Complex dynamics of meiotic recombination initiation in laboratory mouse strains

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NIDDK	GEN-2

* FARE Award Winner

Authors

• KM Brick
• F Smagulova
• G Petukhova
• RD Camerini-Otero

Abstract

In mouse, humans and other mammals, the DNA double strand breaks (DSBs) that initiate meiotic recombination are directed to a subset of genomic loci called hotspots by sequence specific binding of the PRDM9 protein. We have previously developed the first method to directly map the sites of meiotic DSBs genome-wide and here, we exploit this technique to define the recombination initiation landscape in six laboratory mouse strains with different PRDM9 alleles and in their F1 hybrids. We find that DSB hotspots defined by the six different alleles of the PRDM9 protein occur mostly at mutually exclusive loci. A striking finding in F1 mice is the appearance of “novel” DSB hotspots, not present in either parental genome. In some cases, these constitute >30% of all hotspots. We show that most novel hotspots are formed by heteroallelic hotspot initiation whereby the PRDM9 allele from one parental strain targets a DSB to the chromosome of the other. Biased DSB initiation on the non-self chromosome is also observed at other hotspots and generally, such bias results in hotspots that are relatively stronger than in the parental genome. Together with other data, these findings elucidate the complex dynamics of DSB formation in mammalian meiosis.

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