Allele specificity of DNA replication timing in the Angelman/Prader–Willi syndrome imprinted chromosomal region

DNA replication within chromosome 15q11–q13, a region subject to genomic imprinting, was examined by fluorescence in situ hybridization. Asynchronous replication between homologues was observed in cells from normal individuals and in Prader–Willi (PWS) and Angelman syndrome (AS) patients with chromosome 15 deletions but not in PWS patients with maternal uniparental disomy. Opposite patterns of allele–specific replication timing between homologous loci were observed; paternal early/maternal late at D15S63, D15S10 and the γ–aminobutyric acid receptor β subunit gene (GABRB3); and maternal early/paternal late at the more distal γ–aminobutyric acid receptor γ5 subunit gene (GABRA5). At the most distal locus examined, D15S12, both patterns of allele–specific replication timing were detected.