Extended Data Fig. 2: Mutational burden and large-scale rearrangements identified in the liver from A1AT-deficiency and haemochromatosis.

(a) Upper panel: burden of single-nucleotide variants (SNVs) per exome, corrected by sensitivity of mutation detection. Each box plot represents a patient (n = 10 patients; 305 microdissections) and each dot represents one laser-capture microdissected sample. The grey-to-black intensity of the points reflects the median variant allele fraction (VAF) of mutations in each microdissection. Boxes in the box plots indicate median and interquartile range; whiskers denote range. Lower panel: burden of indel variants per exome (n = 10 patients; 305 microdissections). (b) Relative proportional contributions of the six most abundant SBS signatures across A1AT-deficiency (purple-headed columns) and haemochromatosis (green-headed columns) donors. Each bar represents a laser capture microdissection, in ascending order of the number of coding mutations. (c) Chromothripsis involving chromosomes 5 and 10 (upper panel) and chromosomes 7 and 10 (lower panel), observed in patient with haemochromatosis (PD51607). Black points represent corrected read depth along the chromosome. Lines and arcs represent structural variants, coloured by the orientation of the joined ends (purple, tail-to-tail inverted; brown, head-to-head inverted; turquoise, tandem-duplication-type orientation; green, deletion-type orientation).