The International 'HapMap' Project

Looking for a quicker way to identify genes that cause disease, researchers are beginning a $100 million effort to identify blocks of DNA that contain common variations in the human genetic structure, officials announced Tuesday.

The project, expected to take three years, involves nine research groups in five countries and will analyze genetic patterns in blood samples taken from people in Nigeria, Japan and China and from people of northern and western European ancestry in the United States.

The goal is to determine how the 3 billion bits of DNA in the human genome, or genetic structure, are organized into sequence variations, or haplotype blocks, that are shared by many people.

Once these haplotypes are mapped, it will form "a powerful and elegant shortcut" to identifying inherited gene sequences linked to disorders such as diabetes, heart disease and cancer, said Dr. Francis Collins, head of the National Human Genome Research Institute, one of the National Institutes of Health.

"This work will have a profound impact on the future of medicine," Collins said at a news conference announcing the project. He called the effort the International HapMap Project.

Both public and private labs are participating, with many of the same researchers who helped complete the sequencing in 2001 of the human genome.

The human genome comprises about 3 billion pairs of DNA. Each pair is made up of chemicals commonly identified with the letters A, T, C or G. Virtually all the letters are in the same sequence in everyone, but there are an estimated 10 million "spelling" differences, involving a single change where one DNA letter is replaced by another. These are called single nucleotide polymorphisms, or SNPs, and some are thought to be related to disease.

Recent studies have shown that SNPs are organized into DNA neighborhoods called haplotype blocks comprising about 10,000 or more base pairs. Many people share the same haplotype blocks, and common variations are found in virtually all populations. Thus, it is possible to identify a haplotype block by finding a single SNP, instead of a having to check all 10,000 base pairs. In effect, the HapMap project is an effort to find DNA landmarks that identify specific DNA sequences shared by many people. Later research would then look within those sequences to find the genes that cause disease.

As an illustration of how the HapMap would help find disease genes, Collins related it to leaky gas pipes. Suppose, he said, a safety officer knows there are 12 leaking gas pipes somewhere in a city and must quickly find them. It could take years to systematically search the city house by house, said Collins. It would be much quicker for the safety officer first to identify blocks within the city where there are known to be gas leaks, then limit his house-to-house search to those blocks.

By breaking up the human genome into blocks with known genetic variations, researchers can go directly to those blocks and search for disease genes instead of having to search through all 3 billion DNA base pairs, he said.

For instance, if researchers could find a specific haplotype block linked to diabetes, they could focus their search for a diabetes gene to that block instead of having to survey the entire human genome.

By Paul Recer