Absence of correlation between late-replication and spreading of X inactivation in an X;autosome translocation

We have analysed the spread of X inactivation in an individual with an unba lanced 46,X,der(X)t (X; 10)(q26.3;q23.3) karyotype. Despite being trisomic for the region 10q23.3-qter, both the proband and her aunt with the same ka ryotype presented only with secondary amenorrhoea and lacked any features n ormally associated with trisomy of distal 10q. Cytogenetic and molecular st udies showed that the derivative X; 10 chromosome was exclusively inactive. Transcribed polymorphisms were identified in five genes contained within t he translocated region of chromosome 10 and were used to perform allele-spe cific transcription studies. We showed that four of the genes studied are i nactive on the derivative chromosome, directly demonstrating the spread of X inactivation over some 30 Mb of autosomal DNA. However, the most distal g ene examined remained active, indicating that this spreading was incomplete . In contrast to the gene expression data, replication timing studies showe d no spreading of late replication into the translocated portion of 10q. We conclude that silencing of autosomal genes by X inactivation can occur wit hout a delay in the replication timing of the surrounding chromatin. Our fi ndings support the hypothesis that autosomal chromatin lacks certain featur es present on the X chromosome that are required for the effective spread a nd/or maintenance of X inactivation.