Largest genetic study of autism reveals new insights
11 June 2010
The study by the Autism Genome Project Consortium reveals a number of rare insertions or deletions in the human genome associated with autism spectrum disorders (ASDs). The genes and biological pathways affected by these provide a framework from which researchers could develop improved genetic tests and therapies.
ASDs are a group of conditions characterised by highly repetitive behaviour, severely restricted interests, and problems with social interactions and communication. Such disorders are known to be highly heritable (around 90 per cent), but scientists have found it difficult to identify the exact genetic components.
In the new study, published in 'Nature', researchers compared the genomes of 996 people with ASDs and around 1287 people without such conditions. They looked for copy number variations (CNVs), segments of DNA that are inserted or deleted in the genome.
The researchers found that those with ASDs carry a greater number of rare CNVs. Some of these are inherited, and some have arisen for the first time in the individual.
Further analysis revealed sets of genes involved in different aspects of brain development, cell signalling and cell function, as well as some previously linked to other disorders such as intellectual disability.
"Solving how autism develops is like a jigsaw puzzle," said Professor Tony Monaco from the Wellcome Trust Centre for Human Genetics at the University of Oxford, one of the researchers in the study. "The CNVs we have found offer a frame for that puzzle, giving us an idea of what that picture may look like.
"In a jigsaw, we can group pieces together and say some of them represent the sky or the ocean or sand. This study allows us to do something similar, identifying the CNVs that are related to connections between neurons or signalling molecules, for example."
The researchers say these findings could offer potential biomarkers to improve genetic tests and help ascertain whether and how factors such as exposure to chemicals in the environment can lead to ASD. It may also lead to possible targets for drug-based interventions.
The Consortium is now conducting analyses of a further 1500 ASD-affected families, both analysing whole genomes and looking more closely at the genetic areas already identified.
Image: Child with autism spectrum disorder. Credit: Anthea Sieveking, Wellcome Images
Reference
Pinto D et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 2010 [Epub ahead of print].
