Gene discovery in autism spectrum disorders (ASDs) has accelerated in the past several years. However, current efforts have mainly focused on the coding portion of the genome, which reflects approximately 1 percent of the total genome. This focus is partly due to the expense of characterizing the entire genome, as well as difficulties in interpreting the significance of variations in noncoding DNA information.

Autism, intellectual disability, developmental delay and related phenotypes affect more than 1 percent of children worldwide. These conditions can reduce the length and quality of life of affected individuals, and contribute to emotional distress, financial challenges and lifestyle restrictions for affected families. Because these conditions are diverse and sometimes severe, many affected children undergo years of interactions with clinicians and costly testing procedures without ever receiving a precise medical diagnosis.

Autism spectrum disorder (ASD) affects at least 1 child in 68, and imposes a huge psychological and economic burden on affected individuals, their families and society. While significant progress has been made in determining genetic risk factors for ASD, there remains a substantial amount of unidentified genetic change contributing to risk.

Exome sequencing and copy number variant (CNV) analyses have contributed significantly to our understanding of the genetic etiology of autism spectrum disorder (ASD). In particular, de novo and private likely-gene-disruptive (LGD) mutations are major risk factors, contributing to 30 percent and 7 percent of simplex autism, respectively. Despite these successes, roughly 60 percent of the genetic etiology of ASD remains unexplained.