Navigation Links
Gene variants in autism linked to brain development

New research on the genomics of autism confirms that the genetic roots of the disorder are highly complicated, but that common biological themes underlie this complexity. In the current study, researchers have implicated several new candidate genes and genomic variants as contributors to autism, and conclude that many more remain to be discovered. While the gene alterations are individually very rare, they mostly appear to disrupt genes that play important functional roles in brain development and nerve signaling.

While an association between genomic variants in certain nervous system processes and autism has been hypothesized in the past, the current research definitively links these biological functions to autism.

"This large study is the first to demonstrate a statistically significant connection between genomic variants in autism and both synaptic function and neurotransmission," said senior author Peter S. White, Ph.D., a molecular geneticist and director of the Center for Biomedical Informatics at The Children's Hospital of Philadelphia. Synapses are the contact points at which nerve cells communicate with other nerve cells, while neurotransmitters are the chemical messengers carrying those signals.

"Prior genomic studies of autism have successfully identified several genes that appear to confer risk for autism, but each gene appears to contribute to only a small percentage of cases," said the lead author, Xiaowu Gai, Ph.D. "Our approach considered whether groups of genes with common biological functions collectively accounted for a greater percentage of autism risk."

The study appears online today in the journal Molecular Psychiatry.

White and colleagues compared the DNA of more than 1,000 children with autism to control sets of healthy subjects, searching for gene variants called copy number variations (CNVs) appearing in the genomes of autistic individuals and their families, but not in healthy controls. The study team reinforced their findings using information from mouse models, showing that mice with abnormal motor and learning behaviors similar to human autistic behaviors were more likely to have CNVs in genes analogous to human autism genes.

"Because the gene alterations that we found influence brain development, our hope is that they may eventually provide clues to developing diagnostic tests as well as treatments for children with autism," said co-author and lead clinician Josephine Elia, M.D., a child psychiatrist at Children's Hospital.

Unlike changes to single bases in DNA, called single-nucleotide polymorphisms (SNPs or "snips"), CNVs are larger alterations in DNA structuremissing or repeated stretches of dozens or hundreds of bases in sequence. CNVs have been implicated in other neuropsychiatric disorders, such as schizophrenia, bipolar disorder and attention-deficit hyperactivity disorder (ADHD)the latter in a previous study by White and Elia.

In the current research, White and colleagues searched for CNVs in a discovery cohort of 631 children with autism, 1,162 parents of these children, and a healthy control set of 1,775 children. They found nearly 400 inherited CNVs in autism subjects that did not occur in controls. They also analyzed a second cohort of 593 additional autism subjects, 1,109 corresponding parents, and 2,026 healthy controls. This second study found another set of nearly 400 inherited CNVs exclusive to children with autism. Surprisingly, no single gene was frequently disrupted in either set, and only a few genes harbored CNVs in both sets.

Although there was relatively little overlap between sets of CNVs found in the two cohorts, the CNVs tended to occur in genes that affected biological processes relevant to autism. "While individually, CNVs are rare, each of them often appearing only in one family in our study, we found in this study that CNVs tend to occur in genes with similar functional rolesmost especially in affecting synapse function, neurotransmission and brain development," said White. "This suggested to us that there may be many differentpossibly even hundredsof genetic paths to autism, with only a few gene alterations relevant to each individual patient. But if those hundreds of genes have similar roles in the nervous system, the end result may lead to the same diagnosis: an autism spectrum disorder."

With many genes possibly involved in autism, adds White, researchers face a stronger challenge in devising gene-based diagnostic tests and eventually developing drug treatments than would be the case if fewer genes were involved.

However, the fact that the current study consistently pointed to the same functional pathways and gene sets associated with neurological processes strongly suggests these pathways could be fruitful targets for further investigation.


Contact: John Ascenzi
Children's Hospital of Philadelphia

Related biology news :

1. Genetic variants linked to increased risk of common gynecological disease
2. New variants found that indicate a predisposition to type 2 diabetes
3. Autism genome project identifies genetic variants that may make people susceptible to disorder
4. Newly discovered gene variants lead to autism and mental retardation
5. Meta-analysis: Radiotherapy variants improve survival in non-metastatic lung cancer
6. New gene variants associated with glucose, insulin levels, some with diabetes risk
7. Identification of genetic variants affecting age at menopause could help improve fertility treatment
8. Common gene variants influence risk factor for sudden cardiac death
9. Common gene variants increase risk of hypertension, may lead to new therapies
10. International study identifies gene variants associated with early heart attack
11. Mayo: Variants in gene on X chromosome associated with increased susceptibility to Alzheimers
Post Your Comments:
(Date:10/27/2015)... BERLIN, Germany , October 27, 2015 ... 2015. SMI,s Automated Semantic Gaze Mapping technology (ASGM) automatically ... SMI,s Eye Tracking Glasses , so that ... Suite BeGaze. --> Munich, Germany ... technology (ASGM) automatically maps data from mobile eye tracking ...
(Date:10/26/2015)... 26, 2015 ... adds Biometrics Market Shares, Strategies ... well as Emerging Biometrics Technologies: Global ... its collection of IT and Telecommunications ... --> . ...
(Date:10/26/2015)... Calif. , Oct. 26, 2015  Delta ID ... biometric authentication to mobile and PC devices, announced its ... smartphone, the arrows NX F-02H launched by NTT DOCOMO, ... NX F-02H is the second smartphone to include iris ... technology in ARROWS NX F-04G in May 2015, world,s ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... ... 2015 , ... A long-standing partnership between the Academy of ... formalized with the signing of a Memorandum of Understanding. , AMA Executive Director ... Minter and Capt. Albert Glenn Tuesday, November 24, 2015, at AMA Headquarters in ...
(Date:11/24/2015)... ... November 24, 2015 , ... The United States Golf Association (USGA) today ... Green Section Award. Presented annually since 1961, the USGA Green Section Award recognizes an ... turfgrass. , Clarke, of Iselin, N.J., is an extension specialist of turfgrass ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... ... event of the year and one of the premier annual events for pharmaceutical ... ran from 8–11 November 2015, where ISPE hosted the largest number of attendees ...
(Date:11/24/2015)... ... 2015 , ... The Academy of Model Aeronautics (AMA), led by its Executive ... Multirotor Grand Prix, to represent the First–Person View (FPV) racing community. , FPV racing ... this type of racing and several new model aviation pilots have joined the community ...
Breaking Biology Technology: