New DNA Mapping Project to Trace Genetic Ills

Nicholas Bakalar
for National Geographic News
October 26, 2005
Mapping the three billion letters of the human genome has helped researchers better understand the 99.9 percent of DNA that is identical in all humans.

Now a new project aims to map the 0.1 percent of DNA where differences occur. The International HapMap Project will look at variations that dictate susceptibility to genetic influences, such as environmental toxins and inherited diseases.

Researchers "read" DNA code by its structural units called nucleotides. These chemical building blocks are designated by the letters A (adenine), C (cytosine), G (guanine), and T (thymine).

Single-letter variations in genes—called single nucleotide polymorphisms, or SNPs (pronounced "snips")—are often the culprits behind a wide range of genetic diseases. For example, changing an A to a T in the gene for the blood molecule hemoglobin causes sickle cell anemia.

But most diseases and disorders are not caused by a single gene. Instead they are caused by a complex combination of linked genetic variations at multiple sites on different chromosomes.

Gene Mapping

Haplotypes are sets of adjacent SNPs that are closely associated and are inherited as a group.

Certain haplotypes are known to have a role in diseases, including Alzheimer's, deep vein thrombosis, type 2 diabetes, and age-related macular degeneration, a leading cause of blindness.

Identifying the haplotypes that lead to disease, or immunity from disease, will provide scientists with a deeper understanding of genetic illness.

Researchers hope a map of haplotypes will provide the raw material to answer basic questions, such as how many genes are involved in each disorder? How do gene variants interact with each other? How do genes and combinations of genes interact with environmental factors to cause disease or provide immunity?

The first phase of establishing a haplotype map is reported in tomorrow's issue of the journal Nature.

Human DNA contains about ten million common SNPs. It would be impossible, and impossibly expensive, to analyze all of them.

But researchers can draw conclusions from looking at only a fraction of the SNPs.

Peter Donnelly, professor of statistical science at the University of Oxford in England and a paper co-author, draws a useful analogy: "Imagine if you knew there was a group of five people who always caught the same bus," he said.

"If you want to know which particular bus they're on, you don't have to find all of them. You just have to look for one particular individual … The other four people are likely to be there as well."

"The motivation for the HapMap," Donnelly said, "is to create a resource which catalogs these correlations, and which researchers can then use with only five or ten percent of the effort and expense" of looking at all the possible SNPs.

Team Effort

The haplotype mapping project started in October 2002 with the creation of the International HapMap Consortium.

This large international group of scientists came together to create a public database of common human sequence variations that would be used to guide future genetic studies.

The consortium now has a map of more than a million of the most common SNPs grouped into haplotypes, and two million more will be added soon.

The early haplotype map uses DNA from 269 individuals spanning four different populations—90 people from Ibadan, Nigeria; 90 Americans from Utah; 45 Han Chinese from Beijing; and 44 Japanese residents of Tokyo.

The authors caution that these populations, although varied geographically, should not be taken to be representative of larger populations, such as all of Africa, North America, or Asia.

The common variants in the four sampled populations are nearly complete.

But subtle structural differences need to be mapped before a complete picture of genetic variation among these four human populations can be drawn.

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