2381/12078
Shriparna Sarbajna
Shriparna
Sarbajna
Matthew Denniff
Matthew
Denniff
Alec J. Jeffreys
Alec J.
Jeffreys
Rita Neumann
Rita
Neumann
María Soler Artigas
María Soler
Artigas
Amelia Veselis
Amelia
Veselis
Celia A. May
Celia A.
May
A major recombination hotspot in the XqYq pseudoautosomal region gives new insight into processing of human gene conversion events
University of Leicester
2012
Base Sequence
Chromosome Pairing
Chromosomes
Human
Crossing Over
Genetic
DNA
Gene Conversion
Heterozygote
Histone-Lysine N-Methyltransferase
Intracellular Signaling Peptides and Proteins
Male
Meiosis
Polymorphism
Single Nucleotide
Recombination
2012-10-24 08:55:02
Journal contribution
https://figshare.le.ac.uk/articles/journal_contribution/A_major_recombination_hotspot_in_the_XqYq_pseudoautosomal_region_gives_new_insight_into_processing_of_human_gene_conversion_events/10108724
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.