Figure 3.

Somatic mutation calls in PRNP’s OPR. (a) Somatic mutation calls per sample, as percentage of the number of reads. (b) Number of somatic mutation calls as a function of the change it generated in the OPR. For example, a 3 OPRI somatic mutation call on the mutated OPR haplotype of a 4 OPRI sample was counted as a − 1 change. Of the N = 94 somatic mutation calls from haplotype-phased samples, 55 (59%) removed one repeat from the OPR (− 1 changes). (c) Somatic mutation calls, as percentage of reads of each sample, as a function of the OPR length of each sample. The length is given compared to the reference OPR: 0 corresponds to the reference OPR, negatives correspond to OPR deletions (e.g. − 2 is 2 OPRD), and positives correspond to OPR insertions (e.g. 8 is 8 OPRI). The black dashed line is the line of best fit by linear regression: % somatic mutation calls = 0.036 + 0.017 × OPR length. OPR length is a significant predictor of the percentage of somatic mutation calls, R² = 0.53, ***p < 0.001 by linear regression. (d) Somatic mutation calls, as percentage of reads of each sample, for four inherited CJD cases which had genomic DNA from both blood and brain sequenced. For each individual, there was a decrease in somatic mutation calls in brain compared to blood. p = 0.068 by one-sample one-sided t test (null hypothesis was no significant decrease between blood and brain). (e) Changes in the OPR introduced by PCR amplification of a reference OPR, as in (a).