Editing Single-nucleotide polymorphism (section)

{{short description|Single nucleotide  in genomic DNA at which different sequence alternatives exist}}
{{redirect|SNPs|the singular|SNP (disambiguation)}}
[[File:dna-SNP.svg|306x306px|thumb|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''' {{IPAc-en|s|n|ɪ|p}}; plural '''SNPs''' {{IPAc-en|s|n|ɪ|p|s}}) 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),<ref>{{Cite web|title = single-nucleotide polymorphism / SNP {{!}} Learn Science at Scitable|url = http://www.nature.com/scitable/definition/single-nucleotide-polymorphism-snp-295|website = www.nature.com|access-date = 2015-11-13|url-status = live|archive-url = https://web.archive.org/web/20151110112814/http://www.nature.com/scitable/definition/single-nucleotide-polymorphism-snp-295|archive-date = 2015-11-10}}</ref> many publications<ref>{{cite journal |title=dbSNP—Database for Single Nucleotide Polymorphisms and Other Classes of Minor Genetic Variation |year=1999|pmid=10447503|last1=Sherry|first1=S. T.|last2=Ward|first2=M.|last3=Sirotkin|first3=K.|journal=Genome Research|volume=9|issue=8|pages=677–679|doi=10.1101/gr.9.8.677|s2cid=10775908|doi-access=free}}</ref><ref>{{cite journal |pmid=11237011|title = Initial sequencing and analysis of the human genome|year = 2001|last1 = Lander|first1 = E. S.|last2 = Linton|first2 = L. M.|last3 = Birren|first3 = B.|last4 = Nusbaum|first4 = C.|last5 = Zody|first5 = M. C.|last6 = Baldwin|first6 = J.|last7 = Devon|first7 = K.|last8 = Dewar|first8 = K.|last9 = Doyle|first9 = M.|last10 = Fitzhugh|first10 = W.|last11 = Funke|first11 = R.|last12 = Gage|first12 = D.|last13 = Harris|first13 = K.|last14 = Heaford|first14 = A.|last15 = Howland|first15 = J.|last16 = Kann|first16 = L.|last17 = Lehoczky|first17 = J.|last18 = Levine|first18 = R.|last19 = McEwan|first19 = P.|last20 = McKernan|first20 = K.|last21 = Meldrim|first21 = J.|last22 = Mesirov|first22 = J. P.|last23 = Miranda|first23 = C.|last24 = Morris|first24 = W.|last25 = Naylor|first25 = J.|last26 = Raymond|first26 = C.|last27 = Rosetti|first27 = M.|last28 = Santos|first28 = R.|last29 = Sheridan|first29 = A.|last30 = Sougnez|first30 = C.|journal = Nature|volume = 409|issue = 6822|pages = 860–921|doi = 10.1038/35057062| bibcode=2001Natur.409..860L |display-authors = 1|doi-access = free|hdl = 2027.42/62798|hdl-access = free}}</ref><ref>{{cite journal |pmid=26432245|title = A global reference for human genetic variation|journal = Nature|year = 2015|volume = 526|issue = 7571|pages = 68–74|doi = 10.1038/nature15393|pmc = 4750478|last1 = Auton|first1 = Adam|last2 = Abecasis|first2 = Gonçalo R.|last3 = Altshuler|first3 = David M.|last4 = Durbin|first4 = Richard M.|last5 = Abecasis|first5 = Gonçalo R.|last6 = Bentley|first6 = David R.|last7 = Chakravarti|first7 = Aravinda|last8 = Clark|first8 = Andrew G.|last9 = Donnelly|first9 = Peter|last10 = Eichler|first10 = Evan E.|last11 = Flicek|first11 = Paul|last12 = Gabriel|first12 = Stacey B.|last13 = Gibbs|first13 = Richard A.|last14 = Green|first14 = Eric D.|last15 = Hurles|first15 = Matthew E.|last16 = Knoppers|first16 = Bartha M.|last17 = Korbel|first17 = Jan O.|last18 = Lander|first18 = Eric S.|last19 = Lee|first19 = Charles|last20 = Lehrach|first20 = Hans|last21 = Mardis|first21 = Elaine R.|last22 = Marth|first22 = Gabor T.|last23 = McVean|first23 = Gil A.|last24 = Nickerson|first24 = Deborah A.|last25 = Schmidt|first25 = Jeanette P.|last26 = Sherry|first26 = Stephen T.|last27 = Wang|first27 = Jun|last28 = Wilson|first28 = Richard K.|last29 = Gibbs|first29 = Richard A.|last30 = Boerwinkle|first30 = Eric|bibcode = 2015Natur.526...68T|display-authors = 1}}</ref> do not apply such a frequency threshold.

For example, a [[Guanine|G nucleotide]] present at a specific location in a [[reference genome]] may be replaced by an [[Adenine|A]] in a minority of individuals. The two possible nucleotide variations of this SNP&nbsp;– G or A&nbsp;– are called [[allele]]s.<ref name="pmid 28696921">{{cite journal|date=September 2017|title=ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy|journal=G3|volume=7|issue=9|pages=2931–2943|doi=10.1534/g3.117.044024|pmid=28696921|doi-access=free|last1=Monga|first1=Isha|last2=Qureshi|first2=Abid|last3=Thakur|first3=Nishant|last4=Gupta|first4=Amit Kumar|last5=Kumar|first5=Manoj|pmc=5592921}}</ref>

