Several newly-identified genes may make children more susceptible to developing autism, according to a study from the Autism Genome Project, an international consortium that includes Nationwide Children’s Hospital. These second-phase results appear in Nature.
Autism is a complex neurobiological disorder that inhibits a person’s ability to communicate and develop social relationships, and is often accompanied by behavioral challenges. Years of strong evidence suggests that genetics play an important factor in causing autism.
To further clarify the influence of rare genomic variants, Autism Genome Project investigators examined genetic data of more than 1,000 individuals with autism spectrum disorder and 1,300 without autism spectrum disorder, looking for submicroscopic insertions and deletions called copy number variants (CNVs) in their genomes. They found that individuals with autism do not carry more CNVs than control patients do. However, in individuals with autism spectrum disorder, more of these CNVs tend to disrupt genes previously reported to be associated with autism or intellectual disabilities. Some of these CNVs appeared to be inherited, while others are considered new mutations, because they are found only in affected offspring and not in the parents.
The study also identified potential new autism susceptibility genes including SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53–PTCHD1 locus. Some of these genes belong to synapse-related pathways, while others are involved in cellular proliferation, projection and motility, and intracellular signaling.
“These findings further support the concept that autism is highly genetically heterogeneous, that is, linked to many different genetic changes any one of which might be involved in only a very small proportion of cases,” said Veronica Vieland, PhD, director of the Battelle Center for Mathematical Medicine in The Research Institute at Nationwide Children’s Hospital and one of the study’s principal investigators. “Current studies are aimed at revealing underlying biological pathways common to multiple such changes and to characterizing their causal relationships, perhaps in terms of interactions among multiple genes. The hope is that insights we gain into causal mechanisms can be translated into better methods for diagnosis and targeted treatments.”
The Autism Genome Project consists of 120 scientists from more than 50 institutions representing 12 countries who formed a first-of-its-kind autism genetics consortium. The Battelle Center for Mathematical Medicine is the project’s Data Coordinating Site, playing a significant role in the management of the data collected for this research. Nationwide Children’s has collected data from all the collaborating institutions and created one comprehensive database, supplying consistent, accurate information back to all investigators working on this research.
Pinto D…Vieland VJ…Functional impact of global rare copy number variation in autism spectrum disorders. Nature. 2010 Jun 9. [Epub ahead of print]