Nature Genetics36, 151 - 156 (2004)
Published online: 4 January 2004; | doi:10.1038/ng1287
There is an Erratum (April 2004) associated with this Letter.
Intense and highly localized gene conversion activity in human meiotic crossover hot spots
Alec J Jeffreys
& Celia A May
Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
Correspondence should be addressed to Alec J Jeffreys ajj@le.ac.uk
Meiotic gene conversion has an important role in allele diversification and in the homogenization of gene and other repeat DNA sequence families1,
2,
3,
4,
5, sometimes with pathological consequences6,
7. But little is known about the dynamics of gene conversion in humans and its relationship to meiotic crossover. We therefore developed screening and selection methods to characterize sperm conversions in two meiotic crossover hot spots in the major histocompatibility complex (MHC)8 and one in the sex chromosomal pseudoautosomal pairing region PAR1 (ref. 9). All three hot spots are active in gene conversion and crossover. Conversion tracts are short and define a steep bidirectional gradient centered at the peak of crossover activity, consistent with crossovers and conversions being produced by the same recombination-initiating events. These initiations seem to be spread over a narrow zone, rather than occurring at a single site, and seem preferentially to yield conversions rather than crossovers. Crossover breakpoints are more broadly diffused than conversion breakpoints, suggesting either differences between conversion and crossover processing after initiation or the existence of a quality control checkpoint at which short interactions between homologous chromosomes are preferentially aborted as conversions.
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