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 gamma-aminobutyric acid receptor beta3 subunit gene (GABRB3); and maternal early/paternal late at the more distal gamma-aminobutyric acid receptor alpha5 subunit gene (GABRA5). At the most distal locus examined, D15S12, both patterns of allele-specific replication timing were detected.