Quinn, Liam James;
(2020)
Genetic Study of Kuru.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Kuru was the first documented epidemic of prion disease in humans. It took place in a restricted region of the Papua New Guinea Highlands during the twentieth century, with the final cases occurring in the first decade of the twenty-first century. Over 2,700 deaths were recorded in the period 1957-2004 when surveillance was carried out in the region. The epidemic impacted greatly upon affected communities as a result of its high incidence, and its association with practices of sorcery in the region. This project sought to further understand the genetic impact of kuru using a genotyped data from 943 individuals from 21 ethno-linguistic groups in the Eastern Highlands region of Papua New Guinea (EHPNG). Analysis was conducted to classify the population structure in the region using a suite of population genetic tools. Linguistic group membership was the strongest descriptor of population genetic structure in the region, informing experimental design in subsequent analyses. A drop in genetic diversity was observed in the most affected South Fore linguistic group during the course of the epidemic, confirming that the drastic impact on the ground left a genetic signature. A new tool (Chromomatcher) was developed and incorporated in attempts to find genetic variants under positive selection during the kuru epidemic. Several genetic variants show evidence of being under recent positive-selection. Finally, polygenic architecture of prion diseases was investigated revealing a significant polygenic architecture for sporadic Creutzfeldt–Jakob disease (sCJD) with a substantial portion shared with variant Creutzfeldt–Jakob disease. No shared architecture was observed between sCJD and kuru, reflecting the challenges of applying this technology to under-studied populations.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Genetic Study of Kuru |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10096608 |
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