Just imagine: You're turning 40 this year, and your New Year's resolution was to work on your future health issues. You make an appointment to have your genome sequenced and learn that you have a strong genetic tendency toward cardiovascular disease and colon cancer, as well as some markers for Alzheimer's. Chastened, you head back to the gym, schedule screening tests for the all three diseases and start investigating long-term care options.

This scenario is still in the realm of science fiction, but perhaps not for much longer. The cost of genome sequencing will begin to fall, and its applications to health care will follow.

In 2007, the journal Nature Genetics posed "The Question of the Year, " asking geneticists all over the world what research they would do if the entire human genome could be sequenced for a $1,000 US — rather than the $3 billion US that the first sequence cost. Their responses, posted on the journal's website, illuminate the questions we'll be facing in the years to come.

The first complete genome of an individual person, that of geneticist J. Craig Venter, was published in September 2007 in the Public Library of Science (PLOS) journal Biology. Over four years, an international team sifted through some 20 billion base pairs of DNA to assemble Venter's genetic profile. A team from Toronto's Hospital for Sick Children, lead by Stephen Scherer, a senior scientist there in genetics and genome biology and a professor at the University of Toronto, collaborated on the project.

As a result of this work, and the work of other research teams, the $1000 US genome may not be so far off. In November, deCODE, a company based in Iceland, began offering customers a genetic profile covering one million genetic variants (providing disease risk factors and ancestry information) for $985 US. On Jan. 22, the biotech firm 23andMe announced that it would offer its $999 US genetic profile to customers in Canada as well as in Europe. The company, which made news last spring when Google invested $3.9 million US in it, scans some half-million locations on the genes known to have variations significant for disease and ancestry. The whole genome, however, has some six billion locations or DNA "letters" altogether, and while the partial genetic information available commercially is intriguing, it is difficult to interpret and the medical applications are still limited.

People willing to have their entire genome made public may volunteer with the Personal Genome Project, initiated by George Church, a Harvard professor of genetics. Or, if you'd like to keep your genome private, a company called Knome (also co-founded by Church) will sequence your whole genome for $350,000 US — if you are among the first 20 people to ask — according to a press release dated Nov. 29.

Your personal blueprint

So what good is all this genetic information?

Many geneticists posting on the Nature Genetics site speculate that widely available genome sequencing would illuminate common intractable diseases.

In answer to the journal's question of the year, Francis Collins of the National Human Genome Research Institute in the U.S. said that at $1,000 US per genome, he would sequence the genomes of people affected by diseases that have at least some genetic component — such as cancer, arthritis, Alzheimer's, diabetes, cardiovascular disease and depression. He would also look at the genomes of people who have lived a century or more in order to explore "the genetics of good health and longevity in all humans."

Understanding genetic components of disease would also widen the availability of "personalized medicine," transforming it from "a luxury to a birthright," as George Church puts it on the website.

Personalized medicine — already used in limited ways — relies on genetic testing to predict how people will respond to particular medications, such as antidepressants and chemotherapy drugs. However, Scherer cautions that, "In the short term, personalized medicine will mainly only benefit those people who can access [afford] it and who have the wherewithal to make sense of the data."

Scherer, who plans to enroll in the Personal Genome Project this year, is looking for autism susceptibility genes, but points out that the technology is still too expensive for sequencing to apply directly to the study of disease. Still, he says, his team spends a lot of time "trying to make the links of DNA sequence changes to medical outcomes."

In the meantime, he is making progress using high-resolution arrays, he says. Scherer directs the Autism Genome Project, supported by Genome Canada, which will screen the genomes of more than 6,000 members of 1,600 families to search for clues to causes and treatments.

Some geneticists are particularly interested in genetic variation. One of the surprises from the sequencing of Venter's genome was how much people's genes vary and how even the numbers of copies we have differ. This variation can be the basis both for genetic diversity and for disease.

Other geneticists who posted on the Nature Genetics website would look not at humans, but at mice, dogs, cats, plant organisms, bacteria and the microbes that inhabit the human body. Indeed, one geneticist — Michael D. Rhodes from Applied Biosystems, which sponsored the Question of the Year project — proposed what he called the Gaia Project, in which the genomes of all species on the planet would be sequenced, both to represent the diversity of the world and to record the genomes of species becoming extinct.

The down side of DNA testing

What are the risks of all this sequencing?

In countries that lack universal health coverage, such as the U.S., people could be denied health insurance if negative genetic information were in their records.

Jonathan Pritchard of the University of Chicago wonders in his entry whether he would have his three-year-old son's genome sequenced "to help determine his genetic liabilities and strengths." He concludes that although sequencing raises serious ethical questions for the patient, for the people who share his genes and for society and poses practical challenges when it comes to interpreting the genetic data, "it is hard to believe that the clinical value of such information will not, ultimately, outweigh the risks."

Don Francis, an American epidemiologist formerly with the Centers for Disease Control who has recently founded the non-profit company Global Solutions for Infectious Diseases, is intrigued by the potential of gene-specific medicine. But he's troubled by the disparity in health care between industrialized countries and the rest of the world.

"How can we justify this expense when we are still trying to eliminate polio in distant corners of the world?" he asks.

But even geneticists from developing countries are enthusiastic about the ramifications of the $1,000 US genome. Muntaser E. Ibrahim, head of molecular biology at the University of Khartoum, Sudan, wrote: "Given the current pace of spread and utility of information in developing countries, it is reassuring that these countries will not be isolated from the advantages of affordable sequencing."

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