Understanding genetic recombination in a multi-cellular organism

2012

Challenge

Genetic recombination is the defining phenomenon in genetics. It drives the evolution of genomes, yet it occurs at hotspots whose features are mostly unknown in organisms other than yeast. To better understand human disease, researchers needed to understand where and how recombination occurs in complex organisms.

Advance

IRP researchers led by Rafael Daniel Camerini-Otero M.D., Ph.D., in collaboration with Galina Petukhova, Ph.D., of the Uniformed Services University of Health Sciences, constructed the first high-resolution, genome-wide physical map of recombination hotspots in a multi-cellular organism (the mouse).

Impact

The map revealed previously unknown molecular features at hotspots, as well as the mechanism for actively sequestering recombination away from functional genomic elements, such as promoters and enhancers. The recombination map has advanced our understanding of both how genetic recombination works in complex organisms and how it is initiated, giving additional insight into the role of genomic rearrangements in evolutionary processes leading to shifts in allele frequencies and the development of heritable genetic diseases.

Publications

Smagulova, F., Gregoretti, I.V., Brick, K., Khil, P.P., Camerini-Otero, R.D., and Petukhova, G.V. (2011). Genome-Wide Analysis Reveals Novel Molecular Features of Mouse Recombination Hotspots. Nature. 472(7343), 375-8.

Brick, K.M., Smagulova, F., Khil, P.P., Camerini-Otero, R.D., and Petukhova, G.V. (2012). Genetic recombination is directed away from functional genomic elements in mice. Nature 485(7400), 642-5.

Pratto, F., Frick, K., Khil, P., Smagulova, F., Petukhova, G.V., and Camerini-Otero, R.D. (2014). DNA recombination. Recombination initiation maps of individual human genomes. Science 346(6211), 1256442.