IMPRINTED CHROMOSOMAL REGIONS OF THE HUMAN GENOME DISPLAY SEX-SPECIFIC MEIOTIC RECOMBINATION FREQUENCIES

Background: Meiotic recombination events do not occur randomly along a chromosome, but appear to be restricted to specific regions. In addit ion, some regions in the genome undergo recombination more frequently in the germ cells of one sex than the other. Genomic imprinting, the p rocess by which the two parental alleles of a gene are differentially marked, is another genetic phenomenon associated with inheritance from only one parent or the other. The mechanisms that control meiotic rec ombination and genomic imprinting are unknown, but both phenomena nece ssarily depend on the presence of some DNA signal sequences and/or on the structure of the surrounding chromatin domain. Results: In the pre sent study, we compared the frequencies of sex-specific recombination events in three chromosomal regions of the human genome that contain c lustered imprinted genes. Alignment of the genetic and physical maps o f the ZNF127-SNRPN-IPW-PAR-5-PAR-1 region on chromosome 15q11-q13 (ass ociated with Prader-Willi and Angelman syndromes) and the IGF2-H19 reg ion on chromosome 11p15.5 (associated with Beckwith-Wiedemann syndrome ) shows that both regions recombine with very high frequency during ma le meiosis, and with very low frequency during female meiosis. A third region around the WT-1 gene on chromosome 11p13 also recombines with higher frequency during male meiosis. Conclusions: The results show th at the two best-known imprinted regions in the human genome are charac terized by significant differences in recombination frequency during m ale and female meioses. A third, less well-characterized, imprinted re gion shows a similar sex-specific bias. On the basis of these observat ions, we propose a model suggesting that the region-specific different ial accessibility of DNA that leads to differential recombination rate s during male and female meioses also leads to the male- and female-sp ecific modification of the signal sequences that control genomic impri nting.