DEFINITION OF THE MINIMAL MEN1 CANDIDATE AREA BASED ON A 5-MB INTEGRATED MAP OF PROXIMAL 11Q13 - THE EUROPEAN CONSORTIUM ON MEN1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant di sorder with a high penetrance characterized by tumors of the parathyro id glands, the endocrine pancreas, and the anterior pituitary. The MEN 1 gene, 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 regio n. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, b y hybridization to DNA from somatic cell hybrids containing various pa rts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positio ned and ordered by physical mapping and genetic linkage in 86 MEN1 fam ilies with 452 affected individuals. Two critical recombinants identif ied in two affected cases placed the MEN1 gene in an approximate to 2- Mb region around PYGM, flanked by D11S1883 and D11S449. (C) 1996 Acade mic Press, Inc.