EVIDENCE FOR A COMMON ORIGIN OF MOST FRIEDREICH ATAXIA CHROMOSOMES INTHE SPANISH POPULATION

Haplotype analysis is a powerful approach to understand the spectrum o f mutations accounting for a disease in a homogeneous population, We s how that haplotype variation for 10 markers linked to the Friedreich a taxia locus (FRDA) argues in favor of an important mutation homogeneit y in the Spanish population, and positions the FRDA locus in the regio n where it has been recently isolated. We also report the finding of a new single nucleotide polymorphism called FAD1. The new marker shows a very strong linkage disequilibrium with Friedreich ataxia (FA) in bo th the Spanish and French populations, suggesting the existence of an ancient and widespread FRDA mutation, Inclusion of FAD1 in the extende d haplotype analysis has allowed to postulate that this main FRDA muta tion could account for 50-90% of the disease chromosomes, The results indicate that FA, despite clinical heterogeneity, could have originate d from a few initial mutations.