1. Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations.
- Author
-
Berg, Ingrid L., Neumann, Rita, Sarbajna, Shriparna, Odenthal-Hesse, Linda, Butler, Nicola J., and Jeffreys, Alec J.
- Subjects
- *
GENETIC polymorphisms , *NUCLEOTIDE sequence , *ETHNOLOGY , *ZINC , *DNA , *POPULATION - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF