New autism genes discovered
World’s leading autism experts announce results from the Autism Genome Project
9 June 2010
Losses and duplications of whole chunks of DNA at sites across our genomes are likely to play a role in autism spectrum disorders, according to a new international study co-funded by the Medical Research Council (MRC).
Autism spectrum disorders are known to have a predominantly genetic basis from twin and family studies but the genetic changes responsible are varied and remain largely unknown.
Stretches of DNA are often lost or duplicated in our genomes. Sometimes these genetic variations, called copy number variants, are inherited from parents, while some appear for the first time in offspring. Scientists had wondered if some copy number variants that occur only rarely (in fewer than one in 100 people) might account for a significant proportion of autism’s missing genetic component.
With technology now available to search for rare copy number variants across the whole human genome, the Autism Genome Project (AGP) – an international collaboration established with help from the MRC and involving researchers in the USA, Canada and Europe – set out to compare the incidence of rare copy number variants in 996 people with autism spectrum disorders and 1287 unaffected people, all with European ancestry.
The study found that people with autism spectrum disorders had on average 19% more copy number variants that disrupted genes than people in the control group.
Within the copy number variants that were found, the researchers were able to identify where they had been inherited and where they had newly emerged by looking at parent-child transmission.
Many of the lost or duplicated DNA chunks occurred in genetic regions already known to be important in autism. But they were also found in many new gene regions, suggesting these genes offer new biological pathways that might be involved in autism spectrum disorders.
Professor Tony Monaco from the University of Oxford and a lead author of the study said:
“Our research strongly suggests that this type of rare genetic variation is important and accounts for a significant portion of the genetic basis of autism. By identifying the genetic causes of autism, we hope in the future to be able to improve the diagnosis and treatment of this condition which can affect children and their families so severely.”
“Just knowing about these genetic changes can help the families involved come to terms with why their child has autism, but it can also be important where there are siblings too in determining future risk.”
Professor Chris Kennard, Chair of the Medical Research Council's Neurosciences and Mental Health Board said:
"This study shows the value of supporting large international consortia to determine the genetic basis of many neurological disorders such as the autism spectrum disorders. The results in this study have revealed highly novel genetic abnormalities in the form of copy number variants, which have lead to the identification of new biological pathways. Such discoveries are crucial to both improving the diagnosis of the autism and identifying new therapies in the future."
The scientists also looked at the functions of the genes interrupted by the copy number variants and found that genes involved in both neural cell development and signalling pathways were unusually common.
Many of these affected genes are also thought to play a role in other neurodevelopmental disorders and these results fit with what is being discovered in other conditions. Rare copy number variants have already been shown to play a role in learning disability, and there seems to be some overlap with the genes implicated in autism as well. There may even be some overlap with other conditions such as epilepsy and schizophrenia. It is becoming clear that affected genes and pathways can lead to very different outcomes in different people.
The research team at Oxford University involved in the AGP now hope to carry out a pilot study to see whether tests that look for this type of genetic change can help diagnose new cases of autism. Similar tests are already in use to help diagnoses of learning disability.
Autism spectrum disorders are a group of developmental disorders that emerge in early childhood. The disorders are characterised by difficulties in social interaction, communication, and understanding other people’s emotions and behaviour. The estimated number of children under 18 in the UK with an autism spectrum disorder is 133,500, according to the National Autistic Society.
The Autism Genome Project (AGP) represents an investment of £7.44 million ($14.5 million) over three years by Autism Speaks, MRC, and the Health Research Board of Ireland (HRB). Genome Canada and Autistica (UK-arm of Autism Speaks) also contributed funding, while the MRC played the central role in establishing the AGP partnership and the multi-partite funding arrangements.
The research in Oxford was funded by the Medical Research Council and Autistica (formerly Autism Speaks UK). The paper is published online today in the journal Nature.
Ends
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