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澳大利亚普通人群哮喘的全基因组关联扫描。

A genome-wide association scan for asthma in a general Australian population.

作者信息

Hui J, Oka A, James A, Palmer L J, Musk A W, Beilby J, Inoko H

机构信息

Western Australian Institute for Medical Research and UWA Centre for Medical Research, B Block, QEII Medical Centre, The University of Western Australia, Nedlands, WA, 6009, Australia.

出版信息

Hum Genet. 2008 Apr;123(3):297-306. doi: 10.1007/s00439-008-0477-9. Epub 2008 Feb 6.

DOI:10.1007/s00439-008-0477-9
PMID:18253752
Abstract

To date, almost every chromosome has been implicated in genetic susceptibility to asthma to some degree. When compared with single nucleotide polymorphism, microsatellite markers exhibit high levels of heterozygosity and therefore provide higher statistical power in association. The objective of this study was to perform a genome-wide association study using 23,465 in-house microsatellite markers to detect asthma susceptibility regions in the Busselton population. In this study, three separate pooled DNA screenings yielded 18 markers with significantly different estimated frequencies in the three separate "case and control" pools: each pool consisting of 60 males and 60 females. These markers were evaluated by individual typing in 360 cases and 360 controls. Two markers showed significant differences between cases and controls (P = 0.001 and P = 0.003). Regions surrounding the two markers were subjected to high-density association mapping with a total of 14 additional markers. We were able to confirm and fine map the association in these two regions by typing 14 additional microsatellite markers (1805A09 (D18S0325i), P = 0.002; 1806D05 (D18S0181i), P = 0.001). Each region contains a predicted gene that showed strong associations with asthma. Further studies are underway to characterize the novel candidate asthma susceptibility genes identified in this genome-wide study.

摘要

迄今为止,几乎每条染色体在某种程度上都与哮喘的遗传易感性有关。与单核苷酸多态性相比,微卫星标记表现出高度的杂合性,因此在关联研究中具有更高的统计效力。本研究的目的是使用23465个内部微卫星标记进行全基因组关联研究,以检测巴瑟尔顿人群中的哮喘易感区域。在本研究中,三次独立的混合DNA筛查产生了18个标记,在三个独立的“病例和对照”混合样本中估计频率有显著差异:每个混合样本由60名男性和60名女性组成。这些标记在360例病例和360例对照中进行个体分型评估。两个标记在病例和对照之间显示出显著差异(P = 0.001和P = 0.003)。围绕这两个标记的区域用另外14个标记进行高密度关联图谱分析。通过对另外14个微卫星标记(1805A09(D18S0325i),P = 0.002;1806D05(D18S0181i),P = 0.001)进行分型,我们能够确认并精细定位这两个区域的关联。每个区域都包含一个与哮喘有强关联的预测基因。进一步的研究正在进行,以表征在这项全基因组研究中鉴定出的新型候选哮喘易感基因。

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