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A total of 40 mouse-human cell hybrids were induced with poly

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 ...

The segregation of the human peptidase-C phenotype in five different series of human-mouse hybrid clones was examined. The chromosome constitution of these hybrids was determined by quinacrine mustard fluorescence, Giemsa banding, and constitutive heterochromatin staining. That the clones could be classified without exception either as human peptidase C positive/ A-1 positive (14 clones), or as peptidase C negative/ A-1 negative (12 clones) indicates that peptidase C can be assigned to the human A-i chromosome. Data from an extensive series of human-mouse clones used provide support for the syntenic association between peptidase C and phosphoglucomutase-1 and by inference a linkage of both to Rh factor group.