Autism mechanism goes beyond genes

A study on identical twins with different autistic traits suggests that epigenetic factors may be important in understanding how the neurological
disorder develops.

'Our findings give us an insight into the biological mechanism
mediating the interaction between gene and environment in autism spectrum
disorder (ASD)', Dr Chloe Wong, a post-doctoral researcher at King's College
London's Institute of Psychiatry and the first author on the study, commented.

Family studies indicate that ASD has a strong genetic component.
However around 30 percent of identical twins with autism show striking discordances
in their ASD symptoms. As identical twins have identical DNA, this suggests
that gene sequences alone cannot completely determine the development of the
condition.

Mechanisms that affect gene expression without altering the
underlying sequence are known as 'epigenetic' and these can be induced by
environmental factors. One important epigenetic mechanism is DNA methylation, where
a small chemical modification is imprinted on the DNA, most often acting to
switch off nearby genes and shut down their expression.

In this study, published in Molecular Psychiatry, researchers analysed
the DNA methylation signature across the genome for 50 identical twin pairs,
including some twins who both exhibited ASD, others in which only one twin
showed signs of the disorder, and a final control group of unaffected twin pairs.

Dr Wong says the team 'identified distinctive patterns of DNA
methylation associated with autism diagnosis, related behaviour traits and
increasing severity of symptoms'.

In the paper, the team suggests that variations in DNA methylation
could alter gene dosage, thereby varying disease susceptibility. They also
argue that their study highlights the notion that 'environmentally mediated
effects on the epigenome may be relatively common and important for disease'.

Optimistically, Dr Jonathan Mill of the Institute of
Psychiatry and the University of Exeter, the paper's lead author, said: 'Epigenetic
changes are potentially reversible, so our next step is to embark on larger
studies to see whether we can identify key epigenetic changes common to the
majority of people with autism to help us develop possible therapeutic
interventions'.