Variations in a gene thought to be involved in the growth and development of nerve cells in the brain could be associated with susceptibility to autism, a new international study led by researchers from Oxford and Bologna Universities, and published in the journal Molecular Psychiatry, suggests.
Related papers by US researchers, which are published in the journal Nature at the same time, have identified other candidate genes associated with increased risk of autism spectrum disorders. These genes are also involved in the formation of connections between nerve cells in the brain.
Together, these three studies begin to build a picture of the complex genetic origins of autism spectrum disorders. It appears that there may be many common gene variants that each increase autism susceptibility by only small amounts, but that many of them play a role in processes to do with making neural connections in the brain.
'Most of the genes that have been identified in these studies are involved in the connections between neurons called synapses,' says Professor Tony Monaco of the Wellcome Trust Centre for Human Genetics at the University of Oxford. 'This does seem to fit with what we know from brain scans - that people with autism may show different or reduced connectivity between different parts of the brain.'
'This new knowledge allows us to focus our studies on developing new treatments and intervention therapies for the future.'
The Oxford University team, along with colleagues from the International Molecular Genetic Study of Autism Consortium at universities in Europe and the US, did a fine scan of regions on chromosome 2 and chromosome 7 that had been previously connected with increased risk of these conditions. They looked for common genetic changes and variations that could be associated with autism spectrum disorders.
The study sample consisted of 126 and 127 affected individuals and their parents for chromosomes 2 and 7, respectively, along with 188 people acting as controls. They analysed single-letter changes in the DNA code at over 3000 positions in each of the two gene regions and also any larger deletions or duplications of whole chunks of DNA.
The researchers found that DOCK4 on chromosome 7 may increase susceptibility to autism spectrum disorders. The DOCK4 gene is thought to be involved in the growth of dendrites - the long arms that extend from nerve cells to connect them and pass electrical signals to other neurons - in the brain.
'This is a new finding - DOCK4 had not previously been associated with autism before,' says Alistair Pagnamenta of Oxford University, one of the lead authors of the study.
'The picture that emerges from these studies is a complex one,' says Professor Monaco. 'There are many genes involved in autism spectrum disorders, each has only a small effect or is found in only a minority of cases. This is not a surprise when clinicians and doctors see such different cases every day.'
'The studies have implications for future diagnostic testing of autism spectrum disorders. I do believe such testing will become a possibility in the future and may offer some clinical benefit to affected children and their families.'
Autism spectrum disorders are a group of developmental disorders that emerge in early childhood which have a large, but complex genetic component. 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.
Simons Foundation Autism Research Initiative: http://sfari.org/
PubMed ID 19401682: http://www.ncbi.nlm.nih.gov/
For more information on Prof Monaco's autism research, click here.
The Guardian Online 29 April: http://www.guardian.co.uk/lifeandstyle/2009/apr/29/autism-genetics-science-research
Daily Express Online 29 April: http://www.express.co.uk/posts/view/97777/DNA-breakthrough-in-treatment-for-autism
Daily Telegraph Online 29 April: http://www.telegraph.co.uk/health/children_shealth/5237474/Gene-mutations-that-may-lead-to-autism-identified-by-scientists.html
Oxford Mail Online 29 April: http://www.oxfordmail.co.uk/news/4328081.Scientists_hail_autism_breakthrough/