MODERATE EXPANSION OF A NORMALLY BIALLELIC TRINUCLEOTIDE REPEAT IN SPINOCEREBELLAR ATAXIA TYPE-2

The gene for spinocerebellar ataxia type 2 (SCA2) has been mapped to 1 2q24.1. A 1.1-megabase contig in the candidate region was assembled in P1 artificial chromosome and bacterial artificial chromosome clones. Using this contig, we identified a CAG trinucleotide repeat with CAA i nterruptions that was expanded in patients with SCA2. In contrast to o ther unstable trinucleotide repeats, this CAG repeat was not highly po lymorphic in normal individuals. In SCA2 patients, the repeat was perf ect and expanded to 36-52 repeats. The most common disease allele cont ained (CAG)(37), one of the shortest expansions seen in a CAG expansio n syndrome. The repeat occurs in the 5'-coding region of SCA2 which is a member of a novel gene family.