Complex genetics of autism unveiled

American researchers have linked hundreds of spontaneous genetic mutations to the group of psychological syndromes called autism spectrum disorders (ASDs).

Two independent studies have linked more than 100 mutated regions to ASDs. Girls with autism were shown to carry more of these mutations than boys with autism, suggesting girls may have better protection against ASDs. 'Overall, the results have dramatically lengthened the list of genes that may have a role in causing autism. This gives us a lot more data that we can use to start to pin autism down', said geneticist Dr Stephen Scherer from the Hospital for Sick Children in Toronto, Canada, who was not involved in the studies.

The new research suggests spontaneous genetic mutations - those not acquired through inheritance - are an important risk for developing autism, particularly in regions coding for genes. Researchers screened the genomes of 1,000 individuals with ASDs for spontaneous mutations and compared these to the genomes of unaffected family members. They identified genetic mutations, resulting in deletions or duplications of the genome, which may cause ASDs, in 130 different regions.

'It is a large number and that will make it harder to develop therapies that will benefit a large fraction of patients', said Professor Michael Wigler, from Cold Spring Harbour Laboratory, New York, who led one of the studies. 'Given the number of genes that might cause autism, one shouldn't expect that one treatment is going to cure them all'.

One region of the genome was linked to autism when duplicated, and is already known to cause the hyper-social disorder Williams-Beuren Syndrome when deleted: '...there's clearly something there that's highly relevant to social behaviour. The neurobiology of that region is going to be extraordinarily interesting', said Professor Matthew State, head of the second study, which was carried out at Yale University, Connecticut.

Professor Wigler and colleagues also noted autistic girls carried more genetic deletions and duplications than autistic boys. 'That may start to explain some of the sex biases, that boys are more vulnerable genetically', said Dr Andy Shih, vice president of scientific affairs for the advocacy group Autism Speaks. There are four times more boys with autism than girls. These results suggest girls possess greater innate protection against the development of autism. 'If you want to think about an approach to therapeutic intervention, perhaps the lessons to be learned are in the females', said Professor Wigler.

Autism falls under the umbrella of autism spectrum disorders (ASDs), which cover a range of conditions. These can vary greatly between individuals and can include difficulties with social interaction and communication. Approximately 6 in every 1,000 children have an ASD, with 1 in every 1,000 presenting with autism. Although ASDs are thought to be highly heritable, the identification of specific genetic factors has proven difficult.

These studies were published in the journal Neuron.