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.

Hilary Coon and Gabor Marth’s labs at the University of Utah will employ innovative genomic methods and analyses to assess two data resources for all types of genetic changes, including those that do not obviously affect the function of genes. The collaborative team from the Coon and Marth labs includes experts in autism genetics, bioinformatics and statistical genetics, and genomics. The approach the team will use involves newly developed genomic software that is at the leading edge of gene discovery.

The group will assess whole-genome sequencing (WGS) data from 540 carefully assessed families in the Simons Simplex Collection (SSC); each of these families has data from an affected and unaffected sibling and both parents. The investigators will also study WGS data and other molecular data from unique, high-risk, large Utah pedigrees that are also carefully assessed. The Utah pedigrees will further magnify the ability to learn more about how genetic mutations occur in families, and will also reveal genetic changes that are hard to find in small nuclear families, as pedigrees show familial repetition of inherited risk factors.

The detailed assessment of behaviors and medical conditions in both cohorts will allow the researchers to uncover associations with specific aspects of ASD (such as language onset or cognitive delay), or with associated psychiatric or medical conditions. Finally, the design may allow the discovery of genetic changes that are more frequent in unaffected siblings, which may reflect protective factors.