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

Gillian P. Crockford, Rachel Linger, Sarah Hockley, Darshna Dudakia, Lola Johnson, Robert Huddart, Kathy Tucker, Michael Friedlander, Kelly Anne Phillips, David Hogg, Michael A.S. Jewett, Radka Lohynska, Gedske Daugaard, Stéphane Richard, Agnes Chompret, Catherine Bonaïti-Pellié, Axel Heidenreich, Peter Albers, Edith Olah, Lajos GecziIstvan Bodrogi, Wilma J. Ormiston, Peter A. Daly, Parry Guilford, Sophie D. Fosså, Ketil Heimdal, Sergei A. Tjulandin, Ludmila Liubchenko, Hans Stoll, Walter Weber, David Forman, Timothy Oliver, Lawrence Einhorn, Mary McMaster, Joan Kramer, Mark H. Greene, Barbara L. Weber, Katherine L. Nathanson, Victoria Cortessis, Douglas F. Easton, D. Timothy Bishop, Michael R. Stratton, Elizabeth A. Rapley

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)443-451
Number of pages9
JournalHuman molecular genetics
Volume15
Issue number3
DOIs
StatePublished - Feb 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    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., Bonaïti-Pellié, C., Heidenreich, A., Albers, P., Olah, E., ... Rapley, E. A. (2006). Genome-wide linkage screen for testicular germ cell tumour susceptibility loci. Human molecular genetics, 15(3), 443-451. https://doi.org/10.1093/hmg/ddi459