The elucidation of the entire human genome has made possible our current effort to develop a haplotype map of the human genome. The haplotype map, or "HapMap," is a tool that allows researchers to find genes and genetic variations that affect health and disease.
The DNA sequence of any two people is 99.5 percent identical. The variations, however, may greatly affect an individual's disease risk. Sites in the DNA sequence where individuals differ at a single DNA base are called single nucleotide polymorphisms (SNPs). Sets of nearby SNPs on the same chromosome are inherited in blocks. This pattern of SNPs on a block is a haplotype. Blocks may contain a large number of SNPs, but a few SNPs are enough to uniquely identify the haplotypes in a block. The HapMap is a map of these haplotype blocks and the specific SNPs that identify the haplotypes are called tag SNPs.
The HapMap is valuable by reducing the number of SNPs required to examine the entire genome for association with a phenotype from the 10 million SNPs that exist to roughly 500,000 tag SNPs. This makes genome scan approaches to finding regions with genes that affect diseases much more efficient and comprehensive, since effort is not wasted typing more SNPs than necessary and all regions of the genome can be included.
In addition to its use in studying genetic associations with disease, the HapMap is a powerful resource for studying the genetic factors contributing to variation in response to environmental factors, in susceptibility to infection, and in the effectiveness of and adverse responses to drugs and vaccines. All such studies are based on the expectation that there are higher frequencies of the contributing genetic components in a group of people with a disease or particular response to a drug, vaccine, pathogen, or environmental factor than in a group of similar people without the disease or response. Using just the tag SNPs, researchers are able to find chromosome regions that have different haplotype distributions in the two groups of people, those with a disease or response and those without. Each region is then studied in more detail to discover which variants in which genes in the region contribute to the disease or response, leading to more effective interventions. This also allows the development of tests to predict which drugs or vaccines would be most effective in individuals with particular genotypes for genes affecting drug metabolism.
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Jean McEwen, J.D., Ph.D.
Last Updated: May 1, 2012