CONSTRUCTION OF A 1.2-MB SEQUENCE-READY CONTIG OF CHROMOSOME-11Q13 ENCOMPASSING THE MULTIPLE-ENDOCRINE-NEOPLASIA TYPE-1 (MEN1) GENE - THE EUROPEAN CONSORTIUM ON TYPE-1 (MEN1) GENE

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant fa milial cancer syndrome characterized by parathyroid, pancreatic, and a nterior pituitary tumors. The MEN1 locus has been previously localized to chromosome 11q13, and a 2-Mb gene-rich region flanked by D11S1883 and D11S449 has been defined. We have pursued studies to facilitate id entification of the MEN1 gene by narrowing this critical region to a 9 00-kb interval between the VRF and D11S1783 loci through meiotic mappi ng. This was achieved by investigating 17 cosmids for microsatellite p olymorphisms, which defined two novel polymorphisms at the VRF and A01 38 loci, and utilizing these to characterize recombinants in MEN1 fami lies. In addition, we have established a 1200-kb sequence-ready contig consisting of 26 cosmids, eight BACs, and eight PACs that encompass t his region. The precise locations for 19 genes and three ESTs within t his contig have been determined, and three gene clusters consisting of a centromeric group (VRF, FKBP2, PNG, and PLCB3), a middle group (PYG M, ZFM1, SCG1, SCG2 (which proved to be the MEN1 gene), and PPP2R5B), and a telomeric group (H4B, ANG3, ANG2, ANG1, FON, FAU, NOF, NON, and D11S2196E) were observed. These results represent a valuable transcrip tional map of chromosome 11q13 that will help in the search for diseas e genes in this region. (C) 1997 Academic Press.