Single nucleotide polymorphisms

Abstract

The particular order of the 4 different bases: Adenine (A), thymine (T), cytosine (C), and guanine (G) that are present in DNA, arranged along the sugarphosphate backbone of DNA is called its sequence; the DNA sequence specifies the exact genetic instructions required to create a particular organism with its own unique traits. The complete set of instructions for making an organism is called its genome. The size of the genome varies from several thousand bases in yeast to 3 billion in human. Genomes of individuals from same species are highly similar with minor variations, e.g., human genomes are known to differ in 1 basepair per 1,000 basepairs (1). A variation that occurs when a single nucleotide in a genome is altered is called single nucleotide polymorphism (SNP). An alteration of the sequence ACCCGGTACT to AACCGGTACT consists of 1 SNP at position 2 where base C is altered to base A. Each individual has many SNPs creating a unique DNA pattern for that person. This fact is being used in DNA testing which has revolutionized forensic science for crime solving. SNPs are of particular interest for expanding our understanding of human disease and henceforth development of drugs. Huge efforts are ongoing for identification of SNPs that are cause of a disease or make an individual genetically predisposed to a disease. With current high throughput technologies it has become possible to sequence genomes or parts of genome of large number of healthy and diseased population. Comparison of SNPs from different population groups will enable the scientific community to identify SNPs that are disease causative mutations from millions of SNPs, of which majority are normal variations. In addition, SNPs are used extensively in efforts to study the evolution of microbial populations in the newly emerging area of environmental genomics. Rest of the section reviews few definitions that are essential in understanding underlying theory of application of SNPs. Crossing-over-Source of majority of SNPs is crossing-over. Crossing-over is part of a complicated process which can occur during meiosis. During meiosis, the precursor cells of the sperm or ova must multiply and at the same time reduce the number of chromosomes to one full set. During the early stages of cell division in meiosis, when homologous chromosomes pair up, exchange of DNA segments between them may occur. This exchange or recombination produces genetic variations in germ cells. Genotype-The genotype is the specific genetic makeup (the specific genome) of an individual, in the form of DNA sequence. It could refer to only one locus or to an entire genome. Haplotypes-Genetic variants in close proximity tend to be inherited together. For example, any individual with base A on chromosome 7 at location 300 instead of G will always have base T on chromosome 7 at location 4,000 and base G on chromosome 7 at location 4,500. Given the base at chromosome 7 at location 300, it is possible to infer bases at other two locations. These regions of linked variants are known as haplotypes. Haplotype may refer to the whole genome or a part of it. Different parts of genomes have different number of haplotypes in a given population but this number in reality is orders of magnitude smaller than the total number of theoretically possible haplotypes. Linkage Disequilibrium (LD)-Linkage disequilibrium describes a situation in which some combinations of alleles or genetic markers occur more or less frequently in a population than would be expected from a random formation of haplotypes from alleles based on their frequencies. Nonrandom associations between genes at different loci are measured by the degree of linkage disequilibrium (LD). © 2008 Humana Press.