Abstract
We have localized the PvuII polymorphism of the glucocerebrosidase gene complex to intron 6 of the active gene. Using the polymerase chain reaction (PCR) to amplify intron 6 of DNA samples from Pv1.1-/Pv1.1+ individuals, we defined the mutation causing this polymorphism as a G----A single-base substitution at position 3931 of the active gene. By analyzing 54 unrelated Gaucher patients we show strong linkage disequilibrium between the Pv1.1- genotype and the common Jewish mutation 1226 causing the adult type of this disease. Gaucher disease patients heterozygous for the 1226 allele and one unidentified allele (1226/?), particularly those of Jewish ancestry, were predominantly of the Pv1.1-/PV1.1+ genotype. This suggests that one of the unknown alleles may be relatively common and linked to the Pv1.1+ genotype.
Full text
PDF



Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baltimore D. Gene conversion: some implications for immunoglobulin genes. Cell. 1981 Jun;24(3):592–594. doi: 10.1016/0092-8674(81)90082-9. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
- Sorge J., Gelbart T., West C., Westwood B., Beutler E. Heterogeneity in type I Gaucher disease demonstrated by restriction mapping of the gene. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5442–5445. doi: 10.1073/pnas.82.16.5442. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Zimran A., Sorge J., Gross E., Kubitz M., West C., Beutler E. Prediction of severity of Gaucher's disease by identification of mutations at DNA level. Lancet. 1989 Aug 12;2(8659):349–352. doi: 10.1016/s0140-6736(89)90536-9. [DOI] [PubMed] [Google Scholar]