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 |
|---|---|
| Pages (from-to) | 443-451 |
| Number of pages | 9 |
| Journal | Human Molecular Genetics |
| Volume | 15 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 1 2006 |
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ASJC Scopus subject areas
- Genetics
Cite this
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
}
TY - JOUR
T1 - Genome-wide linkage screen for testicular germ cell tumour susceptibility loci
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.
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=31544460668&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31544460668&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddi459
DO - 10.1093/hmg/ddi459
M3 - Article
C2 - 16407372
AN - SCOPUS:31544460668
VL - 15
SP - 443
EP - 451
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 3
ER -