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

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