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Abstract

Meiotic recombination re-shuffles genomes from one generation to the next. In
humans and most other mammals, meiotic recombination events are clustered in
1-2 kb wide recombination hotspots, whose locations are determined in trans by
the protein PR-domain containing 9 (PRDM9). Mice lacking PRDM9 direct
recombination to promoters and functional elements, resulting in meiotic defects.
Dogs (Canis familiaris) lack a functional copy of PRDM9, yet linkage data showed
that historical recombination events cluster in functional elements, suggesting that
there may be a mechanism enabling controlled recombination at these locations,
and in the absence of PRDM9. However nothing is known about the de-novo
activity of dog recombination hotspots and the patters of recombination resolution
in this PRDM9 deficient species. I investigated a dog recombination hotspot for
de-novo recombination events using pooled sperm typing, and uncovered high
crossover frequencies affecting up to 1 % of sperm. Frequencies can differ by one
order of magnitude between dogs. Fine-scale analysis of crossover-breakpoints
revealed wide distributions of breaks across up to 10 kb within the hotspot region.
I further detect asymmetric breakpoint distributions between crossover
orientations and crossover-associated transmission distortion, suggesting biased
recombination-initiation or -repair. This work is an elaborate fine-scale dissection
of a mammalian PRDM9-independent active recombination hotspot.