GENOMICS 37, 354 –365 (1996) ARTICLE NO. 0570 Definition of the Minimal M EN1 Candidate Area Based on a 5-Mb Integrated Map of Proximal 11q13 THE EUROPEAN CONSORTIUM ON M EN1 ANOUK C OURSEAUX, 1 J OSIANE GROSGEORGE , AND P ATRICK GAUDRAY LGMCH, CNRS URA 1462, Avenue de Valombrose 06107 Nice, France ANNA A. J. P ANNETT,S IM ON A. F ORBES ,C ATHERINE WILLIAM SON, DUNCAN B ASSETT, AND R AJESH V. T HAKKER MRC Molecular Endocrinology Group, MRC Clinical Sciences Center Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane, London W12 0NN, United Kingdom B IN T. T EH,F ILIP F ARNEBO,J OSEPH S HEPHERD,BRITT S KOGSEID, AND C ATHARINA L ARSSON Department of Molecular Medicine, Karolinska Hospital, L6 Building, S-171 76 Stockholm, Sweden S OPHIE GIRAUD, 2 C HANG X. Z HANG, 2 J ANINE S ALANDRE , AND ALAIN C ALENDER (GENEM 1; Groupe d’Etude des Ne ´oplasiesEndocriniennes Multiples de type 1) Service de Ge ´ne ´tique, Pavillon E, Ho ˆpital Edouard Herriot, Place d’Arsonval, 69437 Lyon, France Received April 19, 1996; accepted August 7, 1996 MEN1 gene in an É2-Mb region around PYGM, flanked by D11S1883 and D11S449.  1996 Academic Press, Inc. 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. The INTRODUCTION MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome Multiple endocrine neoplasia of type 1 (MEN1) is an 11q13 but it remains elusive as yet. We have combined autosomal dominant disorder characterized by tumors the efforts and resources from four laboratories to of the parathyroids, the endocrine pancreas, and the form the European Consortium on MEN1 with the aims anterior pituitary gland (Wermer, 1954). The expres- of establishing the genetic and the physical maps of sion of MEN1 is highly variable within and between 11q13 and of further narrowing the MEN1 region. A 5- families, but linkage analysis in families from different Mb integrated map of the region was established by racial origins indicates a genetic homogeneity (Shep- fluorescence in situ hybridization on both metaphase herd, 1991; Teh et al., 1994; Larsson et al., 1995). The chromosomes and DNA fibers, by hybridization to DNA MEN1 gene was originally mapped to 11q13 by estab- from somatic cell hybrids containing various parts of lishing linkage to the PYGM (Larsson et al., 1988) and human chromosome 11, by long-range restriction map- INT2 (Bale et al., 1989; Thakker et al., 1989) loci. Addi- ping, and by characterization of YACs and cosmids. tional linkage studies have mapped the MEN1 locus Polymorphic markers were positioned and ordered by telomeric to D11S480 and centromeric to the loci physical mapping and genetic linkage in 86 MEN1 fam- D11S913, D11S460, and D11S807 (Nakamura et al., ilies with 452 affected individuals. Two critical recom- 1989; Fujimori et al., 1992; Larsson et al., 1992a,b; binants identified in two affected cases placed the Thakker et al., 1993a; Teh et al., 1995; Pang et al., 1996), an interval estimated to be between 8 and 3.2 1 To whom correspondence should be addressed. Telephone: (33) cM (Fujimori et al., 1992; Pang et al., 1996). However, 93 37 77 27. Fax: (33) 93 53 30 71. E-mail: courseaux@unice.fr. 2 These two authors contributed equally to this work. the phenotypic and genotypic details provided for the 354 0888-7543/96 $18.00 Copyright  1996 by Academic Press, Inc. All rights of reproduction in any form reserved.