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

Stray Prenatal Gene Network Suspected in Schizophrenia

Published: Monday, August 05, 2013
Last Updated: Monday, August 05, 2013
Bookmark and Share
May disrupt birth of new neurons in prefrontal cortex.

Researchers have reverse-engineered the outlines of a disrupted prenatal gene network in schizophrenia (http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml), by tracing spontaneous mutations to where and when they likely cause damage in the brain.

Some people with the brain disorder may suffer from impaired birth of new neurons, or neurogenesis, in the front of their brain during prenatal development, suggests the study, which was funded by the National Institutes of Health.

"Processes critical for the brain's development can be revealed by the mutations that disrupt them," explained Mary-Claire King, Ph.D., University of Washington (UW), Seattle, a grantee of NIH's National Institute of Mental Health (NIMH).

King continued, "Mutations can lead to loss of integrity of a whole pathway, not just of a single gene. Our results implicate networked genes underlying a pathway responsible for orchestrating neurogenesis in the prefrontal cortex in schizophrenia."

King, and collaborators at UW and seven other research centers participating in the NIMH genetics repository, report on their discovery Aug. 1, 2013 in the journal Cell.

"By linking genomic findings to functional measures, this approach gives us additional insight into how early development differs in the brain of someone who will eventually manifest the symptoms of psychosis," said NIMH Director Thomas R. Insel, M.D.

Earlier studies (http://www.nimh.nih.gov/news/science-news/2008/spontaneous-mutations-rife-in-non-familial-schizophrenia.shtml) had linked spontaneous mutations to non-familial schizophrenia and traced them broadly to genes involved in brain development, but little was known about convergent effects on pathways.

King and colleagues set out to explore causes of schizophrenia by integrating genomic data with newly available online transcriptome (http://www.nimh.nih.gov/news/science-news/2009/atlas-will-reveal-when-and-where-genes-turn-on-in-the-brain.shtml) resources that show where in the brain and when in development genes turn on.

They compared spontaneous mutations in 105 people with schizophrenia with those in 84 unaffected siblings, in families without previous histories of the illness.

Unlike most other genes, expression levels of many of the 50 mutation-containing genes that form the suspected network were highest early in fetal development, tapered off by childhood, but conspicuously increased again in early adulthood - just when schizophrenia symptoms typically first develop.

This adds to evidence supporting the prevailing neurodevelopmental model (http://www.nimh.nih.gov/about/director/publications/rethinking-schizophrenia.shtml) of schizophrenia.

The implicated genes play important roles in migration of cells in the developing brain, communication between brain cells, regulation of gene expression, and related intracellular workings.

Having an older father increased the likelihood of spontaneous mutations for both affected and unaffected siblings. Yet affected siblings were modestly more likely to have mutations predicted to damage protein function.

Such damaging mutations were estimated to account for 21 percent of schizophrenia cases in the study sample. The mutations tend to be individually rare; only one gene harboring damaging mutations turned up in more than one of the cases, and several patients had damaging mutations in more than one gene.

The networks formed by genes harboring these damaging mutations were found to vary in connectivity, based on the extent to which their proteins are co-expressed and interact. The network formed by genes harboring damaging mutations in schizophrenia had significantly more nodes, or points of connection, than networks modeled from unaffected siblings.

By contrast, the network of genes harboring non-damaging mutations in affected siblings had no more nodes than similar networks in unaffected siblings.

When the researchers compared such network connectivity across different brain tissues and different periods of development, they discovered a notable difference between affected and unaffected siblings: Genes harboring damaging mutations that are expressed together in the fetal prefrontal cortex of people with schizophrenia formed a network with significantly greater connectivity than networks modeled from genes harboring similar mutations in their unaffected siblings at that time in development.

The study results are consistent with several lines of evidence implicating the prefrontal cortex in schizophrenia. The prefrontal cortex organizes information from other brain regions to coordinate executive functions like thinking, planning, attention span, working memory, problem-solving, and self-regulation.

The findings suggest that impairments in such functions - often beginning before the onset of symptoms in early adulthood, when the prefrontal cortex fully matures - appear to be early signs of the illness.

The study demonstrates how integrating genomic data and transcriptome analysis can help to pinpoint disease mechanisms and identify potential treatment targets.

