Team develops framework to identify genetic missense mutations linked to autism spectrum disorder

June 11, 2018 by Shilo Rea, Carnegie Mellon University
Credit: CC0 Public Domain

Missense mutations occur when there is a change in one gene's DNA base pair, and the change results in the substitution of one amino acid for another in the gene's protein. Mutations that disrupt the function of proteins are widely recognized as a risk source for development disorders such as intellectual disability, congenital heart defects and autism spectrum disorder (ASD).

A new study published in Nature Genetics established a computationally integrated approach to investigate the functional impact of missense mutations. The team, which includes Carnegie Mellon University's Kathyrn Roeder, tested the approach by analyzing genetic structures of individuals with ASD who also had mutations as well as their siblings who did not have the mutations. They found that the framework successfully identified and prioritized missense mutations that contribute to disease or disorder risk.

"Identifying that increase the likelihood of disease is a major challenge to progress for personalized medicine. Using a machine learning model that predicts which mutations are likely to perturb the human interactome network, we showed that these mutations are much more likely to occur in autistic children than their siblings," said Roeder, the UPMC Professor of Statistics and Life Sciences in the Dietrich College of Humanities and Social Sciences. "This result extends to several other mental disorders suggesting that our finding may have even broader applicability."

Explore further: Regulatory mutations missed in standard genetic screening lead to congenital diseases

More information: Siwei Chen et al, An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders, Nature Genetics (2018). DOI: 10.1038/s41588-018-0130-z

Related Stories

Regulatory mutations missed in standard genetic screening lead to congenital diseases

May 25, 2018
Researchers have identified a type of genetic aberration to be the cause of certain neurodevelopmental disorders and congenital diseases, such as autism and congenital heart disease, which are undetectable by conventional ...

New brain development disorder identified by scientists

May 22, 2018
Researchers have identified a new inherited neurodevelopmental disease that causes slow growth, seizures and learning difficulties in humans.

Newly identified gene mutation results in intellectual disability and developmental delay

April 12, 2018
An international group of researchers led by Cold Spring Harbor Laboratory (CSHL) Assistant Professor Gholson Lyon has identified a new genetic mutation associated with intellectual disability, developmental delay, autism ...

A cluster of mutations in neurofibromatosis is important risk factor for severe symptoms

December 28, 2017
Research led by Ludwine Messiaen, Ph.D., professor of genetics at the University of Alabama at Birmingham, shows that missense mutations in a cluster of just five codons in the NF1 gene are an important risk factor for severe ...

The gene causing new brain disorder

March 23, 2018
Newly discovered gene mutations may help explain the cause of a disease that drastically impairs walking and thinking.

Autism spectrum disorder linked to mutations in some mitochondrial DNA

October 28, 2016
Children diagnosed with autism spectrum disorder (ASD) have greater numbers of harmful mutations in their mitochondrial DNA than family members, report Zhenglong Gu of Cornell University in Ithaca, New York, and colleagues, ...

Recommended for you

Ovarian cancer genetics unravelled

August 14, 2018
Patterns of genetic mutation in ovarian cancer are helping make sense of the disease, and could be used to personalise treatment in future.

New genome-editing strategy could lead to therapeutics

August 14, 2018
Researchers at UMass Medical School have developed a genome-editing strategy to correct disease-causing DNA mutations in mouse models of human genetic diseases, according to research published in the Aug. 18 edition of Nature ...

Study reveals broad 'genetic architectures' of traits and diseases

August 13, 2018
Scientists at Johns Hopkins Bloomberg School of Public Health have developed a powerful method for characterizing the broad patterns of genetic contributions to traits and diseases. The new method provides a "big picture" ...

Researchers predict risk for common deadly diseases from millions of genetic variants

August 13, 2018
A research team at the Broad Institute of MIT and Harvard, Massachusetts General Hospital (MGH), and Harvard Medical School reports a new kind of genome analysis that could identify large fractions of the population who have ...

Genetic tools uncover cause of childhood seizure disorder missed by other methods

August 13, 2018
Early childhood seizures result from a rare disease that begin in the first months of life. Researchers at University of Utah Health have developed high-tech tools to uncover the genetic cause of the most difficult to diagnose ...

Evolutionary changes in the human brain may have led to bipolar disorder and schizophrenia

August 9, 2018
The same aspects of relatively recent evolutionary changes that make us prone to bad backs and impacted third molars may have generated long, noncoding stretches of DNA that predispose individuals to schizophrenia, bipolar ...

0 comments

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.