Abstract
Studies have been conducted on eight sets of monozygous and nine sets of dizygous female Negro twins, both members of whom were heterozygous for G-6-PD deficiency. Twins were studied both by assay of erythrocytic G-6-PD activity and by the methemoglobin elution test (MET). The MET is a procedure which identifies histochemically cells with appreciable G-6-PD activity and permits accurate determination of the percentage of such cells in heterozygotes. Monozygous twins showed significantly less “within-pair” variation than dizygous twins with both the MET and G-6-PD assay.
Concerning the significantly greater agreement in MET results in monozygous twins than dizygous twins, our present working hypothesis is that X-chromosomal inactivation in the Negro female is genetically controlled, rather than random. However, certain alternate hypotheses allowing for random X-inactivation have not been excluded; these include somatic cell selection after random X-inactivation, and cell exchange between identical twins in utero/it. Studies in nontwin related heterozygotes now underway should help differentiate among these various possibilities.
In addition to the studies on 17 pairs of female twins heterozygous for G-6-PD deficiency, 26 pairs of nondeficient female Negro twins have been studied by G-6-PD assay. Within-pair variation in monozygous twins was significantly less than within-pair variation in dizygous twins in all cases. The genetic influences detected with the G-6-PD assay in the female twins could theoretically be due to nonrandom X-inactivation, to genetically determined quantitative differences in enzyme activity (e.g., isoalleles), or to both. By appropriate calculations, based on the MET results, we have factored out the effects of X-inactivation on overall enzyme activity in the heterozygous deficient twins. After removal of the effect of X-inactivation, monozygous twins heterozygous for enzyme deficiency continue to show significantly less within-pair variation than dizygous twins. This finding indicates significant genetic influences on quantitative G-6-PD activity other than X-inactivation and other than the deficiency allele. This conclusion has been strengthened by studies on male twins where X-inactivation is not present.
Similar content being viewed by others
References
Atkins, L., and Santesson, B. (1964). The pattern of DNA synthesis in the chromosomes of human cells containing an isochromosome for the long arm of an X-chromosome. Hereditas 51 67.
Barr, M. L., and Bertram, E. G. (1949). A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature 163 676.
Beutler, E., Yeh, M., and Fairbanks, V. F. (1962). The normal human female as a mosaic of X-chromosome activity: Studies using the gene for G-6-PD deficiency as a marker. Proc. Nat. Acad. Sci. (U.S.) 48 9.
Beutler, E., and Baluda, M. C. (1964). The separation of glucose-6-phosphate dehydrogenase deficient erythrocytes from the blood of heterozygotes for glucose-6-phosphate dehydrogenase deficiency. Lancet i 189
Boyer, S. H., Porter, I. H., and Weilbacher, R. G. (1962). Electrophoretic heterogeneity of glucose-6-phosphate dehydrogenase and its relationship to enzyme deficiency in man. Proc. Nat. Acad. Sci. (U.S.) 48 1868.
Brewer, G. J., Tarlov, A. R., and Alving, A. S. (1960). Methemoglobin reduction test: A new simple in vitro test for identifying primaquine sensitivity. Bull. World Health Organ. 22 633.
Brewer, G. J., Gall, J. C., Honeyman, M. S., Gershowitz, H., Dern, R. J., and Hames, C. G. (1965). Inheritance of quantitative expression of G-6-PD deficiency in heterozygous Negro females—A twin study. Clin. Res. 13 265 (abst.).
Carson, P. E., Flanagan, C. L., Ickes, L. E., and Alving, A. S. (1965). Enzymatic deficiency in primaquine-sensitive erythrocytes. Science 124 484.
Childs, B., and Zinkham, W. H. (1959). The genetics of primaquine sensitivity of the erythrocytes. Ciba Foundation Symposium on Biochemistry of Human Genetics. Little, Brown, and Company, Boston, pp. 76–88.
Coulton, D., Hertig, A., and Long, W. N. (1947). Monoamniotic twins. Am. J. Obst. and Gynec. 54 119.
Davidson, R. G., Nitkowsky, H. M., and Childs, B. (1963). Demonstration of two populations of cells in the human female heterozygous for glucose-6-phosphate dehydrogenase variant. Proc. Nat. Acad. Sci. (U.S.) 50 481.
