Editing Microsatellite (section)

==Applications==
Microsatellites are used for assessing chromosomal DNA deletions in cancer diagnosis. Microsatellites are widely used for [[DNA profiling]], also known as "genetic fingerprinting", of crime stains (in forensics) and of tissues (in transplant patients).  They are also widely used in [[kinship]] analysis (most commonly in paternity testing). Also, microsatellites are used for mapping locations  within the genome, specifically in [[genetic linkage]] analysis to locate a gene or a mutation responsible for a given trait or disease. As a special case of mapping, they can be used for studies of [[gene duplication]] or [[genetic deletion|deletion]]. Researchers use microsatellites in [[population genetics]] and in species conservation projects. Plant geneticists have proposed the use of microsatellites for [[marker assisted selection]] of desirable traits in plant breeding.

===Cancer diagnosis===
In [[tumour]] cells, whose controls on replication are damaged, microsatellites may be gained or lost at an especially high frequency during each round of [[mitosis]]. Hence a tumour cell line might show a different [[genetic fingerprint]] from that of the host tissue, and, especially in [[colorectal cancer]], might present with [[loss of heterozygosity]].<ref name="Cancer Diagnostics">{{cite journal | vauthors = Wistuba II, Behrens C, Virmani AK, Mele G, Milchgrub S, Girard L, Fondon JW, Garner HR, McKay B, Latif F, Lerman MI, Lam S, Gazdar AF, Minna JD | display-authors = 6 | title = High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints | journal = Cancer Research | volume = 60 | issue = 7 | pages = 1949–1960 | date = April 2000 | pmid = 10766185 }}</ref><ref>{{cite journal | vauthors = Forgacs E, Wren JD, Kamibayashi C, Kondo M, Xu XL, Markowitz S, Tomlinson GE, Muller CY, Gazdar AF, Garner HR, Minna JD | display-authors = 6 | title = Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers | journal = Oncogene | volume = 20 | issue = 8 | pages = 1005–1009 | date = February 2001 | pmid = 11314036 | doi = 10.1038/sj.onc.1204211 | s2cid = 22893621 | doi-access = free }}</ref> Microsatellites analyzed in primary tissue therefore been routinely used in cancer diagnosis to assess tumour progression.<ref name="vanTilborg2012">{{cite journal | vauthors = van Tilborg AA, Kompier LC, Lurkin I, Poort R, El Bouazzaoui S, van der Keur K, Zuiverloon T, Dyrskjot L, Orntoft TF, Roobol MJ, Zwarthoff EC | display-authors = 6 | title = Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood | journal = PLOS ONE | volume = 7 | issue = 8 | pages = e43345 | year = 2012 | pmid = 22927958 | pmc = 3425555 | doi = 10.1371/journal.pone.0043345 | doi-access = free | bibcode = 2012PLoSO...743345V }}</ref><ref name="Sideris&Papagrigoriadis2014">{{cite journal | vauthors = Sideris M, Papagrigoriadis S | title = Molecular biomarkers and classification models in the evaluation of the prognosis of colorectal cancer | journal = Anticancer Research | volume = 34 | issue = 5 | pages = 2061–2068 | date = May 2014 | pmid = 24778007 }}</ref><ref name="Boland1998">{{cite journal | vauthors = Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S | display-authors = 6 | title = A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer | journal = Cancer Research | volume = 58 | issue = 22 | pages = 5248–5257 | date = November 1998 | pmid = 9823339 }}</ref> Genome Wide Association Studies (GWAS) have been used to identify microsatellite biomarkers as a source of genetic predisposition in a variety of cancers.<ref name="Rivero et al">{{cite journal | vauthors = Rivero-Hinojosa S, Kinney N, Garner HR, Rood BR | title = Germline microsatellite genotypes differentiate children with medulloblastoma | journal = Neuro-Oncology | volume = 22 | issue = 1 | pages = 152–162 | date = January 2020 | pmid = 31562520 | doi = 10.1093/neuonc/noz179 | pmc = 6954392 }}</ref><ref name="Kinney">{{cite journal | vauthors = Kinney N, Varghese RT, Anandakrishnan R, Garner HR | title = ''ZDHHC3'' as a Risk and Mortality Marker for Breast Cancer in African American Women | journal = Cancer Informatics | volume = 16 | pages = 1176935117746644 | date = 2017 | pmid = 29276372 | doi = 10.1177/1176935117746644 | pmc = 5734450 | s2cid = 32129259 }}</ref><ref name="Velmurugan">{{cite journal | vauthors = Velmurugan KR, Varghese RT, Fonville NC, Garner HR | title = High-depth, high-accuracy microsatellite genotyping enables precision lung cancer risk classification | journal = Oncogene | volume = 36 | issue = 46 | pages = 6383–6390 | date = November 2017 | pmid = 28759038 | doi = 10.1038/onc.2017.256 | pmc = 5701090 | s2cid = 21655592 }}</ref>

