DOMAIN ORGANIZATION OF ALLELE-SPECIFIC REPLICATION WITHIN THE GABRB3 GENE-CLUSTER REQUIRES A BIPARENTAL 15Q11-13 CONTRIBUTION

Imprinting marks the parental origin of chromosomes, resulting in alle le-specific changes in chromatin organization, transcription and repli cation. We report a 50-60 kb domain of allele-specific replication bet ween the gamma-aminobutyric acid receptor subunit beta 3 (GABRB3) and alpha 5 (GABRA5) genes. Replication of this domain occurs in early S p hase on the maternal chromosome 15 but is delayed until the end of S p hase on the paternal homologue. In contrast, the genomic regions flank ing this domain exhibit paternal earlier replication in mid to late S phase. Uniparental disomy or hemizygous deletion of chromosome 15 resu lts in altered allele-specific replication kinetics compared with norm als, suggesting that allele-specific replication within the GABRB3/A5 region may be regulated by reciprocal imprints on the maternal and pat ernal chromosomes.