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From: Damien Broderick <[EMAIL PROTECTED]>
Date: Wed, 06 Jul 2005 00:38:22 -0500
To: [EMAIL PROTECTED]
Subject: [GRG] twins ain't twins
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Reply-To: Gerontology Research Group <[EMAIL PROTECTED]>


<http://www.nytimes.com/2005/07/05/health/05gene.html?pagewanted=print>Explaining
 
Differences in Twins
NICHOLAS WADE - The New York Times

Identical twins possess exactly the same set of genes. Yet as they grow 
older, they may begin to display subtle differences.

They may start to look different, develop different diseases or slide into 
different personalities. Women who are identical twins may differ in their 
fertility or in the age at which they reach menopause.

These discrepancies are usually attributed to ill-defined differences in 
environment.

But a whole new level of explanation has been opened up by a genetic survey 
showing that identical twins, as they grow older, differ increasingly in 
what is known as their epigenome. The term refers to natural chemical 
modifications that occur in a person's genome shortly after conception and 
that act on a gene like a gas pedal or a brake, marking it for higher or 
lower activity.

Identical twins have the same set of epigenetic marks on the genome when 
they are born. But differences in the epigenome emerge as the twins grow 
older and become greater the longer they live apart, say a team of 
researchers led by Dr. Manel Esteller of the Spanish National Cancer Center 
in Madrid.

Their report appears in today's issue of The Proceedings of the National 
Academy of Sciences.

"This is one of the most fascinating things I have read," said Dr. Nancy 
Segal, a psychologist who studies twins at California State University at 
Fullerton and the author of "Indivisible by Two," a forthcoming book on 
twins. "By giving us a handle on something specific, it opens up many new 
avenues of inquiry as to why twins are different."

There are two possible explanations for Dr. Esteller's findings. One is 
simply the well- known fact that epigenetic marks are lost as people get 
older. Because the marks are removed randomly, they would be expected to 
occur differently in two members of a twin pair.

A second possible explanation is that personal experiences and elements in 
the environment - including toxic agents like tobacco smoke - feed back 
onto the genome by changing the pattern of epigenetic marks.

Dr. Esteller believes he is seeing both processes at work. The evidence for 
the second process, he said, is that twins who reported that they had lived 
apart the longest also had the greatest differences in their epigenome.

"This is a way for the genome to be responsive to the environment," he 
said, noting that it is easier for chemical marks on the genome to change 
than for the genome itself to mutate.

His study suggests that the epigenome may be involved in many diseases that 
can affect identical twins differently, like schizophrenia, bipolar 
disorder and cancer. Although schizophrenia evidently has a genetic 
component, the epigenome may hold the clue to its nongenetic aspects.

Differences between identical twins could also help pinpoint the epigenetic 
differences that contribute to cancer. "We think that epigenetic changes 
are very common in cancer," said Dr. Peter A. Jones, the president of the 
American Association for Cancer Research and a professor at the University 
of Southern California.

Dr. Jones said Dr. Esteller's finding "is exceptionally interesting in that 
it underlines the importance of epigenetic changes in human development and 
disease."

Dr. Jones recently convened a workshop to discuss starting an international 
human epigenome project. The proposal could rival the Human Genome Project 
in complexity because the human genome is the same in every cell of a 
person's body, while the epigenome is expected to be different for each of 
the 250 or so human cell types.

Among the most important components of the epigenome are small chemical 
handles known as methyl groups, which are added directly to the chemical 
units of DNA.

A wave of demethylation occurs in a sperm's genome shortly after an egg is 
fertilized, followed by the extensive readdition of methyl groups in early 
embryonic development.

These methyl groups, which generally inhibit the activity of the genes in 
which they occur, tend to be lost during aging. Dr. Esteller's team studied 
the total amount of methylation in the twins' genomes, as well as another 
kind of epigenetic modification, the addition of acetyl groups to the 
histone proteins that act as a scaffolding and as a control system for DNA.

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