title: The human HNP36 gene is localized to chromosome 11q13 and produces alternative transcripts that are not mutated in multiple endocrine neoplasia, type 1 (MEN I) syndrome.
abstract: Multiple endocrine neoplasia, type 1 (MEN I), is an autosomal dominant syndrome of selected endocrine neoplasms whose causative gene, a suspected tumor suppressor, has been localized to chromosome 11q13, but has not been identified. Recently, the HNP36 cDNA was identified as a novel growth factor responsive gene of undetermined biological function that is expressed in the pituitary and parathyroid glands. In studies seeking the function of the HNP36 gene product, the gene was localized by fluorescence in situ hybridization within the 11q13 segment. Further analysis of radiation-reduced hybrid DNAs and chromosome 11-specific YAC clones established that the HNP36 gene is within 80 kb of D11S913, a marker tightly linked to the MEN1 gene. Consequently, the HNP36 gene was studied as a candidate for the MEN1 gene. The human HNP36 gene was cloned and determined to consist of 12 exons. Expression of the HNP36 gene from pituitary and parathyroid tissue and four patient tumors or lymphoblasts was confirmed by RT-PCR amplification of the coding sequences, and HNP36 transcripts were analyzed for mutations. All tissues expressed three HNP36 gene transcripts that result from alternative splicing and appear to encode related, but distinct, proteins. However, DNA sequence determination of the RT-PCR products from MEN I-associated tumors found no deletions and identified a single nucleotide difference that may be a polymorphism. Thus, mutations in the coding segments of the HNP36 gene are not the cause of the MEN I syndrome. Nevertheless, the assignment of the HNP36 gene to 11q13 and identification of new potential gene products provides a novel growth-regulated genetic candidate for other disorders whose genes map to this locus.
authors.affiliation: Department of Medicine, and the Vanderbilt Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. john.williams@mcmail.vanderbilt.edu
authors.forename: J B
authors.initials: JB
authors.lastname: Williams
authors.forename: B
authors.initials: B
authors.lastname: Rexer
authors.forename: S
authors.initials: S
authors.lastname: Sirripurapu
authors.forename: S
authors.initials: S
authors.lastname: John
authors.forename: R
authors.initials: R
authors.lastname: Goldstein
authors.forename: J A
authors.initials: JA
authors.lastname: Phillips
authors.forename: L L
authors.initials: LL
authors.lastname: Haley
authors.forename: S N
authors.initials: SN
authors.lastname: Sait
authors.forename: T B
authors.initials: TB
authors.lastname: Shows
authors.forename: C M
authors.initials: CM
authors.lastname: Smith
authors.forename: D S
authors.initials: DS
authors.lastname: Gerhard
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D033722:Equilibrative-Nucleoside Transporter 2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D033722:Equilibrative-Nucleoside Transporter 2; D009687:Nuclear Proteins; D012333:RNA, Messenger; C438654:SLC29A2 protein, human