Replication timing of insulin-like growth factor-2 (IFG2) in Beckwith-Wiedemann syndrome

grantor: University of TorontoGenomic imprinting results in differential allelic transcription during normal mammalian development. Previously fluorescence in situ hybridization (FISH) demonstrated that imprinted genes exhibit allele-specific asynchronous replication. Beckwith-Wiedemann Syndrome (BWS), an overgrowth syndrome associated with embryonal tumours, frequently exhibits loss of imprinting of the insulin-like growth factor 2 (IGF2) gene. Analysis of IGF2 replication timing in two BWS patients with a chromosomal rearrangement and one with biallelic IGF2 expression was performed to determine whether these genetic changes influence asynchronous replication. Maintenance of the expected pattern of asynchronous replication was retained in cells from a BWS patient with biallelic IGF2 expression, and of the two patients with chromosomal rearrangements at 11p15.5, only one exhibited alterations to replication timing. It is concluded that a chromosomal rearrangement 400kb away from IGF2 may alter the pattern of IGF2 replication, and that this change may be a contributing factor to BWS in this patient.M.Sc