Push To Find Disease Genes Begins

Wednesday, July 12th 2000, 12:00 am
By: News On 6

WASHINGTON (AP) — Now that the human genome is almost completely mapped, research organizations are starting a major push to find the genes that cause human disease.

The National Human Genome Research Institute announced Tuesday that three academic centers will start work to find segments in the human gene structure that vary from person to person, a major step toward finding genes that cause heart disease, diabetes and other common diseases.

Collaborating in the effort are the Whitehead Institute for Biomedical Research in Cambridge, Mass.; Washington University School of Medicine in St. Louis, and the Sanger Centre in Hinxton, England.

Researchers will find the variable sequences by searching the 3.1 billion chemical base pairs that make up human DNA. These variable sequences are called single nucleotide polymorphisms, or SNPs. Some of the variations in the SNPs may amount to only a single chemical base pair difference in the DNA sequence of one person compared to another.

The SNPs will be located, or mapped, on the genome. This map then can be used to locate gene variations that cause disease.

The collaboration is being funded by the National Human Genome Research Institute, or NHGRI, and the SNP Consortium, a nonprofit organization that includes the Wellcome Trust and 13 pharmaceutical and technical companies. The NHGRI is the lead agency in the international Human Genome Project, a publicly funded consortium that is mapping and sequencing the entire genome.

Officials said the new search for genetic variations is expected to identify and map up to 750,000 SNPs, but only a fraction of these are expected to be medically significant.

To find the SNPs, researchers will cut the DNA into about two million fragments, each with about 6,000 chemical base pairs of DNA. The DNA to be used will come from 24 anonymous donors who come from diverse geographic regions.

The base pair sequences in the fragments will then be compared to sequences already mapped. This will identify the variations. The SNPs that are found will then be deposited in a computer data base that researchers can download for laboratory studies.

Researchers can use the map of SNPs to identify the genetic differences that cause some people, but not others, to be predisposed toward disease.

The analyzed sequences also may help close some of the few remaining gaps in the working draft of the human genome, officials said.

``This collaboration will yield a bumper crop of genetic variations,'' Dr. Francis Collins, director of the NHGRI, said in a statement. ``As a bonus, it will also improve the assembly of the human genome sequence so that it is closer to the highly polished finished form that is our goal.''

The Human Genome Project, which includes scientists at 16 institutions in the U.S., Great Britain, Japan, Germany, China and France, is expected to complete the highly accurate, finished version of the human genome in 2003.

In a joint announcement with Celera Genomics on June 26, the HGP consortium announced that it had completed a ``working draft'' of the genome that still contained gaps and segments that needed to be rechecked for accuracy.

During the joint announcement, Celera, a private Rockville, Md. firm, said that it had completed a first assembly of the entire genome using a different method.


On the Net:

National Human Genome Research Institute: http://www.nhgri.nih.gov