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Sperm DNA changes linked to autism

20 April 2015

By Meghna Kataria

Appeared in BioNews 798

A study has found a link between DNA methylation levels in sperm and an increased risk of autism in children, indicating that epigenetic changes could explain why the disorder appears to run in families.

Analysing semen from a small group of 44 men, the researchers identified distinct changes in the epigenome of sperm from men whose infants went on to show early signs of autism.

They also found that many of the genes around those sites were involved in neural developmental processes.

'The higher the methylation in the genes we looked at, the higher the score for observational risk for the autistic symptoms in the children,' explained co-author Professor Daniele Fallin of the Johns Hopkins University Bloomberg School of Public Health in Baltimore, USA.

Autism spectrum disorder (ASD) is a complex condition of varying severity and affects communication and social behaviour. It is thought to be influenced by a host of genetic and environmental risk factors, and it has been seen to cluster in families.

While there is evidence of a strong inherited link to the development of ASD, the genetics is complex and in many cases the causes remain unexplained. In this study, the researchers set out to identify whether epigenetic changes, rather than genes themselves, might affect ASD.

'We wondered if we could learn what happens before someone gets autism,' said Professor Andrew Feinberg, from the Johns Hopkins University School of Medicine and a lead author on the study. Professor Fallin added: 'If epigenetic changes are being passed from fathers to their children, we should be able to detect them in sperm.'

The researchers gathered semen samples from 44 fathers-to-be, who already had a child with a diagnosis of ASD, and mapped the methylation changes across 450,000 individual spots in their genomes.

One year after the birth of their children, the researchers then assessed the infants using the Autism Observation Scale for Infants (AOSI), which is thought to predict autism. Comparing the results, they found 193 sites where higher or lower methylation levels in the fathers' sperm DNA meant that the child had a high AOSI score, and hence was more likely to develop the condition.

To further verify their results, the researchers compared similar methylation data available from brain samples of 40 deceased people, half of whom had been diagnosed with autism. Out of 75 sites found in a particular region of the brain, only 18 showed the patterns that were detected in the study, suggesting that the causes of autism are likely to be more complex.

Speaking to the Mail Online, Dr Judith Brown, of The National Autistic Society said: 'This is a thought-provoking piece of research which adds a new angle to the discussion about the complex and substantial role genetics play in autism.

'But this is a small pilot study of 44 fathers, as recognised by the authors, and must be must be replicated on a much larger scale before any significant conclusions can be drawn about the causes of autism.'

The researchers now plan to explore how the fathers' environment might contribute to the condition.

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