Huntington's disease (HD) is a mid-life onset, inherited, neurodegenerativedisorder characterised by motor impairment, involuntary movements (chorea),psychiatric disorders and dementia [<cite idref="PUB00003898"/>]. The disease results from theexpansion of a polyglutamine-encoding CAG repeat in a gene of unknownfunction. Moderate expansion of glutamine-coding CAG repeats has beenfound in other neurological diseases (e.g. spinobulbar muscular atrophyand Machado-Joseph disease), in all of which the pathological mechanismlinked to the expansion of the polyglutamine tract in the protein remainsa mystery.<p>The HD transcript is highly conserved, significant differences, as alreadynoted, occurring in the N-terminal Gln-repeat region. Huntingtin normallycontains 10-35 repeats, but shows 36-120 repeats in the disease form.Migration differences between normal and mutated huntingtin in a denaturingpolyacrylamide gel suggest that the poly-Gln stretch disrupts the proteinconformation. This finding is consistent with the observation thatGln repeats may form tightly-linked beta-sheets that could act as polarzippers [<cite idref="PUB00004844"/>].</p>