Haplotype Analysis of the HFE Gene: Implications for the Origins of Hemochromatosis Related Mutations

Abstract

The Basques live at the Western extremity of the Pyrenees. According to linguistic and genetic data they could be considered as one of the most ancient European populations. Numerous studies have evidenced particular patterns in the frequency of several genetic polymorphisms in this relatively unmixed human group. We discuss herein the puzzling distribution of the two major hemochromatosis HFE mutations associated with hereditary hemochromatosis. Thus, one can observe a low frequency of C282Y and, in contrast, one of the highest European frequencies of H63D. Genetic drift (enhanced by the long history and the small size of this population), long persistence of Paleolithic iron-rich diet, lower exposure to major infectious threats and limited mixing with both Celts and Vikings (who demonstrate the highest prevalence of C282Y) could be the underlying factors explaining these particular genetic features. Historical and environmental data represent key elements for understanding the role of the different evolutionary forces which shape the genetic profile of human populations.