Recombination preferentially occurs at specific sites, 1 to2 kb long, known as hotspots. The location of hotspots is not determined simply by their own DNA sequence but also depends on genetic background. Previous work in our lab has found the first gene that activates hotspots, Prdm9. In addition to hotspot activation, we have also found that the presence of a particular genetic background can also cause suppression and quantitative modulation of hotspot activity.
My project is to search for trans-acting suppressors of hotspot activity. I am using a model system in which the presence of trans-acting CAST alleles suppresses hotspot activity at several individual hotspots on chromosome 1, and I am mapping the trans-acting genes in a B6xCAST F2 cross keeping the hotspots heterozygous while the rest of the genome is segregating. We are currently developing an approach for measuring hotspot activity by cloning individual hotspot sequences from sperm and detecting recombinant molecules by massive parallel sequencing.