Replication timing regulation in adults with chromosomal balance rearrangements

The alternative forms of the alleles in biallelic genes display a synchronous pattern of replication that is different from genes subjected to monoallelic expression, which exhibit an asynchronous mode of replication. The present study sought to gain insight into changes in the allele-specific replication timing in phenotypically normal humans with balanced chromosomal rearrangements, and to investigate the potential mechanism for chromosomal rearrangements. We used fluorescence in situ hybridization and chose biallelic gene expression of RB1 and monoallelic expression of SNRPN in phytohemagglutinin-stimulated lymphocytes to compare differences in the allelic replication timing. We found that compared to genetically normal adult controls, adults with a normal phenotype despite chromosomal rearrangements showed normal replication timing (synchronous or asynchronous) for the RB1 gene and SNRPN genes. Our data support a link between chromosomal aberrations and epigenetic stability in phenotypically normal humans, independent of the breakpoints in chromosomal structural disruption, and represent an epigenetic mark for allelic exclusion in balanced chromosomal rearrangements in patients with normal phenotypes.