title: Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease.
abstract: Gaucher disease results from the deficiency of the lysosomal enzyme glucocerebrosidase (EC 3.2.1.45). Although the functional gene for glucocerebrosidase (GBA) and its pseudogene (psGBA), located in close proximity on chromosome 1q21, have been studied extensively, the flanking sequence has not been well characterized. The recent identification of human metaxin (MTX) immediately downstream of psGBA prompted a closer analysis of the sequence of the entire region surrounding the GBA gene. We now report the genomic DNA sequence and organization of a 75-kb region around GBA, including the duplicated region containing GBA and MTX. The origin and endpoints of the duplication leading to the pseudogenes for GBA and MTX are now clearly established. We also have identified three new genes within the 32 kb of sequence upstream to GBA, all of which are transcribed in the same direction as GBA. Of these three genes, the gene most distal to GBA is a protein kinase (clk2). The second gene, propin1, has a 1.5-kb cDNA and shares homology to a rat secretory carrier membrane protein 37 (SCAMP37). Finally, cote1, a gene of unknown function lies most proximal to GBA. The possible contributions of these closely arrayed genes to the more atypical presentations of Gaucher disease is now under investigation.
authors.affiliation: Clinical Neuroscience Branch, Intramural Research Program (IRP), National Institute of Mental Health, Bethesda, Maryland 20892, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Winfield
authors.forename: N
authors.initials: N
authors.lastname: Tayebi
authors.forename: B M
authors.initials: BM
authors.lastname: Martin
authors.forename: E I
authors.initials: EI
authors.lastname: Ginns
authors.forename: E
authors.initials: E
authors.lastname: Sidransky
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D005776:Gaucher Disease / Q000209:etiology / Q000235:genetics*; D015698:Genomic Library; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000235:genetics; D011544:Pseudogenes; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; C093550:MTX1 protein, human; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D011506:Proteins; C109303:SCAMP3 protein, human; C083429:Scamp1 protein, rat; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D005962:Glucosylceramidase