[[File:Str profile.jpg|thumb|400px|A partial human STR profile obtained using the [[Applied Biosystems]] Identifiler kit]]

=== Forensic and medical fingerprinting ===
Microsatellite analysis became popular in the field of [[forensics]] in the 1990s.<ref name=":0" /> It is used for the [[genetic fingerprinting]] of individuals where it permits forensic identification (typically matching a crime stain to a victim or perpetrator). It is also used to follow up [[bone marrow transplant]] patients.<ref name="pmid11669214">{{cite journal | vauthors = Antin JH, Childs R, Filipovich AH, Giralt S, Mackinnon S, Spitzer T, Weisdorf D | title = Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings of the International Bone Marrow Transplant Registry and the American Society of Blood and Marrow Transplantation | journal = Biology of Blood and Marrow Transplantation | volume = 7 | issue = 9 | pages = 473–85 | year = 2001 | pmid = 11669214 | doi = 10.1053/bbmt.2001.v7.pm11669214 | doi-access = free }}</ref>

The microsatellites in use today for forensic analysis are all tetra- or penta-nucleotide repeats, as these give a high degree of error-free data while being short enough to survive degradation in non-ideal conditions.  Even shorter repeat sequences would tend to suffer from artifacts such as PCR stutter and preferential amplification, while longer repeat sequences would suffer more highly from environmental degradation and would amplify less well by [[polymerase chain reaction|PCR]].<ref name="interpol">{{cite web |title=DNA Profiling  | vauthors = Carracedo A |url= http://www.interpol.int/public/Forensic/dna/conference/DNAProfiling01.asp#note41 |archive-url=http://webarchive.loc.gov/all/20010927081712/http://www.interpol.int/public/forensic/dna/conference/dnaprofiling01.asp |archive-date=2001-09-27 |access-date=2010-09-20}}</ref> Another forensic consideration is that the person's [[medical privacy]] must be respected, so that forensic STRs are chosen which are non-coding, do not influence gene regulation, and are not usually trinucleotide STRs which could be involved in [[Trinucleotide repeat disorder|triplet expansion diseases]] such as [[Huntington's disease]]. Forensic STR profiles are stored in DNA databanks such as the [[UK National DNA Database]] (NDNAD), the American [[CODIS]] or the Australian NCIDD.

===Kinship analysis (paternity testing)===
[[Autosomal]] microsatellites are widely used for [[DNA profiling]] in [[kinship]] analysis (most commonly in paternity testing).<ref>{{cite journal | vauthors = Lászik A, Brinkmann B, Sótonyi P, Falus A | title = Automated fluorescent detection of a 10 loci multiplex for paternity testing | journal = Acta Biologica Hungarica | volume = 51 | issue = 1 | pages = 99–105 | date = 2000 | pmid = 10866366 | doi =  10.1007/BF03542970| s2cid = 28270630 }}</ref> Paternally inherited [[Y-STR]]s (microsatellites on the [[Y chromosome]]) are often used in [[genealogical DNA test]]ing.

===Genetic linkage analysis===
During the 1990s and the first several years of this millennium, microsatellites were the workhorse genetic markers for genome-wide scans to locate any gene responsible for a given phenotype or disease, using [[Mendelian inheritance#Law of Segregation of genes (the "First Law")|segregation]] observations across generations of a sampled pedigree. Although the rise of higher throughput and cost-effective [[single-nucleotide polymorphism]] (SNP) platforms led to the era of the SNP for genome scans, microsatellites remain highly informative measures of genomic variation for linkage and association studies. Their continued advantage lies in their greater allelic diversity than biallelic SNPs, thus microsatellites can differentiate alleles within a SNP-defined linkage disequilibrium block of interest. Thus, microsatellites have successfully led to discoveries of type 2 diabetes ([[TCF7L2]]) and prostate cancer genes (the 8q21 region).<ref name="Gulcher2012">{{cite journal | vauthors = Lu W, Zhang Y, Liu D, Songyang Z, Wan M | title = Telomeres-structure, function, and regulation | journal = Experimental Cell Research | volume = 319 | issue = 2 | pages = 133–141 | date = January 2013 | pmid = 23006819 | pmc = 4051234 | doi = 10.1016/j.yexcr.2012.09.005 }}</ref><ref name="Ott2015">{{cite journal | vauthors = Ott J, Wang J, Leal SM | title = Genetic linkage analysis in the age of whole-genome sequencing | journal = Nature Reviews. Genetics | volume = 16 | issue = 5 | pages = 275–284 | date = May 2015 | pmid = 25824869 | pmc = 4440411 | doi = 10.1038/nrg3908 }}</ref>

