Identification of Three Additional Genes Contiguous to the Glucocerebrosidase Locus on Chromosome 1q21: Implications for Gaucher Disease

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 theGBA 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 forGBA and MTX are now clearly established. We also have identified three new genes within the 32 kb of sequence upstream toGBA, all of which are transcribed in the same direction asGBA. Of these three genes, the gene most distal toGBA 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 toGBA. The possible contributions of these closely arrayed genes to the more atypical presentations of Gaucher disease is now under investigation.[The sequence data described in this paper have been submitted to the GenBank data library under accession no.AF023268.]