Posts Tagged ‘copy number variant’

By Joseph Buxbaum, PhD

Researchers of the Autism Genome Project Consortium (AGP) announced today that they have identified new autism susceptibility genes that may lead to the development of new treatment approaches.

The study results are based on analysis of copy number variants (CNVs) — rare submicroscopic insertions and deletions — identified in high-density genotyping data collected from 1,000 individuals with autism spectrum disorder (ASD) and 1,300 without ASD. The findings were published today in Nature by the international consortium of researchers who make up AGP.

There are several important results from this study. First, the findings provide further support for an emerging consensus within the scientific community that autism is caused in part by many “rare variants,” or genetic changes found in one percent or less of the population. While each of these variants may only account for a small fraction of the cases, collectively they are starting to account for a greater percentage of individuals with autism.  More importantly, they are also providing insights into possible common pathological mechanisms.

Second, the findings show that CNVs disrupting genes are more common in ASD than in controls. Some of the more compelling findings include CNVs in SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53–PTCHD1 locus.

Third, the AGP explicitly tested whether genes previously implicated in intellectual disabilities but not in autism represented autism genes. The evidence was quite clear that such genes are also autism genes. The overlap between autism susceptibility genes and genes previously implicated in intellectual disabilities further supports the hypothesis that at least some genetic risk factors are shared by different psychiatric developmental disabilities.

Finally, the AGP carried out pathway analyses and noted that many of the autism genes that were identified belong primarily to synapse-related pathways, while others are involved in cellular proliferation, projection and motility, and intracellular signaling. Identification of these biological pathways points to new avenues of scientific investigation, as well as potential targets for the development of novel treatments.

Therapies specifically targeted to identified genetic causes (“personalized medicine”) are now being tested in several neurodevelopmental syndromes associated with autism, including Fragile X syndrome, tuberous sclerosis, and Rett syndrome. The identification of additional autism genes will expand such approaches and lead to new therapies.

 Joseph D Buxbaum, PhD is Director of the Seaver Autism Center for Research and Treatment at Mount Sinai and serves as Editor-in-chief of the journal Molecular Autism.  Dr. Buxbaum is one of the leading contributors to the design, analysis, and writing of this study and is a lead AGP investigator.

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