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8-Humans: Epigenetics might explain differences between identical twins



                                  PART I
-------------------------------- GENET-news -------------------------------

TITLE:  Explaining Differences in Twins
SOURCE: The New York Times, USA, by Nicholas Wade
        http://www.nytimes.com/2005/07/05/health/05gene.html
DATE:   5 Jul 2005

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Explaining Differences in Twins

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.


                                  PART II
-------------------------------- GENET-news -------------------------------

TITLE:  A Modern Refrain: My Genes Made Me Do It
SOURCE: The New York Times, USA, by Kent Sepkowitz
        http://www.nytimes.com/2005/07/05/health/05comm.html
DATE:   5 Jul 2005

------------------- archive: http://www.genet-info.org/ -------------------


A Modern Refrain: My Genes Made Me Do It

Our theories about human disease are more the product of current fashion
than we would like to admit. But just as the moment influences the
hemline and the automobile fender, so too does a type of intellectual
currency affect our understanding of how illness happens.

Much of the 20th century was spent in pursuit of external causes of
disease - cigarettes, E. coli, fatty foods, tick bites. Rather like the
hero in an old western, medicine's job was to track down the bad guys,
round 'em up and squish 'em before a real commotion got a-goin'.
Antibiotics, vaccines, heart pills - these were our weapons in the epic
battle between us and them, good versus evil.

More recently, though, we have cast our gaze inward, mesmerized by our
own adorable DNA. Just last decade, after 40 years of intense flirtation,
this relationship was consummated as we cloned the entire human genome.
Promises of improved health and longevity soon followed, as we had
apparently found our way to the bedrock truths that underlie all illness.

But with this orgy of molecular self-admiration has come a fundamental
shift in thinking about human disease. We have moved from our long-held
premise that the outside world (too much ice cream and flesh-eating
bacteria) threatens us to a belief that the trouble arises from something
much closer to home - our own double-crossing genes.

Although packaged with the glint of modernity, this theory actually draws
from something old and wintry - the harsh remedies proposed by John
Calvin, predestination's No. 1 guy. According to Calvin, our fate is
determined at first creation. Similar to this, the articles of gene-ism
would have us believe that our medical fate is sealed by the genes we
receive at conception. Seem a bit grim?

Maybe not. Our unquestioning acceptance of the gene as prime mover has
certain distinct - and ultramodern - advantages. Consider: you are no
longer responsible for anything. Sound familiar? Once it was the devil.
Now it is the gene that made you do it. You are officially off the hook.
It isn't your fault at all. It's your faulty genes.

It gets even better. Not only is it not your fault, but you actually are
a victim, a victim of your own toxic gene pool.

In the Age of Genetics, you no longer have to try to cut out smoking or
think twice about gobbling that candy bar in your desk drawer. And forget
jogging on a cold morning.

The die was cast long ago, from the moment the parental sperm and egg
first integrated their spiraling nucleotides. The resulting package of
chromosomes has programmed every step of your life. So sit back, relax
and leave the driving to someone else.

But one problem remains: this new world order is at sharp odds with an
older theism, that blame can and must be assigned in every human
transaction. We have built a vast judicial-industrial complex that offers
lawsuits for every need, satisfying varied urges like the wish for
fairness or revenge, for getting rich quick or simply getting your due.

This all-blame all-the-time approach applies to much more than
determining culpability should a neighbor trip on your lawn and break an
arm. It also says that people are responsible for their own health - and
illness. It is your fault if you develop cancer or a heart attack because
you didn't eat, think or breathe right. You have allowed the corrosive
effect of unresolved anger or stress or poor self-esteem to undermine
your health. So if you are sick or miserable or both, it's your own
darned fault.

No wonder we fled.

The transition from the chaotic, barking family feud character of
lawsuits to the sleek silence of a future devoted to cloning and splicing
genes surely derives from something larger than scientific opportunity or
our fascination with "Star Trek." How modern to deflect blame suavely
onto a poorly understood high-end concept, the manic twitches of
deoxynucleic acid. Gosh, biology is so much bigger than we are. Nothing
we can do about it, really.

Our wholehearted endorsement of the science of no personal responsibility
may sour as new insights and new intellectual fashion result in new
bedrock truths.

A future generation may castigate us for our unblinking narcissism. What
were we thinking? How could genes be responsible for red hair and bad
memory and atherosclerosis?

But if they come after us wagging their stubby fingers, we have an
airtight explanation. We'll tell them it was not really our idea, the
whole gene thing.

No, we will say, we were victims. Victims of fashion.




--


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