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.
Crockford
Gillian P
GP
Genetic Epidemiology Division, Cancer Research UK Clinical Centre, St James's University Hospital, Leeds,UK.
Linger
Rachel
R
Hockley
Sarah
S
Dudakia
Darshna
D
Johnson
Lola
L
Huddart
Robert
R
Tucker
Kathy
K
Friedlander
Michael
M
Phillips
Kelly-Anne
KA
Hogg
David
D
Jewett
Michael A S
MA
Lohynska
Radka
R
Daugaard
Gedske
G
Richard
Stéphane
S
Chompret
Agnes
A
Bonaïti-Pellié
Catherine
C
Heidenreich
Axel
A
Albers
Peter
P
Olah
Edith
E
Geczi
Lajos
L
Bodrogi
Istvan
I
Ormiston
Wilma J
WJ
Daly
Peter A
PA
Guilford
Parry
P
Fosså
Sophie D
SD
Heimdal
Ketil
K
Tjulandin
Sergei A
SA
Liubchenko
Ludmila
L
Stoll
Hans
H
Weber
Walter
W
Forman
David
D
Oliver
Timothy
T
Einhorn
Lawrence
L
McMaster
Mary
M
Kramer
Joan
J
Greene
Mark H
MH
Weber
Barbara L
BL
Nathanson
Katherine L
KL
Cortessis
Victoria
V
Easton
Douglas F
DF
Bishop
D Timothy
DT
Stratton
Michael R
MR
Rapley
Elizabeth A
EA
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*