Homo sapiens Exome

Approximately six to ten percent of families in the Simons Simplex Collection (SSC) carry large multi-genic de novo copy-number variants (CNVs), those most clearly associated with autism risk. This suggests that higher-resolution detection of de novo point mutations and insertions or deletions may lead to discovery of multiple additional bona fide autism risk genes. The findings also highlight the question of whether these CNVs carry risk as a consequence of being large and therefore more likely to encompass a critical gene, or because they simultaneously disrupt multiple coding or regulatory units. Whole-exome sequencing is an ideal way to pursue these questions: to explore the genome for rare autism-related de novo and transmitted mutations that disrupt proteins, to evaluate whether multiple de novo events in the same individual increase risk, and to determine whether de novo and transmitted point mutations begin to clarify the nature of the risk posed by large multi-genic CNVs.