Davidson, R. G., Childs, B., and Siniscalco, M. (1964). Genetic variations in the quantitative control of erythrocyte glucose-6-phosphate dehydrogenase activity. Ann. Human Genet. 28 61.
Essen-Moller, E. (1941). Empirische ahnlichkeitsdiagnose bei zwillingen. Hereditas 27 1.
Gall, J. C., Brewer, G. J., and Dern, R. J. (1965). Studies of glucose-6-phosphate dehydrogenase activity of individual erythrocytes: The methemoglobin-elution test for identification of females heterozygous for G-6-PD deficiency. Am. J. Human Genet. 17 359.
Gall, J. C., and Brewer, G. J. (1966). Studies of individual RBC in G-6-PD deficient heterozygotes and hemizygotes. Clin. Res. 14 309 (abst.).
Gartler, S. M., and Linder, D. (1964). Selection in mammalian mosaic cell populations. Cold Spring Harbour Symp. Quant. Biol. Vol. 29.
Giannelli, F. (1963). The pattern of X-chromosome deoxyribonucleic acid synthesis in two women with abnormal sex chromosome complements. Lancet i 863.
Grumbach, M. M., Morishima, A., and Taylor, J. H. (1963). Human sex chromosome abnormalities in relation to DNA replication and heterochromatinization. Proc. Nat. Acad. Sci. (U.S.) 49 581.
Kirkman, H. N., and Hendrickson, E. M. (1963). Sex-linked electrophoretic difference in glucose-6-phosphate dehydrogenase. Am. J. Human Genet. 15 241.
London, D. R., Kemp, N. H., Ellis, J. R., and Mittwoch, U. (1964). Turner's syndrome with secondary amenorrhoea and sex chromosome mosaicism. Acta Endocrinol. 46 364.
Lyon, M. F. (1961). Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190 372.
Marks, P. A., Johnson, A. B., and Hirschberg, E. (1958). Effect of age on the enzyme activity in erythrocytes. Proc. Nat. Acad. Sci. (U.S.) 44 529.
Miller, O. J., Mukherjee, B. B., Bader, S., and Christakos, A. C. (1963). Autoradiographic studies of X-chromosome duplication in an XO/X-isochromosome mosaic human female. Nature 200 918.
Muldal, S., Gilbert, C. W., Lajtha, L. G., Lindsten, J., Rowley, J., and Fraccaro, M. (1963). Tritiated thymidine incorporation in an isochromosome for the long arm of the X-chromosome in man. Lancet i 861.
Ohno, S., Kaplan, W. D., and Kinosita, R. (1959). On the sex chromatin of Gallus Domesticus. Exp. Cell Res. 19 180.
Park, W. W. (1957). The occurrence of sex chromatin in early human and macaque embryos. J. Anat. 91 369.
Porter, I. H., Boyer, S. H., Schulze, J., and McKusick, V. (1961). Genetic control of glucose-6-phosphate dehydrogenase production. In Proceedings of the Second International Conference of Human Genetics, Rome, 1961, Vol. 1. Instituto G. Mendel, Rome, pp. 618–621.
Siemens, H. W. (1925). Die diagnose der eineiigkeit. Arch. Gynak. 126 623.
Rowley, J., Muldal, S., Lindsten, J., and Gilbert, C. W. (1964). H3-thymidine uptake by a ring X-chromosome in a human female. Proc. Nat. Acad. Sci. (U.S.) 51 779.
Zinkham, W. E., and Lenhard, R. E. (1959). Metabolic abnormalities of erythrocytes from patients with congenital nonspherocytic hemolytic anemia. J. Pediat. 55 319.
Author information
Authors and Affiliations
Additional information
Supported by USPHS research grants AM-09381, HE-17544, AM-09919, and HE-03341, by USPHS Career Development Award 1-K3-AM-7959 (Dr. Brewer) and by U.S.A.E.C. Contract (11-1)-1552.
Rights and permissions
About this article
Cite this article
Brewer, G.J., Gall, J.C., Honeyman, M. et al. Inheritance of quantitative expression of erythrocyte glucose-6-phosphate dehydrogenase activity in the Negro—a twin study. Biochem Genet 1, 41–53 (1967). https://doi.org/10.1007/BF00487735
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00487735