Ober C, Cox N J, Abney M, Di Rienzo A, Lander E S, Changyaleket B, Gidley H, Kurtz B, Lee J, Nance M, Pettersson A, Prescott J, Richardson A, Schlenker E, Summerhill E, Willadsen S, Parry R
Department of Human Genetics, University of Chicago, 924 East 57th Street, Chicago, IL 60637, USA.
Hum Mol Genet. 1998 Sep;7(9):1393-8. doi: 10.1093/hmg/7.9.1393.
Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.
奠基者群体为绘制遗传性状图谱提供了诸多优势，尤其是对于那些可能具有遗传异质性的复杂性状。为了确定影响哮喘及哮喘相关表型的基因，我们在哈特派人群中开展了一项全基因组筛查，哈特派是一个具有欧洲血统的宗教隔离群体。根据标准化方案，对361名个体的主要样本和292名个体的重复样本进行了哮喘表型评估。使用292个常染色体标记和3个X-Y假常染色体标记完成了全基因组筛查。通过半参数似然比卡方检验和传递不平衡检验，我们在10个区域中鉴定出12个标记，这些标记显示出与哮喘或相关表型可能存在连锁关系（似然比P < 0.01）。四个区域（5q23 - 31、12q15 - 24.1、19q13和21q21）中的标记在主要样本和重复样本中均显示出可能的连锁关系，并且在其他样本中也显示出与哮喘表型的连锁关系；在另一个区域（3p24.2 - 22）中，两个相邻标记显示出可能的连锁关系，这在哈特派人群中是首次报道。结果表明，即使在独立基因组数量相对较少的奠基者群体中，许多基因座上的易感等位基因可能影响哮喘表型，并且这些易感等位基因很可能是人群中的常见多态性。
