THE FRIEDREICH ATAXIA GENE IS ASSIGNED TO CHROMOSOME-9Q13-Q21 BY MAPPING OF TIGHTLY LINKED MARKERS AND SHOWS LINKAGE DISEQUILIBRIUM WITH D9S15

  • 1 January 1990
    • journal article
    • research article
    • Vol. 46  (1) , 133-137
Abstract
Chamberlain et al. have assigned the gene for Friedreich ataxia (FA), a recessive neurodegenerative disorder, to chromosome 9, and have proposed a regional localization in the proximal short arm (9p22-cen), on the basis of linkage to D9S15 and interferon-.beta. (IFNB), the latter being localized in 9p22. We confirmed more recently the close linkage to D9S15 in another set of families but found much looser linkage to IFNB. We also reported closely linked marker, D9S5. Additional families have now been studied, and our updated lod scores are z = 14.30 at .theta. = .00 for D9S15-FA linkage and z = 6.30 at .theta. = .00 for D9S5-FA linkage. Together with the recent data of Chamberlain et al., this shows that D9S15 is very likely within 1 cM of the FA locus. We have found very significantly linkage disequilibrium (.DELTA. Std = .28, .chi.2 = 09.71, P < .01) between FA and the D9S15 MspI RFLP in French families, which further supports the very close proximity of these two loci. No recombination between D9S5 aND D9S15 was found in the FA families or Centre of d''Etude du Polymorphisme Humain families (z = 9.30 at .theta. = .00). Thus D9D5, D9S15, and FA define a cluster of tightly linked loci. We have mapped D9S5 by in situ hybridization to 9q13-q21, and, accordingly, we assign the D9D5, D9S15, and FA cluster to the proximal part of chromosome 9 long arm, close to the heterochromatic region.