Characterisation of minisatellite-associated meiotic recombination hotspots in the human genome

Hypervariable minisatellites form a subset of tandem repeat arrays which show very high rates of germline instability. Previous detection of recombinants near human minisatellite MS32 identified a crossover hotspot that appears to be responsible for driving repeat instability. In this thesis, analysis of the flanking DNA was extended both 5' and 3' to the locus to reveal significant levels of linkage disequilibrium suggesting low frequency of recombination in these regions. In order to determine whether the recombination hotspot is a common feature of minisatellites, analysis of recombinational proficiency was extended to a second hypervariable minisatellite locus, MS31A. Data obtained suggest the presence of a putative MS31A-associated hotspot, localised to an approximate 300bp interval, and embedded in a recombinationally inert region of DNA. This correlates well with the observations at MS32, indicating that both minisatellites mutate by the same mechanism. Regions containing hotspots had more polymorphisms that recombinationally inactive regions, demonstrating a correlation between nucleotide diversity and recombinational activity. However, at MS31A, comparison of human, chimpanzee and gorilla sequences showed no evidence for sequence hyperdivergence, suggesting that the hotspot is unlikely to be a site of accelerated evolution.