Page URL:

New light cast on genetic influences on autism

18 October 2009
Appeared in BioNews 530

A large genetic study has uncovered a single 'letter' change in DNA which is associated with autism. The multi-national collaborative team, who published their findings in Nature, also identified two further regions of the genome which could contain other rarer genetic changes that have an even greater influence on the condition. Coinciding with these discoveries and publishing their findings in the Proceedings of the National Academy of Sciences, a team led by Professor Thomas Sudhof of Stanford University has shed light on how a previously discovered genetic change may be resulting in the human disorder.

Autism is a complex brain disorder characterised by impaired social interaction and communication as well as restricted and repetitive behaviours. The prevalence of autism is currently one to two people per 1000 and is highly heritable - approximately 90 per cent of cases are thought to be at least partly influenced by genes. However, exactly which genes and how they bring about the disorder remain unknown.

In continued pursuit of autism's complex genetic architecture, a large multinational collaboration led by researchers at the Broad Institute of Harvard and MIT, Massachusetts General Hospital, Johns Hopkins University and elsewhere mounted a two-pronged, genome-scale approach.

The first component made use of a family-based method, called 'linkage'. Linkage studies compare the DNA from patients affected by a disorder with their family members in order to detect portions of the genome which could contain causal genetic variants. The results of the study identified regions of chromosome 6 and 20. Although further research is required to pinpoint the exact causal changes within these regions that contribute to autism, study author Mark Daly explains that 'the genomic regions we've identified help shed additional light on the biology of autism and point to areas that should be prioritized for further study'.

The second prong was a population-based method, referred to as an association study. This type of study examines DNA from unrelated individuals and uncovers genetic variants which are associated with a given disorder. With this method, the researchers found a single-letter change in the genetic code known as a SNP (pronounced 'snip') on chromosome 5 near a gene known as semaphorin 5A. This gene encodes a protein thought to help guide the growth of neurons.

'This study is key - it reinforces the notion that deficit in proper neuronal interaction is involved with autism neuropathology' said Dr Andy Shih, vice president of scientific affairs of Autism Speaks. 'If this finding holds and is further supported with additional research such as a functional study of the variant semaphorin 5A, this molecule could represent another biological target for pharmaceutical intervention in the future and possible treatment for some individuals with autism'.

Co-lead author Professor Lauren Weiss states, 'We can now begin to explore the pathways in which this novel gene acts, expanding our knowledge of autism's biology'.

A team led by Professor Thomas Sudhof did just this in response to the discovery that deletion of the gene neurexin-1alpha occurs in about 0.5 per cent of autism cases. 'Because of our longstanding interest in neurexin-1alpha, we already had mice that were bioengineered to be lacking in neurexin-1alpha,' Sudhof explains. 'So we decided to look closely at those mice to see whether this genetic deficiency led to any changes in communication between neurons and, if so, whether the disrupted or altered communication was correlated with any observable behavioural abnormalities reminiscent of those associated with human cognitive disorders such as autism or schizophrenia'.

The researchers noticed that the mutant mice had alterations in their 'synapses' - regions where nerve cells signalled to one another. Furthermore, the defect affected only excitatory synapses, as opposed to inhibitory. 'This selective change in the strength of one type of synapse, but not the other type, alters the balance between the two' said Sudhof.

The mutant mice displayed behavioural traits characteristic of those associated with autism, such as repetitive stereotypical behaviour. Similarly analogous to human patients, mice lacking the neurexin-1alpha gene were not compromised in day-to-day functions. Sudhof goes further to explain that 'they were actually better than the control mice at executing tasks requiring motor coordination, such as balancing atop a rotating rod without falling off'.

Sudhof and his colleagues at the Stanford Institute for Neuro-Innovation and Translational Neurosciences now plan to investigate whether other autism-related genes affect the nervous system, including those identified in the above study published in Nature.
14 December 2009 - by Helen Keeler 
I had wanted to donate my eggs to a woman with fertility problems ever since having children of my own. I frequently tell my three children that I always wanted to be a mother and that every day they make my dreams come true. How wonderful it would be to help make someone else's dreams come true too....
23 October 2009 - by Sandy Starr 
The Progress Educational Trust (PET) debate 'From Autism to Asperger's: Disentangling the Genetics and Sociology of the Autistic Spectrum' took place in the UK Houses of Parliament on the evening of 20 October 2009, two days before the Autism Bill received its third and final reading in the House of Lords....
12 October 2009 - by Dr Elisabeth Hill 
Most of us are familiar in some way or another with autism spectrum disorder (ASD). We have seen news reports, watched films or documentaries trying to explain this puzzling condition and showing examples of a child's unusual social, communication and repetitive behaviours. We may know a child with ASD or have a child with ASD. Recent evidence suggests that about one per cent of the entire population (one in 100 people) fall somewhere on the spectrum (1,2). Whilst we still understand relative...
5 October 2009 - by Professor Simon Baron-Cohen 
Autism and Asperger Syndrome are two subgroups on the autistic spectrum. They both share difficulties in social relationships and in communication, alongside the presence of unusually narrow interests and a strong preference for predictability. They are neurological and, as we now realise, strongly (though not 100 per cent) genetic. These two subgroups are differentiated by the presence of language delay and/or learning difficulties in autism, and by the absence of these in Asperger Sy
21 September 2009 - by Professor Richard Ashcroft 
Autism spectrum disorder (ASD) is rarely far from the news. ASD is a complex, and as yet poorly understood, pervasive developmental disorder. People with ASD display a triad of impairments in social communication, social interaction, and social imagination (1). The impact of these impairments on children and adults with ASD, and on their families, can vary enormously. However, a common reaction to ASD is fear: fear that my child may develop ASD; fear that my child with ASD will suffer;
21 September 2009 - by Dr Michael Fitzpatrick 
The early narrow definition of autism emerged out of the psychiatry of the pre-war years and became widely accepted in the post-war decades. While research revealed a substantial genetic contribution to autism, in the late twentieth century there was an upsurge in the diagnosis of autism, particularly among 'higher functioning' individuals, and the concept of the 'autistic spectrum' became established....
29 June 2009 - by Lorna Stewart 
Scientists at the University of Aberdeen, Scotland, have discovered a gene which may mediate the cognitive effects of autism. After detecting a chromosomal rearrangement in one severely autistic boy, the team, headed by Dr Zosia Miedzybrodzka, was inspired to look for similar genetic faults in other autistic families. Thier findings are published in the latest issue of Journal of Medical Genetics....
Log in to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.