|
|||||
|
|
Linkage disequilibrium studies in multiple endocrine neoplasia type 1 (MEN1) |
|
| Authors: | J H D Bassett A A J Pannett S A Forbes R V Thakker M McCarthy A P Read B T Teh C Larsson S Kytölä J Leisti P Salmela G Weber S Giraud C X Zhang A Calender J W M Höppener H K Ploos van Amstel C J M Lips K Kas W J M Van de Ven P Gaudray |
| Institution: | MRC Molecular Endocrinology Group, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK Tel.: +44-181-383-3014; Fax: +44-181-383-8306 e-mail: rthakker@rpms.ac.uk, GB Unit of Metabolic Medicine, Imperial College School of Medicine, St. Mary’s Hospital, Norfolk Place, London, W2 1PG, UK, NF Department of Medical Genetics, University of Manchester, St. Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK, GB Department of Molecular Medicine, Endocrine Tumour Unit, CMM, Karolinska Hospital, L8: 01, S-171 76 Stockholm, Sweden, SE Department of Clinical Genetics, Oulu University Hospital, Kajaanitie 50, FIN 90220 Oulu, Finland, FI Department of Internal Medicine, Oulu University Hospital, Kajaanitie 50, FIN 90220 Oulu, Finland, FI Department of Molecular Medicine, Clinical Genetics Unit, CMM, Karolinska Hospital, L8: 02, S-171 76 Stockholm, Sweden, SE Service de Génétique, Pavillon E, H?pital Edouard Herriot, Place d’Arsonval, F-69437 Lyon cedex 03, France, FR Department of Pathology, Utrecht University Hospital, H04-312, PO Box 05500, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands, NL Clinical Genetics Centre, Utrecht University Hospital, H04-312, PO Box 05500, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands, NL Department of Internal Medicine, Utrecht University Hospital, H04-312, PO Box 05500, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands, NL Laboratory for Molecular Oncology, Centre for Human Genetics, K U Leuven, Herestraat 49, B-3000 Leuven, Belgium, BE LGMCH, CNRS URA 1462, Faculté de Médecine, Avenue de Valombrose, F-06107 Nice, France, FR |
| Abstract: | Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary. The MEN1 gene has been localised to a 2-Mb region of chromosome 11q13 by meiotic mapping studies in MEN1 families. Such studies may have a limited resolution of approximately 1 cM (i.e. 1 Mb) and we have therefore investigated 96 MEN1 families (40 British, 17 French, 12 Finnish, 7 Swedish, 7 Dutch, 7 North American, 2 Australian, 1 New Zealand, 1 German, 1 Spanish and 1 Danish) for linkage disequilibrium, in order to facilitate a finer mapping resolution. We have utilised five microsatellite DNA sequence polymorphisms from the candidate region and have accurately determined their allele sizes, which ranged from 161 bp to 272 bp. The heterozygosity and number of alleles (given in brackets), respectively, at the loci were: D11S1883 (76%, 11), D11S457 (55%, 5), PYGM (94%, 18), D11S1783 (10%, 4) and D11S449 (87%, 16). Allelic association was assessed by Chi-square 2 ×n contingency tables, by Fisher exact 2 ×n contingency tables and by a likelihood-based approach. The results of haplotype analysis revealed 91 different affected haplotypes in the 96 families, an identical affected haplotype being observed in no more than two families. These results indicate the absence of an ancestral affected haplotype. Significant linkage disequilibrium (P < 0.005) could be established amongst the microsatellite loci but not between the loci and MEN1 in either the total population or in any of the geographical sub-populations. The absence of linkage disequilibrium between MEN1 and the polymorphic loci is probably the result of the occurrence of multiple different disease-causing mutations in MEN1. Received: 1 April 1997 / Accepted: 25 June 1997 |
| Keywords: | |
| 本文献已被 SpringerLink 等数据库收录！ | |