Extended Data Fig. 2: Supplemental data on whole genome sequencing and multiplicity states.

a & c. integrated CN & structural variant plots for patients 4 & 5. As in Fig. 2, the top panel shows intra-chromosomal events as arcs between breakpoint loci, and color denotes the type of SV (black=translocation, red=deletion, blue=duplication, green=inversion). Rearrangements are further separated and annotated based on orientation. D: Deletion, TD: Tandem duplication; HH, head-to-head inverted, TT: tail-to-tail inverted. Inter-chromosomal events are shown with arrows denoting the likely partner chromosome. The middle panel shows the consensus copy number across the chr21 ideogram, depicted in the lowest section of each plot to indicate breakpoint location. Patient 4 has a simple breakage-fusion-bridge event, whereas patient 5 shows a low-level copy number gain and inversion event. b & d. Circos plots for patients 4 & 5 showing global SV burden, demonstrating clustering around chr21. The outer ring shows the chromosome ideogram. The middle ring shows the B allelic frequency and the inner ring shows the intra-and inter-chromosomal SVs with the same color scheme as in a & c. e. Multiplicity states across the gained copy number segment spanning DYRK1A for each case. The x-axis indicates the potential multiplicity states that would be expected to be observed for the segment spanning DYRK1A in each sample given its copy number state. Shaded bars indicate the number of mutations observed in each multiplicity state. f. Multiplicity states observed in segments spanning DYRK1A compared to the entire genome. Red shaded regions indicate the number of mutations in each multiplicity state identified in regions spanning DYRK1A for each sample. Grey shaded regions indicate the number of mutations at each multiplicity state across the entire genome, including the segment spanning DYRK1A. The red and grey bars overlap, rather than being additive. There were insufficient mutations in the region of amplification to assess multiplicity in Patient 5.