Primary and secondary nonrandom X chromosome inactivation in early female XXXX embryos carrying Searle's translocation T(X; 16)16H.

@entity1603 @entity19 @entity72835 @entity72836 @entity9186
By means of a cytological technique involving @entity1603 , @entity9186 , and fluorescence microscopy, the asynchronously replicating, hence genetically inactivated, X chromosome was identified in 6- to 8-day embryos from female @entity19 heterozygous for Searle's translocation T(X;16)16H (abbreviated as @entity72835 ) mated with either karyotypically normal males or males carrying Cattanach's translocation T(X;7)1Ct in order to analyse the way in which the total inactivation of the normal X is achieved in adult @entity72835 heterozygotes. Embryos examined included 9 Xn/X(7);16/16, 3 X 16/Xn;16x/16, 12 @entity72836 /X(7); 16x/16, 5 @entity72836 /Xn;16/16, 8 @entity72836 /X(7); 16/16 and 2 Xn/Y; 16x/16/16. In these notations @entity72836 , 16x, X(7) and Xn represent Searle's X with the centromeric segment of the X, Searle's X with the centomeric segment of chromosome 16, Cattanach's X with insertion of a chromosome 7 segment, and normal X, respectively. The X(7) exerted no apparent effect upon embryonic development up to the 8th day of gestation and X chromosome inactivation. -- The asynchronously replicating X was the Xn in @entity72836 /Xn;16x/16 and X(7) in @entity72836 /X(7);16x/16 embryos except a small number of cells on day 6 (13/493) and on day 7 (1/886) in which almost the entire 16x replicated asynchronously. The @entity72836 , on the other hand, never showed replication asynchrony. That the @entity72836 is indeed unable to become inactivated was indicated by the observation that the @entity72836 as well as Xn or X(7) did not replicate asynchronously in Xn/ @entity72836 ;16/16 and @entity72836 /X(7);16/16 embryos @entity72836 -inactive cell lines, if occurring, should have been genetically less unbalanced than any other cell line in such embryos. It is highly likely therefore that the ultimate inactivation pattern in @entity72835 heterozygotes has been accomplished by (1) the inability of the @entity72836 to become inactive; (2) inactivation in favor of the Xn; and (3) rapid elimination of 16x-inactive cells. Severe growth retardatin and early death of @entity72836 /Xn;16/16 and @entity72836 /X(7);16/16 embryos having no inactive X suggested that functional X disomy is detrimental to embryogenesis. These embryos further indicated that the concurrence of at least two X chromosomal loci separated by the @entity72835 breakpoint is necessary for the homologous X chromosome becoming inactivated.
