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

New de novo Genetic Mutations in Schizophrenia Identified

Published: Thursday, October 04, 2012
Last Updated: Thursday, October 04, 2012
Bookmark and Share
Columbia University Medical Center (CUMC) researchers have identified dozens of new spontaneous genetic mutations that play a significant role in the development of schizophrenia, adding to the growing list of genetic variants that can contribute to the disease.

Although schizophrenia typically onsets during adolescence and early adulthood, many of the mutations were found to affect genes with higher expression during early-to-mid fetal development. Together, the findings show that both the function of the mutated gene and when the gene is expressed are critically important in determining the risk for schizophrenia.

The findings inform epidemiologic studies showing that environmental factors, such as malnutrition or infections during pregnancy, can contribute to the development of schizophrenia. “Our findings provide a mechanism that could explain how prenatal environmental insults during the first and second trimester of pregnancy increase one’s risk for schizophrenia,” said study leader Maria Karayiorgou, MD, professor of psychiatry at CUMC, and acting chief, division of Psychiatric and Medical Genetics, New York State Psychiatric Institute. “Patients with these mutations were much more likely to have had behavioral abnormalities, such as phobias and anxiety in childhood, as well as worse disease outcome.”

In an earlier study of 53 families, the team of investigators found that spontaneous, or de novo, mutations — genetic errors that are present in patients but not in their parents — play a role in a substantial portion of sporadic cases of schizophrenia. The mutations were found in the part of the genome that codes for proteins, known as the exome.

In the larger, current study, the researchers performed whole-exome sequencing on 231 patient “trios” from the United States and South Africa. Each trio consisted of a patient and both of his or her parents, who were unaffected by the disease. By comparing the exomes of the patients with those of their parents, the researchers were able to identify de novo rather than heritable, mutations that may contribute to schizophrenia. This is the first study of this scale to search for single nucleotide variations in the exomes of schizophrenia patients. Previous studies from the Columbia group and others searched for much larger genetic variations, such as gene deletions or duplications.

The researchers identified many mutated genes with diverse functions. They also identified four new genes (LAMA2, DPYD, TRRAP, and VPS39) affected by recurrent de novo events within or across the two populations, a finding unlikely to have occurred by chance.

The researchers estimate that several hundred loci (genetic locations) can contribute to the development of schizophrenia. “The chance that two patients have exactly the same mutation or combination of mutations is rather small” said Dr. Karayiorgou. “What is intriguing is that despite this variability, people with schizophrenia tend to have, more or less, the same phenotype—that is, the same clinical presentation. Our hypothesis is that many neural circuits are extremely important in schizophrenia and that these circuits are vulnerable to a number of influences. So, when any of the genes involved in these circuits are mutated, the end result is the same.”

According to the researchers, the challenge remains to identify the affected biological processes and neural circuits, and to determine how they are affected.

“Although the genetics of schizophrenia are extremely complex, a coherent picture of the disease is beginning to emerge,” said co-director of the study Dr. Joseph Gogos, MD, PhD, and associate professor of physiology and neuroscience at Columbia University Medical Center. “Our studies show that dozens, and perhaps hundreds, of different spontaneous mutations can raise one’s risk for schizophrenia. On the surface, this is daunting, but using these new findings to understand how these mutations affect the same neural circuits, including during early fetal development, raises hopes that it may be possible to develop effective prevention and treatment strategies for the disease.”

The paper is titled, “De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia.” The other contributors are Bin Xu (CUMC), Iuliana Ionita-Laza (CUMC), J. Louw Roos (University of Pretoria, Pretoria, South Africa), Braden Boone (Hudson Alpha Institute for Biotechnology, Huntsville, Ala.), Scarlet Woodrick (CUMC), Yan Sun (CUMC) and Shawn Levy (Hudson Alpha Institute for Biotechnology).

The research was partially supported by National Institute of Mental Health grants MH061399 and MH077235 and the Lieber Center for Schizophrenia Research at Columbia University.

