title: Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations.
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.
authors.affiliation: Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Berg
authors.forename: Rita
authors.initials: R
authors.lastname: Neumann
authors.forename: Shriparna
authors.initials: S
authors.lastname: Sarbajna
authors.forename: Linda
authors.initials: L
authors.lastname: Odenthal-Hesse
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Butler
authors.forename: Alec J
authors.initials: AJ
authors.lastname: Jeffreys
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D003434:Crossing Over, Genetic; D004247:DNA / Q000235:genetics; D005785:Gene Conversion; D005787:Gene Frequency; D014644:Genetic Variation; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008540:Meiosis / Q000235:genetics; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D013094:Spermatozoa / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D004247:DNA; D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human