(a) Total breakpoints in the A38 genome were not significantly enriched within large LOCKs or ECDs. P values represent the results of χ2 analyses of observed breakpoints in each domain versus those expected if rearrangements were uniformly distributed across the genome. (b) Unlike typical LOCKs, rearrangements (breakpoint fusions) located within large LOCKs and ECDs were significantly enriched for joining of the breakpoints within homologous domains (e.g., ECD to ECD). χ2-test P values were calculated as above. (c) Examples of large LOCK domains where instability hotspots clustered, including both intrachromosomal (amplifications) and interchromosomal (translocations) rearrangements.