Linkage disequilibrium and haplotype analysis in German Friedreich ataxia families

The main mutation causing Friedreich ataxia (FRDA) is the expansion of a GA A repeat localized within the intron between exon 1 and exon 2 of the gene X25, This expansion has been observed in 98% of FRDA chromosomes. To analyz e frequencies of markers tightly linked to the Friedreich ataxia gene and t o investigate wheter a limited number of ancestral chromosomes are shared b y German FRDA families, a detailed analysis employing nine polymorphic mark ers was performed. We found strong linkage disequilibria and association of FRDA expansions with a few haplotypes, FRDA haplotypes differ significantl y from control haplotypes, Our results confirm that GAA repeat expansions i n intron 1 of the frataxin gene are limited to a few chromosomes and indica te an obvious founder effect in German patients, Based on these analyses, w e estimate a minimum age of the mutation of 107 generations.