Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease.

Genome research ·Vol. 7 ·No. 10 ·1997-10-00 ·Pages 1020-6

Winfield SL, Tayebi N, Martin BM, Ginns EI, Sidransky E

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.

MeSH Terms

Carrier Proteins/genetics Chromosome Mapping Chromosomes, Human, Pair 1/genetics Conserved Sequence DNA, Complementary/genetics Gaucher Disease/etiology,genetics Genomic Library Glucosylceramidase/genetics Humans Intracellular Signaling Peptides and Proteins Membrane Proteins/genetics Mitochondrial Membrane Transport Proteins Molecular Sequence Data Multigene Family Protein Serine-Threonine Kinases/genetics Protein-Tyrosine Kinases Proteins/genetics Pseudogenes Sequence Analysis, DNA Species Specificity

Chemicals

Carrier Proteins DNA, Complementary Intracellular Signaling Peptides and Proteins MTX1 protein, human Membrane Proteins Mitochondrial Membrane Transport Proteins Proteins SCAMP3 protein, human Scamp1 protein, rat Clk dual-specificity kinases Protein-Tyrosine Kinases Protein Serine-Threonine Kinases Glucosylceramidase

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Winfield S L

Clinical Neuroscience Branch, Intramural Research Program (IRP), National Institute of Mental Health, Bethesda, Maryland 20892, USA.

Tayebi N

Martin B M

Ginns E I

Sidransky E

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Article Info

Journal

Genome research

Abbr.

Genome Res

ISSN

1088-9051

DOI

10.1101/gr.7.10.1020

Published

1997-10-00

Pages

1020-6

Language

English

Region

United States

NLM ID

9518021

PMCID

PMC310674

Subset

Databases

GENBANK

AF023268

Corrections

CommentIn

PMID: 9331364

External Links

PubMed source DOI: 10.1101/gr.7.10.1020 PMC Full Text View journal details

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Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease.

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