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 Researchers unveiled the map of the "epigenome" in the journal
Nature on Wednesday, alongside nearly two dozen related papers. The
mapping effort is being carried out under a 10-year, $240 million
U.S. government research program, the Roadmap Epigenomics Program,
which was launched in 2008.
The human genome is the blueprint for building an individual person.
The epigenome can be thought of as the cross-outs and underlinings
of that blueprint: if someone's genome contains DNA associated with
cancer but that DNA is "crossed out" by molecules in the epigenome,
for instance, the DNA is unlikely to lead to cancer.
As sequencing individuals' genomes to infer the risk of disease
becomes more common, it will become all the more important to figure
out how the epigenome is influencing that risk as well as other
aspects of health. Sequencing genomes is the centerpiece of the
"precision medicine" initiative that U.S. President Barack Obama
announced this month.
"The only way you can deliver on the promise of precision medicine
is by including the epigenome," said Manolis Kellis of the
Massachusetts Institute of Technology, who led the mapping that
involved scientists in labs from Croatia to Canada and the United
States.
 Drug makers including Merck & Co Inc., the Genentech unit of Roche
Holding and GlaxoSmithKline Plc are conducting epigenetics research
related to cancer, said Joseph Costello of the University of
California, San Francisco, director of one of four main labs that
contributed data to the epigenome map.
Epigenetic differences are one reason identical twins, who have
identical DNA, do not always develop the same genetic diseases,
including cancer.
But incorporating the epigenome in precision medicine is daunting.
"A lifetime of environmental factors and lifestyle factors"
influence the epigenome, including smoking, exercising, diet,
exposure to toxic chemicals and even parental nurturing, Kellis said
in an interview. Not only will scientists have to decipher how the
epigenome affects genes, they will also have to determine how the
lives people lead affect their epigenome.
BOOK OF LIFE
The human genome is the sequence of all the DNA on chromosomes. The
DNA is identical in every cell, from neurons to hearts to skin.
It falls to the epigenome to differentiate the cells: as a result of
epigenetic marks, heart muscle cells do not make brain chemicals,
for instance, and neurons do not make muscle fibers.
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The epigenome map published on Wednesday shows how each of 127
tissue and cell types differs from every other at the level of DNA.
Because scientists involved in the Roadmap project have been
depositing their findings in a public database as they went along,
other researchers have been analyzing the information before the map
was formally published.
One of the resulting studies show, for instance, that brain cells
from people who died with Alzheimer's disease had epigenetic changes
in DNA involved in immune response. Alzheimer's has never been seen
as an immune-system disorder, so the discovery opens up another
possible avenue to understand and treat it.
Other researchers found that because the epigenetic signature of
different kinds of cells is unique, they could predict with nearly
90 percent accuracy where metastatic cancer originated, something
that is unknown in 2 percent to 5 percent of patients.
As a result, epigenetic information might offer a life-saving clue
for oncologists trying to determine treatment, said co-senior author
Shamil Sunyaev, a research geneticist at Brigham and Women's
Hospital in Boston.
There is much more to come. Instead of the epigenome map being the
end, said Kellis, "I very much see (it) as beginning a decade of
epigenomics."
(Reporting by Sharon Begley; Editing by Michele Gershberg and Lisa
Shumaker)
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