Single-nucleotide polymorphism

The upper DNA molecule differs from the lower DNA molecule at a single base-pair location (a G/A polymorphism).

In genetics and bioinformatics, a single-nucleotide polymorphism (SNP /snɪp/; plural SNPs /snɪps/) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently large fraction of the population (e.g. 1% or more),[1] many publications[2][3][4] do not apply such a frequency threshold.

For example, a G nucleotide present at a specific location in a reference genome may be replaced by an A in a minority of individuals. The two possible nucleotide variations of this SNP – G or A – are called alleles.[5]

SNPs can help explain differences in susceptibility to a wide range of diseases across a population. For example, a common SNP in the CFH gene is associated with increased risk of age-related macular degeneration.[6] Differences in the severity of an illness or response to treatments may also be manifestations of genetic variations caused by SNPs. For example, two common SNPs in the APOE gene, rs429358 and rs7412, lead to three major APO-E alleles with different associated risks for development of Alzheimer's disease and age at onset of the disease.[7]

Single nucleotide substitutions with an allele frequency of less than 1% are sometimes called single-nucleotide variants (SNVs).[8] "Variant" may also be used as a general term for any single nucleotide change in a DNA sequence,[9] encompassing both common SNPs and rare mutations, whether germline or somatic.[10][11] The term SNV has therefore been used to refer to point mutations found in cancer cells.[12] DNA variants must also commonly be taken into consideration in molecular diagnostics applications such as designing PCR primers to detect viruses, in which the viral RNA or DNA sample may contain SNVs.[citation needed] However, this nomenclature uses arbitrary distinctions (such as an allele frequency of 1%) and is not used consistently across all fields; the resulting disagreement has prompted calls for a more consistent framework for naming differences in DNA sequences between two samples.[13][14]

  1. ^ "single-nucleotide polymorphism / SNP | Learn Science at Scitable". www.nature.com. Archived from the original on 2015-11-10. Retrieved 2015-11-13.
  2. ^ Sherry, S. T.; Ward, M.; Sirotkin, K. (1999). "dbSNP—Database for Single Nucleotide Polymorphisms and Other Classes of Minor Genetic Variation". Genome Research. 9 (8): 677–679. doi:10.1101/gr.9.8.677. PMID 10447503. S2CID 10775908.
  3. ^ Lander, E. S.; et al. (2001). "Initial sequencing and analysis of the human genome". Nature. 409 (6822): 860–921. Bibcode:2001Natur.409..860L. doi:10.1038/35057062. hdl:2027.42/62798. PMID 11237011.
  4. ^ Auton, Adam; et al. (2015). "A global reference for human genetic variation". Nature. 526 (7571): 68–74. Bibcode:2015Natur.526...68T. doi:10.1038/nature15393. PMC 4750478. PMID 26432245.
  5. ^ Monga, Isha; Qureshi, Abid; Thakur, Nishant; Gupta, Amit Kumar; Kumar, Manoj (September 2017). "ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy". G3. 7 (9): 2931–2943. doi:10.1534/g3.117.044024. PMC 5592921. PMID 28696921.
  6. ^ Calippe, Bertrand; Guillonneau, Xavier; Sennlaub, Florian (March 2014). "Complement factor H and related proteins in age-related macular degeneration". Comptes Rendus Biologies. 337 (3): 178–184. doi:10.1016/j.crvi.2013.12.003. ISSN 1631-0691. PMID 24702844.
  7. ^ Husain, Mohammed Amir; Laurent, Benoit; Plourde, Mélanie (2021-02-17). "APOE and Alzheimer's Disease: From Lipid Transport to Physiopathology and Therapeutics". Frontiers in Neuroscience. 15: 630502. doi:10.3389/fnins.2021.630502. ISSN 1662-453X. PMC 7925634. PMID 33679311.
  8. ^ "Definition of single nucleotide variant - NCI Dictionary of Genetics Terms". www.cancer.gov. 2012-07-20. Retrieved 2023-05-02.
  9. ^ Wright, Alan F (September 23, 2005), "Genetic Variation: Polymorphisms and Mutations", eLS, Wiley, doi:10.1038/npg.els.0005005, ISBN 9780470016176, S2CID 82415195
  10. ^ Goya, R.; Sun, M. G.; Morin, R. D.; Leung, G.; Ha, G.; Wiegand, K. C.; Senz, J.; Crisan, A.; Marra, M. A.; Hirst, M.; Huntsman, D.; Murphy, K. P.; Aparicio, S.; Shah, S. P. (2010). "SNVMix: predicting single nucleotide variants from next-generation sequencing of tumors". Bioinformatics. 26 (6): 730–736. doi:10.1093/bioinformatics/btq040. PMC 2832826. PMID 20130035.
  11. ^ Katsonis, Panagiotis; Koire, Amanda; Wilson, Stephen Joseph; Hsu, Teng-Kuei; Lua, Rhonald C.; Wilkins, Angela Dawn; Lichtarge, Olivier (2014-10-20). "Single nucleotide variations: Biological impact and theoretical interpretation". Protein Science. 23 (12): 1650–1666. doi:10.1002/pro.2552. ISSN 0961-8368. PMC 4253807. PMID 25234433.
  12. ^ Khurana, Ekta; Fu, Yao; Chakravarty, Dimple; Demichelis, Francesca; Rubin, Mark A.; Gerstein, Mark (2016-01-19). "Role of non-coding sequence variants in cancer". Nature Reviews Genetics. 17 (2): 93–108. doi:10.1038/nrg.2015.17. ISSN 1471-0056. PMID 26781813. S2CID 14433306.
  13. ^ Karki, Roshan; Pandya, Deep; Elston, Robert C.; Ferlini, Cristiano (July 15, 2015). "Defining "mutation" and "polymorphism" in the era of personal genomics". BMC Medical Genomics. 8 (1). Springer Science and Business Media LLC: 37. doi:10.1186/s12920-015-0115-z. ISSN 1755-8794. PMC 4502642. PMID 26173390.
  14. ^ Li, Heng (March 15, 2021). "SNP vs SNV". Heng Li's blog. Retrieved May 3, 2023.