Domain organization of allele-specific replication within the GABRB3 gene cluster requires a biparental 15q11-13 contribution.

ABSTRACT

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