discordant for atopy and 24 atopic pairs discordant for asthma were analyzed by both TTS and PST methods and 83 pairs with atopic asthma by PST. Some evidence for linkage was observed for two markers in the 8p23.3-p23.2 region; D8S504 for asthma with genetic heterogeneity according to the presence/absence of atopy and D8S503 for atopy with genetic heterogeneity according to the presence/absence of asthma. In the 12q14.2-q21.33 region, there was also some evidence of linkage to two markers, D12S83 and D12S95, for atopy and asthma, respectively, with genetic heterogeneity according to the presence/absence of the associated trait. Provided the small distance between the two markers on either 8p (16 cM) or 12q (21 cM), it is unclear whether one or two genetic factors are involved in either region.
作为EGEA研究的一部分，我们使用了107个至少有两个哮喘患儿的家庭样本，采用两种方法研究了与哮喘（或特应性）的连锁关系以及根据特应性（或哮喘）的有无来判断遗传异质性：（1）三角检验统计量（TTS），它考虑了在另一个相关表型上不一致的患病同胞对之间的同源性（IBD）分布（例如，在特应性方面不一致的哮喘同胞对）；（2）预划分样本检验（PST），它比较了在相关表型上一致和不一致的患病同胞对之间标记等位基因的IBD分布。本文研究了两个已报道与哮喘和特应性均连锁的区域，即8p和12q。通过TTS和PST方法分析了总共20对在特应性方面不一致的哮喘同胞对以及24对在哮喘方面不一致的特应性同胞对，通过PST方法分析了83对特应性哮喘同胞对。在8p23.3 - p23.2区域的两个标记上观察到了一些连锁证据；D8S504与根据特应性的有无存在遗传异质性的哮喘相关，D8S503与根据哮喘的有无存在遗传异质性的特应性相关。在12q14.2 - q21.33区域，也有一些证据表明分别与两个标记D12S83和D12S95存在连锁，它们分别与特应性和哮喘相关，且根据相关性状的有无存在遗传异质性。鉴于8p（16厘摩）或12q（21厘摩）上两个标记之间的距离较小，尚不清楚这两个区域是涉及一个还是两个遗传因素。
