Single nucleotide polymorphisms (SNPs)
Introduction
The DNA of the human genome contains three billion base pairs made up of the four DNA bases: adenine, thymine, guanine and cytosine. While our genetic make up is 99,9 % the same, small differences in our DNA can predispose us to different diseases and make us respond to medicines differently. This differences in our DNA we call Single Nucleotid Polymorphisms (SNPs, pronounced „snips“). A SNP is a specific location in our DNA where different people have different DNA bases. For example, at a specific point in your DNA you may have the DNA base cytosine (C) and another person may have the DNA base thymine (T). If you possess two copies of C or two copies of T at this location, one on each of your pair of chromosomes, you are homozygous. If you possess a C and T at this location you are heterozygous.
SNPs are the most common type of difference in our DNA: there are about 9 million SNPs. The majority of SNPs are thought to be biologically “silent” – they do not effect gene function or inherited traits. Some SNPs may affect gene expression in disease situations or be present in the gene itself and affect protein function. If we find the key to reveal „SNP secret“ we can, predict and diagnose diseases more accurately and to discover new medicines and identify the patients likely to benefit from particular medicines.
Polymorphisms and diseases
The human population has relatively limited genetic diversity, reflecting its young age and historically small size. Many rare genetic variants exist in the human population, but most of the heterozygosity in the population is attributable to common alleles (that is, those that are present at a frequency of > 1 % in the general population). The infrequent variants include the primary causes of rare, mendelian genetic diseases, with these alleles typically being recent in origin and highly penetrant. By contrast, some authors have recently hypothesized that the common variants may contribute significantly to genetic risk for common disease. If this common disease-common variant (CD-CV) hypothesis is true, it permits a conceptually straightforward approach to identifying disease-causing mutations: build a comprehensive catalogue of the limited number of common gene mutations in the human population and test them directly for association to clinical phenotypes. Such an approach is possible due to the human genome project in identifying genes and in the technology for discovering and typing DNA sequence variants. It has been difficult to compare variation among classes of sites within genes, among genes and between populations, owing to the small sample sizes and to differences in the populations studied. To define the nature of variationin human genes, as well as provide a catalogue of gene polymorphisms for association studies, we performed an extensive survey of coding sequence diversity of many genes in many individuals.
Association studies
Human Genome Project is a project to define whole structure of DNA. One of the fruits of this project is the discovery of millions DNA sequence variants in the human genome. The majority of these variants are SNPs. There is SNP Consortium in a world (a consortium of pharmaceutical companies, technology companies, academic centers and the Wellcome Trust) which producing an ordered high-density SNP map of the human genome that is being placed in the public domain. There are over 9 million SNPs in this map (2005). The use of SNPs in small areas of the genome has been shown to rapidly narrow the search for disease susceptibility genes. With a thousand DNA samples in a typical study, each with around 100,000 - 300,000 SNPs, rapid read-out technology must be available to genotype millions of SNPs cost-effectively and reproducibly. Then we will need to correlate patients genotypes (SNPs) with their phenotypes (clinical measurements), which requires complex statistical analysis software.