epigenetics

[Guest guest]

First university-based research center devoted to studying

epigenetics News-Medical.Net 28-Jun-2004

With a $5 million, five-year federal grant, The s Hopkins

University School of Medicine is establishing what is believed to be

the first university-based research center devoted to studying

epigenetics, an effort that will set the stage for learning as much

about our epigenetics as the Human Genome Project taught about the

sequence of building blocks that make up our genes.

Much as our genetic sequence is passed from parent to child,

epigenetic " marks " that sit on our genes are also inherited. These

" marks, " usually small methyl groups, are attached to genes'

backbones and convey information, such as identifying which parent

the gene came from. The marks also normally turn genes on or off. But

just as changes in genes' sequences can cause diseases such as

cancer, gain or loss of epigenetic marks can, too, by improperly

turning genes on or off.

" Epigenetics may be as important in certain conditions, or in

contributing to the risk of developing certain conditions, as the

genetic sequence is in other cases, " says Feinberg, M.D., King

Fahd Professor of Medicine and principal investigator of the

epigenetics grant. " Epigenetics doesn't underlie all human disease,

but we definitely need to develop the technology to figure out when

and where epigenetic changes do influence health and disease. "

Feinberg, who pioneered the study of epigenetics in cancer, will lead

the new Center for the Epigenetics of Common Human Disease at s

Hopkins, which is funded by the National Human Genome Research

Institute and the National Institute of Mental Health. Through the

center's grant, Feinberg and his colleagues will first develop tools

to create comprehensive information about epigenetics and then apply

that information to the study of autism and bipolar disorder. The

epigenetic information and technologies will also be available to

researchers investigating other conditions.

" Having the human DNA sequence is just the first step in our quest to

understand the complexities of the biological systems in the human

body. Epigenetic effects undoubtedly play an important biological

role, and learning more about these effects is essential to

deciphering the mysteries of human health and disease. So, we are

thrilled that s Hopkins has pulled together this world-class team

of researchers to move this important field forward, " says NHGRI

Director Francis S. , M.D., Ph.D.

The ambitious Hopkins center is the ninth grant funded through the

NHGRI's and NIMH's Center for Excellence in Genome Science program,

and the first to focus on epigenetics.

" This center reflects a trend at Hopkins to shift toward

interdisciplinary research, really pulling together those working on

related problems, regardless of their department affiliations, to

tackle important basic questions whose answers will advance human

health, " says Chi Dang, M.D., Ph.D., vice dean for research at the

s Hopkins School of Medicine. He adds that Hopkins' Institute for

Cell Engineering and the Institute for Basic Biomedical Sciences are

both advancing such multidisciplinary research models.

Given its own " multidisciplinary " status, the center will be bigger

than Feinberg's laboratory alone. Among the key players are 15 other

researchers from Hopkins and elsewhere whose work and collaborations

will be critical to the center's success.

" As we studied epigenetics in cancer, it became clear that we needed

to 'genomicize' epigenetics, to really investigate the issue more

broadly than simply its role in cancer, " says Feinberg. " This center

is a first, critically important step toward creating a comprehensive

picture of epigenetics and its role in human health. "

First on the center researchers' to-do list is development of

technology to speed identification of epigenetic marks and their

locations in the genome and then adapt these methods to examine

multiple sections of the genome and many samples at once.

Next, with s Hopkins colleagues and collaborators from a German

company called Epigenomics, the Icelandic Heart Foundation and

Pennsylvania State University, these new technologies will be used to

examine the entire epigenomes of specific groups of people to hunt

for clues to human disease. The first groups to be analyzed will be

families -- at least a " trio " of parents and child -- from two s

Hopkins groups studying the genetic bases of autism and bipolar

disorder, and from the 30-year effort of the Icelandic Heart

Foundation.

" Iceland isn't much different from Northern Europe in terms of its

genetic diversity, but organizations like the Icelandic Heart

Foundation boast great documentation of familial relationships,

medical histories and thorough and quantitative medical examination

to go along with blood and tissue samples, " says Feinberg. " There is

great scientific value in what they have and what they do. "

In particular, Feinberg points out that researchers at the IHF

invented high-throughput, quantitative phenotyping -- the ability to

rapidly assess the biologic traits and characteristics that stem from

genetic, epigenetic and environmental influences. With the IHF

information and samples, Feinberg and his colleagues will determine

whether and how epigenetic marks shift over time and how a child's

epigenetic marks differ from his or her parents'.

