- A single-nucleotide polymorphism (SNP) is the most common type of genetic variation among individuals, involving a change at a single nucleotide position in the DNA sequence. Specifically, an SNP occurs when one base—adenine (A), thymine (T), cytosine (C), or guanine (G)—is replaced by another at a specific genomic location.
- For a variation to be classified as an SNP, it must be present in at least 1% of the population, distinguishing it from rare mutations. SNPs are found throughout the human genome, with an estimated one SNP every 300 base pairs, resulting in millions of these variants across the genome.
- SNPs can occur in coding regions, non-coding regions, or regulatory sequences of genes. Depending on their location and functional impact, they may be silent (synonymous), missense (non-synonymous), nonsense, or occur in non-coding regions that influence gene regulation. Synonymous SNPs do not change the amino acid sequence of a protein, while missense SNPs alter the amino acid, potentially affecting protein structure and function. Nonsense SNPs introduce premature stop codons, which can lead to truncated, nonfunctional proteins. Non-coding SNPs may impact transcription factor binding sites, enhancers, splicing mechanisms, or RNA stability, thereby affecting gene expression.
- Most SNPs are neutral, meaning they do not have any noticeable effect on phenotype or health. However, some SNPs are functionally significant and can influence traits such as drug response, disease susceptibility, and physical characteristics. For example, specific SNPs have been linked to increased risk of diseases such as type 2 diabetes, Alzheimer’s disease, and various cancers. Because of their abundance and relative stability, SNPs serve as powerful genetic markers in population genetics, evolutionary biology, and medical research.
- SNPs are widely used in genome-wide association studies (GWAS) to identify genetic loci associated with complex traits and diseases. In these studies, researchers analyze SNP patterns across large populations to find correlations between particular SNPs and specific phenotypes. When a SNP is statistically associated with a disease or trait, it may serve as a marker for a nearby causal variant, even if the SNP itself is not functionally responsible. This information has been critical in identifying genetic risk factors and biological pathways underlying numerous conditions.
- In addition to disease association, SNPs play an important role in pharmacogenomics, the study of how genetic variation affects individual responses to medications. Certain SNPs can influence drug metabolism enzymes, transporters, and targets, thereby affecting drug efficacy and the risk of adverse effects. For instance, SNPs in genes like CYP2C19 and TPMT are used to guide dosing of drugs such as clopidogrel and thiopurines, respectively, helping to personalize therapy.
