Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Jul;86(13):5049–5053. doi: 10.1073/pnas.86.13.5049

Comparison of the chromosomal localization of murine and human glucocerebrosidase genes and of the deduced amino acid sequences.

R R O'Neill 1, T Tokoro 1, C A Kozak 1, R O Brady 1
PMCID: PMC297554  PMID: 2740343

Abstract

To study structure-function relationships and molecular evolution, we determined the nucleotide sequence and chromosomal location of the gene encoding murine glucocerebrosidase (glucosylceramidase; D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45). In the protein coding region of the murine cDNA, the nucleotide sequence and the corresponding deduced amino acid sequences were 82% and 86% identical to the respective human sequences. All five amino acids presently known to be essential for normal enzymatic activity were conserved between mouse and man. The murine enzyme had a single deletion relative to the human enzyme at amino acid number 273. One ATG translation initiation signal was present in the mouse sequence in contrast to the human sequence, where two start codons have been reported. Nucleotide sequencing of a clone derived from murine genomic DNA revealed that the murine signal for translation initiation was located in exon 2. The locations of all 10 introns were conserved among mouse and man. We mapped the genetic locus for glucocerebrosidase to mouse chromosome 3, at a position 7.6 +/- 3.2 centimorgans from the locus for the beta subunit of nerve growth factor. Comparison of linkage relationships in the human and murine genome indicates that these closely linked mouse genes are also syntenic on human chromosome 1 but in positions that span the centromere.

