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 Geczi; Istvan 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

doi:10.1093/hmg/ddi459

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

Hematology/Oncology

Research output: Contribution to journal › Article

106 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 language	English (US)
Pages (from-to)	443-451
Number of pages	9
Journal	Human molecular genetics
Volume	15
Issue number	3
DOIs	https://doi.org/10.1093/hmg/ddi459
State	Published - 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

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

In: Human molecular genetics, Vol. 15, No. 3, 01.02.2006, p. 443-451.

Research output: Contribution to journal › Article

Crockford, GP, Linger, R, Hockley, S, Dudakia, D, Johnson, L, Huddart, R, Tucker, K, Friedlander, M, Phillips, KA, Hogg, D, Jewett, MAS, Lohynska, R, Daugaard, G, Richard, S, Chompret, A, Bonaïti-Pellié, C, Heidenreich, A, Albers, P, Olah, E, Geczi, L, Bodrogi, I, Ormiston, WJ, Daly, PA, Guilford, P, Fosså, SD, Heimdal, K, Tjulandin, SA, Liubchenko, L, Stoll, H, Weber, W, Forman, D, Oliver, T, Einhorn, L, McMaster, M, Kramer, J, Greene, MH, Weber, BL, Nathanson, KL, Cortessis, V, Easton, DF, Bishop, DT, Stratton, MR & Rapley, EA 2006, 'Genome-wide linkage screen for testicular germ cell tumour susceptibility loci', Human molecular genetics, vol. 15, no. 3, pp. 443-451. https://doi.org/10.1093/hmg/ddi459

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. / Genome-wide linkage screen for testicular germ cell tumour susceptibility loci. In: Human molecular genetics. 2006 ; Vol. 15, No. 3. pp. 443-451.

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title = "Genome-wide linkage screen for testicular germ cell tumour susceptibility loci",

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.",

author = "Crockford, {Gillian P.} and Rachel Linger and Sarah Hockley and Darshna Dudakia and Lola Johnson and Robert Huddart and Kathy Tucker and Michael Friedlander and Phillips, {Kelly Anne} and David Hogg and Jewett, {Michael A.S.} and Radka Lohynska and Gedske Daugaard and St{\'e}phane Richard and Agnes Chompret and Catherine Bona{\"i}ti-Pelli{\'e} and Axel Heidenreich and Peter Albers and Edith Olah and Lajos Geczi and Istvan Bodrogi and Ormiston, {Wilma J.} and Daly, {Peter A.} and Parry Guilford and Foss{\aa}, {Sophie D.} and Ketil Heimdal and Tjulandin, {Sergei A.} and Ludmila Liubchenko and Hans Stoll and Walter Weber and David Forman and Timothy Oliver and Lawrence Einhorn and Mary McMaster and Joan Kramer and Greene, {Mark H.} and Weber, {Barbara L.} and Nathanson, {Katherine L.} and Victoria Cortessis and Easton, {Douglas F.} and Bishop, {D. Timothy} and Stratton, {Michael R.} and Rapley, {Elizabeth A.}",

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AU - Crockford, Gillian P.

AU - Linger, Rachel

AU - Hockley, Sarah

AU - Dudakia, Darshna

AU - Johnson, Lola

AU - Huddart, Robert

AU - Tucker, Kathy

AU - Friedlander, Michael

AU - Phillips, Kelly Anne

AU - Hogg, David

AU - Jewett, Michael A.S.

AU - Lohynska, Radka

AU - Daugaard, Gedske

AU - Richard, Stéphane

AU - Chompret, Agnes

AU - Bonaïti-Pellié, Catherine

AU - Heidenreich, Axel

AU - Albers, Peter

AU - Olah, Edith

AU - Geczi, Lajos

AU - Bodrogi, Istvan

AU - Ormiston, Wilma J.

AU - Daly, Peter A.

AU - Guilford, Parry

AU - Fosså, Sophie D.

AU - Heimdal, Ketil

AU - Tjulandin, Sergei A.

AU - Liubchenko, Ludmila

AU - Stoll, Hans

AU - Weber, Walter

AU - Forman, David

AU - Oliver, Timothy

AU - Einhorn, Lawrence

AU - McMaster, Mary

AU - Kramer, Joan

AU - Greene, Mark H.

AU - Weber, Barbara L.

AU - Nathanson, Katherine L.

AU - Cortessis, Victoria

AU - Easton, Douglas F.

AU - Bishop, D. Timothy

AU - Stratton, Michael R.

AU - Rapley, Elizabeth A.

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