Fig. 3: POLE and POLD1 mutagenesis in other tissues.
From: Increased somatic mutation burdens in normal human cells due to defective DNA polymerases
a, Signature contribution to mutational landscapes of various tissues in individuals with a POLE L424V (PD44594, PD44593, PD44580, PD44589) or POLD1 S478N (PD44584, PD44582) germline mutation. Normal cerebral cortex, skeletal muscle, smooth muscle, artery, blood and sperm were sequenced using a modified duplex sequencing protocol, while other tissues were subjected to low-input WGS after laser-capture microdissection. Groups of mutational signatures are color coded as indicated. b, Estimated genome-wide total mutation rate per year for blood, sperm and endometrium (black dots), as well as yearly mutation burden due to SBS1 and SBS5 (gray dots with 95% CI). Mutation rates of normal controls for blood, sperm and endometrium31 are displayed for reference. c, Early embryonic SBS in individuals with a POLE L424V germline mutation, with a contribution from POLE signatures (blue, SBS10a, SBS10b and SBS28) and normal signatures (red, SBS1 and SBS5). M indicates that the mutation was inherited maternally, P paternally; M* indicates presumed maternal inheritance based on pedigree. P value is the result of a two-sided Wilcoxon rank-sum test on total counts of mutations attributed to SBS10a, SBS10b and SBS28. d, Early embryonic insertions of T at homopolymers of T (indicative of POLD1 mutagenesis) in individuals with POLD1 germline mutations (S478N: PD44581, PD44582, PD44584, PD44585; L474P: PD44588; D316N: PD44590). Again, P and M indicate paternal and maternal inheritance, respectively. P value is the result of a two-sided Wilcoxon rank-sum test on total counts.
