Chromosomal localization of the gene for Gaucher disease
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Chromosomal localization of the gene for Gaucher disease

  • Author(s): Smith, M
  • Devine, EA
  • Arredondo- Vega, FX
  • Shafit-Zagardo, B
  • Desnick, RJ
  • et al.
Creative Commons Attribution 4.0 International Public License
Abstract

Two isozymes with a - glucosidase activity have been identified in normal human tissues using the artificial substrate, 4-methylwnbelliferyl- S-D-glucopyranoside (4MUGlc). The acid (EC 3.2.1. 45) and neutral (EC 3.2.1.21) B- glucosidases (designated GBA and GBN, respectively) have been differentiated by their relative pH optima (Beutler and Kuhl, 1970; Ho, et al., 1972; Turner et al., 1977; Mueller and Rosenberg, 1977), subcellular localizations (Ho, 1972; Peters et al., 1973), substrate specificities (Patrick, 1965; Ho, 1972; Peters et al., 1976), sensitivities to anionic detergents and acidic phospholipids (Peters et al., 1976), affinity for concanavalin A (Beutler et al., 1975; Shafit- Zagardo et al . , 1980) and most recently by their differential electrophoretic migration on cellulose acetate gels (Shafit- Zagardo et al., 1980). The acid isozyme, a membrane bound activity, has been shown to be deficient in the various subtypes of Gaucher disease, lysosomal storage diseases characterized by the accumulation of glucosyl ceramide (Brady, 1978). To date, the chromosomal assignment of the structural gene for either of the human 8 -glucosidase isozymes has not been determined . We report here .the regional assignment of the structural gene for human GBA using human-rodent somatic cell hybrids . A sensitive immunoprecipitation assay was developed for the selective detection of the human enzyme in the presence of mouse 6 -glucosidase activity. Initial data for the regional assignment of the locus on chromosome 1 was obtained from a hybrid clone containing a 11\)USe-hwuan chromosome 1 rearrangement. Further regional localization of the locus for GBA near lqter was obtained using an informative hybrid clone carrying a human chromosome 1 deletion. In addition to the immunoprecipitation assay, use of the specific natural substrate further supported the assignment of the structural gene for GBA to this region.

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