Instability of the Octarepeat Region of the Human Prion Protein Gene
Figure 8
A hairpin structure-based model for mutation of octarepeats.
(A) Diagram of hairpin structures of Oct5 and Oct11b as predicted by mfold. The likely secondary structures of Oct5 and Oct11b octarepeat sequences were examined with the online mfold program (http://mfold.rna.albany.edu/?q=mfold/DNA-Folding-Form). Only the most stable structure for each sequence as predicted by mfold at the PCR annealing condition (50 mM Na+, 1.5 mM Mg2+, 58.5°C) is depicted, but the E.coli condition (170 mM Na+, 37°C) yielded similar results. The three colored hairpins represent the common ones shared by Oct5 and Oct11b sequences; the insertion of 6 extra repeats in Oct11b led to 6 additional hairpins (in black) that are identical to the first hairpin (in orange). (B) Hairpin-based slippage model for contraction or expansion of the octarepeats. The parental DNA strands are in thick lines and the newly synthesized DNA strands (leading strand or lagging stand) are in thin lines. The red lines denote the octarepeat region on parental DNA strands while green lines denote the octarepeat region on the newly synthesized DNA strands; hairpin formation on the parental DNA strand leads to contraction whereas hairpin formation on the lagging strand being synthesized results in expansion. Adopted from Figure 3 in [29].