Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Researchers Observe Overlap in Altered Genes Found in Schizophrenia, Autism and ID

Published: Tuesday, April 29, 2014
Last Updated: Thursday, May 01, 2014
Bookmark and Share
Evidence supports theory that some cases of schizophrenia, autism and intellectual disability, malfunctions in some of the same genes are contributing to pathology.

The team, the product of an ongoing collaboration between Professors W. Richard McCombie of Cold Spring Harbor Laboratory (CSHL) and Aiden Corvin of Trinity College, Dublin, studied a type of gene aberration called de novo mutation, in a sample of 42 “trio” families in which the child, but neither parent, was diagnosed with schizophrenia and/or psychosis and 15 trio families with a history of psychosis. 

Schizophrenia is thought to be caused in many instances by gene mutations passed from parents to children, the effects of which may be enhanced by adverse environmental factors. In contrast, de novo mutations, or DNMs, are gene defects in offspring that neither parent possesses. They are the result of mechanical DNA copying errors, and occur infrequently in every human being during sperm and egg development, typically with no overall impact on human health.   

However, on rare occasions, de novo mutations occur in a gene or genes indispensable for normal development and thus can have devastating consequences. This may be true of several of the genes affected by DNMs that are described in the newly published research.  According to Shane McCarthy, Ph.D., a CSHL research investigator who is lead author of the new study, three genes found among the 42 affected children in the study – AUTS2, CDH8 and MECP2 – have been identified in prior genetic studies of people with autism. Two others, HUWE1 and TRAPPC9, have turned up in studies of people with intellectual disability.

Of these five “overlapping” genes, three (CHD8, MECP2 and HUWE1) have convergent function. They play roles in what scientists call the epigenetic regulation of transcription. That is, they are involved in the reading, writing and editing of chemical marks (called epigenetic marks) on DNA and proteins that help control when particular genes are switched on or off.   

This makes the discovery particularly interesting, because “there’s a growing awareness of the importance of epigenetic regulation during brain development, as well as in cognition in the mature brain,” McCarthy points out.  It is possible, the team speculates, that the genes found to affect the same biological function in multiple disorders are examples of those upon which normal brain development depends.  

“Research made possible by the CSHL-Trinity College collaboration is leading us toward a much better understanding of how complex sets of genes are involved in complex illnesses,” says McCombie, who is director of the Stanley Institute for Cognitive Genomics at CSHL. “Our work and that of other researchers, when taken together, is beginning to clarify our view of causation in these very complex, but also very common illnesses.” 

The Stanley Institute is dedicated to discovering the genetic causes of bipolar disorder, schizophrenia, depression and other cognitive disorders. The Institute’s collaboration with Trinity College Dublin has the broader goal of integrating genetics, neurobiology and clinical application in order to impact current and future treatment of mental illness. 

Professor McCombie notes that many genes can contribute to complex disorders such as schizophrenia. The challenge for scientists, he explains, is that “the number of differences between even healthy individuals is so great that finding which specific variant might contribute to a specific disorder such as schizophrenia from among those that don’t cause problems, is difficult.”

The team’s newly published study narrows down the search to a portion of the human genome called the exome. This is the small fraction – some 3%-4% of the total human genome sequence – that contains protein-encoding genes.  This strategy is especially useful in comparing children with their parents, because children have very few genetic variants – de novo mutations, by definition -- that are not in one or the other parent. “Finding de novo variants in a child compared to their parents is technically relatively simple,” says McCombie, and presents scientists with a particularly strong “signal” of potentially significant genetic variation in children who have an illness like schizophrenia that is not evident in either parent. 

McCarthy adds, “In contrast to other methods of exploring the genome for genetic variation underlying schizophrenia risk, the granularity of exome sequencing enables us to identify specific genes that may be involved in the pathogenesis of the illness. This provides us with new biological insights into the disease that could be targeted with novel therapeutics to treat not just schizophrenia but a range of psychiatric disorders."

The research described in this release was funded by Ted and Vada Stanley and Science Foundation Ireland.

De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability” appears in Molecular Psychiatry April 29, 2014.  The authors are: SE McCarthy, J Gillis, M Kramer, S Yoon, Y Bernstein, P Pavlidis, R Solomon, E Ghiban, E Antoniou, E Kelleher, C O’Brien, G Donohoe, M gill, DW Morris, WR McCombie and A Corvin.  

