Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Suspect Gene Corrupts Neural Connections

Published: Tuesday, August 19, 2014
Last Updated: Monday, August 18, 2014
Bookmark and Share
“Diseases of synapses” demo’d in a dish - NIH-funded study.

Researchers have long suspected that major mental disorders are genetically-rooted diseases of synapses - the connections between neurons. Now, investigators supported in part by the National Institutes of Health have demonstrated in patients’ cells how a rare mutation in a suspect gene disrupts the turning on and off of dozens of other genes underlying these connections.

“Our results illustrate how genetic risk, abnormal brain development and synapse dysfunction can corrupt brain circuitry at the cellular level in complex psychiatric disorders,” explained Hongjun Song, Ph.D. External Web Site Policy, of Johns Hopkins University, Baltimore, a grantee of the NIH’s National Institute of Mental Health (NIMH), a funder of the study.

Song and colleagues, from universities in the United States, China, and Japan, report on their discovery in the journal Nature, August 18, 2014.

“The approach used in this study serves as a model for linking genetic clues to brain development,” said NIMH director Thomas R. Insel, M.D.

Most major mental disorders, such as schizophrenia, are thought to be caused by a complex interplay of multiple genes and environmental factors. However, studying rare cases of a single disease-linked gene that runs in a family can provide shortcuts to discovery. Decades ago, researchers traced a high prevalence of schizophrenia and other major mental disorders - which often overlap genetically - in a Scottish clan to mutations in the gene DISC1 (Disrupted In Schizophrenia-1). But until now, most of what’s known about cellular effects of such DISC1 mutations has come from studies in the rodent brain.

To learn how human neurons are affected, Song’s team used a disease-in-a-dish technology called induced pluripotent stem cells (iPSCs). A patient’s skin cells are first induced to revert to stem cells. Stem cells play a critical role in development of the organism by transforming into the entire range of specialized cells which make up an adult. In this experiment, these particular “reverted” stem cells were coaxed to differentiate into neurons, which could be studied developing and interacting in a petri dish. This makes it possible to pinpoint, for example, how a particular patient’s mutation might impair synapses. Song and colleagues studied iPSCs from four members of an American family affected by DISC1-linked schizophrenia and genetically related mental disorders.

Strikingly, iPSC-induced neurons, of a type found in front brain areas implicated in psychosis, expressed 80 percent less of the protein made by the DISC1 gene in family members with the mutation, compared to members without the mutation. These mutant neurons showed deficient cellular machinery for communicating with other neurons at synapses.

The researchers traced these deficits to errant expression of genes known to be involved in synaptic transmission, brain development, and key extensions of neurons where synapses are located. Among these abnormally expressed genes were 89 previously linked to schizophrenia, bipolar disorder, depression, and other major mental disorders. This was surprising, as DISC1’s role as a hub that regulates expression of many genes implicated in mental disorders had not previously been appreciated, say the researchers.

The clincher came when researchers experimentally produced the synapse deficits by genetically engineering the DISC1 mutation into otherwise normal iPSC neurons - and, conversely, corrected the synapse deficits in DISC1 mutant iPSC neurons by genetically engineering a fully functional DISC1 gene into them. This established that the DISC1 mutation, was, indeed the cause of the deficits.

The results suggest a common disease mechanism in major mental illnesses that integrates genetic risk, aberrant neurodevelopment, and synapse dysfunction. The overall approach may hold promise for testing potential treatments to correct synaptic deficits, say the researchers.


Further Information

Join For Free

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 3,500+ scientific posters on ePosters
  • More than 5,000+ 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 TechnologyNetworks.com 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

“Sixth Sense” More Than a Feeling
NIH study of rare genetic disorder reveals importance of touch and body awareness.
Monday, September 26, 2016
The Genetics of Blood Pressure
Researchers have identifed areas of the genome associated with blood-pressure including 17 previously unknown loci.
Wednesday, September 21, 2016
Catalogue of Human Genetic Diversity Expands
The largest data set of human exomes to date has been assembled to better study seqence variants and their consequences.
Wednesday, September 07, 2016
$12.4M Awarded to Neural Regeneration Projects
The National Institutes of Health will fund six projects to identify biological factors that influence neural regeneration.
Friday, September 02, 2016
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
Public Support for National Study
Survey shows the majority of respondents support or show willingness for national precision medicine study.
Thursday, August 18, 2016
Schizophrenia, Autism Share Genetic Causes
Monkey brain developmental atlas pinpoints when, where genes activate.
Tuesday, August 16, 2016
How Breast Cancers Resist Chemotherapy
Researchers discovered an unexpected way that breast cancers cells with mutant BRCA1 or BRCA2 genes acquire drug resistance and evade chemotherapies.
Wednesday, August 10, 2016
Mutations Linked to Immunotherapy Resistance
Researchers uncover mutations in tumors of three patients with advanced melanoma that allowed the tumors to become resistant to the immune checkpoint inhibitor pembrolizumab (Keytruda®).
Tuesday, August 09, 2016
Genetic Cause of Rare Pediatric Neuropathy Identified
NIH mouse study identifies the mechanism responsible for a rare form of pediatric neuropathy.
Thursday, August 04, 2016
Depression Genetics Insight from Crowd-Sourced Data
Genome sites liked to depression have been discovered from data shared by people who had purchased their genetic profiles online.
Tuesday, August 02, 2016
Uncovering a New Principle in Chemotherapy Resistance in Breast Cancer
The NIH study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.
Thursday, July 21, 2016
NIH Funds Million-Person Medicine Study
NIH announces $55million in awards to build foundations for ambitious Cohort Program that aims to engage 1 million participants in lifestyle, environments and genetics research.
Friday, July 08, 2016
Largest-Ever Study of Breast Cancer Genetics in Black Women
The study will identify genetic factors that may underlie breast cancer disparities.
Thursday, July 07, 2016
Significant Expansion Of Data Available In The Genomic Data Commons
Cancer genomic profile information from 18,000 adult cancer patients will be added to the database.
Wednesday, June 29, 2016
Scientific News
Heart Arrhythmia Caused by Mosaic of Mutant Cells
Researchers have solved the genetic mystery of an infant suffering from heart arrhythmia.
Crispr Toolbox Expanded By Protein
Researchers have shown a newly discovered CRISPR protein has two distinct RNA cutting activities.
Genetic Impact of Endurance Training
Research has found that endurance training changes genetic activity in thousands of genes, giving rise to large number of altered RNA variants.
Wearable Microscope Can Measure Fluorescent Dyes Through Skin
UCLA research could make monitoring disease biomarkers easier and more cost-effective.
“Sixth Sense” More Than a Feeling
NIH study of rare genetic disorder reveals importance of touch and body awareness.
A Diversity of Genomes
New DNA from understudied groups reveals modern genetic variation, ancient population shifts.
Gene Could Reduce Female Mosquitoes
Virginia Tech researchers have found a gene that can reduce female mosquitoes over many generations.
Improving Crop Efficiency with CRISPR
New study of CRISPR-Cas9 technology from Virginia Tech shows potential to improve crop efficiency.
Examining mtDNA May Help Identify Unknown Ancestry That Influences Breast Cancer Risk
Researchers studying mtDNA in a group of triple negative breast cancer patients found that 13 percent of participants were unaware of ancestry that could influence their risk of cancer.
Bacteria Use Ranking Strategy to Fight Off Viruses
Researchers have explained why microbes store virus confrontation information sequentially, with most recent attacks first.
Skyscraper Banner

SELECTBIO Market Reports
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!