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Florida Faculty and Professional Staff
Philippe Bois
Assistant Professor
Department of Cancer Biology
TSRI - 2007
Education
B.Sc. - 1993: University Paris 7 – Denis Diderot, Paris, France (Applied Genetics and Biology)
M.Sc. - 1994: University Paris 7 – Denis Diderot, Paris, France (Oncogenesis)
Ph.D. - 1998: University Paris 7 – Denis Diderot, Paris, France (Biology – Life Science)
Research Focus
Meiotic recombination plays a key role in the maintenance of sequence diversity in higher genomes. While recent works have identified over 25,000 recombination hotspots in the human genome, little is known about the processes of recombination in higher eukaryotes. Sperm typing systems have been developed that allow mammalian (human and mouse) recombination to be analyzed at very high resolutions. The emerging picture is that human and mouse crossovers are not randomly distributed, but are rather targeted to very narrow (1-2 kb) recombinationally permissive regions called “hotspots”. These hotspots are surrounded by large stretches of recombinationally suppressed DNA, suggesting that the bulk of genomic DNA is in the "cold". In addition, recombination hotspots in mice and humans are sites of initiation and resolution of both crossovers and non-crossover gene conversions.
Insights into the molecular mechanisms promoting hotspot activity in mammals have largely come from indirect evidence relying on other model organisms, especially yeast. The primary determinant of the distribution of recombinations in yeast is the distribution of the double-strand breaks (DSBs) that initiate recombination. In other words, recombination hotspots are in fact DSB hotspots. In yeast, the frequency of DSBs is determined by a combination of large-scale chromosomal structural features as well as by local chromatin structure. Therefore, regional variation in crossover frequencies might also reflect differences in the likelihood that a given DSB will give rise to a crossover versus a non-crossover product. The fact that DSBs are highly localized and are separated by recombinationally inert DNA is important in structuring the genome into linkage disequilibrium (LD)/haplotype blocks. Analyses of these hotspots in mammalian genomes are starting to provide fundamental information on the processes of crossover and gene conversion in higher organisms.
Since recombination hotspots in the mouse share similar properties as in humans, the mouse model provides a system where these fundamental genome turnover mechanisms can be easily studied by genetic manipulation. We are taking a genetic approach together with knock-out and knock–in technology to address the fundamental questions about the origin as well as the regulation and resolution pathways at recombination hotspots.
Selected References
Bonhomme F, Rivals E, Orth A, Grant GR, Jeffreys AJ & Bois PRJ* (2007) Species wide distribution of highly polymorphic minisatellite markers reveals long-range gene flow and frequent genetic exchanges among House mouse subspecies. Genome Biology 2007;8(5):R80
Bois PRJ* (2007) A highly polymorphic meiotic recombination hotspot exhibits incomplete repair. Molecular and Cellular Biology2007 Aug 20 [Epub ahead of print]
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