The secrets in your genome
Posted: Wednesday, October 17, 2007 7:15 PM by Alan Boyle
Your genome holds clues to where your ancestors came from – and what medical challenges you might have to deal with as a result. But there are also clues in there for overcoming those challenges. Those are among the lessons from the International HapMap Consortium, which released its second giant batch of data today.
HapMap has documented how evolution is affecting populations from Europe and America, from Asia and from Africa. Looking ahead, one genetic researcher suggests creating a "Genome Commons" that can complement current and future HapMap findings - and even offer new therapies for the genes that ail you.
Today's map of genetic variations, also known as a haplotype map (hence the word HapMap), follows up on the international consortium's first map, issued in 2005. The first map analyzed about 1 million variants in the human genome. This second map charts more than 3.1 million of the variants - also known as single-nucleotide polymorphisms, or SNPs.
"The more SNPs that are on the map, the more precisely researchers can focus their hunts for genetic variants involved in disease," the University of Oxford, one of the partners in the HapMap consortium, explained in a news release.
More than 60 common genetic variants have already been associated with increased risk for diseases ranging from coronary artery disease to Crohn's disease, rheumatoid arthritis and diabetes.
Pardis Sabeti, a biologist at the Broad Institute, is interested in using the HapMap findings to fight yet another killer disease, malaria.
"You can see what are the beneficial tricks that have spread through the human population," said Sabeti, who is co-first author for one of the HapMap reports in Thursday's issue of Nature. "Finding out which specific mutations are the ones that protect [against disease] will help you think about therapeutics as well."
The DNA analyzed for the Phase 2 map came from the same blood collected for the Phase 1 map. Those samples were taken from 270 volunteers in four geographically diverse areas: Nigeria, Japan, China and Utah. The Utah residents traced their ancestry to northern and western Europe, so for the purposes of the study they were considered Europeans.
The study that Sabeti and her colleagues found intriguing correlations between particular genes that showed signs of strong evolutionary pressure, and the physical traits handled by those genes:
- For the Utahns of European ancestry, the genes are involved in determining skin and hair color. That meshes with earlier HapMap findings, suggesting that ancient humans who left Africa for less sunny northern climes came to have lighter skin so they could boost their vitamin D production.
- For the Nigerians, there were signs of strong natural selection pressure in genes that play a role in the body's response to Lassa fever. That scourge is endemic in parts of West Africa. "We still don't have the biological link between Lassa and the gene that we're finding," Sabeti told me. "There are some people who appear to have complete immunity, and there are other people who get hemorrhagic fever and die." As a result of the study, researchers are planning a broader survey of people exposed to Lassa fever in hopes of learning more about the genetics behind immunity, she said.
- For the Asians, the strongly selected genes had to do with hair follicles, sweat glands and teeth. That's a puzzler for evolutionary biologists, although some theories have been proposed. "Hair, and sweat, and how much you keep warm are all physiological adaptations to the environment that seem to be under strong pressure," Sabeti said.
In the years ahead, the HapMap database will be expanded - and among the new populations due to provide their DNA are the Luhya and Maasai peoples of Kenya, Tuscans in Italy, Gujarat Indians in Houston, Chinese in Denver, Mexican-Americans in Los Angeles and African-Americans in the Southwest.
That growing database could well lead to the development of new drugs - for example, vaccines that mimic natural immunity to Lassa fever, or malaria, or AIDS. And many dream of a day when doctors will analyze your own personal genome, identifying tailor-made therapies or risk factors you will have to watch out for.
Genetic entrepreneur J. Craig Venter, who had his own genetic code analyzed for his part of the Human Genome Project, serves as an example. When risk factors for cardiac disease were found in his genome, he altered his diet and started taking cholesterol-lowered statins.
But that's just the start. In fact, Steven Brenner, a computational biologist at the University of California at Berkeley, wonders why more isn't being done with personal genomes.
"If the genome is so revealing, why was so little revealed?" he asks in a commentary written for Nature.
To encourage future revelations, Brenner is calling for the establishment of a Genome Commons - "a public knowledgebase of human genetic variation and its effect, culled from databases, diagnostic laboratories, and the scientific literature."
"It would build upon the HapMap information," Brenner told me today during a phone call from Italy, where he's attending a conference. "The Genome Commons would be more focused on the interpretation of that genetic variation in an individual."
The data contributed to the Commons would not contain information that could identify specific individuals, and thus would not raise privacy concerns, he said. "It wouldn't actually have anyone's individual genome in it, it would have only the summary results," he said.
A diagnostician would work with you on a confidential basis, check your DNA profile against the database using a software "navigator" - and then come back with a treatment plan tailored to your genes. Some researchers are already working on such an approach, using a sampling of genomic data rather than the full genome.
This week's issue of Nature traces a case study involving Hugh Rienhoff, a clinical geneticist whose daughter has an undetermined congenital syndrome. Rienhoff has been chronicling his genetic search for a cure - or at least a diagnosis - on a Web site called MyDaughtersDNA.org.
"I post this information with the hope that I might find others with similar problems, that someone might provide a key insight, and that others - physicians, scientists, patients and parents - might find inspiration to do the same for their own conundrums," Rienhoff writes.
Can HapMap - and the Genome Commons, if it's created - help Rienhoff's daughter and millions of others? Brenner thinks so: "The challenges of building a Genome Commons and navigator are not trivial, but this resource could affect us all personally," he writes.
Brenner plans to keep blogging on the idea on the Genome Commons Web site. And I'd like to hear your comments as well. Please contribute your thoughts on the personal genome and the quest for cures below.
