Isolation of a new gene in the Friedreich ataxia candidate region on human chromosome 9 by cDNA direct selection.

The Friedreich ataxia (FRDA) locus is localized on chromosome 9q13 in an interval less than 1 Mb between markers D9S202/FR1 and FR5. We cloned the FRDA candidate region in YACs, and we started a systematic search for transcripts in this region using the cDNA selection approach. Several overlapping cDNA clones mapping near the telomeric end of the FRDA minimum genetic region were isolated. Zoo blot analysis demonstrated that these cDNAs are well conserved among different species. A transcript of 4.8 kb was identified by hybridization to a Northern blot containing human brain poly(A)+ RNA. Partial sequence of these clones showed 100% homology with a previously described anonymous brain cDNA (EST01251). A search for mutations of this gene in FRDA patients and carriers is in progress. No mutations have been found to date, but we have identified a DNA polymorphism. This polymorphism was nonrecombinant with the disease in a previously described FRDA pedigree in which a recombination had occurred with more telomeric markers.