" The genetic sequence is essentially fixed for life, but we believe

epigenetic marks are more subject to change, " says Feinberg. " The IHF

collaboration will let us really test the stability of epigenetics

and the passage of those marks from parents to child, perhaps even

over successive generations. "

At the heart of the center's work is epigenetics' importance in

proper cell function and in development. One example of epigenetics

is " imprinted " genes -- genes whose activity is determined not by the

regular dominant and recessive rules of Mendel's genetics, but solely

by which parent provided the gene copy. For example, for some

imprinted genes only the copy from the mother is used, while for

other imprinted genes, only the copy inherited from the father is

turned on. (Our cells contain two copies of every gene, one from the

mother and one from the father.)

At some point before, during or after egg meets sperm, epigenetic

marks such as those used for imprinting must be reset and re-

established, so that a gene passed from father to daughter to son is

appropriately marked, for example. Knowing how and when this happens,

and whether the process can be controlled, has important implications

for understanding human development and the viability of animals and

stem cells created through somatic cell nuclear transfer, a process

colloquially known as " cloning. "

As part of the center, Feinberg and his colleagues will also

implement a " minority action plan " to encourage racial and ethnic

minorities to pursue education and careers in genetics and genomics.

The plan offers select local students the chance to conduct genetics

and genomics research during their summer breaks, and Feinberg will

work with staff at the Center for Talented Youth (CTY), a s

Hopkins endeavor with sites across the country, to add a genomics

component to the program's summer classes. Starting in 2005, the

Epigenetics Center will fund four minority students each year to

attend these classes.

" The idea is to groom an interest in science and in genomics from a

young age, hopefully increasing the number of minorities who pursue

education and careers in genome sciences, " says Feinberg.

Others closely involved with the center's work are Karl Broman and

Margaret Fallin, s Hopkins Bloomberg School of Public Health;

Potash, Hengmi Cui, Onyango, J. Deo, Hans

Bjornsson, Nichols and Jef Boeke of the s Hopkins School of

Medicine; Kurt Berlin, Epigenomics AG; Vilmundur Gudnason, Icelandic

Heart Foundation; Webb , Pennsylvania State University;

Green, NHGRI; Tamara , National Institute on Aging; and Lea

Ybarra, The s Hopkins University, Center for Talented Youth.

Nichols and Ybarra will be principally involved with the center's

minority action plan. Feinberg is also a member of the McKusick-

s Institute of Genetic Medicine at s Hopkins.

http://www.hopkinsmedicine.org

[Guest guest]

Everyone,

I just saw a PBS NOVA program that really blew me away regarding

epigenetics. It originally aired on October 16, 2007.

I wish you could all see it. It was amazing.

It was called " Ghost in Your Genes " and I think I finally understand more

about how switches can be thrown in our genes that can predispose us to

disease states.

Here's a link to the show's website...

http://www.pbs.org/wgbh/nova/genes/

You can click and watch a preview. You really need to see the whole show,

though. It explains (SHOWS) how toxins, etc., (even experiences!) can

actually switch our genes on and off. It shows the DNA of identical twins

in youth and how the DNA changes as they age and are exposed to different

things.

After seeing this show, I find it entirely possible that a generation of

genetically predisposed children could have their " switches " thrown by

environmental factors.

You won't regret the hour, believe me!

By the way, a transcript of the show should be posted on the site within a

few weeks.

Caroline

[Guest guest]

For those of you who are reading the conversation on gene expression

changing (epigenetics), if you want to get a better understanding of the

concept, there was a NOVA show on PBS a while back that explained it

beautifully.

It was called ³Ghost in Your Genes²...

Here¹s a link to the website...

http://www.pbs.org/wgbh/nova/genes/

There¹s a program (written) transcript on the site, but the show itself was

amazing. It would be a great DVD to request through your library if you

don¹t want to buy it. The show really opened my eyes to how gene expression

can literally change generations. It explains how, for instance, grandsons

in the Swedish village of Overkalix are four times more likely to die from

an illness related to diabetes if their grandfathers had plenty of food to

eat in late childhood.

I can¹t recommend this show highly enough... it illustrated the concept SO

well.

It was one of the most interesting programs I have ever seen.

Just a thought,

Caroline G.