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Crossover clustering and rapid decay of linkage disequilibrium in the Xp/Yp pseudoautosomal gene SHOX


Crossover between the human sex chromosomes during male meiosis is restricted to the terminal pseudoautosomal pairing regions. An obligatory exchange occurs in PAR1, an Xp/Yp pseudoautosomal region of 2.6 Mb, which creates a male-specific recombination 'hot domain' with a recombination rate that is about 20 times higher than the genome average1,2,3. Low-resolution analysis of PAR1 suggests that crossovers are distributed fairly randomly4. By contrast, linkage disequilibrium (LD)5 and sperm crossover analyses6 indicate that crossovers in autosomal regions tend to cluster into 'hot spots' of 1–2 kb that lie between islands of disequilibrium of tens to hundreds of kilobases7. To determine whether at high resolution this autosomal pattern also applies to PAR1, we have examined linkage disequilibrium over an interval of 43 kb around the gene SHOX8. Here we show that in northern European populations, disequilibrium decays rapidly with physical distance, which is consistent with this interval of PAR1 being recombinationally active in male meiosis. Analysis of a subregion of 9.9 kb in sperm shows, however, that crossovers are not distributed randomly, but instead cluster into an intense recombination hot spot that is very similar in morphology to autosomal hot spots. Thus, PAR1 crossover activity may be influenced by male-specific hot spots that are highly suitable for characterization by sperm DNA analysis.

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Figure 1: DNA diversity and LD around SHOX.
Figure 2: Detecting SHOX recombinants in bulk sperm DNA.
Figure 3: Meiotic recombination in the SHOX region.
Figure 4: Relationship between LD and recombination in the SHOX region.

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We thank the many UK volunteers and the Saami and Romani communities for contributing semen and blood samples, and J. Blower, A. Kozlov and G. Vershubsky for coordinating sample collection. We also thank J. Brookfield, F. Calafell, Y. Dubrova, M. Jobling, Z. Rosser, N. Royle, T. Slingsby, J. Wetton and colleagues for advice and comments on the manuscript. This work was funded by grants to A.J.J. from the UK Medical Research Council, the Wellcome Trust and the Royal Society.

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Correspondence to Celia A. May.

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May, C., Shone, A., Kalaydjieva, L. et al. Crossover clustering and rapid decay of linkage disequilibrium in the Xp/Yp pseudoautosomal gene SHOX. Nat Genet 31, 272–275 (2002).

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