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 genom ic imprinting, was examined by fluorescence in situ hybridization. Asy nchronous replication between homologues was observed in cells from no rmal individuals and in Prader-Willi (PWS) and Angelman syndrome (AS) patients with chromosome 15 deletions but not in PWS patients with mat ernal uniparental disomy. Opposite patterns of allele-specific replica tion timing between homologous loci were observed; paternal early/mate rnal late at D15S63, D15S10 and the gamma-aminobutyric acid receptor b eta3 subunit gene (GABRB3); and maternal early/paternal late at the mo re 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.