Paper: Human Imprinted Chromosomal Regions Are Historical Hot-Spots of Recombination

Human Imprinted Chromosomal Regions Are Historical Hot-Spots of
Recombination

Ionel Sandovici, Sacha Kassovska-Bratinova, Joe E. Vaughan, Rae Stewart,
Mark Leppert, Carmen Sapienza

Human recombination rates vary along the chromosomes as well as between the
two sexes. There is growing evidence that epigenetic factors may have an
important influence on recombination rates, as well as on crossover
position. Using both public database analysis and wet-bench approaches, we
revisited the relationship between increased rates of meiotic recombination
and genome imprinting. We constructed metric linkage disequilibrium (LD)
maps for all human chromosomal regions known to contain one or more
imprinted genes. We show that imprinted regions contain significantly more
LD units (LDU) and have significantly more haplotype blocks of smaller sizes
than flanking nonimprinted regions. There is also an excess of hot-spots of
recombination at imprinted regions, and this is likely to do with the
presence of imprinted genes, per se. These findings indicate that imprinted
chromosomal regions are historical "hot-spots" of recombination. We also
demonstrate, by direct segregation analysis at the 11p15.5 imprinted region,
that there is remarkable agreement between sites of meiotic recombination
and steps in LD maps. Although the increase in LDU/Megabase at imprinted
regions is not associated with any significant enrichment for any particular
sequence class, major sequence determinants of recombination rates seem to
differ between imprinted and control regions. Interestingly, fine-mapping of
recombination events within the most male meiosis-specific recombination
hot-spot of Chromosome 11p15.5 indicates that many events may occur within
or directly adjacent to regions that are differentially methylated in
somatic cells. Taken together, these findings support the involvement of a
combination of specific DNA sequences and epigenetic factors as major
determinants of hot-spots of recombination at imprinted chromosomal regions.

Source: PLoS (Open Access)
http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10%2E1371%2Fjournal%2Epgen%2E0020101

Posted by
Robert Karl Stonjek


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