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Sunday, December 6, 2015

Brain Tissue Reveals More Genetic Clues to Autism

From the Autism Science Foundation

December 2, 2015

A study published today in Neuron examines brain tissue of people diagnosed with autism to better understand the symptoms of autism, and when mutations in the DNA occurred.

In other words, did the genetic mutation originate from the parents' DNA, or did it happen after the egg and the sperm formed an embryo? Knowing when they occurred helps in understanding how autism can be passed on, how standard blood tests for autism should be used, and how often genetic mutations occur in brain tissue.

Alissa D’Gama, from Boston Children’s Hospital and
Harvard University, was first author on the study

To illustrate the importance of different mutations, here is a primer:

Most human genetic diseases are the result of inherited DNA mutations, in other words, those that are present in one of the parents. There is one big exception to this: cancer. But other genetic diseases, like sickle cell disease and cystic fibrosis, result from inherited DNA.

Maybe the parent doesn’t have the same exact mutation, but a geneticist can trace the mutation to one of the parents. Because the mutation came from the parent, the mutation is present when the sperm and egg join and the embryo is formed. These mutations end up in all the tissues of the affected individual: blood, saliva, organs. So you can look at any of these tissues and still see the mutation. A doctor doesn’t need the organ of interest to study them. They are inherited.

In contrast to an “inherited” mutation, is a “heritable” mutation. For example, there is more evidence to show that de novo mutations are important in autism diagnosis. You’ve heard word de novo or “of new”, meaning, they end up in the offspring but can’t be seen in either parent. These mutations may be in the sperm and the egg or the cells that come before the sperm and egg, called the germline, but they aren’t in the blood or spit or cells of the parents.

In other words, to a geneticist without sperm or eggs to study, they are de novo. These sorts of heritable mutations are in all cells, including blood, saliva, skin cells, and organs. More and more, scientists are showing that in autism, these de novo mutations result in psychiatric issues like autism spectrum disorders. Scientists know more about these mutations in the last 5 years than they ever did, and how they cause problems in the genetic code. These are germline mutations.

But what scientists don’t know a lot about is the role of somatic mutations in neurodevelopmental disorders. These are mutations that happen AFTER the embryo started forming, and they affect a certain organ of interest. Because they are not in every cell in the body, they are called somatic mutations. Only a subset of cells, or a specific organ, shows the mutation. This is the sort of mutation you see in cancer, and a biopsy is needed to see them. A doctor would need the specific organ to find it.

This is the sort of mutation that occurs as cells constantly divide through your lifetime. If you think about how many times your cells turn over, it’s inevitable that a mutation is going to happen somewhere at sometime. They can be common and not harmful. However, sometimes, for example in cancer, they are harmful.

If you are lost right now, you are not alone. This is pretty advanced genetics to most people. 

Scientists have the resources to study germline mutations and de novo mutations in blood or saliva. But until recently, it has not been possible to study somatic mutations. How would you know if autism is the result of a somatic mutation? You’d have to study the brains of people with ASD.

And that’s what a group at Boston Children’s Hospital did recently, and just published their findings. While somatic mutations in autism are rare, they do exist. Alissa D’Gama, the first author, explains why the project is important:

“Identifying a few cases with somatic mutations shows us that such mutations can occur in ASD and that somatic mutations may be another genetic mechanism that contributes to ASD risk. Understanding that some mutations can occur late in development and only be present in the brain has important implications for clinical genetic testing, as studying the blood will miss the somatic mutations present only in brain.”

So how does this impact people with autism?

1.) Scientists now know that there are genetic mutations in the brain that are specific to the brain, and not found in other tissues; and,

2.) These somatic mutations may be responsible for the neuropathology of autism spectrum disorders. The word “may” is used because there is still so much researchers do not know, but could know, if there were more brains of people with autism to study.

This type of analysis was only possible through the accrued collection of dozens of brains of people with autism. Please consider registering for the Autism BrainNet at It is not binding like a consent, and when you register, you will continue to receive important updates like this.

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