Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research sees overlap in genes altered in schizophrenia, autism, intellectual disability

29.04.2014

In research published today in Molecular Psychiatry, a multinational team of scientists presents new evidence supporting the theory that in at least some cases of schizophrenia, autism and intellectual disability (ID), 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. The paper can be obtained online at: http://www.nature.com/mp/journal/vaop/ncurrent/index.html

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for the impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 600 researchers and technicians strong and its Meetings & Courses Program hosts more than 12,000 scientists from around the world each year to its Long Island campus and its China center. For more information, visit http://www.cshl.edu.

Peter Tarr | Eurek Alert!

Further reports about: CSHL disability disorders epigenetic genes illness involved mutations schizophrenia

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Automated driving: Steering without limits

OmniSteer project to increase automobiles’ urban maneuverability begins with a € 3.4 million budget

Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...

Im Focus: Microscopy: Nine at one blow

Advance in biomedical imaging: The University of Würzburg's Biocenter has enhanced fluorescence microscopy to label and visualise up to nine different cell structures simultaneously.

Fluorescence microscopy allows researchers to visualise biomolecules in cells. They label the molecules using fluorescent probes, excite them with light and...

Im Focus: NASA's ICESat-2 equipped with unique 3-D manufactured part

NASA's follow-on to the successful ICESat mission will employ a never-before-flown technique for determining the topography of ice sheets and the thickness of sea ice, but that won't be the only first for this mission.

Slated for launch in 2018, NASA's Ice, Cloud and land Elevation Satellite-2 (ICESat-2) also will carry a 3-D printed part made of polyetherketoneketone (PEKK),...

Im Focus: Sinking islands: Does the rise of sea level endanger the Takuu Atoll in the Pacific?

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister picture is being painted evoking the demise of the island states and their cultures. Are the effects of sea-level rise already noticeable on reef islands? Scientists from the ZMT have now answered this question for the Takuu Atoll, a group of Pacific islands, located northeast of Papua New Guinea.

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister...

Im Focus: Energy-saving minicomputers for the ‘Internet of Things’

The ‘Internet of Things’ is growing rapidly. Mobile phones, washing machines and the milk bottle in the fridge: the idea is that minicomputers connected to these will be able to process information, receive and send data. This requires electrical power. Transistors that are capable of switching information with a single electron use far less power than field effect transistors that are commonly used in computers. However, these innovative electronic switches do not yet work at room temperature. Scientists working on the new EU research project ‘Ions4Set’ intend to change this. The program will be launched on February 1. It is coordinated by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).

“Billions of tiny computers will in future communicate with each other via the Internet or locally. Yet power consumption currently remains a great obstacle”,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

DATE 2016 Highlighting Automotive and Secure Systems

26.01.2016 | Event News

 
Latest News

A new potential biomarker for cancer imaging

05.02.2016 | Life Sciences

Graphene is strong, but is it tough?

05.02.2016 | Materials Sciences

Tiniest Particles Shrink Before Exploding When Hit With SLAC's X-ray Laser

05.02.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>