A single-nucleotide polymorphism (SNP, pronounced snip) is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome (or other shared sequence) differs between members of a biological species or paired chromosomes in an individual. For example, two sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. In this case we say that there are two alleles: C and T. Almost all common SNPs have only two alleles. SNPs can occur in both coding and non-coding regions of genome.
Within a population, SNPs can be assigned a minor allele frequency — the lowest allele frequency at a locus that is observed in a particular population. This is simply the lesser of the two allele frequencies for single-nucleotide polymorphisms. There are variations between human populations, so a SNP allele that is common in one geographical or ethnic group may be much rarer in another.
These genetic variations between the individuals (particularly in the non-coding parts of genome) are exploited in DNA fingerprinting, which is used in forensic science. Also, these genetic variations underlie differences in our susceptibility to, or protection from all kinds of diseases. The severity of illness and the way our body responds to treatments are also manifestations of genetic variations. For example, a single base difference in the Apolipoprotein E is associated with a higher risk for Alzheimer's disease.
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Single-nucleotide polymorphisms may fall within coding sequences of genes, non-coding regions of genes, or in the intergenic regions (regions between genes). SNPs within a coding sequence do not necessarily change the amino acid sequence of the protein that is produced, due to degeneracy of the genetic code.
A SNP in which both alleles produce the same polypeptide sequence is called a synonymous polymorphism (sometimes called a silent mutation). If a different polypeptide sequence is produced the polymorphism is a replacement polymorphism. A replacement polymorphism change may be either missense, which results in a different amino acid, or nonsense, which results in a premature stop codon. Over half of all known disease mutations come from replacement polymorphisms.[1]
SNPs that are not in protein-coding regions may still affect gene splicing, transcription factor binding, messenger RNA degradation, or the sequence of non-coding RNA. Gene expression affected by this type of SNP is referred to as an eSNP (expression SNP) and may be upstream or downstream from the gene.
Variations in the DNA sequences of humans can affect how humans develop diseases and respond to pathogens, chemicals, drugs, vaccines, and other agents. SNPs are also thought to be key enablers in realizing the concept of personalized medicine.[2] However, their greatest importance in biomedical research is for comparing regions of the genome between cohorts (such as with matched cohorts with and without a disease) in genome-wide association studies.
The study of SNPs is also important in crop and livestock breeding programs (see genotyping). See SNP genotyping for details on the various methods used to identify SNPs.
They are usually biallelic and thus easily assayed.[3] A single SNP may cause a Mendelian disease. For complex diseases, SNPs do not usually function individually, rather, they work in coordination with other SNPs to manifest a disease condition as has been seen in osteoporosis.[4]
As of October 2011, dbSNP listed 52 million SNPs in humans.[5]
As there are for genes, bioinformatics databases exist for SNPs. dbSNP is a SNP database from the National Center for Biotechnology Information (NCBI). SNPedia is a wiki-style database supporting personal genome annotation, interpretation and analysis. The OMIM database describes the association between polymorphisms and diseases (e.g., gives diseases in text form), the Human Gene Mutation Database provides gene mutations causing or associated with human inherited diseases and functional SNPs, and GWAS Central allows users to visually interrogate the actual summary-level association data in one or more genetic association studies.
The nomenclature for SNPs can be confusing: several variations can exist for an individual SNP and consensus has not yet been achieved. One approach is to write SNPs with a prefix, period and "greater than" sign showing the wild-type and altered nucleotide or amino acid; for example, c.76A>T.[8][9][10] SNPs are frequently referred to by their dbSNP rs number, as in the examples above.
Analytical methods to discover novel SNPs and detect known SNPs include:
- DNA sequencing;[11]
- capillary electrophoresis;[12]
- mass spectrometry;[13]
- single-strand conformation polymorphism (SSCP);
- electrochemical analysis;
- denaturating HPLC and gel electrophoresis;
- restriction fragment length polymorphism;
- hybridization analysis;
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