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|Title:||Analysis of DNA diversity and meiotic recombination in the human MHC class II region|
|Presented at:||University of Leicester|
|Abstract:||There is mounting evidence that recombination events are not randomly distributed in the human genome, but tend cluster into distinct regions, so-called recombination hotspots. My PhD work was focussed on developing an understanding of how meiotic recombination events are distributed in the human Major Histocompatibility (MHC) Class II region. To this end, a large number of SNPs in this region was identified and genotyped, and high-resolution linkage disequilibrium (LD) patterns were examined for evidence of historical recombination. Three regions of LD breakdown, i.e. putative recombination hotspots were localised. For these regions, allele-specific PCR methods were used to selectively amplify recombinant molecules directly from sperm DNA.;This lead to the identification of three novel crossover hotspots, within which I was able to demonstrate an extremely localised nature of crossover breakpoints. Furthermore, molecular characterisation of the three hotspots showed that crossover rates can vary dramatically from one hotspot to the next and that LD patterns cannot be used to readily predict these rates.;I also investigated the relative importance of known recombination hotspots vs. population history in shaping LD in three human populations (UK North Europeans, Saami and Zimbabweans). At least in this segment of the MHC, haplotype structures directly relate to fine-scale patterns of meiotic recombination, even though a distinct paucity of "universal" haplotypes (haplotypes shared by all three populations) was observed.|
|Rights:||Copyright © the author. All rights reserved.|
|Appears in Collections:||Theses, Dept. of Genetics|
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