title: Evidence for a common origin of most Friedreich ataxia chromosomes in the Spanish population.
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.
authors.affiliation: Unitat de Genètica, Hospital Universitari La Fe, València, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Monrós
authors.forename: J
authors.initials: J
authors.lastname: Cañizares
authors.forename: M D
authors.initials: MD
authors.lastname: Moltó
authors.forename: F
authors.initials: F
authors.lastname: Rodius
authors.forename: L
authors.initials: L
authors.lastname: Montermini
authors.forename: M
authors.initials: M
authors.lastname: Cossée
authors.forename: F
authors.initials: F
authors.lastname: Martínez
authors.forename: F
authors.initials: F
authors.lastname: Prieto
authors.forename: R
authors.initials: R
authors.lastname: de Frutos
authors.forename: M
authors.initials: M
authors.lastname: Koenig
authors.forename: M
authors.initials: M
authors.lastname: Pandolfo
authors.forename: J
authors.initials: J
authors.lastname: Bertranpetit
authors.forename: F
authors.initials: F
authors.lastname: Palau
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002874:Chromosome Mapping; D005602:France; D005621:Friedreich Ataxia / Q000209:etiology* / Q000235:genetics*; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010802:Phylogeny; D011110:Polymorphism, Genetic; D013030:Spain; D018911:Trinucleotide Repeats
chemical_list: C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; D009419:Nerve Tissue Proteins