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Specific Variations in RNA Splicing Linked to Breast Cancer
Researchers have identified cellular changes that may play a role in converting normal breast cells into tumors. Targeting these changes could potentially lead to therapies for some forms of breast cancer.
Tuesday, October 06, 2015
Scientists Sequence Genome Of Worm That Can Regrow Body Parts
Worm’s genome could lead to better understanding of its regenerative prowess and advance stem cell biology.
Tuesday, September 22, 2015
Tumor Microenvironment Impacts Cancer Subtype Progression
Scientists report that two different mouse models of breast cancer progressed differently based on characteristics of the tumor microenvironment, which is the area of tissue in which the tumor is embedded.
Friday, May 29, 2015
Using CRISPR, Biologists Find a Way to Comprehensively Identify Anti-Cancer Drug Targets
Scientists at CSHL publish CRISPR gene-editing technology in Nature Biotechnology.
Wednesday, May 13, 2015
3-D Culture System for Pancreatic Cancer has Potential to Change Therapeutic Approaches
Organoid technology with human tissue provides a model for full progression of the disease.
Tuesday, January 06, 2015
CSHL Team Finds a Way to Make shRNA Gene Knockdown More Effective
A powerful algorithm that improves the effectiveness of an important research technology.
Thursday, December 11, 2014
Getting More Out of Nature: Genetic Toolkit Finds New Maximum for Crop Yields
An array of gene variants provides “breakthrough benefits” in tomato yield for breeders; other crops next.
Tuesday, November 04, 2014
CSHL Receives $50M to Establish Simons Center for Quantitative Biology
Center will support research and education programs at one of the world’s leading independent biomedical research institutions.
Tuesday, July 08, 2014
First Animal Model of Adult-Onset SMA Sheds Light on Disease Progression and Treatment
Another proof of principle for TSUNAMI method in modeling spinal muscular atrophy and other splicing-related illnesses.
Thursday, September 12, 2013
Studies Generate ‘Comprehensive’ List of Genes Required to Defend Sex Cells from Transposons
The piRNA pathway protects eggs and sperm from ‘jumping genes’ that can cause developmental defects, sterility.
Monday, May 13, 2013
Boosting Maize Yields with Clever Genetics
A team of plant geneticists at Cold Spring Harbor Laboratory (CSHL) has successfully demonstrated what it describes as a "simple hypothesis" for making significant increases in yields for the maize plant.
Tuesday, February 05, 2013
CSHL Study Uncovers a New Exception to a Decades-Old Rule about RNA Splicing
Discovery alters prevailing view of splicing regulation and has implications for splicing mutations associated with disease.
Thursday, May 24, 2012
CSHL Team Solves a Protein Complex’s Molecular Structure to Explain Role in Gene Silencing
Scientists from Cold Spring Harbor Laboratory and their collaborators at St. Jude’s Research Hospital have discovered new details of how various domains of the protein complex contribute to heterochromatin assembly and gene silencing.
Thursday, December 01, 2011
Single gene dramatically boosts yield, sweetness in tomato hybrids, Israeli study finds
Scientists find the first example of a single gene that causes hybrid vigor
Tuesday, March 30, 2010
Analysis of Microbes, Immune Response Featured in Cold Spring Harbor Protocols
Methods described in the protocol allow the phylogenetic identification of microorganisms in environmental samples.
Wednesday, January 06, 2010
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Promising Drug Combination for Advanced Prostate Cancer
A new drug combination may be effective in treating men with metastatic prostate cancer. Preliminary results of this new approach are encouraging and have led to an ongoing international study being conducted in 196 hospitals worldwide.
A Cellular Symphony Responsible for Autoimmune Disease
Broad Institute researchers have used a novel approach to increase our understanding of the immune system as a whole.
When it Comes to Breast Cancer, Common Pigeon is No Bird Brain
If pigeons went to medical school and specialized in pathology or radiology, they’d be pretty good at distinguishing digitized microscope slides and mammograms of normal vs. cancerous breast tissue, a new study has found.
Editing of LIMS Data Made Faster and More Efficient in Matrix Gemini
The latest version of the Matrix Gemini LIMS (Laboratory Information Management System) from Autoscribe Informatics now provides faster and more efficient editing of LIMS data by eliminating the need for a second editing screen.
University of Edinburgh, Selcia Achieve Key Milestones in Drug Development Program
Scientists from the University of Edinburgh, working with Selcia, have successfully passed the 20-month milestone targets of a 30-month Wellcome Trust SDDi £2.5 million project to design novel treatments for sleeping sickness.
Red Clover Genome to Help Restore Sustainable Farming
The Genome Analysis Centre (TGAC) in collaboration with IBERS, has sequenced and assembled the DNA of red clover to help breeders improve the beneficial traits of this important forage crop.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos