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 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.
LaSalle
J M
JM
Howard Hughes Medical Institute, Boston, Massachusetts.
Lalande
M
M
D000483:Alleles; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004261:DNA Replication / Q000235:genetics; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007700:Kinetics; D008297:Male; D005810:Multigene Family; D011963:Receptors, GABA-A / Q000235:genetics*; D016196:S Phase / Q000235:genetics
D011963:Receptors, GABA-A