Abstract
Haplotype analysis is a powerful approach to understand the spectrum of mutations accounting for a disease in a homogeneous population. We show that haplotype variation for 10 markers linked to the Friedreich ataxia locus (FRDA) argues in favor of an important mutation homogeneity in the Spanish population, and positions the FRDA locus in the region 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 both the Spanish and French populations, suggesting the existence of an ancient and widespread FRDA mutation. Inclusion of FAD1 in the extended haplotype analysis has allowed to postulate that this main FRDA mutation could account for 50–90% of the disease chromosomes. The results indicate that FA, despite clinical heterogeneity, could have originated from a few initial mutations.
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Acknowledgements
We thank Dr. K.K. Kidd and Dr. J.L. Mensua for helpful discussion and comments, Dr. J.L. Mandel for probe 26P, and Dr. J.J. Vilchez and Dr. J. López-Arlandis for clinical assistance. We also acknowledge the Friedreich ataxia families for their enthusiastic cooperation, the Asociación Española de Ataxias Hereditarias and the Association Française de l’ataxie de Friedreich (AFAF). This work was supported by the following institutions: Comisión International de Ciencia y Tecnología and the Generalitat Valenciana (F.P.); Association Française contre les Myopathies and Groupement de Recherche et d’Etudes sur les Génomes (M.K.), and Muscular Dystrophy Association, USA (M.P.). E.M., J.C. and M.D.M. are recipients of a Generalitat Valenciana fellowship; L.M. is recipient of a fellowship from the Italian Telethon.
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Monrós, E., Cañizares, J., Moltó, M.D. et al. Evidence for a Common Origin of Most Friedreich Ataxia Chromosomes in the Spanish Population. Eur J Hum Genet 4, 191–198 (1996). https://doi.org/10.1159/000472198
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DOI: https://doi.org/10.1159/000472198
