Navigation Links
Sporadic mutations identified in children with autism spectrum disorders
Date:5/16/2011

Scientists at the University of Washington (UW) Department of Genome Sciences have identified several sporadic or "de novo" genetic mutations in children with autism spectrum disorder. The researchers applied leading edge molecular biology techniques and massively parallel sequencing to simultaneously examine all of the protein coding portions of the genome, collectively called the exome.

The research was published in advance online Sunday, May 15, in Nature Genetics.

The study was led by Dr. Brian O'Roak, senior fellow in the UW Department of Genome Sciences, and senior authors Dr. Evan Eichler, UW professor of genome sciences and a Howard Hughes Medical Institute investigator, and Dr. Jay Shendure, UW assistant professor of genome sciences.

O'Roak and colleagues analyzed the exomes of 20 individuals with autism spectrum disorder and their parents, an approach called trio-based exome sequencing. Autism spectrum disorders encompass a range of social impairments in language, communicating and interacting with others, repetitive behaviors, and engrossing fascinations. The condition can be mildly to severely disabling.

The researchers found 21 newly occurring mutations, 11 of which altered proteins. Proteins altered by genetic mutations may hold clues to the biological pathways involved in the development of the disease. The abnormal proteins or the pathways they affect could draw interest as targets in the design of preventive or treatment drugs.

O'Roak's fellowship at the UW, as well as part of the research itself, was supported by American Recovery and Reinvestment Act funding from the U.S. government. O'Roak said, "I came to the UW with the specific plan to use the latest genomic technology to study autism because it affects the lives of so many children, adults and their families."

In four of the 20 families studied, O'Roak and colleagues identified disruptive new mutations that are potentially causative for autism. In examining the clinical data on the child in each of the four families, they learned that these children were among the most severely affected of the study group, both in intellectual disability and in their autistic features.

These initial findings point to the possibility that these new sporadic disruptive genetic mutations could contribute substantially to the underlying mechanisms and severity of autism in perhaps 20 percent of the cases in which no larger family history of autism exists. In some cases, the combination of newly appearing mutations and those inherited from the parents may worsen the severity of the disorder.

"The results of the study suggest a multi-hit model as a trend, but this possibility would need to be further explored by comparing a much larger number of affected and unaffected siblings," said Eichler.

In this study, many of the discovered mutations were located in genome areas that were highly conserved during evolution. These parts of the genome likely play a fundamental role in the biology of many animals, including humans. Mutations in these regions tend to have significant repercussions.

"Consistent with the complexity of autism and its symptoms, the new mutations were identified in several different genes," lead author O'Roak said. Moreover, many of these mutated genes have already been associated with other brain disorders, including epilepsy, schizophrenia and intellectual disability -- reflecting a surprising genetic overlap.

Eichler explained that scientists are not sure what the genetic overlap means. It could point to common underlying mechanisms in the development of these neurological diseases, or different manifestations stemming from similar genetic lesions. It might also be due to many other factors, such as environmental triggers or other genes in a person's make-up that influence how and when genes operate, whether or not a disease will appear in a genetically susceptible individual, and what type of disease it will be.

How and why sporadic mutations such as these originate is as yet unknown. However researchers are uncovering clues about risk factors.

In six of the affected children in this study, the scientists were able to trace the original genes that were later mutated in the child back to the father's half the child's genome, and in one case to the mother's half.

These genetic findings further support population studies showing that autism is more common among children of older parents, especially older fathers. Eichler explained that certain genetic mutations might more likely occur during sperm formation as men age.

The scientists wrote, "The identification of de novo events along with disruptive inherited mutations underlying sporadic cases of autism spectrum disorders has the potential to fundamentally transform our understanding of the genetic basis of autism."

"Our results," Shendure noted, "show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for autism spectrum disorders."

From identifying mutations, researchers hope to learn more about the biology of autism and to understand interacting genetic and environmental factors within the context of families with affected and unaffected members.


'/>"/>

Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert  

Related medicine news :

1. New sporadic prion protein disease identified by Case Western Reserve
2. Sporadic breast cancers start with ineffective DNA repair systems, Pitt researchers find
3. Gene Mutations Identified for Charcot-Marie-Tooth Syndrome
4. Study shows that mutations in 1 gene cause many cancers
5. Breast cancer patients with BRCA mutations 4 times more likely to get cancer in opposite breast
6. Gene Mutations Up Risk for Cancer in Opposite Breast
7. Heart Disease Among Childhood Cancer Survivors Tied to Gene Mutations
8. Single Lung Tumor Contains 50,000 Mutations
9. Gene Mutations Offer Clues to Autoimmune Disorders
10. Individual mutations are very slow to promote tumor growth
11. Study finds women with triple negative breast cancer and BRCA mutations have lower risk of recurrence
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Sporadic mutations identified in children with autism spectrum disorders
(Date:6/24/2016)... ... ... a crisis. Her son James, eight, was out of control. Prone to extreme mood shifts ... upset him, he couldn’t control his emotions,” remembers Marcy. “If there was a knife ... and say he was going to kill them. If we were driving on the ...
(Date:6/24/2016)... ... 24, 2016 , ... Global law firm Greenberg Traurig, P.A. announced that 20 ... by their peers for this recognition are considered among the top 2 percent of ... honors as members of this year’s Legal Elite Hall of Fame: Miami Shareholders ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... Comfort Keepers® ... American Cancer Society and the Road To Recovery® program to drive cancer patients to ... and other adults to ensure the highest quality of life and ongoing independence. ...
(Date:6/24/2016)... ... 2016 , ... People across the U.S. are sharpening their pencils and honing ... contest in which patients and their families pay tribute to a genetic counselor by ... Society of Genetic Counselors (NSGC) Annual Education Conference (AEC) this September. , In ...
(Date:6/24/2016)... ... 24, 2016 , ... The Haute Beauty Network, affiliated with ... as a prominent plastic surgeon and the network’s newest partner. , Dr. ... handsome men, look naturally attractive. Plastic surgery should be invisible.” He stands by ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... FRANCISCO, Calif. , June 24, 2016 /PRNewswire/ ... ), a biopharmaceutical company developing novel therapeutics for ... unmet needs, today announced the closing of its ... of common stock, at the public offering price ... in the offering were offered by GBT. GBT ...
(Date:6/24/2016)... , June 24, 2016 The Academy of ... recommendations that would allow biopharmaceutical companies to ... entities that make formulary and coverage decisions, a move ... of new medicines. The recommendations address restrictions ... appear on the drug label, a prohibition that hinders ...
(Date:6/24/2016)... -- According to a new market research ... Safety Pen Needles), Needle Length (4mm, 5mm, 6mm, 8mm, ... Purchase (Retail, Non-Retail) - Trends & Global Forecasts to ... for the forecast period of 2016 to 2021. This ... 2021 from USD 1.65 Billion in 2016, growing at ...
Breaking Medicine Technology: