Findings shed light on why identical twins differ

[abdulhakeem]

Tue Jul 5, 2005 6:43 AM BST

NEW YORK (Reuters Health) - Identical twins are often remarkably similar, yet they have distinct differences. This might seem unexpected since they share all of the same genes, but scientists have come up with an explanation.

Small differences in which genes are turned on or off, and to what degree, account for the subtle differences in physical appearance or other characteristics, according to a report in the Proceedings of the National Academy of Sciences.

For instance, one twin may be more susceptible to a given disease or have certain features not found in the other twin. One possibility underlying these phenomena is that modifications that affect the expression of genes differ between the twins.

These 'epigenetic' modifications determine the level at which a gene's product is produced, which in turn impacts an individual's appearance and disease susceptibility among other things.

To investigate, Dr. Manel Esteller, from the Spanish National Cancer Center in Madrid, and colleagues assessed two epigenetic modifications -- DNA methylation (which tends to silence genes) and histone acetylation -- in 80 identical twins.

In young subjects, no real difference in the epigenetic modifications was seen between each twin. In older subjects, however, marked differences in DNA methylation and histone acetylation were observed.

Further studies are needed to determine how these epigenetic modifications change in each twin over time, the authors conclude.

SOURCE: Proceedings of the National Academy of Sciences, July 4th early edition, 2005.

http://today.reuters.co.uk/news/newsArticle.aspx?type=healthNews&storyID=2005-07-05T054321Z_01_B126304_RTRIDST_0_HEALTH-TWINS-DIFFER-DC.XML

[abdulhakeem]

For twins, nurture can affect nature

Posted on Tue, Jul. 05, 2005
The Washington Post

Study shows that environment can influence DNA

WASHINGTON — A mysterious biological mechanism that subtly changes the way people’s genes behave may account for many of the surprising differences between identical twins, researchers announced Monday.

Geneticists said the new work, by an international team of scientists who studied the DNA of more than 80 twins, strengthens the case that a fledgling research field of epigenetics holds the long-sought answer to one of biology’s toughest questions: How do environmental influences produce lasting and potentially life-altering changes in a person’s DNA?

Beyond its potential importance for understanding differences between identical twins, epigenetics could explain many of the twists of fate that affect ordinary people — for example, why one person may be struck by cancer while another is spared, even though neither’s DNA harbors a cancer-causing mutation.

“This is how the environment talks to the genome,” said Rudolf Jaenisch, a geneticist at the Whitehead Institute for Biomedical Research in Cambridge, Mass., who was not part of the project. “This paper says lifestyle, or environmental influences or whatever you want to call them, have a real influence on your DNA.”

Stephen Baylin, a professor of oncology and medicine at Johns Hopkins Medical Institutions in Baltimore, said the new work points to the roots of a host of chronic diseases, adding, “This could lead to far-reaching revelations about how our environment breeds predispositions for lots of diseases, like diabetes, cancer and heart disease.”

Human cells have tens of thousands of genes inside them, each with its own job, such as producing energy or overseeing cell division. But only certain genes are active at any given time or in any cell type, while the rest are appropriately dormant — a grand orchestration that adds up to a smooth-running life.

The new research, led by Mario F. Fraga and Manel Esteller of the Spanish National Cancer Center in Madrid, focused on two biological mechanisms that influence gene activity. In one, called DNA methylation, enzymes inside a cell attach a minuscule molecular decoration to a gene, deactivating that gene. In the other, called histone acetylation, a dormant gene is made active again.

These altered genetic settings can last a lifetime (though they are not passed down to a person’s offspring) and can be important if, say, the gene that is turned off is one that protects against cancer. The extent to which epigenetic changes are preprogrammed from birth or spurred by factors outside the body has been unclear.

In the new work, described in today’s issue of Proceedings of the National Academy of Sciences, researchers measured the extent to which twins of various ages, from 3 to 74, differed in the number and variety of genes that had been either turned on or shut down by epigenetic processes. They found young twins had almost identical epigenetic profiles but that, with age, their profiles became more and more divergent.

In a finding that scientists said was particularly groundbreaking, the epigenetic profiles of twins who had been raised apart or had especially different life experiences — including nutritional habits, history of illness, physical activity, and use of tobacco, alcohol and drugs — differed more than those who had lived together longer or shared similar environments and experiences.

Small epigenetic events before birth probably account for many of the minor distinguishing differences in the appearance, personality and general health of young twins, Estella said, and a lifetime of further epigenetic changes gradually increases individuality.

“Both nature and nurture are acting on these twins,” Estella said. “Epigenetics is the bridge or the interplay between them.”

First glance

■ In study, adult twins raised together had more similar DNA than those reared apart

http://www.kansascity.com/mld/kansascity/news/nation/12053965.htm

[abdulhakeem]

Twins grow apart as they age

Published online: 4 July 2005
doi:10.1038/news050704-3
Roxanne Khamsi (http://www.nature.com/news/about/aboutus.html#Khamsi)

Genetic tests reveal how the environment changes our DNA.


http://www.nature.com/news/2005/050704/images/twins.jpg
http://www.nature.com/news/images/spacer.gif
Chromosomes from 3-year-old twins (left) are virtually identical. But those from 50-year-old twins (right) show changes in gene expression in red and green. © PNAS



Identical twins may have less in common than they think. A study now shows that the expression of their genes gets more and more different with age.

The findings could help to explain why one twin may develop a genetically influenced disease, such as diabetes, while the other remains perfectly healthy.

Identical twins have identical genes, because they are born of an embryo that splits at a very early stage in development. Such twins are often indistinguishable in outward appearance. But over the course of time they may experience radically dissimilar health.

Most scientists have assumed that environmental and lifestyle differences cause such divergence. These things trigger chemical reactions that affect our DNA and the proteins entwined with our DNA, called histones. One such reaction, known as methylation, influences the expression of genes and so can have an impact on health.

"Most people had the hypothesis that changes in DNA methylation are effected by the environment," says lead author Mario Fraga of the Spanish National Cancer Centre in Madrid. "This is the first time that somebody has demonstrated that this is the case." The findings appear in the Proceedings of the National Academy of Sciences1 (http://www.nature.com/news/2005/050704/full/050704-3.html#B1).

Variations on a theme

To assess the variability in how genes are expressed between identical twins, the researchers studied genetic material from 40 pairs, ranging in age from 3 to 74 years old. They then assessed the amount of methylation of the DNA. The resulting computer-generated images highlights areas with significant differences in methylation.

The degree of chemical modification of DNA and its accompanying histones varied significantly between twins in a third of the pairs overall. But the older the twins were, the greater was the variability. Among the participants older than 28 years, chemical modification of DNA was significantly different in more than 60% of twin pairs.

Such changes can easily affect susceptibility to disease. The team identified one case in which a man with diabetes had an associated gene activated by a chemical change, where his healthy twin did not.

The study also found that the more time twins had spent apart, the more their patterns of gene activation differed. This further supports the notion that environmental factors exert a strong influence on genetic expression.

The team says that similar studies might be helpful in weeding out how much chemical influences on our genes affect risk factors for diseases. "This could be the way to identify the role of the methylation of genes," says team member Manel Esteller, also of the Spanish National Cancer Centre.

http://www.nature.com/news/2005/050704/full/050704-3.html