A second-generation genomewide screen for asthma-susceptibility alleles in a founder population
A second-generation genomewide screen for asthma-susceptibility alleles in a founder population
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DOI：
10.1016/s0002-9297(07)62946-2
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发表时间：
2000-11-01
影响因子：
9.8
通讯作者：
Cox, NJ
中科院分区：
文献类型：
--
作者：
Ober, C;Tsalenko, A;Cox, NJ
使用563个标记，在693个Hutterites中进行了哮喘和特应性易感基因座的全基因组筛查，这些Hutterites是一个15代系谱的成员，几乎是作者早期研究的样本量的两倍。由此产生的功效增加导致在18个染色体区域中鉴定出23个位点，显示出连锁的证据，通常比该群体中先前报道的连锁显著10倍（P <0.001对P <0.01）。此外，在本报告中，首次在哈特人中鉴定了11个染色体区域中的基因座的连锁，其中包括5个区域（5 p、5 q、8 p、14 q和16 q），这5个区域通过似然比（LR）chi（2）显示出连锁的证据，并且通过传递/不平衡检验显示出不平衡的证据。在这项研究中，19号染色体上的一个区域继续显示出连锁的证据。对17个候选基因的研究提供了与IL 4 RA基因（16 p12）、HLA 19类基因（6p 21）和干扰素α基因簇（9 p22）中的变异相关的证据，但缺乏通过LR chi（2）检验在这些区域中连锁的证据，表明这些是次要易感性位点。CD 14基因的多态性与5 q细胞因子簇中尚未鉴定的易感性等位基因连锁不平衡，该区域显示哈特人之间连锁的证据。最后，在哈特人中显示连锁证据的区域中，有10个区域在其他基因组筛选中显示出与相关表型连锁的证据，这表明这些区域可能包含对不同人群中的哮喘和特应性表型具有相对较大影响的共同等位基因。
A genomewide screen for asthma- and atopy-susceptibility loci was conducted, using 563 markers, in 693 Hutterites who are members of a single 15-generation pedigree, nearly doubling the sample size from the authors' earlier studies. The resulting increase in power led to the identification of 23 loci in 18 chromosomal regions showing evidence for linkage that is, in general, 10-fold more significant (P < .001 vs. P < .01) than the linkages reported previously in this population. Moreover, linkages to loci in 11 chromosomal regions were identified for the first time in the Hutterites in this report, including five regions (5p, 5q, 8p, 14q, and 16q) showing evidence both of linkage, by the likelihood ratio (LR) chi (2), and of disequilibrium, by the transmission/disequilibrium test. A region on chromosome 19 continues to show evidence for linkage, by both tests, in this study. Studies of 17 candidate genes provide evidence for association with variation in the IL4RA gene (16p12), the HLA class 19 genes (6p21), and the interferon-alpha gene cluster (9p22), but the lack of evidence for linkage in these regions by the LR chi (2) test suggests that these are minor susceptibility loci. A polymorphism in the CD14 gene is in linkage disequilibrium with an as yet unidentified susceptibility allele in the 5q cytokine cluster, a region showing evidence for linkage among the Hutterites. Finally, 10 of the regions showing evidence for linkage in the Hutterites have shown evidence of linkage to related phenotypes in other genome screens, suggesting that these regions may contain common alleles that have relatively large effects on asthma and atopy phenotypes in diverse populations.