There are literally hundreds of mutated genes associated with autism spectrum disorder (ASD), researchers from the Seaver Autism Center at Icahn School of Medicine at Mount Sinai reported in the journal Neuron.
The scientists explained that genomic technology has completely transformed gene discovery and the understanding of autism. A technology called HTS (high-throughput sequencing) has discovered many new genes that are associated with ASD.
Joseph D. Buxbaum, PhD., wrote:
“These new discoveries using HTS confirm that the genetic origins of autism are far more complex than previously believed.”
With HTS, scientists can obtain the sequence of all 22,000 human genes and the whole human genome in just one experiment, allowing them to rapidly observe a person’s genetic makeup. Being able to do all this in one go makes it much easier for genetic testing and gene discovery.
“HTS shows us that there are not just a few mutations, but potentially hundreds of mutations that are linked to autism. By identifying the many genetic roots of this disorder, we can better understand its biology, which in turn will allow us to develop more tailored treatments for individuals. It is a transformative time for genetic research in autism.”
The following breakthroughs have been achieved thanks to HTS:
- People with an ASD do not share similar gene mutations. Buxbaum describes the “staggering degree of genetic heterogeneity in autism”.
- A growing number of specific genes and chromosomal intervals that confer risk have been identified
- How mutations that developed in the sperm or ovaries of the parents were passed onto children, and their important emerging role in autism
- The specific locations of genes on a chromosome (gene loci) which are associated with autism that overlap other syndromes and illnesses, such as epilepsy and cognitive ability have been identified. Researchers from Duke University Medical Center and Rockefeller University reported in the journal Nature a link between fragile X protein and almost 100 genes involved in autism.
They have already identified from 50 to 100 specific genes and 20 to 40 chromosomal loci conferring ASD risk, Dr. Buxbaum estimates.
Their first studies covered 1,000 families. The scientists predict that there must be several hundred undiscovered genes which are linked to autism. This sudden increase in discoveries of autism-related genes revealed by HTS marks a coming of age for this kind of technology, the authors wrote.
Future HTS processes should focus on either:
- WES – Whole Exome Sequencing. The exome is formed by exons. Exons are the coding portions of genes that are expressed to provide the genetic blueprint that is used when proteins and other function gene products are synthesized. The human genome consists of approximately 180,000 exons, which make up roughly 1% of the total genome.
- WGS – Whole Genome Sequencing
The authors make a special mention of the work carried out by the Autism Sequencing Consortium (ASC) in its gene discovery process. With WES technology they discovered six de novo mutations in patients with ASD: KATNAL2, CHD8, GRIN2B, POGZ, DYRK1A and SCN2A. Future treatment may well target these six genes.
Some of the discoveries were achieved rapidly because the Consortium consists of 25 groups around the globe; they combine their information and share it before publishing. They were thus able to carry out four large studies on 1,000 families.
In order to speed up gene discoveries, the authors say that more than the current 8,000 to 10,000 families available to the Consortium to study are needed.
The authors added “Also needed for the future is increased collaboration among research teams and the integration of autism studies with studies of other psychiatric disorders. In addition, high-capacity supercomputers are needed to analyze the data. The ASC was designed to address these issues, and Mount Sinai has created Minerva, one of the largest academic supercomputers in the world, to help with these goals.”
ASD is a disorder of neural development which causes considerable challenges in social and communication, as well as language delays. It affects approximately 1 in every 88 children in the USA, says the CDC (Centers for Disease Control and Prevention).
Autism has no cure. Some scientists are looking into possible environmental causes of the disorder.
Modern technology has helped researchers realize that the key causes of autism are gene mutations. The authors emphasize that in order to find effective treatments for ASD, new related genes need to be discovered.
Written by Christian Nordqvist