The classical inbred strains predominantly originate from M. The 17 strains include classical inbred strains as well as four wild-derived inbred strains ( Kang et al. Recombination events in the laboratory strains are historical events that occurred over hundreds of generations during the genetic fixation of laboratory strains from wild Mus musculus progenitor subspecies. 2011), in addition to the reference genome, provides a new resource for mapping hotspots. The complete sequencing of 17 inbred strains ( Keane et al. Still, a subset of experimentally tested boundaries of LD blocks in inbred mice was shown to correspond to active recombination hotspots ( Kauppi et al. LD blocks are considerably larger in inbred mice compared to human populations and wild mice ( Laurie et al. There has been one study that showed that recombination rates in outbred mice are associated with patterns of linkage disequilibrium (LD) in inbred strains, but the average distance of 167 kb between SNPs was nevertheless insufficient to attempt replicating the human analysis ( Shifman et al. Recombination initiation sites were found to be associated with testis-specific trimethylation of lysine 4 on histone H3.

A different approach that relies on the binding of RAD51 and DMC1 proteins was recently used to map meiotic DNA double-strand breaks (DSBs) that initiate recombination ( Smagulova et al. The problem with this approach is the high cost of typing SNPs for sufficient numbers of cases in order to define recombination hotspots with power and precision. 2010 Dumont and Payseur 2011 Dumont et al. Until recently, the primary strategy for analysis of recombination hotspots in mice has been to use pedigree analysis in strain crosses ( Paigen et al. The very large number of hotspots and the very high resolution of this mapping made it possible to pinpoint sequence motifs in these hotspots, one of which was instrumental in finding a gene, PRDM9, thought to be a critical component of the recombination mechanism ( Baudat and de Massy 2007 Grey et al. The dense map of single nucleotide polymorphisms (SNPs) created by the HapMap Project enabled the high-resolution mapping of recombination rates in the human genome and led to the identification of ∼33,000 recombination hotspots with a coalescent method ( Myers et al.

RECOMBINATION events are not uniformly distributed across the genome rather they tend to occur at hotspot regions typically 1–2 kb in size ( Jeffreys et al. They also strengthen previous findings on mouse recombination hotspots, and specifically the impact of sequence variants in Prdm9. Our results suggest that inbred strains can be used to characterize and study the dynamics of historical recombination hotspots. Comparing the inferred historical recombination hotspots with the recent genome-wide mapping of double-strand breaks (DSBs) in mouse sperm revealed a significant overlap, especially toward the telomeres. Recombination rates were on average lower near transcription start sites (TSS). Recombination hotspots were found to be enriched for the predicted binding sequences for different alleles of the PRDM9 protein. We show by simulation that inbred mouse strains can be used to identify positions of historical hotspots. In this study, we used single nucleotide polymorphisms (SNPs) from whole-genome resequencing and genotyping studies of mouse inbred strains to estimate recombination rates across the mouse genome and identified 47,068 historical hotspots-an average of over 2477 per chromosome. These studies pointed to the central role of the PRDM9 gene in hotspot modulation. Genetic variation in recombination rates and hotspots usage have been explored in human pedigrees, mouse intercrosses, and by sperm typing. Population genetic data have been used to map and quantify hotspots in the human genome.

Several studies using different approaches have dramatically advanced our understanding of recombination hotspot regulation. Recombination events are not uniformly distributed and often cluster in narrow regions known as recombination hotspots.

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