Abstract
The Friedreich’s ataxia locus (FRDA) maps on chromosome 9q13. Genetic data, obtained from a small number of recombination events, indicated that the FRDA locus might be located centromeric to the D9S15/D9S5 linkage group, the most probable order being cen-FRDA-D9S5-D9S111-D9S15-D9S110-qter. Recently, new centromeric markers have been reported. Analysis of these markers allowed us to localize the recombination breakpoint in some of the recombinant families. However, only one proximal recombination has been found with these markers. To increase the genetic information from FRDA families, we have analyzed the centromeric markers FR1, FR2, FR7, FR8, and FR5 in patients homozygous by descent. These were ascertained because parents were consanguineous or because they were homozygous for the entire haplotype D9S15 or D9S111-D9S5-D9S411E-D9S202. Haplotype divergence for, at least, two contiguous markers was observed in two patients homozygous for the core D9S111-FR2 haplotype and in one third-degree consanguineous family homozygous for haplotype D9S411E-FR5. Interpretation of divergence as the result of ancient meiotic crossovers allowed the definition of three new recombination events which place the FRDA locus within the interval defined by markers D9S411E and FR8. A consanguineous family with first-cousin parents showed homozygosity only at D9S202 and FR2. Further investigations are needed to discern whether two different mutations are segregating in the family or whether two recombinations, one distal and one proximal, have taken place.
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Acknowledgements
We thank Dr. Y. Nakamura and Dr. J.L. Mandel for probes MCT112 and 26P, respectively, and the Friedreich’s ataxia families and the Asociación Española de Ataxias Hereditarias for their enthusiastic cooperation. This study was supported by grants from the Comisión Interministerial de Ciencia y Tecnología, CICYT and from the Generalitat Valenciana (FP), from the Association Française contre les Myopathies and the Groupement de Recherche et d’Etudes sur les Génomes (MK) and from Italian Telethon (MP). EM and JC are recipients of a Generalitat Valenciana Fellowship.
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Monrós, E., Smeyers, P., Rodius, F. et al. Mapping of Friedreich’s Ataxia Locus by Identification of Recombination Events in Patients Homozygous by Descent. Eur J Hum Genet 2, 291–299 (1994). https://doi.org/10.1159/000472373
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DOI: https://doi.org/10.1159/000472373
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