Featured Research

from universities, journals, and other organizations

Overlap in genes altered in schizophrenia, autism, intellectual disability

Date:
April 29, 2014
Source:
Cold Spring Harbor Laboratory
Summary:
New evidence supporting the theory that in at least some cases of schizophrenia, autism and intellectual disability, malfunctions in some of the same genes are contributing to pathology has been released. 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. Researchers used these differences as their focus in the new study.

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.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. S E McCarthy, J Gillis, M Kramer, J Lihm, S Yoon, Y Berstein, M Mistry, P Pavlidis, R Solomon, E Ghiban, E Antoniou, E Kelleher, C O'Brien, G Donohoe, M Gill, D W Morris, W R McCombie, A Corvin. De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability. Molecular Psychiatry, 2014; DOI: 10.1038/mp.2014.29

Cite This Page:

Cold Spring Harbor Laboratory. "Overlap in genes altered in schizophrenia, autism, intellectual disability." ScienceDaily. ScienceDaily, 29 April 2014. <www.sciencedaily.com/releases/2014/04/140429085600.htm>.
Cold Spring Harbor Laboratory. (2014, April 29). Overlap in genes altered in schizophrenia, autism, intellectual disability. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2014/04/140429085600.htm
Cold Spring Harbor Laboratory. "Overlap in genes altered in schizophrenia, autism, intellectual disability." ScienceDaily. www.sciencedaily.com/releases/2014/04/140429085600.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins