SEX-SPECIFIC MEIOTIC RECOMBINATION IN THE PRADER-WILLI/ANGELMAN SYNDROME IMPRINTED REGION

Meiotic recombination is a specifically timed and regulated process which does not occur randomly throughout the genome, but tends to be clustered in 'hotspots'. There is extensive evidence that recombination rate is influenced by chromatin conformation and that events are primarily initiated at gene promoter regions. In an effort to determine the pattern of chromatin condensation and recombination at meiosis in an imprinted region, fine scale genetic; mapping in the approximately 4 Mb Prader-Willi/Angelman syndrome deletion region was undertaken, The results indicate that the male-female recombination ratio can vary significantly over short regions, A male recombination hotspot is localized to between the 3' end of GABRA5 and D15S156, which is adjacent to but outside the putative AS/PWS imprinted regions. In addition, a region of relatively high recombination in females is observed between D15S128 and D15S97, which spans a domain of paternal allele-specific transcription implicated in the Prader-Willi syndrome, It is inferred that the inactivation and relative condensation of this latter region on the maternal chromosome occurs as a post-meiotic modification.