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A major recombination hotspot in the XqYq pseudoautosomal region gives new insight into processing of human gene conversion events

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posted on 24.10.2012, 08:55 by Shriparna Sarbajna, Matthew Denniff, Alec J. Jeffreys, Rita Neumann, María Soler Artigas, Amelia Veselis, Celia A. May
Recombination plays a fundamental role in meiosis. Non-exchange gene conversion (non-crossover, NCO) may facilitate homologue pairing, while reciprocal crossover (CO) physically connects homologues so they orientate appropriately on the meiotic spindle. In males, X–Y homologous pairing and exchange occurs within the two pseudoautosomal regions (PARs) together comprising <5% of the human sex chromosomes. Successful meiosis depends on an obligatory CO within PAR1, while the nature and role of exchange within PAR2 is unclear. Here, we describe the identification and characterization of a typical ∼1 kb wide recombination hotspot within PAR2. We find that both COs and NCOs are strongly modulated in trans by the presumed chromatin remodelling protein PRDM9, and in cis by a single nucleotide polymorphism (SNP) located at the hotspot centre that appears to influence recombination initiation and which causes biased gene conversion in SNP heterozygotes. This, the largest survey to date of human NCOs reveals for the first time substantial inter-individual variation in the NCO:CO ratio. Although the extent of biased transmission at the central marker in COs is similar across men, it is highly variable among NCO recombinants. This suggests that cis-effects are mediated not only through recombination initiation frequencies varying between haplotypes but also through subsequent processing, with the potential to significantly intensify meiotic drive of hotspot-suppressing alleles. The NCO:CO ratio and extent of transmission distortion among NCOs appear to be inter-related, suggesting the existence of two NCO pathways in humans.



Human Molecular Genetics, 2012, 21 (9), pp. 2029-2038


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Human Molecular Genetics


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This is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The definitive publisher-authenticated version [Human Molecular Genetics, 2012, 21 (9), pp. 2029-2038] is available online at: