Genomic technology has revolutionized gene discovery and disease understanding in autism, according to an article published in the December 20 issue of the journal Neuron.
The paper highlights the impact of a genomic technology called high-throughput sequencing (HTS) in discovering numerous new genes that are associated with autism spectrum disorder (ASD).
"These new discoveries using HTS confirm that the genetic origins of autism are far more complex than previously believed," said Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai, and lead author of the article in Neuron.
Dr. Buxbaum is co-founder and co-director of the Autism Sequencing Consortium (ASC), a large multisite collaboration which is a model for future research. The co-authors of the article are Mark J. Daly, Broad Institute and Harvard Medical School; Bernie Devlin, University of Pittsburgh; Thomas Lehner, National Institute of Mental Health; Kathryn Roeder, Carnegie-Mellon University; Matthew W. State (co-director), Yale University, and the ASC.
HTS is a revolutionary new technology that allows scientists to obtain the sequence of all 22,000 human genes and the entire human genome in one experiment. This provides an unparalleled look at an individual's genetic makeup and allows for gene discovery and for genetic testing.
"HTS shows us that there are not just a few mutations, but potentially hundreds of mutations that are linked to autism," said Dr. Buxbaum. "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."
Ground-breaking, highly reproducible discoveries identified through HTS described in the article include:
Dr. Buxbaum estimates that researchers have already identified 50 specific genes and 20-40 chromosomal loci conferring risk. The researchers predict, based on the first studies in 1,000 families, that there are many hundreds of undiscovered ASD associated genes. This surge in the number of genes related to autism revealed by HTS marks a coming of age for high-throughput sequencing, the authors believe. The path forward for new discoveries, they write, is via one of two HTS processes: whole exome sequencing (WES) or whole genome sequencing (WGS) in large cohorts. The exome is the small fraction of the genome that codes for proteins.
The article spotlights the successful work of the ASC, founded in 2010, as a model to bring to fruition an explosive gene discovery process. The ASC member sites, using WES technology also available at Mount Sinai, recently discovered six de novo mutations in autism patients: CHD8, DYRK1A, GRIN2B, KATNAL2, POGZ and SCN2A. These six genes may be targets for future treatments. Some of these discoveries were accomplished rapidly because the Consortium's 25 research groups, located around the world, combined their data and shared it before publication. As a result, they conducted four large studies using 1,000 families.
There are approximately 8,000 to 10,000 families currently available to the Consortium to study autism, but the article suggests many more are needed to speed up gene discoveries. 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.
The Mount Sinai Hospital / Mount Sinai School of Medicine: http://www.mountsinai.org
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Bald eagles have made a comeback. See life in the nest now during peak nesting season.
Photos capture a river otter attacking a gator in a Florida river. The otter then feasted, witnesses say.
The 10-meter long Torvosaurus weighed up to five tons.
Researchers say the key to fighting superbugs is individualized treatment plans, and a new nanochip might pave the way
Some farmers have long sworn by mellow tunes to boost Bessie's milk production. The science is hardly conclusive. But a study hints at what might top the barnyard playlist. (Psst: They liked R.E.M.)
Craig Venter, the U.S. scientist who raced the U.S. government to map the human genome over a decade ago and created synthetic life in 2010, is now on a quest to treat age-related disease.
Dr Dave Hone: The Daohugou Fauna is rich in dinosaurs, lizards, pterosaurs, salamanders and mammalsDr Dave Hone
Suppressing a hormone that governs metabolism boosts your chances of living to a grand old age, but there's a downside
Scientists say it is unlikely that any fish can survive in the oceans deeper than about 8,200m.
The discovery of a previously unknown "giant virus" from 30,000 years ago in the Siberian permafrost is bringing researchers closer to understanding the complexity of viruses.