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Scientists decode human genome's instruction manual
10-17-2009, 11:10 PM,
Scientists decode human genome's instruction manual

Scientists decode human genome's instruction manual

• 'Epigenome' maps how genes work together
• Hope of new drugs to treat cancer and schizophrenia

Ian Sample on the epigenome which is an instruction manual for genes Link to this audio

Almost a decade after the human genome project laid bare the building blocks of life, scientists have figured out how they work together to create a living person.

The genome project identified about 25,000 genes that are needed to make a healthy human being, but said nothing about how they combine to produce everything from hearts and minds to legs and livers.

Now researchers in California have published what is effectively the first manual to show how genes are orchestrated inside cells ‑ a milestone that promises to revolutionise scientists' understanding of human development and how it can sometimes go wrong.

Many scientists believe the work will lead to new treatments for life-threatening diseases such as cancer, and possibly mental disorders such as schizophrenia.

The work is also expected to shed light on intriguing studies that suggest how we live today can have striking repercussions for the health and behaviour of our grandchildren. In one study, scientists found that people who smoked as youngsters went on to have grandchildren who reached puberty early. In another, a person's diet appeared to affect the way their grandchildren burned food.

Scientists have long known that nearly all the cells in the body have the same genetic makeup. What makes a heart cell different from a brain cell comes down to which genes are turned on or off inside it. The process is controlled by chemical switches that stick on to genes and alter how active they are.

For a decade, scientists have been trying to decipher what they call the human "epigenome", or the pattern of chemical switches in all 200 types of human cell. The prefix "epi" means "on", because the chemical switches stick on to genes. Until now, they had only a vague idea of what the epigenome looks like.

A team led by Joseph Ecker at the Salk Institute in La Jolla, California, studied human skin and stem cells to produce the first complete map of the human epigenome. By comparing this with the epigenomes of diseased cells, scientists will be able to work out how glitches in the epigenome lead to cancers and other diseases.

"This knowledge will be extremely valuable for understanding diseases such as cancer and possibly even mental disorders. Right now we just don't know how the epigenome changes during the ageing process or how the epigenome is impacted by our environment or diet," said Ecker, whose paper – first to report among a $190m (£119m) international project to map the human epigenome – appears in the journal Nature.

Previous studies suggest that changes in our environment, from what we eat to what we breathe in, can cause damage to the epigenome. This can throw a wrench into the way genes work, causing a variety of medical conditions.

Ryan Lister, lead author on the Ecker study, said: "What we have now is a reference. What is important now is for other groups to map the epigenomes of cancer cells and compare those to ours."

Manufacturers have already developed drugs that act on the epigenome, but the latest research will help scientists target therapies with far more precision.

Stefan Beck, professor of medical genomics at University College London, said: "We've been working for years to get the epigenome project off the ground and finally it's happening. It is absolutely exciting that the first fruits of the project are coming out."

Beck's work focuses on how changes to the epigenome can lead to cancer. Humans carry a number of genes that stop tumours from growing, but disruption to the epigenome can effectively silence these genes, making it more likely a person will develop cancer.

"Science has matured to a point that we can now map the epigenome of a cell," said Linda Birnbaum, director of the National Institute for Environmental Health Sciences, part of the US National Institutes of Health, which part-funded the work. "This will help us better understand how a diseased cell differs from a normal cell, which will enhance our entire understanding of the pathways of various diseases."
How environment holds the key

If the genetic code were a keyboard, the epigenome would be the pianist. Different chords become the various cell types, and all the notes have to be played perfectly to produce a healthy human being. Damage to the epigenome – the pattern of chemicals that controls our genes – has been linked to medical conditions as diverse as asthma, schizophrenia and cancer.

The epigenome can be disrupted by smoking, ageing, stress, atmospheric pollution, what we eat and drink, and a host of other environmental factors.There is some evidence that the environment causes epigenetic changes that make people more susceptible to asthma. Its role in other conditions, such as heart disease, schizophrenia, autism, abnormal growth and development and the eye disease glaucoma, are all being investigated.

Epigenetic changes are thought to be a major factor in our risk of developing cancer, an area that has attracted an enormous amount of research. Many genes help to prevent tumours from growing, but disruption of the epigenome can switch these protective genes off by accident.

Drug companies have developed some treatments that reset epigenetic information in cancerous cells, making them revert back to being healthy.

Understanding the whole human epigenome is expected to help scientists develop drugs that can reduce our risk of cancer and potentially reverse it even if it has become established.

• This article was amended on Friday 16 October 2009. We said "Almost a decade after the human genome project lay bare the building blocks of life". This has been corrected to "laid bare".

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