Crockford Gillian P, Linger Rachel, Hockley Sarah, Dudakia Darshna, Johnson Lola, Huddart Robert, Tucker Kathy, Friedlander Michael, Phillips Kelly-Anne, Hogg David, Jewett Michael A S, Lohynska Radka, Daugaard Gedske, Richard Stéphane, Chompret Agnes, Bonaïti-Pellié Catherine, Heidenreich Axel, Albers Peter, Olah Edith, Geczi Lajos, Bodrogi Istvan, Ormiston Wilma J, Daly Peter A, Guilford Parry, Fosså Sophie D, Heimdal Ketil, Tjulandin Sergei A, Liubchenko Ludmila, Stoll Hans, Weber Walter, Forman David, Oliver Timothy, Einhorn Lawrence, McMaster Mary, Kramer Joan, Greene Mark H, Weber Barbara L, Nathanson Katherine L, Cortessis Victoria, Easton Douglas F, Bishop D Timothy, Stratton Michael R, Rapley Elizabeth A
Genetic Epidemiology Division, Cancer Research UK Clinical Centre, St James's University Hospital, Leeds,UK.
Hum Mol Genet. 2006 Feb 1;15(3):443-51. doi: 10.1093/hmg/ddi459. Epub 2006 Jan 11.
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.
疾病家族史是睾丸生殖细胞肿瘤（TGCT）的一个重要风险因素。为了确定假定的TGCT易感基因的位置，我们对237个有两例或更多例TGCT的家系进行了连锁分析。179个家系进行了全基因组评估，标记间平均距离为10厘摩。另外58个家系用于更深入地研究几个感兴趣的基因组区域。使用ALLEGRO软件进行遗传连锁分析，采用两种基于模型的参数分析和一种非参数分析。2号染色体p23、3号染色体p12、3号染色体q26、12号染色体p13-q21、18号染色体q21-q23和X染色体q27上的六个基因组区域显示异质性对数优势（HLOD）得分大于1，3号染色体q26处的最大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著差异。先前已报道X染色体q27处有一个TGCT位点。在本研究中检测的237个家系中，66个家系先前未在X染色体q27处进行研究，在这个新的家系组中未观察到与该区域连锁的证据。总体而言，结果表明没有单一的主要位点可以解释TGCT家族聚集的大部分情况，并表明多个弱效应的易感位点与该疾病有关。
