Late replication in an X-autosome translocation in the mouse: correlation with genetic inactivation and evidence for selective effects during embryogenesis

Abstract

A technique involving 5-bromodeoxyuridine, 33258 Hoechst, and fluorescence microscopy has been used to analyze replication kinetics in cells from embryonic and adult mice bearing the Cattanach [T(X;7)ICt] translocation in a balanced or an unbalanced form. In balanced 9- and 13-day female embryos, the translocated X was late replicating in 28 and 22% of the cells, respectively, whereas it was late replicating in only 13% of adult cells. In contrast, in unbalanced females, the translocated X was late replicating in 62 and 70% of 9- and 13-day embryos and in 70% of adult cells. Such divergent late replication frequencies suggest the operation, during development, of selection against cells with extreme genetic imbalance. Within a late-replicating translocated X chromosome, the autosomal segment itself replicated late approximately half of the time, regardless of karyotypic balance. The late replication data are consistent with the measurements of levels of mitochondrial malic enzyme (MOD-2, whose locus is on the autosomal segment) activity in these mice [Eicher E. & Coleman, D. (1977) Genetics 85, 647-658]. The present study also shows a dissociation between the replication timing in X chromatin distal and proximal to the autosomal segment, supporting the hypothesis of at least two inactivation centers in the X chromosome.