Selection and Cell Communication as Determinants of Female Phenotype

  • Barbara R. Migeon
Part of the Basic Life Sciences book series (BLSC, volume 12)


As a consequence of X-chromosome inactivation, one X chromosome becomes the sole determinant of the X-specified characteristics of the cell, leading to potential cellular mosaicism in females. If there were no differences between the maternal and paternal alleles at any X-linked locus, there would be no cellular mosaicism. However, unlike the relatively homogeneous laboratory mouse populations, the human population is very heterogeneous, largely attributable to heterozygosity at many loci. Based on estimates by Harris and Hopkinson (1972), it seems certain that most women are heterozygous at one and probably more than ten X-linked loci. Therefore, with respect to her X-linked genes, the phenotype of the female is determined by the nature of her individual heterozygosity, the effect of random inactivation on the proportions of cells of the two types in each tissue, and the result of selection following inactivation.


Skin Fibroblast Cell Communication Metabolic Cooperation Cold Spring Harbor Symposium Genetic Mosaic 
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  1. Albertini, R. J. and R. DeMars. 1974. Mosaicism of peripheral blood lymphocyte populations in females heterozygous for the Lesch-Nyhan mutation. Biochem. Genet. 11: 397–411.PubMedCrossRefGoogle Scholar
  2. Beutler, E. 1964. Gene inactivation: The distribution of gene products among populations of cells in heterozygous humans. Cold Spring Harbor Symposia on Quantitative Biology, Vol. 29, pp. 261–271.PubMedCrossRefGoogle Scholar
  3. Cattanach, B. M. 1970. Controlling elements in the mouse X chromosome. III. Influence upon both parts of an X divided by rearrangement. Genet. Res. 16: 293–301.PubMedCrossRefGoogle Scholar
  4. Corsaro, C. M. and B. R. Migeon. 1975. Quantitation of contact-feeding between somatic cells in culture. Exp. Cell Res. 95: 39–46.PubMedCrossRefGoogle Scholar
  5. Corsaro, C. M. and B. R. Migeon. 1977. Contact-mediated communication of ouabain resistance in mammalian cells in culture. Nature 268: 737–739.PubMedCrossRefGoogle Scholar
  6. Cox, R. P., M. R. Krauss, M. E. Balis, and J. Dancis. 1970. Evidence for transfer of enzyme product as the basis of metabolic cooperation between tissue culture fibroblasts of Lesch-Nyhan disease and normal cells. Proc. Natl. Acad. Sci. 67: 1573–1579.PubMedCrossRefGoogle Scholar
  7. Dancis, J., P. H. Berman, V. Jansen, and M. E. Balis. 1968. Absence of mosaicism in the lymphocyte in X-linked congenital hyper-uricosuria. Life Sci. 7 587–591.PubMedCrossRefGoogle Scholar
  8. Eller, E., W. Frankenburg, M. Puck, and A. Robinson. 1971. Prognosis in newborn infants with X-chromosomal abnormalities. Pediat. 47: 681–687.Google Scholar
  9. Felix, J. S. and R. DeMars. 1971. Detection of females heterozygous for the Lesch-Nyhan mutation by 8-azuguanine resistant growth of cultured fibroblasts. J. Lab. Clin. Med. 27: 596–604.Google Scholar
  10. Frost, P., G. D. Weinstin, and W. L. Nyhan. 1970. Diagnosis of Lesch-Nyhan syndrome by direct study of skin specimens. JAMA 212: 316–318.PubMedCrossRefGoogle Scholar
  11. Fujimoto, W. Y. and J. E. Seegmiller. 1970. Hypoxanthine-guanine phosphoribosyl transferase deficiency: Activity in normal, mutant and heterozygote-cultured human skin fibroblasts. Proc. Natl. Acad. Sci. 65: 577–584.PubMedCrossRefGoogle Scholar
  12. Gartler, S. M. 1976. X chromosome inactivation and selection in somatic cells. Federation Proceedings, 2191–2194.Google Scholar
  13. Gartler, S. M. and D. Linder. 1964. Selection in mammalian mosaic cell populations. Cold Spring Harbor Symposia on Quantitative Biology 29: 253–259.PubMedCrossRefGoogle Scholar
  14. Gartler, S. M. and R. S. Sparks. 1963. The Lyon-Beutler hypothesis and isochromosome X patients with Turner’s syndrome. Lancet ii: 411.CrossRefGoogle Scholar
  15. Gilula, N. B., O. R. Reeves, and A. Steinbach. 1972. Metabolic coupling, ionic coupling and cell contacts. Nature 235: 262–265.PubMedCrossRefGoogle Scholar
  16. Harris, H. and D. A. Hopkinson. 1972. Average heterozygosity per locus in man: An estimate based on the incidence of enzyme polymorphism. Ann. Hum. Genet. Lond. 36: 9–20.CrossRefGoogle Scholar
