High-Throughput Sequencing Shows Potentially Hundreds of Gene Mutations Related to Autism
Dec. 19, 2012 — Genomic technology has revolutionized gene discovery and disease understanding in autism, according to an article published in the Dec. 20 issue of the journal Neuron
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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 inNeuron.
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:
- the "staggering degree" of genetic heterogeneity in autism, which means that many individuals with autism do not share similar gene mutations;
- the identification of an increasing number of specific genes and chromosomal intervals conferring risk;
- the important emerging role in autism of both rare and "de novo germline mutations," or mutations developed in the sperm or ovaries of parents and passed on to children; and
- gene loci associated with autism that overlap with gene loci associated with other illnesses, such as intellectual disability and epilepsy.
Dr. Buxbaum estimates that researchers have already identified 50-100 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.