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

Gillian Crockford 1 Rachel Linger 2 Sarah Hockley 2 Darshna Dudakia 2 Lola Johnson 2 Robert Huddart 3 Kathy Tucker 4 Michael Friedlander 4 Kelly-Anne Phillips 5 David Hogg 6 Michael Jewett 6 Radka Lohynska 7 Gedske Daugaard 8 Stéphane Richard 9, 10 Agnès Chompret 11 Catherine Bonaïti-Pellié 12 Axel Heidenreich 13 Peter Albers 14 Edith Olah 15 Lajos Geczi 15 Istvan Bodrogi 15 Wilma Ormiston 16 Peter Daly 16 Parry Guilford 17 Sophie Fosså 18 Ketil Heimdal 18 Sergei Tjulandin 19 Ludmila Liubchenko 19 Hans Stoll 20 Walter Weber 20 David Forman 21 Timothy Oliver 22 Lawrence Einhorn 22 Mary Mcmaster 23 Joan Kramer 23 Mark Greene 23 Barbara Weber 24 Katherine Nathanson 24 Victoria Cortessis 25 Douglas Easton 26 D Timothy Bishop 1 Michael Stratton 2 Elizabeth Rapley 2, *
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.
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Gillian Crockford, Rachel Linger, Sarah Hockley, Darshna Dudakia, Lola Johnson, et al.. Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.. Human Molecular Genetics, Oxford University Press (OUP), 2006, 15 (3), pp.443-51. ⟨10.1093/hmg/ddi459⟩. ⟨inserm-00127763⟩

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