Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease.
Analysis of immunologic cross-reacting material in Chinese hamster-human somatic cell hybrids allowed assignment of the structural gene for glucocerebrosidase (glucosylceramidase; beta-D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45) to chromosome 1 bands q21-q32. In situ hybridization of a radiolabeled human glucocerebrosidase cDNA to high resolution human chromosomes demonstrated that a single locus encoding glucocerebrosidase is on 1q21, adjacent to a region of chromosome 1 (1qh) abundant in structural heteromorphisms. We also have identified a hydrophobic leader polypeptide encoded by this locus, permitting a more complete description of the biosynthesis of the enzyme. These results suggest that the type-specific protein polymorphisms in Gaucher disease result from mutations at this single locus, whose segregation might be followed by linkage to visible chromosomal heteromorphisms.
D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D002900:Chromosomes, Human, 1-3; D006224:Cricetinae; D003412:Cricetulus; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics*; D005796:Genes; D005959:Glucosidases / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells / Q000201:enzymology; D008970:Molecular Weight; D009693:Nucleic Acid Hybridization; D021382:Protein Sorting Signals / Q000235:genetics*
D021382:Protein Sorting Signals; D005959:Glucosidases; D005962:Glucosylceramidase