Mitotic and meiotic instability of the CAG trinucleotide repeat in spinocerebellar ataxia type 1

Spinocerebellar ataxia type 1 (SCAI) is an autosomal, dominantly inherited neurodegenerative disease caused by an unstable CAG trinucleotide repeat ex pansion in the ataxin-1 gene located on chromosome 6p22-p23. The expanded C AG repeat is unstable during transmission, and a variation in the GAG; repe at length has been found in different tissues, including sperm samples from affected males. In order further to examine the mitotic and meiotic instab ility of the (CAG), sri-etch we have performed single sperm and low-copy ge nome analysis in SCAI patients and asymptomatic carriers. A pronounced vari ation in the size of the expanded allele was found in sperm cells and perip heral blood leucocytes, with a higher degree of instability seen in the spe rm cells, where an allele with 50 repeat units was contracted in 11.8%, fur ther expanded in 63.5% and unchanged in 24.6% of the single sperm analysed. We found a low instability of the normal alleles; the normal alleles from the individuals carrying a CAG repeat expansion were significantly more uns table than the normal alleles from the control individuals (P<0.001), indic ating an interallelic interaction between the expanded and the normal allel es.