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Wednesday, April 22, 2015

Study Links Autism to Epigenetic Changes in Dads’ Sperm

From Autism Speaks Science Digest

April 15, 2015

Findings suggest fathers’ exposure to environmental hazards may alter gene activity in ways that predispose children to autism. 

Researchers associated children’s autism symptoms with
epigenetic changes on the DNA molecules in their fathers’
sperm cells. In this DNA model, the bright orbs represent
methylation – a major type of epigenetic control of gene expression.

Researchers have found tell-tale “epigenetic” changes in the DNA from the sperm of men whose children have early signs of autism. These changes – which are likely passed on to offspring – may reflect, in part, the men’s exposure to environmental hazards.

The study, co-funded by Autism Speaks and the National Institute of Environmental Health Sciences, appears online today in the International Journal of Epidemiology.

Epigenetics is the study of mechanisms that control gene activity without changing the underlying DNA that makes up our genes. In essence, epigenetic molecules control when and where genes turn on and off to coordinate the body’s development and function. Precise epigenetic control is particularly crucial during brain development.

In the new study, investigators looked for epigenetic contributors to autism, a subject of keen interest in recent years.

"If epigenetic changes are being passed from fathers to their children, we should be able to detect them in sperm," says co-author Daniele Fallin. Dr. Fallin directs the Wendy Klag Center for Autism and Developmental Disabilities, at the Johns Hopkins Bloomberg School of Public Health. She and her team receive Autism Speaks funding to investigate early environmental influences on autism risk. This includes research that may help identify preventive measures and targets for future treatments.

“These findings offer tantalizing clues about the way risk associated with environmental factors can be transmitted from father to child,” comments Andy Shih, Autism Speaks’ senior vice president for scientific affairs.

“It adds to our growing understanding and appreciation of the complexity of gene-environment interaction in autism etiology. It also suggests possible ways to identify relevant environmental risk factors in future studies.” Dr. Shih was not directly involved in the research.

Epigenetics and Environmental Risk Factors for Autism

A growing body of research has suggested that environmental influences – including infection and exposure to toxic chemicals – can produce epigenetic changes in the cells that make sperm and eggs. Sperm-making cells may be particularly vulnerable to such environmental exposures.

Many experts believe that this explains why autism rates are significantly higher among the children of older dads. Their germ cells have been exposed to more environmental “hits” over the course of a lifetime.

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In their new study, the Johns Hopkins investigators analyzed the epigenetic markers on DNA in the sperm from 44 dads. The men were part of the ongoing Early Autism Risk Longitudinal Investigation (EARLI). EARLI enrolls families that have a child with autism and follows them through subsequent pregnancies and the birth and development of younger siblings.

Early in their wives’ pregnancies, the men provided sperm samples for DNA and epigenetic analysis. One year after birth, the younger siblings were assessed for early signs of autism.

The researchers then looked at the likelihood that a child’s autism symptoms corresponded to an epigenetic change at a particular site in a father’s sperm DNA. They found 193 such sites. At each of these sites, epigenetic changes were significantly associated with children’s autism symptoms.

When the researchers looked at which genes were near the “high risk” sites, they found that many are in or near genes crucial to brain development.

In a related analysis, the investigators found several of the tell-tale epigenetic changes in the post-mortem brain tissue of individuals with autism – providing further evidence that these changes may predispose to autism.

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