Fig. 4: Mutation burden, mutational processes and biallelic TP53 variants.

a Mutation burden (number of SNVs) as a function of age for ten individuals with SDS. Each circle represents one colony genome, with the black horizontal bars representing the median burden per individual. Two timepoints from SDS5 are shown at different ages. Circles coloured black (normal) representing mutation burdens from three haematopoietically healthy (non-SDS) individuals (published data³) are shown for comparison. The blue line represents the regression line through the colonies from individuals with SDS. b Trinucleotide context of somatic mutations. The two mutational signatures were identified across all genomes. SBS1^{42, 43} is characterised by spontaneous deamination of cytosines, and the second mutational signature, termed SBSBlood^{1, 2, 41} represents mutations typical of endogenous mutations in HSCs. c Number of SNVs attributable to the mutational signatures SBS1 (green) and SBSblood (blue) across each colony from each individual with SDS. Each bar represents the genome from one colony. Note SDS8 has a higher total mutation burden due to increased SBS1 mutations. d Copy number variation for two representative colony genomes with heterozygous/mono-allelic TP53 mutation (from different individuals) and two clonally related colonies from SDS8 with biallelic TP53 mutations. Ploidy is shown on the y-axis and genomic ___location on the x-axis, for the two parental alleles (green and red). CNA copy number aberration. Source data are provided as a Source Data file.