  17. Hülser, D. F. and J. H. Peters. 1972. Contact cooperation in stimulated lymphocytes. II. Electrophysiological investigations on intercellular communication. Exp. Cell Res. 74: 319–326.PubMedCrossRefGoogle Scholar
  18. Johnson, L. A., R. B. Gordon, and B. T. Emmerson. 1976. Two populations of heterozygote erythrocytes in moderate hypoxanthine guanine phosphoribosyltransferase deficiency. Nature 264: 172–174.PubMedCrossRefGoogle Scholar
  19. Kirkman, H. N. and E. M. Hendrickson. 1963. Sex-linked electro-phoretic difference in glucose-6-phosphate dehydrogenase. Amer. J. of Hum. Genet. 15: 241–258.Google Scholar
  20. Leisti, J. T., M. M. Kaback, and D. L. Rimoin. 1975. Human X-autosome translocations: Differential inactivation of the X chromosome in a kindred with an X-9 translocation. Amer. J. of Hum. Genet. 27: 441–453.Google Scholar
  21. Migeon, B. R. 1970. X-linked HGPRT deficiency: Detection of heterozygotes by selective medium. Biochem. Genet. 4: 377–383.PubMedCrossRefGoogle Scholar
  22. Migeon, B. R. 1971. Studies of skin fibroblasts from 10 families with HGPRT deficiency, with reference to X-chromosomal inactivation. Amer. J. Hum. Genet. 23: 199–210.PubMedGoogle Scholar
  23. Migeon, B. R. 1978. X-chromosome inactivation as a determinant of female phenotype. In, Genetic Mechanisms of Sexual Development, L. Vallet and I. Porter, Eds. Academic Press, New York. In press.Google Scholar
  24. Migeon, B. R. and T. T. Do. 1978. Study of the placenta from newborns heterozygous for glucose-6-phosphate dehydrogenase in search of nonrandom X inactivation. In, Genetic Mosaics and Chimeras in Mammals, Liane B. Russell, Ed. Plenum Press, New York and London.Google Scholar
  25. Migeon, B. R. and J. F. Kennedy. 1975. Evidence for the inactivation of an X chromosome early in the development of the human fetus. Amer. J. Hum. Genet. 27: 233.PubMedGoogle Scholar
  26. Migeon, B. R., J. A. Sprenkle, I. Liebaers, J. F. Scott, and E. F. Neufeld. 1977. X-linked Hunter syndrome: The heterozygous phenotype in cell culture. Amer. J. Hum. Genet. 29: 448.Google Scholar
  27. Nance, W. E. 1964. Genetic tests with a sex-linked marker: Glu-cose-6-phosphate dehydrogenase. Cold Spring Harbor Symposia on Quantitative Biology 29: 415–424.PubMedCrossRefGoogle Scholar
  28. Nyhan, W. L., B. Bakay, J. D. Connor, J. F. Marks, and D. K. Keele. 1970. Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome. Proc. Natl. Acad. Sci. 65: 214–218.PubMedCrossRefGoogle Scholar
  29. Oliveira-Castro, G. M., M. A. Barcinski, and S. Cukierman. 1973. Intercellular communication in stimulated human lymphocytes. J. of Immunol. 111: 1616–1619.Google Scholar
  30. Rinaldi, A., G. Filippi, and M. Siniscalco. 1976. Variability of red cell phenotypes between and within individuals in an unbiased sample of 77 certain heterozygotes for G6PD deficiency in sardinias. Amer. J. of Hum. Genet. 28: 496–505.Google Scholar
  31. Russell, L. B. 1961. Genetics of mammalian sex chromosomes. Science 133: 1795–1803.PubMedCrossRefGoogle Scholar
  32. Russell, L. B. and N. L. A. Cacheiro. 1978. Cell selection in X-autosome translocation mosaics in genetic mosaics and chimeras in mammals. In, Genetic Mosaics and Chimeras in Mammals. Liane B. Russell, Ed. Plenum Press, New York and London.Google Scholar
  33. Russell, L. B. and C. S. Montgomery. 1969. Comparative studies on X-autosome translocations in the mouse. I. Origin, viability, fertility, and weight of five T(X;1)’s. Genetics 63: 103–120.PubMedGoogle Scholar
  34. Simpson, I., B. Rose, and W. R. Loewenstein. 1976. Size limit of molecules permeating the junctional membrane channels. Science 195: 294–296.CrossRefGoogle Scholar
  35. Subak-Sharpe, H., R. Bürk, and J. Pitts. 1966. Metabolic cooperation by cell-to-cell transfer between genetically different mammalian cells in tissue culture. Heredity 21: 342.Google Scholar
  36. Szybalski, W., E. H. Szybalska, and G. Ragni. 1962. Genetic studies with human cell lines. In, National Cancer Institute Monograph 7: 75–89.Google Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • Barbara R. Migeon
    • 1
  1. 1.Department of Pediatrics, School of MedicineJohns Hopkins UniversityBaltimoreUSA

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