SNPs can help explain differences in susceptibility to a wide range of [[disease]]s across a population. For example, a common SNP in the [[Factor H|CFH]] gene is associated with increased risk of age-related [[macular degeneration]].<ref>{{Cite journal |last1=Calippe |first1=Bertrand |last2=Guillonneau |first2=Xavier |last3=Sennlaub |first3=Florian |date=March 2014 |title=Complement factor H and related proteins in age-related macular degeneration |url=https://comptes-rendus.academie-sciences.fr/biologies/articles/10.1016/j.crvi.2013.12.003/|journal=Comptes Rendus Biologies |volume=337 |issue=3 |pages=178–184 |doi=10.1016/j.crvi.2013.12.003 |issn=1631-0691 |pmid=24702844}}</ref> 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 [[Apolipoprotein E|''APOE'']] gene, [[rs429358]] and rs7412, lead to three major [[Apolipoprotein E#Polymorphisms|APO-E alleles]] with different associated risks for development of [[Alzheimer's disease]] and age at onset of the disease.<ref name=":1">{{Cite journal|last1=Husain|first1=Mohammed Amir|last2=Laurent|first2=Benoit|last3=Plourde|first3=Mélanie|date=2021-02-17|title=APOE and Alzheimer's Disease: From Lipid Transport to Physiopathology and Therapeutics|journal=Frontiers in Neuroscience|volume=15|page=630502|doi=10.3389/fnins.2021.630502|pmid=33679311|pmc=7925634|issn=1662-453X|doi-access=free}}</ref>

Single nucleotide substitutions with an allele frequency of less than 1% are sometimes called '''single-nucleotide variants''' ('''SNVs''').<ref>{{Cite web |date=2012-07-20 |title=Definition of single nucleotide variant - NCI Dictionary of Genetics Terms |url=https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/single-nucleotide-variant |access-date=2023-05-02 |website=www.cancer.gov |language=en}}</ref> "Variant" may also be used as a general term for any single nucleotide change in a DNA sequence,<ref name="Wright 2005 p.">{{citation |last=Wright |first=Alan F |title=eLS |chapter=Genetic Variation: Polymorphisms and Mutations |date=September 23, 2005 |publisher=Wiley |doi=10.1038/npg.els.0005005|isbn=9780470016176 |s2cid=82415195 |doi-access=free }}</ref> encompassing both common SNPs and rare [[mutation]]s, whether [[Germline mutation|germline]] or [[Somatic mutation|somatic]].<ref>{{cite journal |title=SNVMix: predicting single nucleotide variants from next-generation sequencing of tumors |year=2010|pmid=20130035|last1=Goya|first1=R.|last2=Sun|first2=M. G.|last3=Morin|first3=R. D.|last4=Leung|first4=G.|last5=Ha|first5=G.|last6=Wiegand|first6=K. C.|last7=Senz|first7=J.|last8=Crisan|first8=A.|last9=Marra|first9=M. A.|last10=Hirst|first10=M.|last11=Huntsman|first11=D.|last12=Murphy|first12=K. P.|last13=Aparicio|first13=S.|last14=Shah|first14=S. P.|journal=Bioinformatics|volume=26|issue=6|pages=730–736|doi=10.1093/bioinformatics/btq040|pmc=2832826}}</ref><ref>{{Cite journal|last1=Katsonis|first1=Panagiotis|last2=Koire|first2=Amanda|last3=Wilson|first3=Stephen Joseph|last4=Hsu|first4=Teng-Kuei|last5=Lua|first5=Rhonald C.|last6=Wilkins|first6=Angela Dawn|last7=Lichtarge|first7=Olivier|date=2014-10-20|title=Single nucleotide variations: Biological impact and theoretical interpretation|url=|journal=Protein Science|volume=23|issue=12|pages=1650–1666|doi=10.1002/pro.2552|pmid=25234433|pmc=4253807|issn=0961-8368}}</ref> The term SNV has therefore been used to refer to [[point mutation]]s found in cancer cells.<ref>{{Cite journal|last1=Khurana|first1=Ekta|last2=Fu|first2=Yao|last3=Chakravarty|first3=Dimple|last4=Demichelis|first4=Francesca|last5=Rubin|first5=Mark A.|last6=Gerstein|first6=Mark|date=2016-01-19|title=Role of non-coding sequence variants in cancer|url=|journal=Nature Reviews Genetics|volume=17|issue=2|pages=93–108|doi=10.1038/nrg.2015.17|pmid=26781813|s2cid=14433306|issn=1471-0056}}</ref> DNA variants must also commonly be taken into consideration in molecular diagnostics applications such as designing [[Polymerase chain reaction|PCR]] primers to detect viruses, in which the viral RNA or DNA sample may contain SNVs.{{Citation needed|date=May 2023}} 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.<ref name="Karki Pandya Elston Ferlini 2015">{{cite journal |last1=Karki |first1=Roshan |last2=Pandya |first2=Deep |last3=Elston |first3=Robert C. |last4=Ferlini |first4=Cristiano |date=July 15, 2015 |title=Defining "mutation" and "polymorphism" in the era of personal genomics |journal=BMC Medical Genomics |publisher=Springer Science and Business Media LLC |volume=8 |issue=1 |page=37 |doi=10.1186/s12920-015-0115-z |pmid=26173390 |pmc=4502642 |issn=1755-8794 |doi-access=free }}</ref><ref name="Li 2021">{{cite web |last=Li |first=Heng |date=March 15, 2021 |title=SNP vs SNV |url=http://lh3.github.io/2021/03/15/snp-vs-snv |access-date=May 3, 2023 |website=Heng Li's blog}}</ref>