Human Genome Project is beginning to bear fruit

MCT photo illustration

WASHINGTON — Four years ago, scientists triumphantly announced that they’d finished reading the entire human genome — the 3 billion "letters" of DNA that are the instruction manual for making a person.

Trouble was, they didn’t know how to make sense of the bewildering clutter of A's, C’s, G’s and T’s in the so-called "book of life."

Now the genome project is beginning to bear fruit. A bumper crop of fresh discoveries connects specific bits of DNA to numerous diseases, including cancer, diabetes, blindness and AIDS.

New findings are being published almost weekly in scientific journals. Scientists say they're important steps toward future treatments or cures.

"A whole series of studies is coming down the pike," Teri Manolio, a geneticist at the National Human Genome Research Institute in Bethesda, Md., told a genome conference in Boston this summer. "This is an unprecedented opportunity to apply genetics to disease."

The latest discovery is a report published in the journal Nature on Sunday declaring that two tiny changes in human DNA may add more than an inch to an individual’s height.

An Aug. 2 paper in The New England Journal of Medicine identified other DNA variants that may predispose a person to a heart attack. Armed with such knowledge, doctors can recommend changes in lifestyle, such as losing weight and stopping smoking, that could save a patient’s life.

These discoveries are the product of a booming new area of genetic research known as "Genome-Wide Association" (GWA) studies. GWA researchers are taking advantage of two developments since the completion of the Human Genome project in 2003.

  • New technologies that allow them to survey as many as 500,000 bits of DNA at once. This makes it possible to scan a person’s entire genome rapidly and cheaply, instead of laboriously studying one gene at a time.
  • A catalog called the HapMap, completed in October 2005 that lists 11 million tiny variations in the human genome, such as an A where there should be a T. Even such a small change can drastically alter a gene’s function.
  • GWA researchers use powerful computer programs to compare the genomes of tens of thousands of persons — half of them sick and half well — trying to spot the subtle differences that may lie behind a disease. Changes in the height gene, for example, were discovered after British researchers scanned the DNA of 24,000 people.

    Aravinda Chakravarti, a geneticist at the Johns Hopkins University School of Medicine in Baltimore, likened the process to "panning for gold."

    "We’re mining genomic data," said Deborah Nickerson, a researcher at the University of Washington in Seattle. "We’re finding variations in the human genome that make it possible to do experiments that we wouldn’t dream were possible a few years ago. It’s very exciting (but) it’s just the tip of the iceberg."

    The detection of a DNA variant related to a disease doesn’t mean that a cure is just around the corner. Some variants raise the risk of disease only slightly, and multiple genes are usually involved in complex diseases. The variant itself may not be to blame, but it shows the location along a strand of DNA where the trouble lies, helping researchers find the culprit.

    The current wave of GWA discoveries began with a March 2005 report on a gene variant associated with macular degeneration, the most common cause of blindness in the elderly.

    Last September, mutations linked to breast and colon cancer were reported. In October, a variant showed up in a gene linked to memory. In December, it was the turn of inflammatory bowel disease. April saw a flurry of reports on prostate cancer, obesity and heart disease.

    In June, rheumatoid arthritis, hypertension, bipolar disorder, type 1 and type 2 diabetes and coronary heart disease were added to the list. In July, GWA researchers identified three gene variants associated with HIV and AIDS.

    "This is a new dawn in the genetics of common human diseases," said Peter Donnelly, the leader of a GWA research team at Oxford University in England.

    Pharmaceutical companies are already using the insights to explore possible new drugs, according to Human Genome Research Institute Director Francis Collins.

    "This could be a totally new way to approach disease," Collins said.


    More information on Genome Wide Association studies.