Analysis of spinocerebellar ataxia type 2 gene and haplotype analysis: (CCG)(1-2) polymorphism and contribution to founder effect

Spinocerebellar ataxia type 2 is a familial spinocerebellar ataxia with aut osomal dominant inheritance. The gene responsible was recently cloned and t his disorder was found to be the result of a CAG expansion in its open read ing frame. We analysed 13 SCA2 patients in seven unrelated families in Gunm a Prefecture, Japan. In four of the seven families, we detected CCG or CCGC CG interruptions in only the expanded alleles. Cosegregation of these polym orphisms with SCA2 patients was established within each family. Together wi th the results of haplotype analyses, we considered that at least two found ers were present in our area and that these (CCG)(1-2) polymorphisms may ma ke analysis of founder effects easier. By sequencing analysis we found that although the number of the long CAG repeat varied in each subclone of expa nded alleles, these polymorphisms did not change their configuration. This finding suggests that CCG or CCGCCG sequences are stable when surrounded by the long CAG repeat and a single GAG. Moreover, the presence of these poly morphisms may lead to miscounting the repeat size by conventional estimatio n using a size marker such as an M13 sequencing ladder. Therefore we should consider these polymorphisms and accurately determine the repeat size by s equencing.