One major concern on the wave adjustment is that genuine CNVs may be abolished by the procedure that attempts to flatten wavy signal patterns across the genome. To investigate this issue, we selected six CNV regions and measured their copy numbers in 48 individuals by Q-PCR. The six regions include three deletions (with copy number 0 and 1) and three duplications (with copy number 3 and 4), and each of them is present in 6–29 individuals in the pedigree. We then applied the PennCNV algorithm (18) on the adjusted signal intensity on the 48 individuals, and found that there are only three false negative calls without false positive calls for these six CNV regions (Table 2). We note that the same false negative calls were also made in the absence of signal adjustment. Although wave adjustment did not reduce the false negative rate here (3.5%, 3/85 CNV calls), the adjustment procedure preserves signals from genuine CNVs in these CNV regions and does not introduce false positive calls. To further validate this visually, we plotted examples of signal intensities before and
