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Twin Data Highlight Genetic Changes

By Rick Weiss

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 yesterday.

Geneticists said the new work, by an international team of scientists who

studied the DNA of more than 40 pairs of twins, strengthens the case that a

fledgling research field called epigenetics holds the long-sought answer to one

of biology's toughest questions: How do environmental influences, such as

exposure to pollutants, consumption of certain foods or perhaps even powerful

emotional experiences, produce lasting and potentially life-altering changes in

a person's DNA?

Beyond its potential importance for understanding differences in identical

twins, epigenetics could explain many of the twists of fate that affect ordinary

people -- why one person may be struck by cancer, for example, 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. "

Baylin, a professor of oncology and medicine at s Hopkins Medical

Institutions in Baltimore, said the new work points to the roots of a host of

chronic diseases. " 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 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 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 that 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. "

Francis , director of the National Human Genome Research Institute, said

the work adds to an emerging recognition that scientists must move beyond their

long-standing focus on the inherited spelling of people's DNA code and the

occasional mutation or outright " misspelling. " Epigenetic changes do not alter

genetic spellings but may account for as many cases of cancer and other diseases

as full-blown gene mutations, he said.

" Here's something where Mendel, and Crick all seem to have missed some

crucial goodies, " said , referring to pioneers of genetic research.

's institute, along with the National Cancer Institute and others,

intends to launch a major effort to identify the many epigenetic changes that

contribute to cancer.

Scientists want to identify the epigenetic changes wrought by specific

environmental exposures -- whether dietary factors, environmental toxins or more

nuanced influences such as persistent stress -- and develop drugs that can

reverse those alterations.

, director of the Norris Comprehensive Cancer Center at the

University of Southern California in Los Angeles, likened epigenetic alterations

to the clothes worn by genes. " The clothes are really what determine how the

genome works, " he said. " The clothes can get tattered by these changes, which

can lead to different susceptibilities to disease. "

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Thanks for posting this interesting article. It certainly does make

sense.

Hugs kathy

-- In , saxony01@y... wrote:

> You have been sent this message from saxony01@y... as a courtesy

of washingtonpost.com

>

> Personal Message:

> Very interesting article. . . This may behind why some women (and

children) tolerate implants better than others.

>

> Twin Data Highlight Genetic Changes

>

> By Rick Weiss

>

> 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 yesterday.

>

> Geneticists said the new work, by an international team of

scientists who studied the DNA of more than 40 pairs of twins,

strengthens the case that a fledgling research field called

epigenetics holds the long-sought answer to one of biology's

toughest questions: How do environmental influences, such as

exposure to pollutants, consumption of certain foods or perhaps even

powerful emotional experiences, produce lasting and potentially life-

altering changes in a person's DNA?

>

> Beyond its potential importance for understanding differences in

identical twins, epigenetics could explain many of the twists of

fate that affect ordinary people -- why one person may be struck by

cancer, for example, 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. "

>

> Baylin, a professor of oncology and medicine at s

Hopkins Medical Institutions in Baltimore, said the new work points

to the roots of a host of chronic diseases. " 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 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 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 that 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. "

>

> Francis , director of the National Human Genome Research

Institute, said the work adds to an emerging recognition that

scientists must move beyond their long-standing focus on the

inherited spelling of people's DNA code and the occasional mutation

or outright " misspelling. " Epigenetic changes do not alter genetic

spellings but may account for as many cases of cancer and other

diseases as full-blown gene mutations, he said.

>

> " Here's something where Mendel, and Crick all seem to have

missed some crucial goodies, " said , referring to pioneers of

genetic research. 's institute, along with the National

Cancer Institute and others, intends to launch a major effort to

identify the many epigenetic changes that contribute to cancer.

>

> Scientists want to identify the epigenetic changes wrought by

specific environmental exposures -- whether dietary factors,

environmental toxins or more nuanced influences such as persistent

stress -- and develop drugs that can reverse those alterations.

>

> , director of the Norris Comprehensive Cancer Center

at the University of Southern California in Los Angeles, likened

epigenetic alterations to the clothes worn by genes. " The clothes

are really what determine how the genome works, " he said. " The

clothes can get tattered by these changes, which can lead to

different susceptibilities to disease. "

>

>

> Would you like to send this article to a friend? Go to

> http://www.washingtonpost.com/ac2/wp-dyn/emailafriend?

contentId=AR2005070400845 & sent=no & referrer=emailarticle

>

>

>

> Visit washingtonpost.com today for the latest in:

>

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>

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referrer=emailarticle

>

> Entertainment - http://www.washingtonpost.com/wp-

dyn/content/artsandliving/entertainmentguide/?referrer=emailarticle

>

> Travel - http://www.washingtonpost.com/wp-

dyn/content/artsandliving/travel/?referrer=emailarticle

>

> Technology - http://www.washingtonpost.com/wp-

dyn/content/technology/?referrer=emailarticle

>

>

>

>

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