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Second-Generation Map of Human Genetic Variation

Jane Ades, NHGRI.

The International HapMap Consortium has published analyses of its second-generation map of human genetic variation, which contains more than 3.1 million genetic variants. The improved HapMap will help researchers find DNA variants that influence the risk of disease and other traits.

Any 2 humans are more than 99% identical at the genetic level. The small fraction of DNA that varies among people can help explain differences in susceptibility to disease, response to drugs or reaction to environmental factors. Variations tend to be clustered and inherited together. Scientists call these clusters haplotypes. The map of human genetic variations is known as a haplotype map, or HapMap.

The initial version of the HapMap was published in 2005 by the International HapMap Consortium, a public-private partnership of researchers and funding agencies from around the world. The U.S. component is led by NIH's National Human Genome Research Institute (NHGRI). The DNA came from blood collected from 270 volunteers from 4 diverse populations: Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Han Chinese in Beijing; and Utah residents with ancestry from northern and western Europe.

In the October 18, 2007, issue of Nature, the consortium reported that the Phase II HapMap, which was produced using the same DNA samples, contains more than 3.1 million genetic variations, or single nucleotide polymorphisms (SNPs). That's 3 times more than the initial version. The researchers estimate that the HapMap now captures 25-35% of common genetic variation in the populations surveyed.

The consortium's decision to make its SNP datasets immediately available in public databases has already helped researchers around the globe to associate dozens of common DNA variants with the risk for diseases and other traits. NHGRI Director Dr. Francis S. Collins explains, "This new approach to research, called genome-wide association studies, has recently uncovered new clues to the genetic factors involved in type 2 diabetes, cardiovascular disease, prostate cancer, multiple sclerosis and many other disorders. These results have opened up new avenues of research, taking us to places we had not imagined in our search for better ways to diagnose, treat and prevent disease."

A related study in the same issue of Nature described how the enhanced map can provide insights into the biological forces underlying natural selection in humans. For example, the researchers found 2 differences, common primarily in Asian populations, in genes involved in the formation of hair follicles and sweat glands as well as other structures. The researchers also identified DNA variations in African populations that may be linked to resistance to Lassa fever, a viral infection common in Western Africa.

The improved SNP coverage offered by the Phase II HapMap, along with better statistical methods, promises to further increase the accuracy and reliability of genome-wide association studies. NHGRI plans to extend the HapMap even further, with samples being donated by populations from Kenya, Italy, Gujarati Indians in Houston and others.