[The molecular mechanisms of the instability of the CAG repeat]

Expansion of CAG trinucleotide repeats coding for polyglutamine stretches has been identified for seven neurodegenerative diseases including Machado-Joseph disease (MJD). There are many common features shared among these disease such as genetic anticipation i.e. accelerated age at onset in successive generations, which is also a result of intergenerational increase in the size of expanded CAG repeats. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat in the MJD1 gene affects intergenerational instability. We suggested that an inter-allelic interaction is involved in the intergenerational instability of the CAG repeat and provide a clue to the molecular mechanisms of the instability of the CAG repeat.