Definition of the MinimalMEN1Candidate Area Based on a 5-Mb Integrated Map of Proximal 11q13: THE EUROPEAN CONSORTIUM ON MEN1 |
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Authors: | Anouk Courseaux Josiane Grosgeorge Patrick Gaudray Anna AJ Pannett Simon A Forbes Catherine Williamson Duncan Bassett Rajesh V Thakker Bin T Teh Filip Farnebo Joseph Shepherd Britt Skogseid Catharina Larsson Sophie Giraud Chang X Zhang Janine Salandre Alain Calender and GENEM Groupe d'Etude des Néoplasies Endocriniennes Multiples de type |
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Institution: | aLGMCH, CNRS URA 1462, Avenue de Valombrose, 06107, Nice, France;bMRC Molecular Endocrinology Group, MRC Clinical Sciences Center Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane, London, W12 0NN, United Kingdom;cDepartment of Molecular Medicine, Karolinska Hospital, L6 Building, S-171 76, Stockholm, Sweden;dService de Génétique, Pavillon E, Hôpital Edouard Herriot, Place d'Arsonval, 69437, Lyon, France |
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Abstract: | Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. TheMEN1gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescencein situhybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed theMEN1gene in an ≈2-Mb region aroundPYGM,flanked by D11S1883 and D11S449. |
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