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, $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.
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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