There are now many published reports of the significant role of rare, de novo CNVs with major phenotypic effects in various human disease populations, including intellectual disabilities, autism spectrum disorders, epilepsy, and schizophrenia, among others. Many of these studies are based on well-phenotyped research cohorts that were originally collected and characterized to optimize the ability to detect small effects in genome-wide association studies. Although positive associations have been identified for a few common diseases through these efforts, a surprising and remarkable finding has been the identification of rare, de novo CNVs with major phenotypic effects, particularly in neurocognitive and behavioral disorders. Because these events are rare, obtaining adequate evidence for their functional role in disease causation requires very large sample sizes as well as large control populations.
