PHYSICAL EVIDENCE FOR THE POSITION OF THE FRIEDREICHS ATAXIA LOCUS FRDA PROXIMAL TO D9S5

Orientation of the Friedreich's ataxia locus (FRDA) with respect to D9 S15 and D9S5 has proved critical to the design of subsequent cloning s trategies. The rarity of recombination events between FRDA and these m arkers, originally used to determine assignment to human chromosome re gion 9q13-->q21.1, has necessitated the instigation of physical mappin g studies to determine order and, hence, the precise location of the d isease gene. Simultaneous fluorescence in situ hybridisation using cos mid clones located in close proximity to the ends of a 1.2-Mb yeast ar tificial chromosome clone extending into the FRDA candidate region pro vides physical evidence for the order of the marker loci to be cen-D9S 202-D9S5-D9S15-qter. The possibility that a pericentric inversion, occ urring naturally in similar to 1% of the normal population, may affect the order of markers within this region has been eliminated. Consider ed in association with the interpretation of a recombination event det ected in a single affected individual, these data indicate that the FR DA locus is located proximal to D9S5.