Single-nucleotide polymorphism

DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/T polymorphism).

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 species (or between 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.

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.

"SNP"

In the past, SNPs with a minor allele frequency of greater than or equal to 1% (or 0.5%, etc.) were given the title "SNP".^[1] Some used "mutation" to refer to variations with low allele frequency. With the advent of a better understanding of evolution, this definition is no longer necessary, e.g., a database such as dbSNP includes "SNPs" that have lower allele frequency than 1%.^[2]

Types of SNPs

Single nucleotides may be changed (substitution), removed (deletions) or added (insertion) to a polynucleotide sequence. Ins/del SNP may shift translational frame.^[3][4][5].

Single nucleotide polymorphisms may fall within coding sequences of genes, non-coding regions of genes, or in the intergenic regions between genes. SNPs within a coding sequence will 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 forms lead to the same polypeptide sequence is termed synonymous (sometimes called a silent mutation) — if a different polypeptide sequence is produced they are nonsynonymous. A nonsynonymous change may either be missense or nonsense, where a missense change results in a different amino acid, while a nonsense change results in a premature stop codon. SNPs that are not in protein-coding regions may still have consequences for gene splicing, transcription factor binding, or the sequence of non-coding RNA.

Use and importance of SNPs

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.^[6] 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).

The study of single-nucleotide polymorphisms 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.^[7]

Examples

• rs6311 and rs6313 are SNPs in the HTR2A gene on human chromosome 13.
• A SNP in the F5 gene causes a hypercoagulability disorder with the variant Factor V Leiden.
• rs3091244 is an example of a triallelic SNP in the CRP gene on human chromosome 1.^[8]
• TAS2R38 codes for PTC tasting ability, and contains 6 annotated SNPs.^{[citation needed]}

Databases

As there are for genes, there are also bioinformatics databases for SNPs. dbSNP is a SNP database from National Center for Biotechnology Information (NCBI). SNPedia is a wiki-style database from a hybrid organization. The OMIM database describes the association between polymorphisms and, e.g., diseases in text form, while HGVbaseG2P allows users to visually interrogate the actual summary-level association data.

Nomenclature

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.^[9][10][11]

See also

• Single-base extension
• Variome
• TaqMan
• Affymetrix
• International HapMap Project
• tag SNP

Notes

References

• Nature Reviews Glossary
• Human Genome Project Information — SNP Fact Sheet
• Relation of SNP's with Cancer

External links

• NCBI resources — Introduction to SNPs from NCBI
• The SNP Consortium LTD — SNP search
• NCBI dbSNP database — "a central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms"
• International HapMap Project — "a public resource that will help researchers find genes associated with human disease and response to pharmaceuticals"
• HGVbaseG2P — The Human Genome Variation database of Genotype-to-Phenotype information
• 1000 Genomes Project — A Deep Catalog of Human Genetic Variation
• Glovar Variation Browser — variation information in a genomic context
• SIFT — "An online tool that predicts on the effect of SNPs on protein function"
• WatCut — an online tool for the design of SNP-RFLP assays
• SNPStats — SNPStats, a web tool for analysis of genetic association studies
• Restriction HomePage — a set of tools for DNA restriction and SNP detection, including design of mutagenic primers
• American Association for Cancer Research Cancer Concepts Factsheet on SNPs
• PharmGKB — The Pharmacogenetics and Pharmacogenomics Knowledge Base, a resource for SNPs associated with drug response and disease outcomes.
• GEN-SNiP — Online tool that identifies polymorphisms in test DNA sequences.
• Online tool that predicts on the effects of SNPs on protein function
• Rules for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat
• HGNC Guidelines for Human Gene Nomenclature