A Transcript Map for the 2.8-Mb Region Containing the Multiple Endocrine Neoplasia Type 1 Locus
- Siradanahalli C. Guru1,6,
- Sunita K. Agarwal2,6,
- Pachiappan Manickam1,
- Shodimu-Emmanuel Olufemi1,
- Judy S. Crabtree5,
- Jane M. Weisemann3,
- Mary Beth Kester2,
- Young S. Kim2,
- Yingping Wang5,
- Michael R. Emmert-Buck4,
- Lance A. Liotta4,
- Allen M. Spiegel2,
- Mark S. Boguski3,
- Bruce A. Roe5,
- Francis S. Collins1,
- Stephen J. Marx2,
- Lee Burns2, and
- Settara C. Chandrasekharappa1,7
- 1Laboratory of Gene Transfer, National Human Genome Research Institute (NHGRI), 2Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 3National Center for Biotechnology Information, National Library of Medicine, and 4Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; 5Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019
Abstract
Multiple endocrine neoplasia type 1 (MEN 1) is an inherited cancer syndrome in which affected individuals develop multiple parathyroid, enteropancreatic, and pituitary tumors. The locus for MEN1 is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis places the MEN1 gene within a 2-Mb interval flanked by the markers D11S1883 and D11S449. Loss of heterozygosity studies in MEN 1 and sporadic tumors suggest that theMEN1 gene encodes a tumor suppressor and have helped to narrow the location of the gene to a 600-kb interval between PYGM andD11S449. Focusing on this smaller MEN1 interval, we have identified and mapped 12 transcripts to this 600-kb region. A precise ordered map of 33 transcripts, including 12 genes known to map to this region, was generated for the 2.8-Mb D11S480–D11S913interval. Fifteen candidate genes (of which 10 were examined exhaustively) were evaluated by Southern blot and/or dideoxy fingerprinting analysis to identify the gene harboring disease-causing mutations.
[The sequence data described in this paper have been submitted to GenBank under accession nos. EST06996, U93236,AF001540–AF001547, AF001433–AF001436, AF001891–AF001893,N55476, R19205, and W37647 (see Table 1 for listing of transcripts). The BAC clone sequences have been submitted to GenBank under accession nos. AC000134, AC000159, and AC000353.]
