Palmer L J, Daniels S E, Rye P J, Gibson N A, Tay G K, Cookson W O, Goldblatt J, Burton P R, LeSöuef P N
Department of Paediatrics and Centre for Molecular Immunology and Instrumentation, University of Western Australia, Perth, Australia.
Am J Respir Crit Care Med. 1998 Dec;158(6):1825-30. doi: 10.1164/ajrccm.158.6.9804037.
Asthma is a genetically complex disease, and the investigation of putative linkages to candidate loci in independent populations is an important part of the gene discovery process. This study investigated the linkage of microsatellite markers in the 5q and 11q regions to asthma-associated quantitative traits in 121 Australian Caucasian nuclear families. The families were recruited on the basis of a child proband: a cohort of 95 randomly recruited families of unselected probands (n = 442 subjects) and a cohort of 26 families of probands selected on the basis of severe symptomatic asthma (n = 134 subjects). The quantitative traits assessed included serum levels of total IgE and specific IgE to house dust mite and mixed grass, blood eosinophil counts, and the dose-response slope (DRS) of FEV1 to histamine provocation. Multipoint linkage analysis using Haseman-Elston sib-pair methods provided evidence of significant linkage between the chromosome 5q markers and loge total serum IgE levels, specific serum IgE levels, and loge blood eosinophil counts. The chromosome 11q markers showed evidence of significant linkage to specific serum IgE levels. Neither region demonstrated significant linkage to the loge DRS to histamine. Phenotypes were residualized for age and sex. These data are consistent with the existence of loci regulating asthma-associated quantitative traits in both the 5q31-33 and 11q13 chromosomal regions.
哮喘是一种基因复杂的疾病，在独立人群中研究与候选基因座的假定连锁关系是基因发现过程的重要组成部分。本研究调查了5q和11q区域中的微卫星标记与121个澳大利亚白种人核心家庭中哮喘相关数量性状的连锁关系。这些家庭是根据儿童先证者招募的：一组95个随机招募的未选择先证者的家庭（n = 442名受试者）和一组26个基于严重症状性哮喘选择的先证者家庭（n = 134名受试者）。评估的数量性状包括血清总IgE水平、对屋尘螨和混合草的特异性IgE水平、血液嗜酸性粒细胞计数以及FEV1对组胺激发的剂量反应斜率（DRS）。使用Haseman-Elston同胞对方法进行的多点连锁分析提供了证据，表明染色体5q标记与血清总IgE水平的对数、特异性血清IgE水平以及血液嗜酸性粒细胞计数的对数之间存在显著连锁关系。染色体11q标记显示出与特异性血清IgE水平存在显著连锁的证据。两个区域均未显示出与组胺的DRS对数存在显著连锁关系。对年龄和性别进行了残差分析。这些数据与在5q31 - 33和11q13染色体区域中存在调节哮喘相关数量性状的基因座一致。
