title: Human minisatellites, repeat DNA instability and meiotic recombination.
abstract: Minisatellites include some of the most variable loci in the human genome and are superb for dissecting processes of tandem repeat DNA instability. Single DNA molecule analysis has revealed different mutation processes operating in the soma and germline. Low-level somatic instability results in simple intra-allelic rearrangements. In contrast, high frequency germline instability involves complex gene conversions and is therefore recombinational in nature, almost certainly occurring at meiosis. To determine whether true meiotic crossovers occur at human minisatellites, we have used polymorphisms near the repeat array to recover recombinant DNA molecules directly from sperm DNA. Analysis of minisatellite MS32 has revealed an intense and highly localised meiotic crossover hotspot centred upstream of the array, the first example of a human hotspot defined at the molecular level. This hotspot extends into the beginning of the repeat array, resulting in unequal and equal crossovers. Array crossovers occur much less frequently than array conversions but appear to arise by a common process, most likely by alternative processing of a recombination initiation complex. The location of MS32 at the boundary of a recombination hotspot suggests that this locus has evolved as a by-product of localised meiotic recombination activity, and that minisatellites might in general mark recombinationally proficient hotspots or hot domains in the genome. Finally, sperm crossover analysis makes it possible to explore the molecular rules that govern human meiotic recombination, and to detect phenomena such as meiotic drive that could provide a possible connection between recombination and DNA sequence diversity itself.
authors.affiliation: Department of Genetics, University of Leicester, UK. ajj@le.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Jeffreys
authors.forename: R
authors.initials: R
authors.lastname: Barber
authors.forename: P
authors.initials: P
authors.lastname: Bois
authors.forename: J
authors.initials: J
authors.lastname: Buard
authors.forename: Y E
authors.initials: YE
authors.lastname: Dubrova
authors.forename: G
authors.initials: G
authors.lastname: Grant
authors.forename: C R
authors.initials: CR
authors.lastname: Hollies
authors.forename: C A
authors.initials: CA
authors.lastname: May
authors.forename: R
authors.initials: R
authors.lastname: Neumann
authors.forename: M
authors.initials: M
authors.lastname: Panayi
authors.forename: A E
authors.initials: AE
authors.lastname: Ritchie
authors.forename: A C
authors.initials: AC
authors.lastname: Shone
authors.forename: E
authors.initials: E
authors.lastname: Signer
authors.forename: J D
authors.initials: JD
authors.lastname: Stead
authors.forename: K
authors.initials: K
authors.lastname: Tamaki
mesh_terms: D004247:DNA / Q000235:genetics*; D006801:Humans; D008540:Meiosis / Q000235:genetics*; D018598:Minisatellite Repeats; D011995:Recombination, Genetic
chemical_list: D004247:DNA