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.
authors.affiliation: Genetic Epidemiology Division, Cancer Research UK Clinical Centre, St James's University Hospital, Leeds,UK.
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Crockford
authors.forename: Rachel
authors.initials: R
authors.lastname: Linger
authors.forename: Sarah
authors.initials: S
authors.lastname: Hockley
authors.forename: Darshna
authors.initials: D
authors.lastname: Dudakia
authors.forename: Lola
authors.initials: L
authors.lastname: Johnson
authors.forename: Robert
authors.initials: R
authors.lastname: Huddart
authors.forename: Kathy
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authors.lastname: Tucker
authors.forename: Michael
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authors.lastname: Friedlander
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Phillips
authors.forename: David
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authors.lastname: Hogg
authors.forename: Michael A S
authors.initials: MA
authors.lastname: Jewett
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authors.lastname: Lohynska
authors.forename: Gedske
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authors.lastname: Daugaard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard
authors.forename: Agnes
authors.initials: A
authors.lastname: Chompret
authors.forename: Catherine
authors.initials: C
authors.lastname: Bonaïti-Pellié
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.forename: Edith
authors.initials: E
authors.lastname: Olah
authors.forename: Lajos
authors.initials: L
authors.lastname: Geczi
authors.forename: Istvan
authors.initials: I
authors.lastname: Bodrogi
authors.forename: Wilma J
authors.initials: WJ
authors.lastname: Ormiston
authors.forename: Peter A
authors.initials: PA
authors.lastname: Daly
authors.forename: Parry
authors.initials: P
authors.lastname: Guilford
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fosså
authors.forename: Ketil
authors.initials: K
authors.lastname: Heimdal
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Tjulandin
authors.forename: Ludmila
authors.initials: L
authors.lastname: Liubchenko
authors.forename: Hans
authors.initials: H
authors.lastname: Stoll
authors.forename: Walter
authors.initials: W
authors.lastname: Weber
authors.forename: David
authors.initials: D
authors.lastname: Forman
authors.forename: Timothy
authors.initials: T
authors.lastname: Oliver
authors.forename: Lawrence
authors.initials: L
authors.lastname: Einhorn
authors.forename: Mary
authors.initials: M
authors.lastname: McMaster
authors.forename: Joan
authors.initials: J
authors.lastname: Kramer
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Weber
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.forename: Victoria
authors.initials: V
authors.lastname: Cortessis
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rapley
mesh_terms: D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D010375:Pedigree; D013736:Testicular Neoplasms / Q000235:genetics*