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Title: Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations.
Authors: Berg, IL
Neumann, R
Sarbajna, S
Odenthal-Hesse, L
Butler, NJ
Jeffreys, AJ
First Published: 26-Jul-2011
Citation: PROC NATL ACAD SCI U S A, 2011, 108 (30), pp. 12378-12383
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 view of PRDM9 regulation, in terms of motifs 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 African-enhanced hotspots nevertheless share very similar properties with their counterparts activated by the A variant. The specificity of hotspot activation is such that individuals with differing PRDM9 genotypes, even within 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.
DOI Link: 10.1073/pnas.1109531108
eISSN: 1091-6490
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Genetics

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