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 clon ed the FRDA candidate region in YACs, and we started a systematic sear ch for transcripts in this region using the cDNA selection approach. S everal overlapping cDNA clones mapping near the telomeric end of the F RDA minimum genetic region were isolated. Zoo blot analysis demonstrat ed that these cDNAs are well conserved among different species. A tran script of 4.8 kb was identified by hybridization to a Northern blot co ntaining 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 c arriers is in progress. No mutations have been found to date, but we h ave identified a DNA polymorphysm. This polymorphism was nonrecombinan t with the disease in a previously described FRDA pedigree in which a recombination had occurred with more telomeric markers. (C) 1994 Acade mic Press, Inc.