Summary
A new case of an unbalanced X/autosome translocation, karyotype 46,X,der(X),t(X;14)(q22;q11), is described. The derivative X chromosome was inactivated and showed various degrees of incomplete spreading of late replication into the translocated autosome. This enabled us to test the hypothesis that the extent of this spreading is primarily determined during X inactivation in the early embryo so that the various DNA replication patterns of the derivative X occur in a clonal fashion. However a dilution plating experiment gave no evidence that such a clonality exists. In the inactivated autosome, late-replicating bands obviously turned to earlier replication during cell aging in vitro. It is suggested that the degree of spreading of X inactivation into an autosome is not primarily induced but results from ineffective maintenance of the inactivation on the autosome, presumably due to an irreversible loss of methyl cytosine.
Similar content being viewed by others
References
Cattanach BM (1974) Position effect variegation in the mouse. Genet Res 23:291–306
Cohen MM, Lin CC, Sybert V, Orecchino EJ (1972) Two human X-autosome translocation identified by autoradiography and fluorescence. Am J Hum Genet 24:583–597
Crandall BF, Carrel RF, Howard J, Schroeder WA, Müller H (1974) Trisomy 13 with 13-X translocation. Am J Hum Genet 26: 385–392
Disteche CM, Eicher EM, Latt SA (1981) Late replication pattern in adult and embryonic mice carrying Searle's X-autosome translocation. Exp Cell Res 133:357–362
Engel W, Vogel W, Reinwein H (1971) Autoradiographische Untersuchungen an einer X-Autosom Translokation beim Menschen: 45,X,15-,tan(15qXq+). Cytogenetics 10:87–98
Gartler SM, Riggs AD (1983) Mammalian X chromosome inactivation. Annu Rev Genet 17:155–190
Hagemeijer A, Hoovers J, Smit EME, Bootsma D (1977) Replication pattern of the X chromosomes in three X/autosomal translocation. Cytogenet Cell Genet 18:333–348
Hoehn H, Bryant EM, Au K, Norwood TH, Boman H, Martin GM (1975) Variegated translocation mosaicism in human skin fibroblast cultures. Cytogenet Cell Genet 15:282–298
Keitges EA, Palmer CG (1986) Analysis of sperading of inactivation in eight X autosome translocations utilizing the high resolution RGB technique. Hum Genet 72:231–236
Krumlauf R, Chapman VM, Hammer RE, Brinster R, Tilghman SM (1986) Differential expression of alpha-fetoprotein genes on the inactive X chromosome in extraembryonic and somatic tissues of a transgenic mouse line. Nature 319:224–226
Leisti JT, Kaback MM, Rimoin DL (1975) Human X autosome translocations: differential inactivation of the X chromosome in a kindred with an X-9 translocation. Am J Hum Genet 27:441–453
Lyon MF (1961) Gene action in the X chromosome of the mouse (Mus musculus L.). Nature 190:372–373
Mikkelsen M, Dahl G (1973) Unbalanced X-autosomal translocation with inactivation of the normal X chromosome. Cytogenet Cell Genet 12:357–366
Mohandas T, Sparkes RS, Hellkuhl B, Grzeschik KH, Shapiro LJ (1980) Expression of an X-linked gene from an inactive human X chromosome in mouse-human hybrid cells: further evidence for the noninactivation of the steroid sulfatase locus in man. Proc Natl Acad Sci USA 77:6759–6763
Mohandas T, Sparkes RS, Shapiro LJ (1981) Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science 211:393–396
Salk D, Au K, Hoehn H, Martin GM (1981) Cytogenetics of Werner's syndrome cultured skin fibroblasts: variegated translocation mosaicism. Cytogenet Cell Genet 30:92–107
Schwarzacher HG, Wolf U (1974) Methods in human cytogenetics. Springer, Berlin Heidelberg New York
Shafer DA, Priest JH (1984) Reversal of DNA methylation with 5-azacytidine alters chromosome replication patterns in human lymphocyte and fibroblast cultures. Am J Hum Genet 36:534–545
Shmookler-Reis RJ, Goldstein S (1982) Variability of DNA methylation pattern during serial passage of human diploid fibroblasts. Proc Natl Acad Sci USA 79:3949–3953
Summitt RL, Tipton RE, Wilroy RS, Martens PR, Phelan JP (1978) X-autosome translocations: a review. Birth Defects 14:219–247
Taylor JH (1960) Asynchronous duplication of chromosomes in cultured cells of Chinese hamster. J Biophys Biochem Cytol 7:455–464
Vogel W, Schempp W, Sigwarth J (1978) Comparison of thymidine, fluorodeoxyuridine, hydroxyurea and methotrexate blocking at the G1/S phase transition of the cell cycle, studied by replication patterns. Hum Genet 45:193–198
Vogel W, Trautmann T, Hörler H, Pentz B (1983) Cytogenetic and biochemical investigations on fibroblast cultures and clones with one and two active X chromosomes of 69,XXY triploidy. Hum Genet 64:246–248
Wareham KA, Lyon MF, Glenister PH, Williams ED (1987) Age related reactivation of an X-linked gene. Nature 327:725–727
Wigler M, Levy D, Perucho M (1981) The somatic replication of DNA methylation. Cell 24:33–40
Wilson VL, Jones PA (1983) DNA methylation decreases in aging but not immortal cells. Science 220:1055–1057
Wolf SF, Migeon BR (1982) Studies of X chromosome DNA methylation in normal human cells. Nature 295:667–671
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schanz, S., Steinbach, P. Investigation of the “variable spreading” of X inactivation into a translocated autosome. Hum Genet 82, 244–248 (1989). https://doi.org/10.1007/BF00291163
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00291163