A new study published in the journal Nature Neuroscience, looking at some 6,000 families, demonstrates that mutations that occur after fertilisation play an important role in autism.

Over the last decade, mutations in more than 60 different genes have been linked to autism spectrum disorders (ASD). Some of these are spontaneous, non–inherited mutations and are present in only a few of our cells. Such mutations can occur in a sperm or egg, or in some of the embryo’s cells after fertilisation. These mutations are called postzygotic mutations, PZMs, or somatic mutations. The later the PZMs occur during embryonal development, the fewer the cells that will carry them, making it more difficult to detect them. If the mutation occurs in a very small percentage of the cells, there is a risk it will be missed during regular gene mapping, so–called exome sequencing.

To detect PZMs, researchers in the new study used data that had previously been collected from 5,947 families who had a child with autism spectrum disorder. They then re–sequenced parts of the DNA from these children using three independent sequencing techniques in parallel. This mapping revealed that 7.5% of the children had autism spectrum disorder that was related to PZMs. Of these, 83% had not been detected at the original analysis of their genome. Some PZMs affect genes that are known to be linked with autism or other neuropsychiatric disorders, while others affect genes that are known to be active in brain development but have not previously been linked with ASD.

By comparing sequencing data, which is primarily on DNA from blood, with data from the public brain banks, which shows when in development (from fetus to adult) these genes are expressed, the researchers also discovered the time point in development when the mutations occurred, and in which areas of the brain they occurred. These analyses showed that PZMs in individuals with ASD occur disproportionately often in the amygdala.

“This was exciting for us because the amygdala has been proposed as a region of the brain that is important in autism. The study contributes by further supporting the hypothesis that complex disturbances in the brain, such as epilepsy, intellectual disorders, schizophrenia and brain malformations, can originate from non–inherited mutations that occur at a certain point in prenatal development”, said Christina Hultman, Professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and responsible for Swedish data on autism.