Abstract
Skin fibroblasts from five unrelated males with X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency and from their families have been exposed to medium containing 6-thioguanine. This purine analogue selects against cells with normal hypoxanthine-guanine phosphoribosyl transferase activity and therefore permits detection of mutant cells in heterozygous populations. The results of these studies are compared to those obtained by autoradiography of single-cell clones of skin fibroblasts from the same subjects. In each case, the results of the selective method are similar to those obtained by clonal analysis. The use of selective medium therefore provides a sensitive means to detect heterozygosity at this locus and may provide a general method to select cells with X-linked markers from heterozygous populations.
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References
Bürk, R. R., Pitts, J. D., and Subak-Sharpe, J. H. (1968). Exchange between hamster cells in culture. Exptl. Cell Res. 53 297.
Dancis, J., Berman, P. H., Jansen, V., and Balis, M. E. (1968). Absence of mosaicism in the lymphocyte in X-linked congenital hyperuricosuria. Life Sci. 7 587.
DeMars, R., Sarto, G., Felix, J. S., and Benke, P. (1969) Lesch-Nyhan mutation: Prenatal detection with amniotic fluid cells. Science 164 1303.
Fujimoto, W. Y., Uhlendorf, B. W., Jacobson, C. B., and Seegmiller, J. E. (1968). Biochemical diagnosis of an X-linked disease in utero. Lancet 2 511.
Kelley, W. N., Greene, M. L., Rosenbloom, F. M., Henderson, J. F., and Seegmiller, J. E. (1969). Hypoxanthine-guanine phosphoribosyl-transferase deficiency in gout. Ann. Internal Med. 70 155.
Lesch, M., and Nyhan, W. L. (1964). A familial disorder of uric acid metabolism and central nervous system function. Am. J. Med. 36 561.
Lyon, M. F. (1961). Gene action in the X-chromosome of the mouse. Nature 190 372.
Lyon, M. F. (1962). Sex chromatin and gene action in the mammalian X-chromosome. Am. J. Human Genet. 14 135.
Migeon, B. R., Der Kaloustian, V. M., Nyhan, W. L., Young, W. J., and Childs, B. (1968). X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: Heterozygote has two clonal populations. Science 160 425.
Rosenbloom, F. M., Kelley, W. N., Henderson, J. F., and Seegmiller, J. E., (1967). Lyon hypothesis and X-linked disease. Lancet 2 305.
Salzmann, J., DeMars, R., and Benke, P. (1968). Single-allele expression at an X-linked hyperuricemia locus in heterozygous human cells. Proc. Natl. Acad. Sci. 60 545.
Seegmiller, J. E., Rosenbloom, F. M., and Kelley, W. N. (1967). Enzyme defect associated with a sexlinked human neurological disorder and excessive purine synthesis. Science 155 1682.
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This work was supported by grants from the U.S.P.H.S. (#HD 00486), The Joseph P. Kennedy, Jr., Memorial Fluid Research Fund, and the National Foundation for Neuromuscular Diseases, Inc.
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Migeon, B.R. X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: Detection of heterozygotes by selective medium. Biochem Genet 4, 377–383 (1970). https://doi.org/10.1007/BF00485754
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DOI: https://doi.org/10.1007/BF00485754