Particularly convincing has been the recent discovery of the role of large-effect de novo (arising in gametes) mutations in ASD, where the first genome-wide studies of de novo mutations in psychiatric disorders revealed a role for rare (<0.1%) de novo CNVs in ASD (23, 24). Studies indicate that large (>500 kb) rare de novo gene–containing CNVs occur in ~5 to 7% of people with nonsyndromic ASD, versus ~1% of unaffected siblings (25). Several of these rare CNVs are recurrent, some inherited from apparently unaffected parents (such as 15q11-13 or 16p11.2), and none individually account for more than 1% of cases of ASD. Studies of smaller gene-disrupting CNVs also suggest a role for inherited CNVs with lower penetrance (26).
