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Chunk #40 — METHODS — Novel, exon-altering CNV discovery

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A copy number variation morbidity map of developmental delay.
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common copy number polymorphisms or deletions seen in multiple control individuals16,42,43,59. This yielded 829 candidates for follow-up, each of which were manually reviewed to eliminate cassettes in which all candidate deletions clustered within a single array type suggestive of a batch artifact and noisy cassettes resulting from probes embedded within SDs (for examples, see Supplementary Figure 6). Subsequently, 19 cassettes were chosen for validation, manually divided into two qualitative tiers based on the totality of the evidence (follow-up potential of the affected gene, visual analysis of probe intensity distributions, etc.). We designed a custom NimbleGen oligonucleotide array, spanning each of the 19 genes and their flanks at very high density (Supplementary Note), and performed CGH on 98 samples, chosen by cassette score and availability and predicted to carry a deletion at one of the 19 genes.