Genome-wide linkage screen for testicular germ cell tumour susceptibility loci
Genome-wide linkage screen for testicular germ cell tumour susceptibility loci
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DOI：
10.1093/hmg/ddi459
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发表时间：
2006-02-01
影响因子：
3.5
通讯作者：
Rapley, EA
中科院分区：
文献类型：
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作者：
Crockford, GP;Linger, R;Rapley, EA
家族疾病史是睾丸生殖细胞肿瘤（TGCT）的一个重要危险因素。为了确定假定的 TGCT 易感基因的位置，我们对 237 个具有两个或多个 TGCT 病例的家系进行了连锁搜索。对 179 个家系进行了全基因组评估，平均标记间距离为 10 cM。另外 58 个谱系被用来更深入地研究几个感兴趣的基因组区域。使用 ALLEGRO 软件使用两种基于模型的参数分析和非参数分析进行遗传连锁分析。染色体 2p23、3p12、3q26、12p13-q21、18q21-q23 和 Xq27 上的 6 个基因组区域显示异质性 LOD (HLOD) 得分大于 1，其中 3q26 的最大 HLOD 为 1.94。全基因组模拟研究表明，观察到的大于 1 的 HLOD 峰数量与偶然预期的数量没有显着差异。之前已报道过 Xq27 处的 TGCT 基因座。在本研究中检查的 237 个谱系中，有 66 个谱系之前未在 Xq27 上进行过研究，在这个新的谱系集中没有观察到与该区域存在关联的证据。总体而言，结果表明，没有一个主要位点可以解释 TGCT 家族聚集的大部分，并表明多个效应较弱的易感位点导致了该疾病。
A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.