Analysis of SV has been a major focus in ASD research (Table 2, Figure S1). Implicated loci to date are generally rare and potent risk factors but incompletely penetrant and not specific to ASD. As these large events impact the dosages of many genes, biological insight has been slow to emerge; however, pathway analyses of genes within SV do implicate neuronal processes of etiological relevance. 45–47 Large SVs are present in 5–10% of ASD cases, and the number of ASD SVs could total 130–234. 80 There is also consistent evidence for increased SV burden in ASD. 49,80–82 For example, 5.8% of ASD probands had ≥1 rare de novo SV versus 1.7% of their unaffected siblings (OR=3.5), and this difference was more pronounced for SV that intersected genes. 80 The 16p11.2 SV associated with ASD and SCZ has been termed a “mirror image” SV since the deletion and duplication are associated with increased and reduced head and body size. However, it is difficult to understand the clinical features of ASD and SCZ as mirror images and, more importantly, ASD is associated with both 16p11.2 deletions and duplications.
