Linkage disequilibrium at the SCA2 locus

Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unsta ble CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 3 3 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families wit h at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which ( D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was i ntragenic. Many different haplotypes were observed, indicating the occurren ce of several ancestral mutations. However, the same haplotype, not observe d in controls, was detected in the German, the Serbian, and some of the Fre nch families, suggesting a founder effect or recurrent mutations on an at r isk haplotype.