Fig. 1.

Image A shows the location of the Huntington’s disease gene in band 4p16.3 of chromosome 4 (Adapted from Figure 1 of Gusella et al., 1994). Image B illustrates the huntingtin protein, showing that it contains a polyglutamine region (polyQ) and a proline-rich domain (PRD) at its N-terminus, and 10 HEAT repeats clustered in three domains in the N-terminal half of the protein (Adapted from Figs. 1 and 2 of Harjes and Wanker, 2003). Numbers indicate amino acids. Image C shows a graph depicting the relationship between CAG repeat and Huntington’s disease age of onset. Note the overall significant negative correlation between HD onset and the expanded repeat length (n = 609, r² = 0.65, p = 0.0001). Nonetheless, the relationship is more complex than this. For example, while there is a strong correlation between CAG repeat and age of onset for adult-onset cases (>20 years) over the 35-55 repeat range, in the case of juvenile (<20 years) onset increasing CAG does not notably advance age of onset highlighted (by dark and pale shading). Moreover, this is also true for the few HD cases found with repeats >200 CAG (not shown in graph). The textured box highlights anomalous adult onset cases with expansion beyond the 60 CAG typically associated with juvenile onset (Adapted from Fig. 4 of Squitieri et al., 2006). (For color version of this figure, the reader is referred to the web version of this book.)