Investigation of the "variable spreading" of X inactivation into a translocated autosome

Abstract

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.