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Martin Vanek, Filip Mravec, Martin Szotkowski, Dana Byrtusova, Andrea Haronikova, Milan Certik, Volha Shapaval and Ivana Marova
Mahmut C. Ergören, Rita Neumann, Ingrid Berg and Alec J. Jeffreys
PRDM9 plays a key role in specifying meiotic recombination hotspot locations in humans. To examine the effects of both the 13-bp sequence motif (cis-regulator) and trans-regulator PRDM9 on crossover frequencies and distribution, we studied Hotspot DA. This hotspot had the motif at its centre, and a single nucleotide polymorphism (SNP) that disrupts the motif. The crossover frequency showed Hotspot DA to be a regular hotspot with an average crossover rate (~8 X10-4) among hotspots assayed on autosomes. Our results show that, comparing the rates and distributions of sperm crossover events between donors heterozygous for the disrupting SNP showed that there was a huge asymmetry between the two alleles, with the derived, motif-disrupting allele completely suppressing hotspot activity. Intensive biased gene conversion, both in to crossovers and noncrossovers, has been found at Hotspot DA. Biased gene conversion that influences crossover and non-crossover hotspot activity correlates with PRDM9 allele A. In Hotspot DA, the lifetime of the hotspot mostly depends on the cis-regulatory disrupting SNP, and on the trans-regulatory factor PRDM9. Overall, our observation showed that Hotspot DA is the only evidence for human crossover hotspot regulation by a very strong cisregulatory disrupting SNP.