Specific epigenetic biomarkers in human sperm associated with autism in offspring

Epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence. The term includes any process that alters gene activity without changing the DNA sequence and which leads to modifications that can be transmitted to daughter cells (note: some epigenetic changes can be reversed).

The main types of epigenetic processes¹ so far identified include:

DNA methylation

• addition or removal of a methyl group (CH₃), predominantly where cytosine bases occur consecutively
• Methylation can change the activity of a DNA segment without changing the sequence.

Histone modification

• Acetylation: chromatin modification by addition of an acyl group (CH₃CO) to histone proteins
• Phosphorylation: addition of a phosphoryl entity (PO₃^2-) to histone proteins
• Ubiquitylation: addition of the small protein, ubiquitin, to histone proteins
• Sumolyation: addition or detachment of SUMO proteins .

Epigenetic mechanisms are essential to many functions of an organism but if they occur improperly there can be major adverse health and behavioral effects. For instance, epigenetic changes are responsible for diseases including Fragile X syndrome, Angelman’s syndrome, Prader-Willi syndrome and various cancers.

Now, researchers from Valencia University in Spain and Washington State University in the US, believe they have identified biomarkers in human sperm, which can indicate a propensity to sire offspring with autism.

In the study² the researchers investigated two groups of men: 13 who had fathered sons with autism and 13 with children without the disorder.  They identified 805 separated DNA methylation regions that could potentially act as epigenetic biomarkers for hereditary autism and then tested their findings by attempting to identify fathers of autistic children purely from sperm samples.

In blind tests of 18 men, they correctly identified all the fathers of autistic children with an accuracy rate of nearly 90%. Professor Michael Skinner, Washington State University said, “We can now potentially use this to assess whether a man is going to pass autism on to his children. It is also a major step toward identifying what factors might promote autism.”

He believes that, with further research, this biomarker could be utilised to trace how the epigenetic changes occurred in the first place. Professor Skinner continued, “We found out years ago that environmental factors can alter the germline, the sperm or the egg, epigenetics. With this tool we could do larger population-based studies to see what kinds of environmental factors may induce these types with epigenetic changes.”

More work and expanded trials need to be done to develop the study findings into a potential clinical tool and the team are now working on an extended study involving much larger numbers of men.