Asynchronous replication of biallelically expressed loci: a new phenomenon in Turner syndrome.

Purpose: Transcriptional activity of genes is related to their replication timing; alleles showing the common biallelic mode of expression replicate synchronously, whereas those with a monoallelic mode of expression replicate asynchronously. Here the level of synchronization in replication timing of alleles was determined in subjects with Turner syndrome.

Methods: Fluorescence in situ hybridization was used for three loci not linked to X chromosome, in lymphocytes derived from 12 controls, 3 individuals with Turner, and 4 with mosaic Turner syndrome.

Results: In cells derived from controls, each pair of alleles replicated synchronously; yet these same alleles replicated asynchronously in cells monosomic for X chromosome derived from Turner and mosaic Turner patients. When the level of 45,X was low in the mosaic samples, the replication pattern of the 46,XX cells was normal. However, in samples with a high level of mosaicism, a significantly increased asynchronous replication was detected in the 46,XX cells.

Conclusion: An altered temporal replication control in Turner syndrome affecting the aneuploid and euploid cells is shown. This alteration may potentially be involved in the determination of the syndrome.