Role of Genetic Changes in Autism


Genes might play a very important role in the disorder, but it was shown by the studies that the genes involved are not mutated but rather have de novo alterations of expression. This means that there are some non-genetic factors leading to these alterations. In this section, we discuss some of the commonly altered genes and genetic modules. To understand how these alterations occur, read the next section The Role of Inflammation in Autism.

The Role of Genetic Alterations

After it was found out that autistic kids are characterized by some alterations in the brain, the first genetic study was conducted in 1977 in order to determine whether genes play a role in atypical brain formation.


Michael Rutter revealed that parents who already had a child with autism had 50 times higher risk of having another child with this diagnosis than parents of healthy children. In addition, he showed with 21 pairs of twins that when the twins were homozygous, autism in one of them meant an 82% chance that the second twin would have autism, while the heterozygous twins had a 10% chance.

To date, the number of studies on the genetics of autism — hundreds, if not thousands — is a direction in autism research that gets more grants than any other direction. However, there is still no clear knowledge of this. There are studies that show about 5000 genes involved in autism, and there are also studies, results of which indicate that there are only 60 of such genes.

However, everyone understands that such a large number of children cannot have spontaneous mutations for no reason.

Epigenetic diseases are diseases in which the expression of certain genes is affected by the influence of external, non-genetic factors. According to research, heredity in autism is important by 20-50%, all other changes are the result of external factors. Studies show that de novo genetic changes in autism are much more common than mutations. These de novo changes are usually suppression/overexpression of certain genes. These genes are mainly involved in synaptic transmission, transcriptional regulation, and RNA processing functions and are usually expressed in the brain before birth.

The expression of several gene modules that are often affected in ASD children was analyzed in pre- and postnatal periods (Geschwind and State 2015). Module, in this context, refers to a set of genes that are enriched in de novo alterations.


There were five modules analyzed in the study: M2, M3, M13, M16, and M17.  M2 includes 24 genes, 10 of which possess LoF (loss of function) and 11 are missense. M3 includes 150 genes, some of which are postsynaptic density genes. Mainly, these genes are responsible for cognitive ability, processing speed, and delayed recall. The hubs of M13 include the NMDA and GABA receptor subunits GRIN2A and GABRA1, which regulate a synaptic activity. M16 encoded proteins responsible for cation transporter activity, homophilic cell adhesion and nervous system development. Some of the proteins encoded by the M17 module are responsible for calcium-dependent regulation of synaptic activity.


In fetuses that will have the autistic phenotype in the future, from week 10 to 17 in utero, M2 and M3 are overexpressed, while M13, M16, and M17 are suppressed.

 After week 23, M13, M16, and M17 are overexpressed, while M2 and M3 are suppressed. This state of gene expression is maintained after birth. This study supports that:

  • ASD is initiated in the prenatal period

  • ASD is associated with alterations in gene complexes

  • Gene alterations, such as changes in the level of expression, are more common in ASD children than mutations.

It was also found that cellular epigenomic modifications, including DNA methylation, are common in ASD.

And methylation, in turn, is the result of DNA damage. This may explain the unhealthy expression or inhibition of certain genes responsible for brain development.

These and other studies show that the nervous system is very vulnerable to DNA damage due to the limited ability to replace cells, which leads to the accumulation of damaged and irreplaceable terminally differentiated neurons. 

However, knowing these genes and genetic modules won't help your child. We need to understand why these alterations occur. 

As was said above, ASD is an epigenetic disorder, meaning that the genetic changes occur as a result of the influence of external or non-genetic factors. Inflammation is one of these factors

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