Autism often has a genetic component, which may differ between low-functioning and high-functioning individuals. (Source: Flickr)

Autism often has a genetic component, which may differ between low-functioning and high-functioning individuals. (Source: Flickr)

Researchers at the Cold Spring Harbor Laboratory have found an association between rare genetic mutations and extreme forms of autism. The strength of the associations suggests that mutations in these genes can actually cause autism. This goes against the theory that common mutations can accumulate to increase the risk of autism development (1).

The researchers looked at the genomes of over 2400 families with simplex autism, in which only one family member had the disorder. They found that about half of these cases come from de novo mutations, which occur between generations. The mutation in question would be absent in the parents but present in the child (2).

These genes are termed “vulnerable” in that a single mutation is likely to cause autism on its own. The form of autism is often severe and results in children with lower IQs. Unsurprisingly, mutations in these genes are rare and selected against, as children with severe autism are less likely to reproduce (1, 2).

The researchers initially found 500 genes likely cause autism, but were later able to narrow their list to 200 that had the best chance of being causal (1). Many of these genes are expressed in the brain prenatally, but shut down after birth. There could be many more such genes, as this study looked only at mutations in the exome, the portion of DNA that is converted into proteins (2).

A few of these causal genes were inherited from mothers, which supports previous studies that found that the risk for autism could be spread through a shared maternal lineage (2). This, combined with the fact that there are four times as many boys with autism than girls, suggests that females may have a protective factor against developing autism (1).

Researchers further speculate that high-functioning autism is not caused by any single de novo mutation, but by a combination of genes. They expect the genes involved to be less likely to be selected against, and thus more likely to accumulate in the general population. In contrast to the “causal” gene mechanism, these genes could be directly inherited from one or both parents, which would increase the risk of autism (2).

Additionally, the parents may display endophenotypes, which involves having symptoms of autism but not the disorder itself. Oddly, the mothers of high-functioning children are more likely to display endophenotypes. This is despite the proposed “protection” that females tend to display against autism. Alternately, researchers theorize that high-functioning autism may not be caused by genetic factors, but by the environment instead (2). Whichever the case, the hope is that future research may yield insight into how to not only mitigate the chance of autism, but also treat those on the autistic spectrum.

References

  1. Cold Spring Harbor Laboratory. (2015, September 22). Genetic analysis supports prediction that spontaneous rare mutations cause half of autism: Quantitative study identifies 239 genes whose ‘vulnerability’ to devastating de novo mutation makes them priority research targets. ScienceDaily. Retrieved September 24, 2015 from sciencedaily.com/releases/2015/09/150922150236.htm
  2. Ivan Iossifov, Dan Levy, Jeremy Allen, Kenny Ye, Michael Ronemus, Yoon-ha Lee, Boris Yamrom and Michael Wigler. Low load for disruptive mutations in autism genes and their biased transmission. PNAS, September 2015 DOI: 1073/pnas.1516376112