To date, the number of definitive replicated findings from these studies has remained small and all evidence has pointed to a highly heterogeneous allelic architecture as no risk variant is present in more than ~1% of affected individuals. In addition, examples of incomplete penetrance (not all mutation carriers have disease), and affected siblings not sharing the same risk variant, have been the rule rather than the exception. Moreover, remarkably diverse outcomes have been identified for apparently identical CNVs. For example, chromosome 16p11.2 deletions and duplications have been found in individuals with ASD and intellectual disability (ID) (Weiss et al., 2008), seizure disorder (Mefford et al., 2009), obesity (Bochukova et al., 2010), macrocephaly, and schizophrenia (McCarthy et al., 2009). These complexities suggest that the use of association strategies to demonstrate an excess of specific de novo CNVs will play an important role in definitively implicating loci in ASD.
