Summary
Gene localization studies revealed the presence of two structural β-galactosidase (βGAL) loci on the human chromosomes 3 and 22 (de Wit et al., 1979). To determine the function of these genes, proliferating hybrid cell lines were isolated following fusion of fibroblasts from two different patients with a βGAL deficiency and Chinese hamster cells. The hybrids were analyzed electrophoretically and immunologically.
Fibroblasts from a patient with an adult type of βGAL deficiency associated with a neuraminidase deficiency were used for the first fusion. No evidence for a structural βGAL mutation was found in these hybrids. The absence of a structural βGAL mutation is consistent with a primary defect in neuraminidase in this adult patient.
Fibroblasts from a patient with the infantile type 1 GM1-gangliosidosis were used for the second fusion. It is concluded that the human determinants present in the isolated hybrid lines occur in heteropolymeric man-Chinese hamster molecules. The heteropolymeric isoenzyme in (+3–22) hybrids is very labile and is sensitive to neuraminidase treatment. Therefore it is concluded that the infantile type 1 patient is mutated in the structural βGAL gene on chromosome 3. Because this patient has a primary defect in GM1-βGAL, the βGAL gene on chromosome 3 is apparently a G M1-βGAL gene. Interaction of the two βGAL loci results in an additional band of βGAL activity on electrophoresis. This suggests that the gene on chromosome 22 is also a structural G M1-βGAL gene.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bruns, G. A. P., Leary, A. C., Regina, V. M., Gerald, P. S.: Lysosomal β-d-galactosidase in man-hamster somatic cell hybrids. In: Winnipeg Conference 1977: Fourth International Workshop on Human Gene Mapping. Birth Defects: Orig. Art. Ser. XIV, 4, 177-182, The National Foundation, New York
Chen, T. R.: In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp. Cell Res. 104, 255–262 (1977)
Chern, C. J.: Detection of heteropolymeric β-glucuronidase in hybrids between mouse cells and human fibroblasts with β-glucuronidase deficiency. Proc. Natl. Acad. Sci. USA 74 (7), 2948–2952 (1977)
Frost, R., Holmes, E., Norden, A. G. W., O'Brien, J. S.: Characterization of purified human liver β-galactosidase A2 and A3. Biochem. J. 175, 181–189 (1978)
Galjaard, H., Reuser, A. J. J.: Clinical, biochemical and genetic heterogeneity in gangliosidosis. In: The cultured cell and inherited metabolic disease, Harkness, R. A., Cockburn, F. (eds.), pp. 139–160. MIT Press Lancaster 1977
Galjaard, H., Hoogeveen, A., Keijzer, W., De Wit-Verbeek, H. A., Vlek-Noot, C.: The use of quantitative cytochemical analysis in rapid prenatal detection and somatic cell genetic studies of metabolic diseases. Histochem. J. 6, 491–509 (1974)
Galjaard, H., Hoogeveen, A., Keijzer, W., De Wit-Verbeek, H. A., Reuser, A. J. J., Ho, M. W., Robinson, D.: Genetic heterogeneity in GM1-gangliosidosis. Nature 257, 60–62 (1975)
Gillin, F. D., Roufa, D. J., Beaudet, A. L., Caskey, C. T.: 8-Azaguanine resistance in mammalian cells. I. Hypoxanthine guanine phosphoribosyltransferase. Genetics 72, 239–252 (1972)
Hamers, M. N.: Immunological studies on Fabry's disease. Thesis, Amsterdam, 1978
Hoeksema, H. L., Van Diggelen, O. P., Galjaard, H.: Intergenic complementation after fusion of fibroblasts from different patients with β-galactosidase deficiency. Biochim. Biophys. Acta 566, 72–79 (1979)
Littlefield, J. W.: Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants. Science 145, 709–710 (1964)
Loonen, M. C. B., Van der Lugt, L., Francke, C. L.: Angiokeratoma corporis diffusum and lysosomal enzyme deficiency. Lancet 1974 II, 785
