Autistic Spectrum Disorder (ASD): unraveling genetic causes

The Autistic Spectrum Disorder (ASD) encompasses a group of neurodevelopmental disorders that are characterized by impaired ability to socially interact and communicate, and by the presence of stereotyped and repetitive behaviors. These symptoms can vary widely among patients (they may be mild, moderate or severe) and other clinical manifestations may be present, such as intellectual disability, epilepsy, anxiety, macrocephaly and hypotonia, among others [1].

Genetic aspects

Although environmental factors, such as infections and exposure to certain toxic agents during pregnancy, can increase the risk of developing ASD, the DNA also can contain changes in its sequence of bases, that cause or contribute to ASD. But, what do we know today about the genetic causes of ASD?

Especially through the use of more recent genomic analysis methodologies on a large scale, such as CGH arrays (comparative genomic hybridization) and the Next-Generation Sequencing of exomes or genomes, it is possible to identify rare and high-risk genetic variants (that is, responsible for the clinical picture) in approximately 25% of the patients. Yet, in many patients, not only one rare genetic alteration is identified, but two or more in a model called inheritance oligogen (oligogenic = of a few/few genes).

These genetic variants may come from:

  • One or both parents (even though they do not have ASD or have only very slight signs of the disorder).
  • Formation of the egg or sperm and, therefore, are only found in children with ASD, which we call new genetic variants. 

A significant portion of ASD cases of unknown cause appear to follow a multifactorial model of inheritance, in which the disorder is the result of a combination of more frequent and low risk genetic factors associated with predisposing environmental factors. In these situations, little is known about which and how many genetic variants per individual are needed to cause ASD. 

The ASD can be considered a complex disease, and may involve different mutational mechanisms and inheritance models. Because of this complexity, knowledge about the genetic causes of ASD has required a lot of effort, high costs and has evolved more slowly.

Author: Andréa Laurato Sertié, PhD.


[1] An African HIV-1 sequence from 1959 and implications for the origin of the epidemic. Nature. 1998 Feb 5;391(6667):594-7

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