International HapMap Project
The goal of the International HapMap Project is the mapping of the haplotypes of the human genome. This HapMap will describe the patterns of genetic variation in humans.
The project is a collaboration of academic researchers, non-commercial biomedical research groups and companies in Japan, Great Britain, Canada, China, Nigeria and the United States.
It is believed that the HapMap is a key component for the identification of genes, particularly those that have an influence on human health or the response to environmental stimuli, and drugs. The results of the project will be provided researchers worldwide.
The International HapMap Project officially began with a conference on 27 - 29th October 2002 and was scheduled for a period of three years. It consists of two phases; the results of Phase I were published on 27 October 2005. Completion of work will enable a variety of work, such as the Japanese working groups will study 300,000 people to identify the haplotypes of 47 diseases. The UK labor groups, however, want to try to perform genotyping of patients with diabetes mellitus, bipolar disorder, rheumatoid arthritis, heart disease and other common diseases.
Importance of studying genetic variation
The most common diseases such as diabetes, cancer, strokes, depression or asthma are influenced by a variety of genes and environmental factors. Although people differ from one another only by about 0.1 % of their DNA, this variation affects disease risk and the effectiveness of drugs. Therefore, the exploration of this variation provides a way to understand the complex causes of human diseases.
To this end, researchers compared a group of affected persons with a group of non-diseased persons. Chromosome those areas in which the groups differ from each other in the haplotype frequency, may include genes which influence on the disease. Theoretically, researchers this genotype the entire genetic variations of each one base pair ( the so-called single nucleotide polymorphisms, SNPs). However, these methods at the current state of the art are too expensive. The HapMap is to identify the much smaller amount of special marker SNPs, with which a large part of the genetic variation patterns can be extracted.
Investigated peoples
The most common haplotypes do not occur in all human peoples, but in the same frequency. For this reason the collection of data from a plurality of groups is necessary to identify the tag SNPs. Pilot projects have a sufficient spread of the haplotype frequencies in samples from Nigeria ( Yoruba), Japan, China and the United States to a limitation of the HapMap studies to justify these population groups. A parallel project examined the haplotypes of other nations in order to assess the benefit of more detailed investigation of the HapMap.
The DNA samples for the HapMap derived from a total of 270 persons: each 30 sets of parents with adult child from the Yoruba in Ibadan (Nigeria ) and from the U.S., and one each 45 unrelated individuals from Tokyo ( Japan) and Beijing (China). With this choice it should be possible to identify all the haplotypes that occur at least 5% frequency.
Ethical issues
The project raises a number of ethical questions. The samples are collected, however, so that although a geographical assignment is possible, the donor itself, however, can not be identified. In this way, the haplotype frequency of individual nations can recorded and compared between them. There is thus the risk of stigmatization or discrimination, if a particular cluster disease predisposing haplotypes may be associated with a particular ethnic origin.
Scientific strategy
To develop the HapMap at least one million SNPs in the human genome are genotyped. At the beginning of the project, about 2.8 million SNPs were in the public database dbSNP. However, many chromosome regions showed only a few SNPs, some of which rarely appeared to be truly meaningful. More 2.8 million were identified by September 2003.
Genotyping was performed by ten centers in Canada, China, Japan, the UK and the USA. Each center, examining specific chromosomes. It will be used for this purpose five different techniques of genotyping. The initial HapMap to provide a map of 600,000 SNPs evenly distributed across the genome, which corresponds to a density of approximately one SNP per 5,000 base pairs. More SNPs are typed to define the haplotypes. The quality of the typing is assured by cross-checking the same samples.
Access to the data and copyright
The research results are made available in the public domain of the scientific public.
The new SNPs, samples for genotyping, and the frequency of SNP alleles, genotypes and haplotypes will be published shortly after identification. When the SNPs are typed sufficiently to define associated regions thereof are included haplotypes Genotype and the public SNP marker without limitation provided. Up to this point, the individual genotype data are available at a minimal Privacy Policy, which ensures a controlled mainly disclosure and non- restricting access to others.