Crockford, G. P., Linger, R., Hockley, S., Dudakia, D., Johnson, L., Huddart, R., Tucker, K., Friedlander, M., Phillips, K. A., Hogg, D., Jewett, M. A. S., Lohynska, R., Daugaard, G., Richard, S., Chompret, A., Bonaiti-Pellie, C., Heidenreich, A., Albers, P., Olah, E., Geczi, L., Bodrogi, I., Ormiston, W. J., Daly, P. A., Guilford, P., Fossa, S. D., Heimdal, K., Tjulandin, S. A., Liubchenko, L., Stoll, H., Weber, W., Forman, D., Oliver, T., Einhorn, L., McMaster, M., Kramer, J., Greene, M. H., Weber, B. L., Nathanson, K. L., Cortessis, V., Easton, D. F., Bishop, D. T., Stratton, M. R., Rapley, E. A. (2006) Genome-wide linkage screen for testicular germ cell tumour susceptibility loci. HUMAN MOLECULAR GENETICS, 15 (3). pp. 443-451. ISSN 0964-6906

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Abstract

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci 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.

Item Type:	Article
Authors (ICR Faculty only):	Huddart, Robert and Rapley, Liz and Stratton, Mike
All Authors:	Crockford, G. P., Linger, R., Hockley, S., Dudakia, D., Johnson, L., Huddart, R., Tucker, K., Friedlander, M., Phillips, K. A., Hogg, D., Jewett, M. A. S., Lohynska, R., Daugaard, G., Richard, S., Chompret, A., Bonaiti-Pellie, C., Heidenreich, A., Albers, P., Olah, E., Geczi, L., Bodrogi, I., Ormiston, W. J., Daly, P. A., Guilford, P., Fossa, S. D., Heimdal, K., Tjulandin, S. A., Liubchenko, L., Stoll, H., Weber, W., Forman, D., Oliver, T., Einhorn, L., McMaster, M., Kramer, J., Greene, M. H., Weber, B. L., Nathanson, K. L., Cortessis, V., Easton, D. F., Bishop, D. T., Stratton, M. R., Rapley, E. A.
Uncontrolled Keywords:	European countries; genetic maps; cancer; localization; families; models; tests; risk
Research teams:	ICR divisions > Radiotherapy and Imaging > Clinical Academic Radiotherapy (Huddart) ICR divisions > Breast Cancer Research > Genetic Susceptibility ICR divisions > Genetics and Epidemiology > Genetic Susceptibility
Depositing User:	EPrints Services
Date Deposited:	10 Aug 2007 20:55
Last Modified:	20 Apr 2010 10:31
URI:	http://publications.icr.ac.uk/id/eprint/2743

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