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Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations

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Citation

Berg, I. L., Neumann, R., Sarbajna, S., Odenthal-Hesse, L., Butler, N. J., & Jeffreys, a. A. J. (2011). Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations. Proceedings of the National Academy of Sciences of the United States of America, 108(30), 12378-12383. doi:10.1073/pnas.1109531108.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0028-63D2-D
Abstract
PRDM9 is a major specifier of human meiotic recombination
hotspots, probably via binding of its zinc-finger repeat array to
a DNA sequence motif associated with hotspots. However, our
viewof PRDM9 regulation, in terms ofmotifs defined and hotspots
studied, has a strong bias toward the PRDM9 A variant particularly
common in Europeans. We show that population diversity can
reveal a second class of hotspots specifically activated by PRDM9
variants common in Africans but rare in Europeans. These Africanenhanced
hotspots nevertheless share very similar propertieswith
their counterparts activated by the A variant. The specificity of
hotspot activation is such that individuals with differing PRDM9
genotypes, evenwithin the same population, can use substantially
if not completely different sets of hotspots. Each African-enhanced
hotspot is activated by a distinct spectrum of PRDM9 variants,
despite the fact that all are predicted to bind the same
sequence motif. This differential activation points to complex
interactions between the zinc-finger array and hotspots and identifies
features of the array that might be important in controlling
hotspot activity.