Full text

PDF
5049

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BRADY R. O., KANFER J. N., SHAPIRO D. METABOLISM OF GLUCOCEREBROSIDES. II. EVIDENCE OF AN ENZYMATIC DEFICIENCY IN GAUCHER'S DISEASE. Biochem Biophys Res Commun. 1965 Jan 18;18:221–225. doi: 10.1016/0006-291x(65)90743-6. [DOI] [PubMed] [Google Scholar]
  2. BRADY R. O., KANFER J., SHAPIRO D. THE METABOLISM OF GLUCOCEREBROSIDES. I. PURIFICATION AND PROPERTIES OF A GLUCOCEREBROSIDE-CLEAVING ENZYME FROM SPLEEN TISSUE. J Biol Chem. 1965 Jan;240:39–43. [PubMed] [Google Scholar]
  3. Bachmair A., Finley D., Varshavsky A. In vivo half-life of a protein is a function of its amino-terminal residue. Science. 1986 Oct 10;234(4773):179–186. doi: 10.1126/science.3018930. [DOI] [PubMed] [Google Scholar]
  4. Choudary P. V., Barranger J. A., Tsuji S., Mayor J., LaMarca M. E., Cepko C. L., Mulligan R. C., Ginns E. I. Retrovirus-mediated transfer of the human glucocerebrosidase gene to Gaucher fibroblasts. Mol Biol Med. 1986 Jun;3(3):293–299. [PubMed] [Google Scholar]
  5. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dinur T., Osiecki K. M., Legler G., Gatt S., Desnick R. J., Grabowski G. A. Human acid beta-glucosidase: isolation and amino acid sequence of a peptide containing the catalytic site. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1660–1664. doi: 10.1073/pnas.83.6.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  8. Ginns E. I., Choudary P. V., Tsuji S., Martin B., Stubblefield B., Sawyer J., Hozier J., Barranger J. A. Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7101–7105. doi: 10.1073/pnas.82.20.7101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graves P. N., Grabowski G. A., Eisner R., Palese P., Smith F. I. Gaucher disease type 1: cloning and characterization of a cDNA encoding acid beta-glucosidase from an Ashkenazi Jewish patient. DNA. 1988 Oct;7(8):521–528. doi: 10.1089/dna.1.1988.7.521. [DOI] [PubMed] [Google Scholar]
  10. Hoggan M. D., Halden N. F., Buckler C. E., Kozak C. A. Genetic mapping of the mouse c-fms proto-oncogene to chromosome 18. J Virol. 1988 Mar;62(3):1055–1056. doi: 10.1128/jvi.62.3.1055-1056.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Horowitz M., Wilder S., Horowitz Z., Reiner O., Gelbart T., Beutler E. The human glucocerebrosidase gene and pseudogene: structure and evolution. Genomics. 1989 Jan;4(1):87–96. doi: 10.1016/0888-7543(89)90319-4. [DOI] [PubMed] [Google Scholar]
  12. Kolodny E. H., Ullman M. D., Mankin H. J., Raghavan S. S., Topol J., Sullivan J. L. Phenotypic manifestations of Gaucher disease: clinical features in 48 biochemically verified type 1 patients and comment on type 2 patients. Prog Clin Biol Res. 1982;95:33–65. [PubMed] [Google Scholar]
  13. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maruyama T., Gojobori T., Aota S., Ikemura T. Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res. 1986;14 (Suppl):r151–r197. doi: 10.1093/nar/14.suppl.r151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mucenski M. L., Taylor B. A., Copeland N. G., Jenkins N. A. Chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myeloid tumors. Oncogene Res. 1988 Feb;2(3):219–233. [PubMed] [Google Scholar]
  16. Osiecki-Newman K., Fabbro D., Legler G., Desnick R. J., Grabowski G. A. Human acid beta-glucosidase: use of inhibitors, alternative substrates and amphiphiles to investigate the properties of the normal and Gaucher disease active sites. Biochim Biophys Acta. 1987 Sep 2;915(1):87–100. doi: 10.1016/0167-4838(87)90128-2. [DOI] [PubMed] [Google Scholar]
  17. Reiner O., Wilder S., Givol D., Horowitz M. Efficient in vitro and in vivo expression of human glucocerebrosidase cDNA. DNA. 1987 Apr;6(2):101–108. doi: 10.1089/dna.1987.6.101. [DOI] [PubMed] [Google Scholar]
  18. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Searle A. G., Peters J., Lyon M. F., Evans E. P., Edwards J. H., Buckle V. J. Chromosome maps of man and mouse, III. Genomics. 1987 Sep;1(1):3–18. doi: 10.1016/0888-7543(87)90099-1. [DOI] [PubMed] [Google Scholar]
  20. Sorge J. A., West C., Kuhl W., Treger L., Beutler E. The human glucocerebrosidase gene has two functional ATG initiator codons. Am J Hum Genet. 1987 Dec;41(6):1016–1024. [PMC free article] [PubMed] [Google Scholar]
  21. Sorge J., West C., Westwood B., Beutler E. Molecular cloning and nucleotide sequence of human glucocerebrosidase cDNA. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7289–7293. doi: 10.1073/pnas.82.21.7289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  23. Takasaki S., Murray G. J., Furbish F. S., Brady R. O., Barranger J. A., Kobata A. Structure of the N-asparagine-linked oligosaccharide units of human placental beta-glucocerebrosidase. J Biol Chem. 1984 Aug 25;259(16):10112–10117. [PubMed] [Google Scholar]
  24. Tsuji S., Choudary P. V., Martin B. M., Stubblefield B. K., Mayor J. A., Barranger J. A., Ginns E. I. A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease. N Engl J Med. 1987 Mar 5;316(10):570–575. doi: 10.1056/NEJM198703053161002. [DOI] [PubMed] [Google Scholar]
  25. Tsuji S., Choudary P. V., Martin B. M., Winfield S., Barranger J. A., Ginns E. I. Nucleotide sequence of cDNA containing the complete coding sequence for human lysosomal glucocerebrosidase. J Biol Chem. 1986 Jan 5;261(1):50–53. [PubMed] [Google Scholar]
  26. Tsuji S., Martin B. M., Barranger J. A., Stubblefield B. K., LaMarca M. E., Ginns E. I. Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2349–2352. doi: 10.1073/pnas.85.7.2349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wigderson M., Firon N., Horowitz Z., Wilder S., Frishberg Y., Reiner O., Horowitz M. Characterization of mutations in Gaucher patients by cDNA cloning. Am J Hum Genet. 1989 Mar;44(3):365–377. [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES