Schizophrenia Research Forum - A Catalyst for Creative Thinking
Home Profile Membership/Get Newsletter Log In Contact Us
 For Patients & Families
What's New
Recent Updates
SRF Papers
Current Papers
Search All Papers
Search Comments
News
Research News
Conference News
Plain English
Forums
Current Hypotheses
Idea Lab
Online Discussions
Virtual Conferences
Interviews
Resources
What We Know
SchizophreniaGene
Animal Models
Drugs in Trials
Research Tools
Grants
Jobs
Conferences
Journals
Community Calendar
General Information
Community
Member Directory
Researcher Profiles
Institutes and Labs
About the Site
Mission
History
SRF Team
Advisory Board
Support Us
How to Cite
Fan (E)Mail
The Schizophrenia Research Forum web site is sponsored by the Brain and Behavior Research Foundation and was created with funding from the U.S. National Institute of Mental Health.
Research News
back to News Search
Painting a Better Picture of Twin Discordance
Article appears by special arrangement with Alzheimer Research Forum. See original article with additional links/commentary.

13 July 2005. Twin discordance—the manifestation of vastly different behaviors and susceptibilities to disease despite genetic identity—is a bit of a mystery. Some might attribute it to exposure to quite different environments after birth. But is this nurture argument sufficient to explain why one identical twin falls victim to something like Alzheimer disease, for example, while the other does not?

An international study led by Manel Esteller at the Spanish National Cancer Center in Madrid paints a slightly more detailed picture of twin discordance. Reporting in last week’s PNAS online, first author Mario Fraga and colleagues show that as twins age they accumulate vast numbers of epigenetic differences. In short, nurture may be altering nature.

Epigenetic differences, such as DNA methylation or histone acetylation, can have a profound impact on gene expression. To see if this might explain twin discordance, Fraga and colleagues, including researchers in Spain, Sweden, England, and the US, examined DNA and histone modification patterns in tissue samples taken from 80 identical (monozygotic) twins (30 female, 50 male). The authors found that in very young twins (3 years old), there were no statistical differences in overall cytosine methylation or in acetylation of histones H3 and H4. Samples from older twins told a different story, however. While the majority of twin pairs exhibited few differences, in 35 percent of twin pairs, all three parameters varied considerably. In one pair of 50-year-old twins, DNA methylation was 3.5 percent in one twin and 4.5 percent in the other, while histone H3 and H4 acetylations were about 60 vs. 48 percent and 24 vs. 18 percent, respectively.

The data suggest that in at least some cases, epigenetic characteristics that were similar close to birth have diverged as the twins aged. What’s more, this divergence may have an impact on health. Fraga and colleagues found that those twins who had discernibly different health and medical histories were those who had the greatest epigenetic differences. Twins who spent less of their lifetimes together also turned out to have greater epigenetic discordance than those who were closely knit.

For the most part, Fraga and colleagues focused on changes in lymphocytes. But they also examined epigenetic profiles of epithelial, fat, and skeletal muscle cells, finding similar patterns of divergence as for the blood cells. Functionally, the differences do seem important. For example, when the authors examined loci where methylation differences were observed, they found that about 34 percent of the loci matched expressed sequence tags, while 13 percent matched single copy genes. Zeroing in on a few specific sequences, Fraga and colleagues found that a pattern of hypomethylation in one twin and hypermethylation in the other was common.

So might these differences affect gene expression? To answer that, the authors used gene array analysis to compare mRNA levels between twins. They found that, as with methylation and acetylation patterns, portraits of gene expression showed the greatest differences in older twins and that transcript levels correlated with epigenetic changes. Twins with the most severe hypomethylation and hyperacetylation, for example, had the highest numbers of overexpressed genes, up to almost 4,000.

What seems clear from this study is that epigenetic changes can accumulate as people age. What is less clear is the cause of these changes. The authors suggest that they could be due to “epigenetic drift,” defects in the transmission of epigenetic changes during cell division. But they also suggest that external factors such as smoking habits, physical activity, or diet can also be influential, a suggestion backed up by the fact that twins with the most divergent natural health histories also had the greatest epigenetic differences. In the wider context of disease, “our comparison of MZ [monozygotic] twins suggests that external and/or internal factors can have an impact in the phenotype by altering the pattern of epigenetic modifications and thus modulating genetic information,” conclude the authors.—Tom Fagan.

Reference:
Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Ruioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu Y-Z, Plass C, Esteller M. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005 Jul 11; [Epub ahead of print] Abstract

 
Comments on News and Primary Papers
Comment by:  Robert Peers
Submitted 20 December 2005 Posted 1 January 2006

The more knowledge we get on discordant twins, the better, especially in schizophrenia. Professor David Castle of Melbourne's Mental Health Research Institute once told me that the so-called "normal" twin is often, in fact, seen to have schizotypal personality.

There is an important lesson here that may shed light on the true nature of schizophrenia, which may be not a pure disease, but an aggravated form of schizotypy, in which differences in pre- and postnatal nutrition (for example) convert benign eccentricity into a serious psychotic illness.

People with mere schizotypy are odd, have magical thinking, can talk a lot, and can be intensely spiritual—character traits that may have been useful and appealing in primitive hunter-gatherer groups and early farming societies. Any overlap with bipolar traits would have added mental energy and leadership qualities as well. So there might be something good in schizotypy that has been given a bad name by schizophrenia.

Schizotypy that had not been converted into schizophrenia was probably common, but unnoticed, in...  Read more


View all comments by Robert Peers
Submit a Comment on this News Article
Make a comment on this news article. 

If you already are a member, please login.
Not sure if you are a member? Search our member database.

*First Name  
*Last Name  
Affiliation  
Country or Territory  
*Login Email Address  
*Confirm Email Address  
*Password  
*Confirm Password  
Remember my Login and Password?  
Get SRF newsletter with recent commentary?  
 
Enter the code as it is shown below:
This code helps prevent automated registrations.

I recommend the Primary Papers

Please note: A member needs to be both registered and logged in to submit a comment.

Comment:

(If coauthors exist for this comment, please enter their names and email addresses at the end of the comment.)

References:


SRF News
SRF Comments
Text Size
Reset Text Size
Email this pageEmail this page

Share/Bookmark
Copyright © 2005- 2014 Schizophrenia Research Forum Privacy Policy Disclaimer Disclosure Copyright