We performed high-resolution genome-wide copy-number scans, using the Nimblegen HD2 2.1 M array CGH platform, on all subjects and their biological parents. Complete details for microarray intensity data processing, CNV discovery, and quality control (QC) measures for sample hybridizations are provided in Supplemental Experimental Procedures. In brief, dual-color microarray hybridizations were performed at the service laboratory of Roche NimbleGen according to the manufacturer's specifications. Raw intensity data were normalized in a two step process, first involving “spatial” normalization which is an adjustment for regional variation in probe intensities across the surface of the array, and second involving “invariant set normalization,” which normalizes the distribution of intensities for test and reference samples. CNV detection from the Log2 probe ratios was performed using two segmentation algorithms, HMM Seg and Genome Alteration Detection Analysis (GADA).