For example, the mutant genes in the patients studied suggest the possible efficacy of medications targeting glutamate and calcium channel pathways, say the researchers.

"These results are striking, as they show that the genetic architecture of schizophrenia cannot be understood without an appreciation of how genes work in temporal and spatial networks during neurodevelopment," said Thomas Lehner, Ph.D., chief of the NIMH Genomics Research Branch.


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 2,500+ scientific posters on ePosters
  • More than 3,800+ 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

NIH Grants Seek Best Ways To Combine Genomic Information and EHRs
Researchers seek to better understand genomic basis of disease, provide tailored care to patients.
Friday, September 04, 2015
Cellular Factors that Shape the 3D Landscape of the Genome Identified
Researchers have identified 50 cellular factors required for the proper 3D positioning of genes by using novel large-scale imaging technology.
Tuesday, August 18, 2015
Nuclear Process in the Brain That May Affect Disease Uncovered
Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease.
Tuesday, August 18, 2015
Tell-tale Biomarker Detects Early Breast Cancer in NIH-funded Study
The study published online in the issue of Nature Communications.
Thursday, August 13, 2015
Scientists Adopt New Strategy to Find Huntington’s Disease Therapies
Large, international NIH-supported study uses precision medicine to tackle neurological disorders.
Tuesday, August 11, 2015
Study Shows Promise of Precision Medicine for Most Common Type of Lymphoma
The study appeared online July 20, 2015, in Nature Medicine.
Tuesday, July 21, 2015
NIH Study Identifies Gene Variant Linked to Compulsive Drinking
Mice carrying the Met68BDNF gene variant would consume excessive amounts of alcohol.
Tuesday, July 21, 2015
In Blinding Eye Disease, Trash-Collecting Cells Go Awry, Accelerate Damage
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Friday, July 03, 2015
Potential Therapeutic for Blinding Eye Disease
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Thursday, July 02, 2015
NCI-MATCH Trial will Link Targeted Cancer Drugs to Gene Abnormalities
Precision medicine trial will open to patient enrollment in July.
Tuesday, June 09, 2015
A New Role for Zebrafish: Larger Scale Gene Function Studies
A relatively new method of targeting specific DNA sequences in zebrafish could dramatically accelerate the discovery of gene function and the identification of disease genes in humans.
Monday, June 08, 2015
NIH Researchers Pilot Predictive Medicine by Studying Healthy People’s DNA
New study sequence the genomes of healthy participants to find “putative,” or presumed, mutations.
Friday, June 05, 2015
Linking Targeted Cancer Drugs to Gene Abnormalities
Investigators at the NIH have announced a series of clinical trials that will study drugs or drug combinations that target specific genetic mutations.
Wednesday, June 03, 2015
Scientists Create Mice with a Major Genetic Cause of ALS and FTD
NIH-funded study provides new platform for testing treatments for several neurodegenerative disorders.
Friday, May 22, 2015
Mice With a Major Genetic Cause of ALS and FTD Created
NIH-funded study provides new platform for testing treatments for several neurodegenerative disorders.
Thursday, May 21, 2015
Scientific News
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Growing Hepatitis C in the Lab
Recent discovery allows study of naturally occurring forms of hepatitis C virus (HCV) in the lab.
Inciting an Immune Attack on Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
Reprogramming Cancer Cells
Researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.
Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
CHOP genomics expert leads analysis of genetic architecture, with eye on repurposing existing drugs.
Surprising Mechanism Behind Antibiotic-Resistant Bacteria Uncovered
Now, scientists at TSRI have discovered that the important human pathogen Staphylococcus aureus, develops resistance to this drug by “switching on” a previously uncharacterized set of genes.
How DNA ‘Proofreader’ Proteins Pick and Edit Their Reading Material
Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have discovered how two important proofreader proteins know where to look for errors during DNA replication and how they work together to signal the body’s repair mechanism.
Fat in the Family?
Study could lead to therapeutics that boost metabolism.
Tissue Bank Pays Dividends for Brain Cancer Research
Checking what’s in the bank – the Brisbane Breast Bank, that is – has paid dividends for UQ cancer researchers.
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!