When the project was launched in October 2002, the consortium set September 2005 as the target for completing its map of common patterns of human genetic variation, also known as haplotypes. By the end of February 2005, however, the group already will have reached completion of its first draft of the human haplotype map, or HapMap, which will consist of 1 million markers of genetic variation, called single nucleotide polymorphisms (SNPs).
The consortium's new goal is to build an improved version of the HapMap that is about five times denser than the original plan. This "Phase II" HapMap will take advantage of the rapid, high-throughput genotyping capacity of Perlegen Sciences, Inc., of Mountain View, Calif., to test another 4.6 million SNPs from publicly available databases, and add that information to the map. As a result of a grant competition last summer, Perlegen received a $6.1 million award from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), to add data on 2.25 million additional SNPs to HapMap. The new development, enabled by a partnership among multiple funding sources, will expand that effort and test virtually the entire known catalog of human variation on the HapMap samples. This will increase the density of SNP "signposts" across the genome from the current average of one every 3,000 bases to about one every 600 bases.
"This will help us create a far more powerful HapMap than we ever imagined. We sincerely thank all those who are giving their time, technology and money to help turn this dream into reality. The payoff will be a better underst anding of the genetic risk factors underlying a wide range of diseases and conditions," said NHGRI Director Francis S. Collins, M.D., Ph.D.
The first phase of the HapMap Project has allowed scientists to make important analyses of the human genome that were not possible with just the human DNA sequence, and the International HapMap Consortium plans to publish its comprehensive analysis of this data later this year. The second phase of the project will provide researchers with a denser map that will enable them to more precisely narrow gene discovery to specific regions of the genome.
The effort to expand the HapMap is made possible by $3.3 million in additional support from a unique public-private partnership, including the following organizations: the Wellcome Trust, London, $624,000; Genome Canada/Genome Quebec, $260,000; Bristol-Myers Squibb Co., New York, $100,000; Pfizer Inc., New York, $100,000; Perlegen Sciences, at least $1.2 million (based on "in kind" services); and NHGRI, $1 million. The donations from the two pharmaceutical companies were coordinated by The SNP Consortium, Ltd., of Deerfield, Ill.
"Researchers are already using HapMap data to accelerate the search for genes involved in common diseases, as well as genes involved in drug responsiveness," said Karen Kennedy, Ph.D., science program manager at the Wellcome Trust. "When the more comprehensive version of the HapMap is completed this fall, such studies will be able to be carried out with even greater speed and efficiency."
To create the HapMap, DNA was taken from blood samples from volunteer donors from the following populations: Han Chinese in Beijing, Japanese in Tokyo, Yoruba in Ibadan, Nigeria and Utah residents with ancestry from northern and western Europe. No medical or personal identifying information was obtained from the 270 donors. However, the samples are identified by the population from which they were collected.
Although any two people are 9 9.9 percent identical at the genetic level, understanding the one-tenth of one percent difference is important because it helps explain why one person may be more susceptible to a certain disease than another. For any given disease, such as type II diabetes or coronary artery disease, researchers can use the HapMap to compare the genetic variation patterns of a group of people known to have the disease with a group of people without the disease. Finding a certain pattern more often in people with the disease identifies a genomic region that may contain genes contributing to the condition. Because the Phase II HapMap will be so detailed, researchers will be able to use its SNP signposts to zero in on that particular genomic region and search for specific genes involved in that disorder. This approach can reduce the work and expense of searching the genome for hereditary factors in common disease by a factor of 20 to 40 compared with current, brute force approaches.
"This new partnership underscores the private sector's enthusiasm for the HapMap and its potential as a tool for the understanding of disease. The willingness of these firms to contribute to building an even better map follows the collaborative tradition established by The SNP Consortium," said Arthur Holden, chairman and chief executive of The SNP Consortium.
In addition to affecting risk of disease, genetic variation has been shown to affect the response of people to therapeutic drugs, toxic substances and environmental factors, and the HapMap can assist in the identification of those variants. Since not all genetic variants are deleterious, the HapMap also may be used to help to pinpoint genetic variations that contribute to good health, such as those protecting against infectious diseases or promoting longevity.
"We are excited by the opportunity to apply our technology to all publicly available SNPs. This effort is so important that Perlegen is willing to contribute some of its own resources to make this possible," said Kelly A. Frazer, Ph.D., vice president of genomics at Perlegen. "We are confident that the end result of this public-private collaboration will be an outstanding human haplotype map that will provide a major new tool in the effort to combat human disease through an understanding of its genetic components."
Researchers around the globe can quickly access the HapMap data through free public databases, such as the HapMap Data Coordination Center (http://www.hapmap.org), the NIH-funded National Center for Biotechnology Information's dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP/) and the JSNP Database in Japan (http://snp.ims.u-tokyo.ac.jp/).
"Adding this large number of new SNPs to the map will make it even easier for researchers to correlate genetic variation with gene function. Such information is crucial for the development of therapies and preventive strategies tailored to each person's unique genetic makeup," said Martin Godbout, Ph.D., president and CEO of Genome Canada, who also was speaking on behalf of Genome Quebec.