TCD Researchers Discover New Autism Genes as Part of Major International Research Project

Posted on: 10 June 2010

New autism genes have been discovered by researchers at Trinity College Dublin and University College Dublin as part of a Global Autism Genome Project, involving 50 institutions worldwide. The findings were published online this week in the international peer-reviewed publication, Nature. The research programme has received significant funding from the Health Research Board in Ireland.

The Irish  component of the work of the Autism Genome Project involves a collaboration between TCD and UCD and focused on the identification and study of children with autism and their families from across Ireland (TCD);  the production of the vast amounts of data on the genetic variation in the individuals and their families (UCD); the analysis of the data, some of which is in the present report (UCD and TCD) and the coordination of The Autism Simplex Collection (TASC) project across the international clinical sites (TCD).

Trinity College Dublin’s Professor Michael Gill and Dr Louise Gallagher from the TCD Department of Psychiatry in the School of Medicine, and University College Dublin’s Professor Andrew Green and Dr Sean Ennis from the UCD School of Medicine and Medical Science are co-lead investigators in the Global Autism Genome Project.

A large sample of individuals and families with autism has been recruited in Ireland and around the world by the Autism Genome Project (AGP) consortium. Research was carried out to identify genetic variation contributing to the risk for autism. Researchers analysed genetic variation from across the genome of over 1,000 individuals with autism and related disorders, their parents and a control sample of 1,300 individuals without autism. The Autism Genome Project reported that individuals with autism have submicroscopic sections of DNA that occur more often (duplications) or less often (deletions), called copy number variants (CNV) in their genome. These are also found as frequently as individuals with no autism, but in autism they are more likely to disrupt certain genes and in particular those previously reported to be associated with autism or intellectual disabilities. Some of these CNVs appear to be inherited, while others are de novo, or new, because they are found only in affected offspring and not in the parents.

The Autism Genome Project study also identified new autism susceptibility genes including SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. Some of these genes belong to synapse-related pathways (the mechanism whereby one nerve cell connects with another), while others are involved in nerve cell proliferation, projection and motility in the brain, and the signaling between nerve cells in the brain. These findings will help researchers better understand the brain mechanisms involved in autism and could become targets that may lead to the development of new treatment approaches.

Commenting on the significance of the findings, TCD’s Dr Louise Gallagher said: “This work significantly extends our knowledge of the genes involved in autism leading to new insights into underlying biology.”

“With further research work, these and other recent findings have very real potential to lead to the development of novel interventions and treatments for these disorders,” continued TCD’s Professor Michael Gill, also of the Irish Autism Research Group.

“Because of matching investment by the Irish government through the Health Research Board, over half of the laboratory work for this project was carried out in Ireland,” said UCD’s Dr Sean Ennis. “The results show that Irish researchers and Ireland can truly contribute to scientific discovery on the global stage.”

“The global reach of this research consortium enables scientists to magnify their discoveries in order to bring understanding and in turn therapies to individuals and families affected by autism,” concluded UCD’s Professor Andrew Green.

The findings further support an emerging consensus within the scientific community that autism is caused in part by many “rare variants” or genetic changes found in less than one percent 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, as well as providing insights into possible common pathogenic mechanisms. The overlap between autism susceptibility genes and genes previously implicated in learning disabilities further supports the hypothesis that at least some genetic risk factors for autism overlap with those implicated in learning disability. Finally, identification of these biological pathways points to new avenues of scientific investigation, as well as potential targets for the development of novel treatments.

The genetic discoveries published in Nature are from the second phase of the collaborative study.

For media queries contact:

TCD Press Officer, Caoimhe Ní Lochlainn: tel: (353 -1)- 8962310/ (0)87-9958014

Notes to Editor

About the Autism Genome Project

The Autism Genome Project consists of 120 scientists from more than 50 institutions representing 19 countries who formed a first-of-its-kind autism genetics consortium. The AGP began in 2002 when researchers from around the world decided to come together and share their samples, data, and expertise to facilitate the identification of autism susceptibility genes. This continuing collaboration and its unique scientific assets (e.g., large sample set and multidisciplinary expertise) created scientific opportunities that otherwise would not exist. The AGP is well positioned to build on these extraordinary findings in the field of autism genetics research in the coming years, and the TCD/UCD alliance intends to play a central role in this research. The researchers would like to acknowledge the generous support from the Irish Government through the Health Research Board in Ireland that has enabled them to participate in this exciting international collaboration. They would finally and most importantly like to acknowledge and thank all the Irish families affected by autism that have participated in this research.

About Autism

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 and is associated with disability throughout the lifespan. Autism can have a major impact not just on the individual but also on carers and families and improved treatments and interventions are urgently required. Autism spectrum disorders are diagnosed in one in 110 children in the United States, affecting four times as many boys as girls. International prevalence rates are around 1% for all types of autistic spectrum disorders, from severe to mild. Current data regarding exact prevalence in Ireland is not available although it is likely to be a similar rate. An Irish autism prevalence study is currently underway. Prevalence rates have increased by 57% between 2002 and 2006, influenced in part by changing diagnostic patterns and increased recognition. The Centers for Disease Control and Prevention have called autism a national public health crisis whose cause and cure remain unknown.Full-title of Nature publication: ‘Functional Impact of Global Rare Copy Number Variation in Autism Spectrum Disorder’