The causes of autism spectrum disorder (ASD) are myriad and complex. However, because the disorder tends to run in families, researchers previously thought that the genes could be inherited. However, a new largest-ever autism genome study reveals that most siblings with ASD have different autism-linked genes.
ASD is a developmental disorder that manifests during the first three years of life. The disorder is characterized by impaired social interaction and verbal and non-verbal communication and by restricted, repetitive, or stereotyped behavior.
Autism currently affects one in 68 children in the United States. Boys are almost five times more likely to suffer from the disorder than girls. Children of parents with autism have a two to 18 percent increased risk of also developing the disorder, and the identical twin of an individual with autism have 36 to 95 percent chance of having the disorder as well.
For the present study published in the journal Nature Medicine and funded by Autism Speaks, researchers led by Stephen Scherer of The Hospital for Sick Children in Ontario used whole genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD. Whole genome sequencing (full genome sequencing, complete genome sequencing, entire genome sequencing) is a laboratory process that determines the complete DNA sequence of the genome of an orgasm at a single time.
The study surprisingly revealed that 69.4 percent of siblings carried different autism-related genetic mutations while only 30.6 percent of siblings carried the same autism-risk genes.
Additionally, the siblings with different genes displayed more variability in autism symptoms than the siblings with the same genes.
The results of the study support the hypothesis that autism may be caused by gene mutations that have “developed sporadically.”
Comment the researchers:
“Although it is possible that other undetected or uncharacterized combinations of rare variants not considered in this study or other common variants may be contributing,” the researchers say, “many autism-risk genes implicated in these families are considered on their own to be sufficiently penetrant to cause autism-relevant phenotypes.”
Adds Dr. Scherer:
“Initially this surprised us, but when we thought more about it, based on what we know, it seems to make sense. Lots of different genes are involved [in autism] – more than 100 – and based on all of the different potential combinations of events, it would be more likely for different genes to be involved than the same gene.
“We knew that there were many differences in autism, but our recent findings firmly nail that down. We believe that each child with autism is like a snowflake – unique from the other.”
The findings additionally support the importance of whole genome sequencing, suggesting that clinicians should not just search for suspected autism-related genes using diagnostic genetic testing. Explains Dr. Scherer:
“What often happens now is that if there is an older child with an autism diagnosis and the gene involved is known, in future children – for reasons of genetic counseling – they often just sequence the known gene to look for mutations in the siblings or other family members. Our story shows you need to go deeper than that and preferably sequence the entire genome.”
Another recent study found that genetics plays a bigger role in autism than environmental factors, with 52 percent of autism risk coming from common genes.
The data from the present study form a part of the MSSNG project, a collaboration between Autism Speaks and Google, which aims to produce a database of at least 10,000 autism genomes openly available for global research.
Says Dr. Scherer:
“This is a historic day as it marks the first time whole genome sequences for autism will be available for research on the MSSNG open-science database. This is an exemplar for a future when open-access genomics will lead to personalized treatments for many developmental and medical disorders.”
Adds co-author Robert Ring, chief science officer of Autism Speaks:
“By using the cloud to make data like this openly accessible to researchers around the world, we’re breaking down barriers in a way never done before. As always, our goal at Autism Speaks is to accelerate scientific discovery that will ultimately improve the lives of individuals with autism at home and around the world.”
The goal of the MSSNG project is to improve understanding of autism and aid the development of personalized treatments for the disorder.
Largest-ever autism genome study finds most siblings have different autism-risk genes: http://www.eurekalert.org/pub_releases/2015-01/as-lag012115.php
Study finds most siblings with autism have different risk genes: http://www.medicalnewstoday.com/articles/288574.php
Whole-genome sequencing of quartet families with autism spectrum disorder: http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3792.html#affil-auth
Brothers on Alphabet Mat: http://www.freeimages.com/photo/1125700