This is, to our knowledge, the first report of the identification of rare, disease-associated CNVs in a region initially discovered through common SNP association. Genes implicated in Mendelian disorders, however, have frequently been found to display a broad spectrum of mutations. In the cystic fibrous gene, CFTR, more than 1600 mutations have been identified (Cystic Fibrosis Mutation Database; http://www.genet.sickkids.on.ca/cftr/app), including large structural events. Rare, risk-conferring sequence mutations have also been identified in genes such as PNPLA3 that were initially uncovered through common SNP association.9 Similarly, some genes such as TCF2 first connected to disease through rare, highly penetrant risk alleles were later found, through GWA studies, to harbor common susceptibility alleles of modest effect.37 At CNTNAP2, the earliest reports associated rare SNPs with epilepsy and autism;38 more recently, evidence of the association of common SNPs with autism, although not at the genome-wide significant level, has been described,39,40 and rare structural variants in individuals with autism have also been identified.41–43
