Genetically, autism can broadly be segregated into syndromic and non-syndromic forms. Accounting for a small percentage of total ASD cases, syndromic ASD includes incidences of the disease with known genetic cause and unique clinical presentation, while non-syndromic ASD with unknown genetic etiology accounts for the remaining majority of ASD cases (Sztainberg and Zoghbi, 2016). The genetic underpinnings of non-syndromic ASD likely involve small effects of many genes and/or rare de novo mutations in a susceptible genetic background (de la Torre-Ubieta et al, 2016). Unfortunately, non-syndromic ASD is difficult to model precisely because of this genetic heterogeneity. The use of human-induced pluripotent stem cells (hiPSCs) offers an opportunity to uncover some of the molecular mechanisms behind non-syndromic ASD. hiPSCs possess the same genetic make-up of the individual they were derived from. Thus, hiPSCs derived from individuals with non-syndromic ASD can accurately recapitulate the heterogeneous genetics found in this form of the disease.

Recently, our laboratory and collaborators utilized hiPSCs to model non-syndromic ASD by generating hiPSC lines from eight non-syndromic ASD males (diagnosed via behavior consistent with DSM-IV criteria) along with five healthy male control individuals (Marchetto et al, 2017). Known syndromic forms of ASD were ruled out in all individuals involved with this study via exome sequencing and copy-number variant analysis. On the basis of MRI scans conducted between 2–4 years of age, all ASD individuals were found to possess mild to severe macrocephaly, defined as larger than average total brain volume compared with typically developing individuals. We hypothesized that ASD individuals sharing a co-morbidity would also share disruptions in common cellular phenotypes and signaling pathways, thereby increasing our ability to detect disruptions in these processes.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD