DNA diversity and meiotic crossover distribution in the Xp/Yp pseudoautosomal region

High resolution analyses indicate that meiotic crossovers in human autosomes tend to cluster into 1-2 kb hotspots separated by blocks of high LD tens to hundreds of kilobases long. In contrast, low resolution data suggest only modest regional variation in recombination efficiency across the 2.6 Mb Xp/Yp pseudoautosomal region (PAR1), a male-specific recombination hot domain with a recombination rate about twenty times higher than the genome average. Recent data suggest a more complex picture of PAR1 recombination. Around the SHOX gene, 500 kb from the telomere, LD decays extremely rapidly with physical distance, but nearly all crossovers cluster into a highly localised hotspot about 2 kb wide. In contrast, SNPs in a 1.5 kb region immediately adjacent to the PAR1 telomere are in intense LD, implying that this region is recombinationally inert and that male crossover activity terminates at a currently unidentified boundary in the distal region of PAR1. To further investigate PAR1 recombination, the PGPL gene, 80 kb from the telomere, was targeted for analysis. This region had to be sequenced prior to SNP discovery and recombination analysis, revealing a novel gene that is potentially the most telomeric gene in PAR1. SNP analysis of a 33 kb PGPL interval showed that this region is in free association with the telomere, suggesting recombinational activity in the intervening region, which this study proved to be rich in tandem repeats. Within the PGPL region, LD decays slowly with physical distance at a rate consistent with randomly-distributed crossovers occurring at close to the genome average rate. However, sperm crossover analysis revealed it to be the most recombinationally active region of DNA yet identified. Moreover, the novel distribution of crossovers in the region, suggests that there is not a unified set of hotspot-based rules that govern meiotic recombination in the human genome.