Extended Data Figure 5: Features of the early embryonic mutations identified in this study.

a, As expected for early embryonic mutations, we observe no relationship between the age of individuals and the number of mutations found in an individual. In case of late mutations, we find more mutations in the aged individuals (Fig. 1f). b, Features of mutations in the samples (n = 7) with four early embryonic mutations suggest that these mutations are not likely to be related with a neoplastic clonal expansion: VAFs of mutations are diverse and a fraction of these mutations are shared with the matched cancer. The corresponding VAFs in the matched tumour tissues are shown in numbers above the bars. c, Samples with neoplastic clonal expansions (that is, PD9568b, PD9752b and PD9569b) show different features: mutations show similar VAFs each other and are not shared by cancer cells. d, Enrichment of early mutations according to ENCODE dataset. We find higher mutation frequency in transcriptionally repressed (R) than active (T) regions, but the difference is non-significant in our study (χ² test, degrees of freedom = 1, P value = 0.4696), presumably due to the insufficient number of early embryonic mutations (n = 163). R, repressed chromatin; T, transcribed chromatin; CTCF, CTCF-bound regions; E, enhancer related; TSS/PF, promoter related. e, From a simulation study using 1,000 in silico embryonic mutations, we assessed the detection sensitivity of early embryonic mutations from 32× whole-genome sequencing (see Methods). This sensitivity was used in downstream analyses (for example, likelihood tests for understanding the asymmetry of cell doublings and tests for the calculation of the early embryonic mutation rates. Error bars denote 95% confidence interval using exact Poisson tests.