Variants of the Protein PRDM9 Differentially Regulate a Set of Human Meiotic Recombination Hotspots Highly Active in African Populations

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Jul 14

PMID 21750151

Citations 94

Authors

Ingrid L Berg

Rita Neumann

Shriparna Sarbajna

Linda Odenthal-Hesse

Nicola J Butler

Alec J Jeffreys

Affiliations

Soon will be listed here.

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.

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