Fig. 5

Extreme chromoanagenesis manifests by multiple mutational mechanisms in three participants with developmental anomalies. We applied WGS to resolve microscopically visible cxSVs in three unrelated participants with developmental abnormalities. a, b Circos representations of two cases of extreme and largely balanced chromothripsis, involving > 40 breakpoints, > 40 Mb, and > 12 genes across four chromosomes [9, 115]. Points plotted around the inner ring represented estimated copy number alterations; deletions are highlighted in red. Links represent non-reference junctions on derivative chromosomes. c Circos representation of a somatic mosaic chromoanasynthesis event of chromosome 19 [115]. Duplications are shaded in blue and interspersed duplications are designated by shaded ribbons leading from the duplicated sequence to their insertion site. d CMA and WGS analysis of the mosaic chromoanasynthesis from panel c (participant TL009) revealed all nine CNVs involved in the rearrangement to have arisen on the maternal homologue and that 6/8 duplications were apparently mosaic (2.57 ± 0.02 copies, 95% CI; median coverage shown in yellow; yellow shading indicates 95% CI). Surprisingly, 2/8 duplications (outlined in teal) exhibited significantly greater copy numbers than the other six (p = 9.18 × 10^–8), were linked by an underlying interstitial inversion and appeared to represent approximately three copies, suggesting this rearrangement might have originated as a de novo dupINVdup cxSV in the maternal germline (Additional file 2: Figure S7)