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By Sharon Begley
NEW YORK, Feb 18 (Reuters) - Scientists for the first timehave mapped out the molecular "switches" that can turn on orsilence individual genes in the DNA in more than 100 types ofhuman cells, an accomplishment that reveals the complexity ofgenetic information and the challenges of interpreting it.
Researchers unveiled the map of the "epigenome" in thejournal Nature on Wednesday, alongside nearly two dozen relatedpapers. The mapping effort is being carried out under a 10-year,$240 million U.S. government research program, the RoadmapEpigenomics Program, which was launched in 2008.
The human genome is the blueprint for building an individualperson. The epigenome can be thought of as the cross-outs andunderlinings of that blueprint: if someone's genome contains DNAassociated with cancer but that DNA is "crossed out" bymolecules in the epigenome, for instance, the DNA is unlikely tolead to cancer.
As sequencing individuals' genomes to infer the risk ofdisease becomes more common, it will become all the moreimportant to figure out how the epigenome is influencing thatrisk as well as other aspects of health. Sequencing genomes isthe 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 precisionmedicine is by including the epigenome," said Manolis Kellis ofthe Massachusetts Institute of Technology, who led the mappingthat involved scientists in labs from Croatia to Canada and theUnited States.
Drug makers including Merck & Co Inc., the Genentechunit of Roche Holding and GlaxoSmithKline Plc are conducting epigenetics research related to cancer, saidJoseph Costello of the University of California, San Francisco,director of one of four main labs that contributed data to theepigenome map.
Epigenetic differences are one reason identical twins, whohave identical DNA, do not always develop the same geneticdiseases, including cancer.
But incorporating the epigenome in precision medicine isdaunting.
"A lifetime of environmental factors and lifestyle factors"influence the epigenome, including smoking, exercising, diet,exposure to toxic chemicals and even parental nurturing, Kellissaid in an interview. Not only will scientists have to decipherhow the epigenome affects genes, they will also have todetermine how the lives people lead affect their epigenome.
BOOK OF LIFE
The human genome is the sequence of all the DNA onchromosomes. The DNA is identical in every cell, from neurons tohearts to skin.
It falls to the epigenome to differentiate the cells: as aresult of epigenetic marks, heart muscle cells do not make brainchemicals, for instance, and neurons do not make muscle fibers.
The epigenome map published on Wednesday shows how each of127 tissue and cell types differs from every other at the levelof DNA. Because scientists involved in the Roadmap project havebeen depositing their findings in a public database as they wentalong, other researchers have been analyzing the informationbefore the map was formally published.
One of the resulting studies show, for instance, that braincells from people who died with Alzheimer's disease hadepigenetic changes in DNA involved in immune response.Alzheimer's has never been seen as an immune-system disorder, sothe discovery opens up another possible avenue to understand andtreat it.
Other researchers found that because the epigeneticsignature of different kinds of cells is unique, they couldpredict with nearly 90 percent accuracy where metastatic canceroriginated, something that is unknown in 2 percent to 5 percentof patients.
As a result, epigenetic information might offer alife-saving clue for oncologists trying to determine treatment,said co-senior author Shamil Sunyaev, a research geneticist atBrigham and Women's Hospital in Boston.
There is much more to come. Instead of the epigenome mapbeing the end, said Kellis, "I very much see (it) as beginning adecade of epigenomics."
(Reporting by Sharon Begley; Editing by Michele Gershberg andLisa Shumaker)
