247. Use of modern population genetic techniques to investigate the effects of the epidemic of kuru, a unique prion disease in the Papua New Guinea highlands
Liam Quinna, Jerome Whitfielda, Garrett Hellenthalb, Michael Alpersc,d, John Collingea, and Simon Meada
aMRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, UK; bDepartment Genetics, Evolution & Environment, University College London; cCentre for International Health, Curtin University, Perth, Australia; dPapua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
CONTACT Liam Quinn l.quinn@prion.ucl.ac.uk; Jerome Whitfield j.whitfield@prion.ucl.ac.uk
ABSTRACT
Background: Kuru was the first observed and to this day remains the largest human prion disease epidemic. It devastatingly affected the Fore linguistic and nearby groups in the Papua New Guinea (PNG) highlands. The condition was transmitted by consumption of prion infected material at mortuary rituals. Over the first 20 documented years of the epidemic ~2,400 people died from kuru in communities with populations of ~40,000 individuals. The Eastern Highlands of Papua New Guinea where the Fore speaking communities reside is marked for its cultural and linguistic diversity. During the kuru epidemic the region was undergoing a marked transition with European contact and colonial administration. These factors present challenges to further understanding the population response to kuru specifically and approaches to find novel variants that affected disease predisposition.
Materials and Methods: We analysed a unique genome wide array dataset of 1,513 individuals from the affected communities from 22 linguistic groups and 50 across the Eastern Highlands of PNG. We used population genetic techniques including Chromopainter analysis and fineStructure clustering to understand the population structure of the region, analyse patterns of gene flow and migration, tested for evidence of historical admixture events and evidence of genetic signatures of the impact of kuru on the Fore region including the marked sex bias in cases observed during the epidemic.
Results: We find a strong population structure with Principal Component Analysis and fineStructure clustering showing a strong tendency for individuals to cluster with individuals from the same linguistic grouping. Mean FST values observed in the Eastern Highlands were 0.02, far greater than those observed in the United Kingdom (0.0007) reflecting the degree of distinction between groups. Although we find that linguistic group membership explains many aspects of population structure we also find that topographical features and cultural differences also exert strong forces. Gene flow between linguistic groups is evident with the presence of individuals reflecting historical processes of short and long distance migration.
Conclusion: We show that the affected populations have displayed remarkable resilience with no perceptible derivation in population genetic parameters overall despite facing such an existential threat. The marked population structure in the region and processes of gene flow present challenges for ongoing investigations into the genetic response and genetic architecture of kuru disease.
KEYWORDS: Kuru; population genetics; natural selection; genetic epidemiology
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