Editing Single-nucleotide polymorphism (section)

== Frequency ==

More than 600&nbsp;million SNPs have been identified across the human genome in the world's population.<ref>{{Cite web |title=What are single nucleotide polymorphisms (SNPs)?: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/understanding/genomicresearch/snp/ |access-date=2023-03-22 |website=medlineplus.gov |language=en}}</ref> A typical genome differs from the reference human genome at 4–5&nbsp;million sites, most of which (more than 99.9%) consist of SNPs and short [[indel]]s.<ref name="100genome">{{cite journal | vauthors = Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR | title = A global reference for human genetic variation | journal = Nature | volume = 526 | issue = 7571 | pages = 68–74 | date = October 2015 | pmid = 26432245 | pmc = 4750478 | doi = 10.1038/nature15393 | bibcode = 2015Natur.526...68T }}</ref>

=== Within a genome ===
The genomic distribution of SNPs is not homogenous; SNPs occur in [[Noncoding DNA|non-coding regions]] more frequently than in [[coding region]]s or, in general, where natural selection is acting and "fixing" the [[allele]] (eliminating other variants) of the SNP that constitutes the most favorable genetic adaptation.<ref name="Barreiro">{{cite journal | vauthors = Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L | s2cid = 205357396 | title = Natural selection has driven population differentiation in modern humans | journal = Nature Genetics | volume = 40 | issue = 3 | pages = 340–5 | date = March 2008 | pmid = 18246066 | doi = 10.1038/ng.78 }}</ref> Other factors, like [[genetic recombination]] and mutation rate, can also determine SNP density.<ref name="Nachman">{{cite journal | vauthors = Nachman MW | title = Single nucleotide polymorphisms and recombination rate in humans | journal = Trends in Genetics | volume = 17 | issue = 9 | pages = 481–5 | date = September 2001 | pmid = 11525814 | doi = 10.1016/S0168-9525(01)02409-X }}</ref>

SNP density can be predicted by the presence of [[Microsatellite (genetics)|microsatellites]]: AT microsatellites in particular are potent predictors of SNP density, with long (AT)(n) repeat tracts tending to be found in regions of significantly reduced SNP density and low [[GC content]].<ref name="Varela">{{cite journal | vauthors = Varela MA, Amos W | title = Heterogeneous distribution of SNPs in the human genome: microsatellites as predictors of nucleotide diversity and divergence | journal = Genomics | volume = 95 | issue = 3 | pages = 151–9 | date = March 2010 | pmid = 20026267 | doi = 10.1016/j.ygeno.2009.12.003 | doi-access =  }}</ref>

=== Within a population ===
Since there are variations between human populations, a SNP allele that is common in one geographical or ethnic group may be rarer in another. However, this pattern of variation is relatively rare; in a global sample of 67.3&nbsp;million SNPs, the [[Human Genome Diversity Project]] "found no such private variants that are [[fixed allele|fixed]] in a given continent or major region. The highest frequencies are reached by a few tens of variants present at >70% (and a few thousands at >50%) in Africa, the Americas, and Oceania. By contrast, the highest frequency variants private to Europe, East Asia, the Middle East, or Central and South Asia reach just 10 to 30%."<ref name="pmid32193295">{{cite journal| author=Bergström A, McCarthy SA, Hui R, Almarri MA, Ayub Q, Danecek P | display-authors=etal| title=Insights into human genetic variation and population history from 929 diverse genomes. | journal=Science | year= 2020 | volume= 367 | issue= 6484 | pages=  eaay5012| pmid=32193295 | doi=10.1126/science.aay5012 | pmc=7115999 }}</ref>

Within a population, SNPs can be assigned a [[minor allele frequency]] (MAF)—the lowest allele frequency at a [[locus (genetics)|locus]] that is observed in a particular population.<ref>{{cite journal | vauthors = Zhu Z, Yuan D, Luo D, Lu X, Huang S | title = Enrichment of Minor Alleles of Common SNPs and Improved Risk Prediction for Parkinson's Disease | journal = PLOS ONE | volume = 10 | issue = 7 | pages = e0133421 | date = 2015-07-24 | pmid = 26207627 | pmc = 4514478 | doi = 10.1371/journal.pone.0133421 | bibcode = 2015PLoSO..1033421Z | doi-access = free }}</ref> This is simply the lesser of the two allele frequencies for single-nucleotide polymorphisms.

