ABSTRACT
Based on the amino acid sequence of the huntingtin protein, it is predicted to contain a number of HEAT repeats. Each HEAT repeat is about 40 amino acids and is composed of two a-helices joined by a short loop. During evolution of the huntingtin protein in vertebrates, the size of the polyQ region was increased in mammals, suggesting that thereby the properties of huntingtin were changed. This may seem a hazardous means of modifying its activity, as a too extensive repeat expansion causes Huntington's disease (HD). The size of the polyQ repeat determines both solubility and interactions with other proteins. The chapter shows that HD is a dominantly inherited neuropsychiatric disorder that progresses slowly. Many of the triplet repeats resulting in disorders are not in the coding region of a protein. The chapter focuses on coding sequence changes a glutamine codon repeats that result in different forms of spinocerebellar ataxias.
