A 2.8-Mb Clone Contig of the Multiple Endocrine Neoplasia Type 1 (MEN1) Region at 11q13

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder that results in parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tumors in affected individuals. TheMEN1locus is tightly linked to the markerPYGMon chromosome 11q13, and linkage analysis has placed theMEN1gene within a 2-Mb interval flanked byD11S1883andD11S449.As a step toward cloning theMEN1gene, we have constructed a 2.8-Mb clone contig consisting of YAC and bacterial clones (PAC, BAC, and P1) for theD11S480toD11S913region. The bacterial clones alone represent nearly all of the 2.8-Mb contig. The contig was assembled based on a high-density STS-content analysis of 79 genomic clones (YAC, PAC, BAC, and P1) with 118 STSs. The STSs included 22 polymorphic markers and 20 transcripts, with the remainder primarily derived from the end sequences of the genomic clones. An independent cosmid contig for the 1-MbPYGM–SEAregion was also generated. Support for correctness of the 2.8-Mb contig map comes from an independent ordering of the clones by fiber-FISH. This sequence-ready contig will be a useful resource for positional cloning ofMEN1and other disease genes whose loci fall within this region.