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Title: The landscape of recombination in African Americans : leveraging human population variation to investigate homologous recombination
Author: Hinch, Anjali Gupta
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2012
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Abstract:
Homologous recombination is a highly regulated and complex biological process required for sexual reproduction in humans and many other species. The mechanisms of initiation and control of this process, however, are only partially understood. The aim of this work is to tease apart and utilize the differences in recombination localization between human populations to understand the underlying biological processes. Prior to this work, recombination had been extensively studied in European populations, revealing that recombination events cluster in thousands of narrow segments of the genome, known as hotspots. However, much less was known about other human populations. I have developed an approach that leverages the recent mixture of peoples of West African and European ancestry in the Americas to build a map specifying the location of recombination events in a large number of African Americans. I showed that this map is significantly different from the European map at the scale of hotspots, demonstrating evolution of recombination patterns within the human lineage. I find that the African-American map is more diverse than the European map, with thousands of hotspots active in African Americans but not in Europeans. I performed genome-wide association analysis, which shows that a single gene, PRDM9, largely controls the switch between different hotspot landscapes. Prior research had implicated PRDM9, a zinc-finger histone methyltransferase, as an important factor in determining the location of recombination events. This work shows that the switch is functionally due to variation in the zinc finger array, and that PRDM9 is likely to be the dominant factor determining the genome-wide distribution of hotspots. Further, there is no evidence that hotspots are shared between individuals with PRDM9 variants containing significantly different zinc finger arrays. I find that, despite profound differences between hotspot locations, stochasticity in individual meioses, and large differences between the sexes, rates at mega-base scales are highly conserved between populations. Finally, I investigate recombination in the pseudoautosomal region
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.606260  DOI: Not available
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