With this knowledge, scientists have developed new methods in analyzing population structures in less studied species.<ref>{{Cite journal|last1=Hivert|first1=Valentin|last2=Leblois|first2=Raphaël|last3=Petit|first3=Eric J.|last4=Gautier|first4=Mathieu|last5=Vitalis|first5=Renaud|date=2018-07-30|title=Measuring Genetic Differentiation from Pool-seq Data|journal=Genetics|volume=210|issue=1|pages=315–330|doi=10.1534/genetics.118.300900|pmid=30061425|pmc=6116966|issn=0016-6731|doi-access=free}}</ref><ref>{{Cite journal|last1=Ekblom|first1=R|last2=Galindo|first2=J|date=2010-12-08|title=Applications of next generation sequencing in molecular ecology of non-model organisms|journal=Heredity|volume=107|issue=1|pages=1–15|doi=10.1038/hdy.2010.152|pmid=21139633|pmc=3186121|issn=0018-067X|doi-access=free}}</ref><ref>{{Cite journal|last=Ellegren|first=Hans|date=January 2014|title=Genome sequencing and population genomics in non-model organisms|url=|journal=Trends in Ecology & Evolution|volume=29|issue=1|pages=51–63|doi=10.1016/j.tree.2013.09.008|pmid=24139972|bibcode=2014TEcoE..29...51E |issn=0169-5347}}</ref> By using pooling techniques, the cost of the analysis is significantly lowered.{{citation needed|date=October 2020}} These techniques are based on sequencing a population in a pooled sample instead of sequencing every individual within the population by itself. With new bioinformatics tools, there is a possibility of investigating population structure, gene flow, and gene migration by observing the allele frequencies within the entire population. With these protocols there is a possibility for combining the advantages of SNPs with micro satellite markers.<ref>{{Cite journal|last1=Dorant|first1=Yann|last2=Benestan|first2=Laura|last3=Rougemont|first3=Quentin|last4=Normandeau|first4=Eric|last5=Boyle|first5=Brian|last6=Rochette|first6=Rémy|last7=Bernatchez|first7=Louis|date=2019|title=Comparing Pool-seq, Rapture, and GBS genotyping for inferring weak population structure: The American lobster (Homarus americanus) as a case study|url= |journal=Ecology and Evolution|language=en|volume=9|issue=11|pages=6606–6623|doi=10.1002/ece3.5240|issn=2045-7758|pmc=6580275|pmid=31236247|bibcode=2019EcoEv...9.6606D }}</ref><ref>{{Cite journal|last1=Vendrami|first1=David L. J.|last2=Telesca|first2=Luca|last3=Weigand|first3=Hannah|last4=Weiss|first4=Martina|last5=Fawcett|first5=Katie|last6=Lehman|first6=Katrin|last7=Clark|first7=M. S.|last8=Leese|first8=Florian|last9=McMinn|first9=Carrie|last10=Moore|first10=Heather|last11=Hoffman|first11=Joseph I.|title=RAD sequencing resolves fine-scale population structure in a benthic invertebrate: implications for understanding phenotypic plasticity|url= |journal=Royal Society Open Science|year=2017|volume=4|issue=2|pages=160548|doi=10.1098/rsos.160548|pmc=5367306|pmid=28386419|bibcode=2017RSOS....460548V}}</ref> However, there is information lost in the process, such as linkage disequilibrium and zygosity information.