Genome-wide screens for de novo mutation have become an essential approach for gene discovery in psychiatric disease. (Kirov et al., 2011; Levy et al., 2011; Malhotra et al., 2011; Marshall et al., 2008; Sanders et al., 2011; Sebat et al., 2007; Xu et al., 2008). Some fraction of disease alleles occurs as de novo mutations, and overall this class of mutations has a low frequency (30–100 nucleotide substitutions per generation and 0.07–0.12 SVs per generation). Hence, the numbers of neutral variants in the genome are small, and de novo mutations have consistently shown the strongest genetic effect (Kirov et al., 2011; Levy et al., 2011; Malhotra et al., 2011; Marshall et al., 2008; Sanders et al., 2011; Sebat et al., 2007; Xu et al., 2008).