The authors declare no financial conflict of interest.

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 2,600+ 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 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

New Link Between Obesity and Diabetes Found
Targeting a single enzyme that raises both sugar and insulin levels in the obese could prevent and treat diabetes.
Monday, November 25, 2013
Is There a Role for Vitamins in Cancer Prevention?
According to recent national surveys, approximately 40 percent of U.S. adults take multivitamins/multiminerals.
Monday, August 12, 2013
Study Reveals Genes That Drive Brain Cancer
About 15 percent of glioblastoma patients could receive personalized treatment with drugs currently used in other cancers.
Tuesday, August 06, 2013
Key Molecular Pathways Leading to Alzheimer’s Identified
Research approach highlights potential therapeutic targets.
Thursday, July 25, 2013
New Genetic Cause of Pulmonary Hypertension Identified
Study finds druggable target for rare fatal lung disease.
Thursday, July 25, 2013
Mutation Linked to Congenital Urinary Tract Defects
Findings point to new diagnostic category.
Thursday, July 18, 2013
Mouse Study Suggests Lead May Trigger Schizophrenia
Behavioral and MRI study in mice points to a synergistic relationship between lead exposure and schizophrenia gene.
Monday, June 10, 2013
Many Birth Defects in Heart Caused by Spontaneous Mutations
A study has found that at least 10 percent of cases stem from genetic mutations that occur spontaneously early in development.
Thursday, May 30, 2013
Common Childhood Asthma Not Rooted in Allergens, Inflammation
Discovery of origins of a unique form of asthma may lead to a precision medicine approach to treatment.
Friday, May 24, 2013
Looking for the Telltale Gene
A new genetic test allows parents to peer into their unborn children's medical future.
Friday, May 24, 2013
Hundreds of Alterations and Potential Drug Targets to Starve Tumors Identified
A massive study analyzing gene expression data from 22 tumor types has identified multiple metabolic expression changes associated with cancer.
Monday, April 22, 2013
New Gene Associated with Almost Doubled Alzheimer’s Risk in African-Americans
ABCA7, a minor gene variant in whites, is major player in African-Americans.
Wednesday, April 10, 2013
Schizophrenia Gene Networks Found, and a Link to Autism
Although schizophrenia is highly genetic in origin, the genes involved in the disorder have been difficult to identify.
Thursday, November 15, 2012
New de novo Genetic Mutations in Schizophrenia Identified
Columbia University Medical Center (CUMC) researchers have identified dozens of new spontaneous genetic mutations that play a significant role in the development of schizophrenia, adding to the growing list of genetic variants that can contribute to the disease.
Thursday, October 04, 2012
Tom Maniatis: A Deep Sense that Science Must Be Shared
History books are filled with the technical advances that made genetic engineering possible, from the discovery of enzymes that cut and paste DNA to the development of techniques for reading the sequence of genes.
Tuesday, September 11, 2012
Scientific News
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
Lung Repair and Regeneration Gene Discovered
New role for hedgehog gene offers better understanding of lung disease.
3 Ways Viruses Have Changed Science for the Better
Viruses are really good at what they do, and we’ve been able to harness their skills to learn about – and potentially improve – human health in several ways.
Mixed Up Cell Transportation Key Piece of ALS and Dementia Puzzle
Researchers from the University of Toronto are one step closer to solving this incredibly complex puzzle, offering hope for treatment.
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Five New Genetic Variants Linked to Brain Cancer Identified
The biggest ever study of DNA from people with glioma – the most common form of brain cancer – has discovered five new genetic variants associated with the disease.
Predictive Model for Breast Cancer Progression
Biomedical engineers have demonstrated a proof-of-principle technique that could give women and their oncologists more personalized information to help them choose options for treating breast cancer.
Fatty Liver Disease and Scarring Have Strong Genetic Component
Researchers say that hepatic fibrosis, which involves scarring of the liver that can result in dysfunction and, in severe cases, cirrhosis and cancer, may be as much a consequence of genetics as environmental factors.
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos