A common disease haplotype segregating in spinocerebellar ataxia 2 (SCA2) pedigrees of diverse ethnic origin

The identification of a CAG trinucleotide repeat expansion, located within the coding sequence of the ataxin-2 gene, as the mutation underlying spinoc erebellar ataxia 2 (SCA2) has facilitated direct investigation of pedigrees previously excluded from linkage analysis due to insufficient size or pedi gree structure. We have previously described the identification of the ance stral disease haplotype segregating in the Cuban founder population used to assign the disease locus to chromosome 12q23-24.1. We now report evidence for the segregation of the identical core haplotype in pedigrees of diverse ethnic origin from India, Japan and England, established by the analysis o f the loci D12S1672 and D12S1333 located 20 kb proximal and 200 kb distal t o the triplet repeat motif respectively. Interpretation of this data is sug gestive that for these pedigrees at least, the mutation has arisen on a sin gle ancestral or predisposing chromosome.