(>10) were excluded. After this initial screen with relaxed criteria to capture as many potential de novos as possible, we measured probe Log2 ratios derived from PennCNV.27 We then used a slight modification of the MeZOD algorithm12 (Supplementary Section 3) to visualise outlier signals in probands potentially indicative of de novos (Figure 1). Again, we used relaxed criteria, only excluding clear false positives (Supplementary Section 3). For those whose patterns were either highly suggestive of a de novo (N=40, Figure 1a) or were ambiguous (N=33, Figure 1b), proband and parent DNAs were examined on custom Agilent SurePrint G3 Human CGH Microarrays on which 50–200 probes were placed to cover each CNV (depending on CNV size). For quality control purposes, we also included probes on all putative de novos identified by the first-pass Genotyping Console analysis, but that were subsequently rejected as false positives by the MeZOD method.
