Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutations not inherited from parents cause more than half the cases of schizophrenia

08.08.2011
Columbia University Medical Center researchers have shown that new, or "de novo," protein-altering mutations—genetic errors that are present in patients but not in their parents—play a role in more than 50 percent of "sporadic" —i.e., not hereditary—cases of schizophrenia. The findings will be published online on August 7, 2011, in Nature Genetics.

A group led by Maria Karayiorgou, MD, and Joseph A. Gogos, MD, PhD, examined the genomes of patients with schizophrenia and their families, as well as healthy control groups. All were from the genetically isolated, European-descent Afrikaner population of South Africa.

These findings build on earlier studies by Karayiorgou, professor of psychiatry at Columbia University Medical Center. More than 15 years ago, Karayiorgou and her colleagues described a rare de novo mutation that accounts for 1-2 percent of sporadic cases of schizophrenia. With advances in technology, three years ago the Columbia team was able to search the entire genome for similar lesions that insert or remove small chunks of DNA. The mutations found accounted for about 10 percent of sporadic cases.

Encouraged by their progress, they wondered whether other, previously undetectable, de novo mutations accounted for an even greater percentage of sporadic cases. Using state-of-the-art "deep sequencing," they examined the nucleotide bases of almost all the genes in the human genome. This time they found 40 mutations, all from different genes and most of them protein-altering. The results point the way to finding more, perhaps even hundreds, of mutations that contribute to the genetics of schizophrenia—a necessary step toward understanding how the disease develops.

"Identification of these damaging de novo mutations has fundamentally transformed our understanding of the genetic basis of schizophrenia," says Bin Xu, PhD, assistant professor of clinical neurobiology at Columbia University Medical Center and first author of the study.

"The fact that the mutations are all from different genes," says Karayiorgou, "is particularly fascinating. It suggests that many more mutations than we suspected may contribute to schizophrenia. This is probably because of the complexity of the neural circuits that are affected by the disease; many genes are needed for their development and function." Karayiorgou and her team will now search for recurring mutations, which may provide definitive evidence that any specific mutation contributes to schizophrenia.

The potentially large number of mutations makes a gene-therapy approach to treating schizophrenia unlikely. Researchers suspect, however, that all of the mutations affect the same neural circuitry mechanisms. "Using innovative neuroscience methods," says co-author Dr. Joseph Gogos, MD, PhD, and associate professor of physiology and neuroscience at Columbia University Medical Center, "we hope to identify those neural circuit dysfunctions, so we can target them for drug development."

The study's results also help to explain two puzzles: the persistence of schizophrenia, despite the fact that those with the disease do not tend to pass down their mutations through children; and the high global incidence of the disease, despite large environmental variations.

The study's authors are Bin Xu (CUMC), J. Louw Roos (University of Pretoria), Phillip Dexheimer (HudsonAlpha Institute), Braden Boone (HudsonAlpha Institute), Brooks Plummer (HudsonAlpha Institute), Shawn Levy (HudsonAlpha Institute), Joseph A. Gogos (CUMC), and Maria Karayiorgou (CUMC).

The study was supported by NIMH, the Lieber Center for Schizophrenia Research at Columbia University, and NARSAD.

The authors declare no financial conflict of interest.

Columbia University Medical Center provides international leadership in basic, pre-clinical, and clinical research; in medical and health sciences education; and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.

Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the Nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders. Located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Medical Center campus in the Washington Heights community of Upper Manhattan, the department enjoys a rich and productive collaborative relationship with physicians in various disciplines at Columbia University's College of Physicians and Surgeons. Columbia Psychiatry is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders, and childhood psychiatric disorders.

Ann Rae Jonas | EurekAlert!
Further information:
http://www.columbia.edu

More articles from Architecture and Construction:

nachricht Construction Impact Guide
18.05.2018 | Hochschule RheinMain

nachricht New, forward-looking report outlines research path to sustainable cities
24.01.2018 | National Science Foundation

All articles from Architecture and Construction >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Superconducting vortices quantize ordinary metal

Russian researchers together with their French colleagues discovered that a genuine feature of superconductors -- quantum Abrikosov vortices of supercurrent -- can also exist in an ordinary nonsuperconducting metal put into contact with a superconductor. The observation of these vortices provides direct evidence of induced quantum coherence. The pioneering experimental observation was supported by a first-ever numerical model that describes the induced vortices in finer detail.

These fundamental results, published in the journal Nature Communications, enable a better understanding and description of the processes occurring at the...

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Rapid water formation in diffuse interstellar clouds

25.06.2018 | Physics and Astronomy

Using tree-fall patterns to calculate tornado wind speed

25.06.2018 | Earth Sciences

'Stealth' material hides hot objects from infrared eyes

25.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>