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Researchers map human epigenome

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Postby rath » Thu Oct 15, 2009 7:15 am

15 October 2009.

A complete map of the chemical switches governing the operation of a human genome has been plotted for the first time, further extending the reach of medical research.

The year-long project by an international team led by Australian scientist Dr Ryan Lister, identified 50 million cytosine methylation sites that act as chemical switches to turn human genes on and off, potentially affecting every function of the body.

These switches have previously been shown to be affected by a person's lifestyle and environment, with some changes being passed on to subsequent generations.

The paper outlining the work to identify the methylation sites that together are called the epigenome, is published in today's issue of Nature and an outline of the epigenetic layout appears on the Salk Institute's website.

"It's providing a map that you can place over the top of the genome sequence itself to explain the way that genes are regulated," says co-author Professor Harvey Millar of University of Western Australia.

Medical potential

Until now, epigenetic research has been done using small segments of the epigenome without the breadth or detail allowed by the new approach.

The ability to map the entire epigenome will allow researchers to examine the characteristics of diseased cells in much greater detail, design medication to govern particular epigenetic changes, and to ensure medication doesn't inadvertently affect other genetic switches.

"If a disease has an epigenetic basis, this information provides researchers with a very broad landscape of what's happening - which genes are modified by methylation - which could ultimately be changed if you could design the right drug," says Millar.

Epigenetic research is already being used in cancer treatment, but the new approach will enable much more targeted interventions, says Dr Jeff Craig, an epigenetic specialist with the Murdoch Children's Research Institute.

"At the moment epigenetic drugs are still very blunt instruments in cancer treatment."

He says it's another step towards super-personalised medicine.

"People talk about the personal genome project, and the personal epigenome project will occur soon afterwards."

Stem cell clues

In addition to the mapping work, Lister and his colleagues have uncovered fundamental differences in the epigenetic operation of stem cells. This may assist in understanding how stem cells differentiate into specialist cell.

"The significance of this lies in what will happen in the future as a result of this technology and this information being available in the future," says Millar.

"It's a continuing process of working out the complexity and how much human differences and human diseases are impacted not just by the DNA sequence, but by the way in which the DNA is packed in our cells and the way in which it's chemically modified.

"These are things that are potentially reversible … within our own lifetimes."
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