File:1-s2.0-S0959437X14000756-gr1.jpg

English: Figure 1. Features of expansion and its threshold. (a) Generic representation of threshold limits for some representative disease alleles from distinct TNR disorders. The inverted purple triangles represent the size ranges associated with the normal, threshold, and disease length TNR alleles. In white is the threshold length for representative TNRs: CGG in the 5′-untranslated (5′UT) region characterizes the FMR-1 gene; GAA in an intron (lines) characterizes Friedreich's ataxia gene; CAG in a coding region (exon) characterizes the Huntington's gene; CTG in the 3′-untranslated (3′UT) region characterizes the myotonic dystrophy 1 (DM1) gene. The threshold limit is also referred to as the premutation length, as all full mutations arise from lengths at the upper range of normal allele and the lower edge of disease allele lengths. Below that range are stable normal repeats, and above the ranges at which expansion exists. The premutation lengths as shown are approximate sizes since there is no precise range THD is threshold. (b) The three most basic steps of expansion. (c) Distinct types of heteroduplex DNA loops are proposed as precursors to expansion: hairpins (1); cruciform (2); quadraplex (3); H-DNA triplet helix (4).