Why are boys more likely to develop autism spectrum disorders and Tourette syndrome than girls? New research from scientists at University of Exeter and King's College London provides some insight into the sex specific tendencies of these and other neurological conditions. When comparing fetal brains of males and females, the researchers observed significant differences in DNA methylation, suggesting this process may contribute to differences in behavior, brain function, and even disease.

“Our data indicate that considerable epigenomic changes take place in the human brain during fetal brain development,” wrote the authors in their published paper.

What is DNA Methylation?

When genes are active — or expressed — they are capable of producing proteins, which run all the processes occurring in our bodies. When genes, also known as DNA, are inactive or unexpressed, they cannot transcribe proteins. DNA methylation, then, is a common epigenetic tool used by our cells to lock genes in the off (inactive) position.

Epigenetics is all about which genes get switched on or off and also which proteins get transcribed and go to work in our bodies. In a chemical sense, epigenetics refers to chemical marks on DNA that produce long-lasting changes in gene expression without changing the actual genetic code. Chemically, DNA methylation is the addition of a single methyl group to a specific site on a gene and from there the methyl group blocks the transcription of proteins. This is the simplest explanation of how DNA methylation inactivates genes.

As you probably imagine, our developing brains involve an intricate choreography of epigenetic changes, genetic expression, and protein transcription. In the prenatal period, transcriptional changes occur more swiftly than at any other stage of our lives. Precise timing of each protein process is necessary for the proper development of our brain’s structure and function.

For the current study, then, the team of researchers focused on DNA methylation and its timing in the prenatal brain. In particular, they examined differences between male and female brains. Obtaining brain samples from human fetuses, the team measured genome-wide patterns of DNA methylation in the 179 samples (100 male, 79 female). The age range of the samples spanned 23 days to about six and a half months post-conception.

Immediately, the researchers identified “highly significant” changes in DNA methylation at more than seven percent of the nearly 400,000 sites explored.

However, key differences specific to DNA methylation occurred in the male and female brains. A small number of regions showed “sex-specific DNA methylation trajectories across brain development,” noted the researchers. Though the dissimilarities affected few regions, every nuance matters when it comes to the complex process of brain development.

“The prenatal period is a time of dramatic plasticity, when the brain is laying down the structures that control neurobiological function across life,” Dr. Jonathan Mill, professor and lead author of the study, said in a release. “Understanding the way in which genes are activated during this important period in the brain could teach us about the origins of disorders with a neurodevelopmental component, such as autism and schizophrenia.”

Source: Spiers H, Hannon E, Schalkwyk LC, et al. Methylomic trajectories across human fetal brain development. Genome Research. 2015.