BioEd Online

Geneticists are brewing plans for a collective effort, loosely patterned on the Human Genome Project, that would map subtle changes in DNA. Some say that these changes are just as important to our understanding of disease as straight mutations.

As many as half of the genetic alterations that cause cancer, for example, may be 'epigenetic' changes rather than mutations, says Stephen Baylin, a tumour biologist at Johns Hopkins University in Baltimore, Maryland, who is involved with the proposal.

In mutations, letters of the genetic code can be changed or stretches of DNA deleted. But in a common epigenetic change, for example, a small molecule simply latches on to DNA in a process called methylation. This does not change the genetic sequence, but it can still shut a gene down.

The plan for a Human Epigenome Project, backed by dozens of scientists, is published on 15 December in the journal Cancer Research¹. Supporters say that have not encountered much resistance. But they add that this is probably because their proposal does not yet come with a price tag.

Organizations looking into the project, including the US National Cancer Institute and the American Association of Cancer Research, have not yet committed any funds.

"Nobody is denying that the epigenome project would be useful," says Michael Stratton, who heads a cancer genome project at the Wellcome Trust Sanger Institute in Hinxton, UK. "The constraint is always the cost."

Dark side of the genome

Researchers have only realized the importance of epigenetic changes in the past five years, says Baylin. In addition to cancer, the changes are known to underlie other diseases, including neurological disorders. And stem cells have been found to rely heavily on epigenetic processes, turning genes on and off as they divide and mature.

Each type of human cell comes with its own set of epigenetic settings. Understanding those, say proponents, would set the stage for understanding what goes wrong during disease, and would help select genes to target with drugs.

"You can go into the dark parts of the genome that you would never have imagined would yield drug targets and find things," says Stratton.

The technology for detecting methylation has advanced rapidly in the past few years. Several epigenetic projects are under way, and the Sanger Institute and others are running a pilot project looking at individual chromosomes. The Human Epigenome Project would coordinate these efforts and set research priorities.

Cancer atlas

The proposal comes on the heels of an announcement earlier this week that the US National Institutes of Health will allocate US$100 million in pilot funds for The Cancer Genome Atlas, a project that aims to catalogue the genetic changes associated with cancer (see ' Big money for cancer genomics').

This project will include an epigenetics component. But experts say there is much more scope for work in epigenetics than could be encompassed by the cancer atlas.

"If you went at it full scale, it would be as big or bigger" than the cancer project, says Baylin. "It could get huge."