General Background
In 2001, the International HapMap Consortium launched the International HapMap Project to develop a haplotype map (“HapMap”) of the human genome - a resource that describes the common patterns of human DNA sequence variation. The HapMap has become an important tool for researchers to use to find genes that affect health, disease, and response to drugs and environmental factors. All HapMap data are freely available to the public through the database dbSNP. A graphical browser for HapMap genotypes is also available at http://www.hapmap.org/cgi-perl/gbrowse/gbrowse.

Further information can be found at the International HapMap Project website. The Project is also described at Nature 426:789-796,2004 [PMID: 14685227]; Nature Reviews Genetics 5: 467-475, 2004 [PMID: 14685227]). The associated ethical issues are described at Nature Reviews Genetics 5: 467-475, 2004 [PMID: 15153999]. The general process of community engagement used in connection with the collection of samples for the Project is described at Community Genetics.

Phase I
In 2005, the International HapMap Consortium released the Phase I HapMap, a resource consisting of over a million accurate and complete SNP genotypes generated in 269 individuals from four geographically diverse populations: The Yoruba in Ibadan, Nigeria; Japanese in Tokyo, Japan; Han Chinese in Beijing, China; and the CEPH (U.S. Utah residents with ancestry from northern and western Europe).

The Phase I HapMap includes data from ten 500-kb regions (the “ENCODE regions”) in which essentially all information about common DNA variation has been extracted. The Phase I HapMap documents the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbors. This resource will guide the design and analysis of genetic association studies. It also sheds light on structural variation and recombination and identifies loci that may have been subject to natural selection during human evolution.

The Phase I HapMap is described at Nature 437:1299-1320, 2005.

Phase II
In 2007, the International HapMap Consortium released the Phase II HapMap, which added over 2.1 million SNPs to the original map in the same 269 individuals. The Phase II HapMap enables an improved choice of tag SNPs, a better understanding of how well studies capture patterns of genetic variation, and the potential to increase the power of association experiments using fixed marker sets through imputation. It also reveals novel aspects of the structure of linkage disequilibrium, including the importance of recent co-ancestry among individuals and the distribution and causes of untaggable SNPs. In addition, it improves the resolution of the fine-scale genetic map and location of recombination hotspots and provides new information about the influence of natural selection on protein-changing variants. .

The Phase II HapMap is described at Nature 449:851-862, 2007.

Analysis of Samples from Additional Populations
U.S. investigators supported by NHGRI have launched an effort to expand and the Phase I/II HapMap by sequencing, and then genotyping, samples from seven additional populations: Maasai in Kinyawa, Kenya; Luhya in Webuye, Kenya; Chinese in the metropolitan Denver, CO, USA area; Gujarati Indians in Houston, TX, USA; Toscani in Italia (Tuscans in Italy); African ancestry in the Southwest USA; and Mexican ancestry in Los Angeles, CA, USA.

First, a subset of the samples collected from these populations will be sequenced in 2 mb of the ENCODE regions (20 regions of 100 kb each). Next, most of the samples from these populations will be genotyped across the genome for at least 470,000 SNPs. This combination of sequencing and genotyping will allow comparison of genome-wide patterns of variation and of comprehensive patterns of variation in specific regions. It will also make it possible to assess the transferability of the tag SNPs based on the study of the initial 269 samples to the new populations.

HapMap Samples
No identifying of phenotypic information is available for the samples used to develop the HapMap that are housed in the NHGRI Repository. However, all of the samples were collected with extensive community engagement, including discussions with members of the donor communities about the ethical and social implications of human genetic variation research. Donors gave broad consent to future uses of the samples, including their use for extensive genotyping and sequencing, gene expression and proteomics studies, and all other types of genetic variation research, with the data publicly released.

Investigators can order the HapMap microtiter plates containing full sets of the DNA samples used to develop or expand the HapMap, individual DNA samples, or individual cell cultures. The biomaterials currently available are shown in the table below:

Populations Included in Phase I/II HapMap

Additional Populations