Consortium Publishes Phase II Map of Human Genetic Variation

The second phase of the HapMap Project ( - created to identify and catalogue genetic similarities and differences among populations around the world - has been completed by scientists from six countries, including Oxford researchers.

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

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 neighbourhoods, 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.

In two papers in 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. The first phase of HapMap is already revolutionising scientists' ability to study the genetic basis of human disease.

The International HapMap Consortium is a public-private partnership of researchers and funding agencies from the United Kingdom, Canada, China, Japan, Nigeria and the United States. Much of the analyses of both phases of HapMap was undertaken at the University of Oxford, the only British university selected to be involved with the project.

One of the co-chairs of the analysis group, Professor Peter Donnelly, FRS, Director of Oxford University's Wellcome Trust Centre for Human Genetics, said: 'Understanding the differences between people's genomes, and why those differences exist, is at the core of many questions in modern biomedical research. The HapMap project has transformed this area of research, giving new insights into areas as diverse as why some people are more susceptible to disease and our evolutionary history.'

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 fuelled 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,' says Professor Gil McVean of the University of Oxford's Department of Statistics and Wellcome Trust Centre for Human Genetics, who co-led the analysis of Phase II HapMap and is one of two corresponding authors on the paper. '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.'

The Phase II HapMap was produced using the same DNA samples studied 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 labelled by population group.

To provide information on less common variations and to enable researchers to conduct genome-wide association studies in additional populations, there are 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 people 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 captured 90 to 96 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.

The overview paper also reports that the Phase II HapMap has provided new insights into the structure of human genetic variation. One new finding was the surprising extent of recent common ancestry found in all the population groups. Taking advantage of the map's increased resolution, the researchers identified stretches of identical DNA between pairs of donor chromosomes and then compared these stretches both within and across individuals. Their analysis showed that 10 to 30 per cent of the DNA segments analyzed in each population showed shared regions, indicating descent from a common ancestor within 10 to 100 generations.