Evidence for a common origin of most Friedreich ataxia chromosomes in the Spanish population.

Autores de IIS La Fe

• Susana Monros Sanchez

  Autor

• M. Dolores Molto Ruiz

  Autor

• 

  Francisco Martínez Castellano

  Autor

• Felix Prieto Garcia

  Autor

• Noelia Cubero De Frutos

  Autor

• Francesc Palau Martinez

  Autor

Participantes ajenos a IIS La Fe

• Cañizares J
• Rodius F
• Montermini L
• Cossée M
• Koenig M
• Pandolfo M
• Bertranpetit J

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 mutations. 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.