Researchers discover new genes contributing to autism, links to psychiatric disorders

April 19, 2012, Massachusetts General Hospital

A new approach to investigating hard-to-find chromosomal abnormalities has identified 33 genes associated with autism and related disorders, 22 for the first time. Several of these genes also appear to be altered in different ways in individuals with psychiatric disorders such as schizophrenia, symptoms of which may begin in adolescence or adulthood. Results of the study by a multi-institutional research team will appear in the April 27 issue of Cell and have been released online.

"By sequencing the genomes of a group of children with neurodevelopmental abnormalities, including , who were also known to have abnormal chromosomes, we identified the precise points where the are disrupted and segments exchanged within or between chromosomes. As a result, we were able to discover a series of that have a strong individual impact on these disorders," says James Gusella, PhD, director of the Massachusetts General Hospital Center for Human Genetic Research (MGH CHGR) and senior author of the Cell paper. "We also found that many of these genes play a role in diverse clinical situations – from severe intellectual disability to adult-onset – leading to the conclusion that these genes are very sensitive to even subtle perturbations."

Physicians evaluating children with neurodevelopmental abnormalities often order tests to examine their chromosomes, but while these tests can detect significant abnormalities in chromosomal structure, they typically cannot identify a specific gene as being disrupted. Structural variants known as balanced chromosome abnormalities (BCAs) – in which DNA segments are moved into different locations in the same chromosome or exchanged with segments in other chromosomes, leaving the overall size of the chromosomes unchanged – are known to be significantly more common in individuals with autism spectrum disorders than in a control population. Several years ago Gusella and Cynthia Morton, PhD, of Brigham and Women's Hospital initiated the Developmental Anatomy Project to identify developmentally important genes by investigating BCAs, but the task of identifying specific chromosome breakpoints has been slow and laborious.

To get a clearer view of the potential impact of BCAs on autism, the research team took advantage of a new approach developed by Michael Talkowski, PhD, of the MGH CHGR, lead author of the Cell paper, which allows the sequencing of an individual's entire genome in a way that detects the breakpoints of BCAs. The whole procedure can be accomplished in less than two weeks rather than the many months previously required. Screening the genomes of 38 individuals diagnosed with autism or other neurodevelopmental disorders found chromosomal breakpoints and rearrangements in non-protein-coding regions that disrupted 33 genes, only 11 of which previously had been suspected in these disorders.

As they compiled their results, the researchers were struck by how many of the BCA-disrupted genes they identified had been associated with psychiatric disorders in previous studies. To test their observation, they examined data from the largest genome-wide association study in schizophrenia to date – in collaboration with Mark Daly, PhD, also of the MGH CHGR who led that study – and found that a significant number of the BCA-disrupted genes identified in the current study were associated with schizophrenia when altered by more subtle variants that are common in the population.

"The theory that schizophrenia is a neurodevelopmental disorder has long been hypothesized, but we are just now beginning to uncover specific portions of the genetic underpinnings that may support that theory," says Talkowski. "We also found that different gene variations – deletion, duplication or inactivation – can result in very similar effects, while two similar changes at the same site might have very different neurodevelopmental manifestations. We suspected that the genetic causes of autism and other neurodevelopmental abnormalities are complex and likely to involve many genes, and our data support this."

Adds Gusella, who is the Bullard Professor of Neurogenetics at Harvard Medical School, "Our results suggest that many genes and pathways are important to normal brain development and that perturbation of some can lead to a great variety of developmental or psychiatric conditions, warranting extensive further study. We're hoping to investigate how these gene disruptions alter other genes and pathways and how prevalent these rearrangements are in the general population. This is a first step in what will be a long journey toward understanding genes underlying the pathophysiology of neurodevelopmental and and developing new clinical treatments."

Explore further: Researchers find alterations of a single gene associated with intellectual disability, epilepsy and autistic features

Related Stories

Researchers find alterations of a single gene associated with intellectual disability, epilepsy and autistic features

October 7, 2011
(Medical Xpress) -- Virginia Commonwealth University School of Medicine researchers, working with an international team of colleagues, have identified a gene that may play a role in causing a neurodevelopmental disorder that ...

Study characterizes epigenetic signatures of autism in brain tissue

November 7, 2011
Neurons in the prefrontal cortex of individuals with autism show changes at numerous sites across the genome, according to a study being published Online First by the Archives of General Psychiatry.

Mutations in 3 genes linked to autism spectrum disorders

April 4, 2012
Mutations in three new genes have been linked to autism, according to new studies including one with investigators at Mount Sinai School of Medicine. All three studies include lead investigators of the Autism Sequencing Consortium ...

Study identifies gene expression abnormalities in autism

March 22, 2012
A study led by Eric Courchesne, PhD, director of the Autism Center of Excellence at the University of California, San Diego School of Medicine has, for the first time, identified in young autism patients genetic mechanisms ...

Recommended for you

Genes contribute to biological motion perception and its covariation with autistic traits

January 22, 2018
Humans can readily perceive and recognize the movements of a living creature, based solely on a few point-lights tracking the motion of the major joints. Such exquisite sensitivity to biological motion (BM) signals is essential ...

Nearly imperceptible fluctuations in movement correspond to autism diagnoses

January 17, 2018
A new study led by researchers at Indiana University and Rutgers University provides the strongest evidence yet that nearly imperceptible changes in how people move can be used to diagnose neurodevelopmental disorders, including ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Being bilingual may help autistic children

January 16, 2018
Children with Autism Spectrum Disorders (ASD) often have a hard time switching gears from one task to another. But being bilingual may actually make it a bit easier for them to do so, according to a new study which was recently ...

No rise in autism in US in past three years: study

January 2, 2018
After more than a decade of steady increases in the rate of children diagnosed with autism in the United States, the rate has plateaued in the past three years, researchers said Tuesday.

Autism therapy: Brain stimulation restores social behavior in mice

December 13, 2017
Scientists are examining the feasibility of treating autistic children with neuromodulation after a new study showed social impairments can be corrected by brain stimulation.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.