Of all CNVs detected in this case cohort, most (~76%) were individually rare and not mediated by segmental duplications. This large group of CNVs provides a resource to examine regions of the genome that contain multiple CNVs with overlapping segments of deleted or duplicated material to define genotype-phenotype correlations. As an example, we highlight three recently described regions (2p15 deletion,50 16q24.3 deletion51 and 17p13 duplication52) where overlapping de novo CNVs were characterized to define the associated phenotype and identify candidate genes. In the ISCA case cohort, we found four de novo deletions in 2p15 with a smallest region of overlap (SRO) of ~2.4 Mb, five de novo deletions in 16q24 with a SRO of ~450 kb, and four de novo duplications in 17p13 with a SRO of ~312 kb. As the ISCA database grows, cases such as these will prove invaluable for identifying disease-causing genes.
