Recombinations in individuals homozygous by descent localize the Friedreich ataxia locus in a cloned 450-kb interval
- Laboratoire de Genetique Moleculaire du CNRS, Strasbourg (France)
- Centre d'Etude du Polymorphisme Humain, Paris (France); and others
The locus for Friedreich ataxia (FRDA), a severe neurodegenerative disease, is tightly linked to markers D9S5 and D9S15, and analysis of rare recombination events has suggested the order cen-FRDA-D9S5-D9S15-qter. The authors report here the construction of a YAC contig extending 800 kb centromeric to D9S5t and the isolation of five new microsatellite markers from this region. In order to map these markers with respect to the FRDA locus, all within a 1-cM confidence interval, they sought to increase the genetic information of available FRDA families by considering homozygosity by descent and association with founder haplotypes in isolated populations. This approach allowed identification of one phase-known recombination and one probable historic recombination on haplotypes from Reunion Island patients, both of which place three of the five markers proximal to FRDA. This represents the first identification of close FRDA flanking markers on the centromeric side. The two other markers allowed narrowing of the breakpoint of a previously identified distal recombination that is >180 kb from D9S5 (26P). Taken together, the results place the FRDA locus in a 450-kb interval, which is small enough for direct search of candidate genes. A detailed rare cutter restriction map and a cosmid contig covering this interval were constructed and should facilitate the search of genes in this region. 26 refs., 3 figs., 2 tabs.
- OSTI ID:
- 6974849
- Journal Information:
- American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 54:6; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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