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

More articles from Health and Medicine:

nachricht Light beam replaces blood test during heart surgery
28.02.2017 | University of Central Florida

nachricht Cells adapt ultra-rapidly to zero gravity
28.02.2017 | Universität Zürich

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: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Scientists reach back in time to discover some of the most power-packed galaxies

28.02.2017 | Physics and Astronomy

Nano 'sandwich' offers unique properties

28.02.2017 | Materials Sciences

Light beam replaces blood test during heart surgery

28.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>