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Human β-glucuronidase: Assignment of the structural gene to chromosome 7 using somatic cell hybrids

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Abstract

β-Glucuronidase (GUS) has become an important enzyme model for the genetic study of molecular disease, enzyme realization, and therapy, and for the biogenesis and function of the lysosome and lysosomal enzymes. The genetics of human β-glucuronidase was investigated utilizing 188 primary man-mouse and man-Chinese hamster somatic cell hybrids segregating human chromosomes. Cell hybrids were derived from 16 different fusion experiments involving cells from ten different and unrelated individuals and six different rodent cell lines. The genetic relationship of GUS to 28 enzyme markers representing 19 linkage groups was determined, and chromosome studies on selected cell hybrids were performed. The evidence indicates that the β-glucuronidase gene is assigned to chromosome 7 in man. Comparative linkage data in man and mouse indicate that the structural gene GUS is located in a region on chromosome 7 that has remained conserved during evolution. Involvement of other chromosomes whose genes may be important in the final expression of GUS was not observed. A tetrameric structure of human β-glucuronidase was demonstrated by the formation of three heteropolymers migrating between the human and mouse molecular forms in chromosome 7 positive cell hybrids. Linkage of GUS to other lysosomal enzyme genes was investigated. β-Hexosaminidase HEX B) was assigned to chromosome 5; acid phosphatase2 (ACP 2) and esterase A4 (ES-A 4) were assigned to chromosome 11; HEX A was not linked to GUS; and α-galactosidase (α-GAL) was localized on the X chromosome. These assignments are consistent with previous reports. Evidence was not obtained for a cluster of lysosomal enzyme structural genes. In demonstrating that GUS was not assigned to chromosome 9 utilizing an X/9 translocation segregating in cell hybrids, the gene coding for human adenylate kinase1 was confirmed to be located on chromosome 9.

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Authors and Affiliations

  1. New York State Department of Health, Biochemical Genetics Section, Roswell Park Memorial Institute, Buffalo, New York

    P. A. Lalley, R. L. Eddy, L. L. Haley, M. G. Byers, A. P. Goggin & T. B. Shows

  2. VA-NCI Oncology Branch, Veterans Hospital, Washington, D.C.

    P. A. Lalley

  3. Department of Human Genetics, Medical College of Virginia, Richmond, Virginia

    J. A. Brown

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  1. P. A. Lalley
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  2. J. A. Brown
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  3. R. L. Eddy
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  4. L. L. Haley
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  5. M. G. Byers
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  6. A. P. Goggin
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  7. T. B. Shows
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Additional information

Supported by NIH Grants HD 05196, GM 20454, and GM 06321, by NSF Grant BMS 73-07072, and by HEW Maternal and Child Health Service, Project 417.

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Lalley, P.A., Brown, J.A., Eddy, R.L. et al. Human β-glucuronidase: Assignment of the structural gene to chromosome 7 using somatic cell hybrids. Biochem Genet 15, 367–382 (1977). https://doi.org/10.1007/BF00484467

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  • DOI: https://doi.org/10.1007/BF00484467

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