SNP Technologies

A single nucleotide polymorphism (SNP or “snip”) is a single base pair variation at a particular location in the deoxyribonucleic acid (DNA) sequence that occurs in more than 1 percent of the population. SNPs are used as markers to identify regions in the genome associated with disease states such as obesity, diabetes, heart disease, and Alzheimer's. The discovery of such markers requires that a high number of SNPs be analyzed within large study populations. Many different technologies have been developed for SNP analysis that are rapid, accurate, and cost effective to increase the number of SNP markers suitable for use in determining effective medical care.

The human genome is composed of 3 billion base pairs of DNA, approximately 99.9 percent of which is identical between individuals. The 0.1 percent of genetic variation that occurs between us is responsible for differences in our appearance, personalities, and physiologies. These variations in DNA sequence, or “polymorphisms,” occur as deletions, insertions, sequence repeats, or SNPs. Mutations differ from polymorphisms in that they occur in less than 1 percent of the population.

SNPs account for approximately 90 percent of polymorphisms in the human genome, and over 9 million have been identified. Some SNPs are directly responsible for a disease process or for how an individual responds to a drug. When found within the coding region of a gene, a SNP may cause changes in the structure and possibly the function of the protein encoded by that gene. This could result from either a direct amino acid substitution or by affecting the splicing of the messenger ribonucleic acid (mRNA). If a SNP occurs in the regulatory region of a gene, the expression pattern of the gene could be significantly altered, with possible serious consequences to the cell or the organism.

Figure 1. Example of Two Alleles Represented by an SNP

Most SNPs, however, are found in the 98 percent of the human genome that does not encode protein. Even when a SNP has no obvious affect on the expression of a gene, it may still be useful as a genetic or physical marker due to its proximity to a specific gene of interest. This is the basis for using SNPs to identify genes that either cause or influence various medical conditions, or to determine if an individual has a particular gene that predisposes him or her to a disease.

To understand how this works, it is first necessary to define a few terms. An allele is an alternative DNA sequence that occurs at a specific genetic locus. Figure 1 gives an example of two alleles represented by an SNP. At this location within the genome, a T-A base pair occurs 85 percent of the time, and a C-G base pair 15 percent in a given population. Most SNPs are biallelic, meaning only two sequence variations are found at that location. A few are known to be tri- or tetraallelic.

A particular combination of alleles on a given region of a chromosome is called a haplotype, whereas a collection of alleles within the entire genome is called a genotype.Figure 2 illustrates two different haplotypes, in which two SNPs are located near one another on a given chromosome.

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