Rare and common mutations play critical roles in the genetic underpinnings of autism

July 24, 2014

Rare genetic variants have a strong role in autism (ASD), but recent findings also point to more common mutations in the development of the disorder.

In a study published online July 20, a US NIMH-funded team announced findings based on Swedish data indicating that common variations are responsible for most of the risk of developing autism. Two months earlier, a team led by Dr. Stephen Scherer, co-PI of NeuroDevNet’s Autism Research Group, published findings in Nature Genetics focusing on rare variations and deletions in what has been described as a genetic code for ASD that will help aid early diagnosis of ASD.


Scherer’s team identified almost 4,000 exons in more than 1,700 genes that play a role in brain development, a process that is highly dependent on exons “switching on” in brain cells in the right time, and in the right place.

“The fact that these genes could be turned on prenatally gives us a clue as to when autism starts to develop,” says Scherer. “With this study, we’ve finally discovered a unifying set of characteristics in the DNA that we can weave into a ‘genetic formula’ that helps calculate which genetic mutations have the highest probability of causing autism,” Dr. Scherer says. “Equally important, these findings also indicate which gene alterations do not play a role.

“The big question in the field is, why do some mutations in brain genes cause autism, while others do not,” continues Scherer. “In our paper, we found that patterns of genes, in particular segments of genes called exons gave us the answer. The big victory is that nobody had figured out this pattern before.”

Scherer describes the finding, as “a game-changer in how we think about the “genetic expression” of autism. Our findings implicate more than just a few prenatal genes and indicate that this autism trajectory starts very early.” So far all 100 known ASD risk genes fall into the grouping identified in the Nature Genetics study, “so we expect that the remainder of the set will help explain to families why autism came about in their children.”

The more recent findings drew on a Swedish national public health database that enabled comparision of DNA variations in almost 3,000 individuals. Sweden’s population is very homogenous, with only about 10 percent of residents from other ethnic backgrounds.

The paper, produced by a team led by Joseph Buxbaum, of the Icahn School of Medicine at Mount Sinai, in New York City is important, according to Scherer, “as it represents a first attempt to estimate the role of common genetic variants in autism using a large epidemiological dataset.

“Their speculations may also provide ways to explain the wide range of behavioral features that we often see with autism,” Dr. Scherer said, in an online article published by Autism Speaks.