Finally, the discovery of atypical and smaller deletions among patients with virtually identical phenotypes helps to refine the smallest region of overlap for known syndromes. The atypical deletions of 17q21.31 exclude deletions of CRHR1 as playing a role in this syndrome (although deletions of long-range regulatory elements that change CRHR1 expression cannot be ruled out) and narrow the likely candidates to three genes, including MAPT, which is disrupted by proximal breakpoints in two cases (Figure 3B). Overall, we identified 615 deleted genes and 325 duplicated genes significantly enriched in cases when compared to controls. The dosage imbalance of these genes should not be considered as proven but rather as candidates with higher prior probability of dosage sensitivity for future studies. It is encouraging that this set includes a number of previously hypothesized and novel associations between genes and particular traits (Supplementary Table 12). In addition, our data show that even older, low-resolution microarray data afford discovery opportunities for CNVs that have not previously been detectable. Indeed, we successfully identified and confirmed dozens of small deletion events, several of which have
