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SELECTION VERSUS DRIFT IN THE RISE OF DELETERIOUS MUTATIONS: THE CASE OF FAMILIAL MEDITERRANEAN FEVER

Project description

Evolutionary insight into familial Mediterranean fever

Familial Mediterranean fever (FMF) is a hereditary disorder associated with recurrent episodes of fever and inflammation in the chest and joints. Mutations in the gene pyrin are frequently encountered in FMF individuals of East Mediterranean origin. Pyrin is an intracellular pattern recognition receptor that triggers inflammation upon recognition of an invading pathogen. It is, however, unknown if the high mutational load of FMF in the Mediterranean region resembles that of malaria and is due to high selective pressure. Funded by the Marie Skłodowska-Curie Actions (MSCA) programme, the FeverTime project explores this question by analysing the ancient DNA of the Armenian population. Results will elucidate the evolution of FMF with obvious ramifications for disease management.

Objective

Familial Mediterranean Fever (FMF) is the most frequent monogenic autoinflammatory disease worldwide. It is caused by mutations in the gene pyrin which are surprisingly frequent (up to 20%) in individuals of East Mediterranean ancestry. The evolutionary forces behind such a high local mutation load are unknown but it has been suggested as an example of balancing selection with a selection pressure from past infections. Hemoglobin disease variants conferring malaria protection are the (rare) textbook examples of such but are atypical with recent and unusually high selective pressure. By taking advantage of the human population history of Armenia, the excellent preservation conditions of archaeological remains in the region, and remarkably high frequency of FMF disease in the Armenian population, the FeverTime project aims to develop the most comprehensive real time account on the role of evolutionary forces in the local mutation burden. FeverTime will leverage ancient DNA time series data from Armenia within a sophisticated population genomic analytical framework to yield key results regarding the evolution and spread of the disease. The findings will have broad implications for genetic epidemiology, reflecting EU policy priorities

Coordinator

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Net EU contribution
€ 199 694,40
Address
COLLEGE GREEN TRINITY COLLEGE
D02 CX56 DUBLIN 2
Ireland

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Region
Ireland Eastern and Midland Dublin
Activity type
Higher or Secondary Education Establishments
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Total cost
No data