Lowden, J. A., O'Brien, J. S.: Sialidosis: A review of human neuraminidase deficiency. Am. J. Hum. Genet. 31, 1–8 (1979)
Meera Khan, P., Wijnen, L. M. M., Pearson, P. L.: Assignment of the mitochondrial aconitase gene (ACONm) to human chromosome 22. In: Winnipeg Conference 1977: Fourth International Workshop on Human Gene Mapping. Birth Defects: Orig. Art. Ser. XIV, 4, 212–215. The National Foundation, New York, in press (1977)
Meisler, M., Rattazzi, M. C.: Immunological studies of β-galactosidase in normal human liver and in GM1-gangliosidosis. Am. J. Hum. Genet. 26, 683–691 (1974)
Norden, A. G. W., Tennant, L., O'Brien, J. S.: GM1-ganglioside β-galactosidase A. Purification and studies of the enzyme from human liver. J. Biol. Chem. 249 (24), 7969–7976 (1974)
O'Brien, J. S.: Molecular genetics of GM1-β-galactosidase. Clin. Genet. 8, 303–313 (1975)
O'Brien, J. S., Norden, A. G. W.: Nature of the mutation in adult β-galactosidase deficient patients. Am. J. Hum. Genet. 29, 184–190 (1977)
Okada, S., O'Brien, J. S.: Generalized gangliosidosis: Betagalactosidase deficiency. Science 160, 1002–1004 (1968)
Rushton, R. A., Dawson, G.: Genetic linkage studies of the human glycosphingolipid β-galactosidases. Biochem. Genet. 15, 1071–1082 (1977)
Schram, A., Hamers, M. N., Brouwer-Kelder, B., Donker-Koopman, W. E., Tager, J. M.: Enzymological properties and immunological characterization of α-galactosidase isoenzymes from normal and Fabry human liver. Biochim. Biophys. Acta 482, 125–137 (1977)
Seabright, M.: A rapid banding technique for human chromosomes. Lancet 1971 II, 971–972
Shows, T. B., Scrafford-Wolff, L. R., Brown, J. A., Meisler, M.: GM1-gangliosidosis: chromosome 3 assignment of the β-galactosidase A gene (βGALA). Somatic Cell Genetics 5 (2), 147–158 (1979)
Suzuki, Y., Nakamura, N., Fukuoka, K., Shimada, Y., Uono, M.: β-Galactosidase deficiency in juvenile and adult patients. report of six Japanese cases and reviews of literature. Hum. Genet. 36, 219–229 (1977)
Wenger, D. A., Tarby, T. J., Wharton, C.: Macular cherry-red spots and myoclonus with dementia: coexistent neuraminidase and β-galactosidase deficiencies. Biochem. Biophys. Res. Commun. 82 (2), 589–595 (1978)
Westerveld, A., Meera Khan, P., Visser, R. P. L. S., Bootsma, D.: Loss of human genetic markers in man-Chinese hamster somatic cell hybrids. Nature New Biol. 234, 20–24 (1971)
Wijnen, L. M. M., Monteba-van Heuvel, M., Pearson, P. L., Meera Khan, P.: Assignment of a gene for glutathione peroxidase (GPX-1) to human chromosome 3. In: Winnipeg Conference 1977: Fourth International Workshop on Human Gene Mapping. Birth Defects: Orig. Art. Ser. XIV, 4, 232–239, The National Foundation, New York
Wit, J. de, Hoeksema, H. L., Halley, D., Hagemeijer, A., Bootsma, D., Westerveld, A.: Regional localization of a β-galactosidase locus on human chromosome 22. Somatic Cell Genetics 3, 351–363 (1977)
Wit, J. de, Hoeksema, H. L., Bootsma, D., Westerveld, A.: Assignment of structural β-galactosidase loci to human chromosomes 3 and 22. Hum. Genet. (in press, 1979)
Wit-Verbeek, H. A. de, Hoogeveen, A., Galjaard, H.: Complementation studies with enucleated fibroblasts from different variants of β-galactosidase deficiency. Exp. Cell Res. 113, 215–218 (1978)
Wolfe, L. S., Callahan, J., Fawcett, J. S., Anderman, F., Scriver, C. R.: GM1-gangliosidosis without chondrodystrophy or visceromegaly. Neurology 20, 23–44 (1970)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hoeksema, H.L., De Wit, J. & Westerveld, A. The genetic defect in the various types of human β-galactosidase deficiency. Hum Genet 53, 241–247 (1980). https://doi.org/10.1007/BF00273505
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00273505