The over-representation of large de novo CNVs in ASD has been replicated in studies ranging from 60 to 393 simplex trios (Itsara et al., 2010; Marshall et al., 2008; Pinto et al., 2010), and two of the three studies (Marshall et al., 2008; Pinto et al., 2010) have confirmed a greater abundance in simplex versus multiplex ASD families. The burden of rare de novo CNVs in simplex probands (i.e. the percentage of individuals carrying ≥1 rare events) has ranged from 5.0-11% (Table S1). Rare structural variants, both transmitted and de novo, also show varying degrees of evidence for association with ASD. These include deletions and/or duplications at specific loci, including: 1q21.1, 15q11.2-13.1, 15q13.2-13.3, 16p11.2, 17q12, and 22q11.2 as well as recurrent structural variations involving one or a small number of genes, including: Neurexin 1 (NRXN1), Contactin 4 (CNTN4), Neuroligin 1 (NLGN1), Astrotactin 2 (ASTN2), and the contiguous genes Patched Domain Containing 1 (PTCHD1) and DEAD box Protein 53 (DDX53) (Bucan et al., 2009; Glessner et al., 2009; Kumar et al., 2008; Marshall et al., 2008; Moreno-De-Luca et al., 2010; Noor et al., 2010; Pinto et al., 2010; Weiss et al., 2008).
