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Epigenetic differences are one
reason identical twins, who have identical DNA, do not always develop the same
genetic diseases, including cancer.
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Scientists
for the first time have mapped out the molecular "switches" that can
turn on or silence individual genes in the DNA in more than 100 types of human
cells, an accomplishment that reveals the complexity of genetic information and
the challenges of interpreting it.
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, US$240 million U.S. government research
program, the Roadmap Epigenomics Program, which was launched in 2008, according to Worldbulletin/News desk.
The report continues:
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.
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."
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