LOCALIZATION OF FRIEDREICH ATAXIA PHENOTYPE WITH SELECTIVE VITAMIN-E-DEFICIENCY TO CHROMOSOME-8Q BY HOMOZYGOSITY MAPPING

Friedreich ataxia and ataxia with selective vitamin E deficiency (AVED ) share very similar clinical phenotypes. We have mapped the AVED locu s to proximal 8q with only three large consanguinous Tunisian families , representing to our knowledge the first use of homozygosity mapping for primary linkage analysis. Subsequently, three additional families showed linkage with the same markers. A maximum lod score of 17.9 was obtained at theta = 0 for the haplotype D8S260-D8S510, consisting of t he two closest markers. With only 6 families, the AVED locus is theref ore mapped precisely as illustrated by the lod-1 confidence interval o f 2.4 cM on either side of D8S260-D8S510. Isolation of a yeast artific ial chromosome contig >800 kilobases (kb) showed that D8S260 and D8S51 0 are less than 400 kb apart.