HapMap Consortium Publishes Phase II Map of Human Genetic Variation

The International HapMap Consortium has published analyses of its second-generation map of human genetic variation, which contains three times more markers than the initial version unveiled in 2005.

In two papers in the journal "Nature", the consortium describes how the higher resolution map offers greater power to detect genetic variants involved in common diseases, explore the structure of human genetic variation and learn how environmental factors, such as infectious agents, have shaped the human genome.

Any two humans are more than 99 percent the same at the genetic level. However, it is important to understand the small fraction of genetic material that varies among people because it can help explain individual differences in susceptibility to disease, response to drugs or reaction to environmental factors. Variation in the human genome is organized into local neighborhoods, called haplotypes, that usually are inherited as intact blocks of information. Consequently, researchers refer to the map of human genetic variation as a haplotype map, or HapMap.

The International HapMap Consortium is a public-private partnership of researchers and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the United States.

"Thanks to this consortium's pioneering efforts to map human genetic variation, we are already seeing a windfall of results that are shedding new light on the complex genetics of common diseases," said NHGRI Director Francis S. Collins, M.D., Ph.D.

"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."

The second-generation haplotype map, or Phase II HapMap, contains more than 3.1 million genetic variants, called single nucleotide polymorphisms (SNPs) -- three times more than the approximately 1 million SNPs contained in the initial version. The more SNPs that are on the map, the more precisely researchers can focus their hunts for genetic variants involved in disease. The rapid growth of genome-wide association studies over the past year and half has been fueled by the HapMap consortium's decision to make its SNP datasets immediately available in public databases, even before the first and the second versions of the map were fully completed.

"We are thrilled that the worldwide scientific community is taking advantage of this powerful new tool and we anticipate even more exciting findings in the future. 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," said Gil McVean, Ph.D., of the University of Oxford in England, who co-led the group that analyzed the HapMap data.

The Phase II HapMap was produced using the same DNA samples used in the Phase I HapMap. That DNA came from blood collected from 270 volunteers from four geographically diverse populations: Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Han Chinese in Beijing; and Utah residents with ancestry from northern and western Europe. No medical or personal identifying information was obtained from the donors, but the samples were labeled by population group.

To provide information on less common variations and to enable researchers to conduct genome-wide association studies in additional populations, NHGRI plans to extend the HapMap even further. Among the populations donating additional DNA samples are: Luhya in Webuye, Kenya; Maasai in Kinyawa, Kenya; Tuscans in Italy; Gujarati Indian in Houston; Chinese in metropolitan Denver; people of Mexican ancestry in Los Angeles; and people of African ancestry in the southwestern United States.

In its overview paper in "Nature", the consortium estimates that the Phase II HapMap captures 25 percent to 35 percent of common genetic variation in the populations surveyed.

The consortium also confirmed that use of Phase II HapMap data has helped to improve the coverage of various commercial technologies currently being used to identify disease-related variants in genome-wide association studies. Researchers did note, however, that current technologies tend to provide better coverage in non-African populations than in African populations because of the greater degree of genetic variability in African populations.

A related study appearing in the same issue of "Nature" describes how the enhanced map can help pinpoint pivotal changes in the human genome that arose in recent history. These changes, now common among various populations worldwide, became prevalent through natural selection - meaning they were somehow beneficial to human health. Although these DNA variants may still be important, their biological significance remains largely unknown.