The techniques of somatic cell genetics have been used to establish the linkage relationships of loci coding for two forms (A and B) of hexosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-B-D-glucoside acetamidodeoxyglucohydrolase) and to determine whether a structural relationship exists between these forms. In a series of human-mouse hybrid cell lines, hexosaminidase A and B segregated independently. Our results and those reported by other investigators are used to analyze the proposed structural models for hexosaminidase. We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man. Tbere is thus a linkage between specific human autosomes and enzymes implicated in the production of lipid storage diseases.The lipid storage diseases are a family of inherited disorders characterized by the excessive accumulation of sphingolipids in the body's tissues. In each, the metabolic derangement appears to be the result of a deficiency of a specific lysosomal hydrolase which is involved in the catabolism of these complex lipids (1). One of these enzymes, P-N-acetylglucosaminidase (Hex; EC 3.2.1.30) is thought to be responsible for at least two lipodystrophies, Tay-Sachs' disease (TSD; GM2 gangliosidosis, type I) and Sandhoff's disease (SD; GM2 gangliosidosis, type II). When examined electrophoretically, this enzyme is found to exist in multiple forms, two of which (Hex A and B) have been well characterized biochemically (2). A third form of the enzyme (Hex C), about which relatively little is known, has recently been described (3). TSD is associated with a deficiency of Hex A and an increased activity of Hex B, and SD is associated with a deficiency of both Hex A and B (4,5). No individual has yet been reported in whom Hex A is present in the absence of Hex B.Biochemical, genetic, and immunological evidence suggests that a structural relationship exists between Hex A and B. Two theories concerning this relationship have recently been advanced (2, 6). The first proposes that Hex A is a conversion product of Hex B (2). TSD would then result from the deficiency of a functional conversion enzyme, and SD would re- sult from a defect in the gene coding for the basic Hex protein.The second theory proposes that Hex A and B are each composed of multiple subunits, one of which is common to both forms (6). In this hypothesis, TSD would result from the deficiency of the Hex A-specific subunit and SD from the deficiency of the common subunit. It is also possible that the two forms of Hex are not structurally related. Hex A and B may be controlled by two independent genes. TSD would then result from an effective deficiency of the normal Hex A structural gene product and SD might result from a mutation in a locus controlling expression of both enzymes or required for their activation. A series of human-mouse hybrid cell ...
Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12–13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.