=== Population genetics ===
[[File:Consensus neighbor-joining tree of the 249 human populations and six chimpanzee populations.svg|thumb|[[Computational phylogenetics#Consensus Tree|Consensus]] [[neighbor-joining]] tree of 249 human populations and six chimpanzee populations. Created based on 246 microsatellite markers.<ref name="PembertonDeGiorgio2013">{{cite journal | vauthors = Pemberton TJ, DeGiorgio M, Rosenberg NA | title = Population structure in a comprehensive genomic data set on human microsatellite variation | journal = G3 | volume = 3 | issue = 5 | pages = 891–907 | date = May 2013 | pmid = 23550135 | pmc = 3656735 | doi = 10.1534/g3.113.005728 }}</ref>]]
Microsatellites were popularized in [[population genetics]] during the 1990s because as [[Polymerase chain reaction|PCR]] became ubiquitous in laboratories researchers were able to design primers and amplify sets of microsatellites at low cost. Their uses are wide-ranging.<ref>{{Cite journal| vauthors = Manel S, Schwartz MK, Luikart G, Taberlet P |date=2003-04-01|title=Landscape genetics: combining landscape ecology and population genetics | journal=Trends in Ecology & Evolution|volume=18|issue=4|pages=189–197|doi=10.1016/S0169-5347(03)00008-9|s2cid=2984426 }}</ref> A microsatellite with a neutral evolutionary history makes it applicable for measuring or inferring [[Population bottleneck|bottlenecks]],<ref>{{cite journal | vauthors = Spencer CC, Neigel JE, Leberg PL | title = Experimental evaluation of the usefulness of microsatellite DNA for detecting demographic bottlenecks | journal = Molecular Ecology | volume = 9 | issue = 10 | pages = 1517–28 | date = October 2000 | pmid = 11050547 | doi = 10.1046/j.1365-294x.2000.01031.x | bibcode = 2000MolEc...9.1517S | s2cid = 22244000 }}</ref> [[local adaptation]],<ref>{{cite journal | vauthors = Nielsen R | title = Molecular signatures of natural selection | journal = Annual Review of Genetics | volume = 39 | issue = 1 | pages = 197–218 | date = 2005-01-01 | pmid = 16285858 | doi = 10.1146/annurev.genet.39.073003.112420 | s2cid = 3063754 }}</ref> the allelic [[fixation index]] (F<sub>ST</sub>),<ref>{{cite journal | vauthors = Slatkin M | title = A measure of population subdivision based on microsatellite allele frequencies | journal = Genetics | volume = 139 | issue = 1 | pages = 457–62 | date = January 1995 | doi = 10.1093/genetics/139.1.457 | pmid = 7705646 | pmc = 1206343 | url = http://www.genetics.org/content/139/1/457 }}</ref> [[population size]],<ref>{{cite journal | vauthors = Kohn MH, York EC, Kamradt DA, Haught G, Sauvajot RM, Wayne RK | title = Estimating population size by genotyping faeces | journal = Proceedings. Biological Sciences | volume = 266 | issue = 1420 | pages = 657–63 | date = April 1999 | pmid = 10331287 | pmc = 1689828 | doi = 10.1098/rspb.1999.0686 }}</ref> and [[gene flow]].<ref>{{cite journal | vauthors = Waits L, Taberlet P, Swenson JE, Sandegren F, Franzén R | title = Nuclear DNA microsatellite analysis of genetic diversity and gene flow in the Scandinavian brown bear (Ursus arctos) | journal = Molecular Ecology | volume = 9 | issue = 4 | pages = 421–31 | date = April 2000 | pmid = 10736045 | doi = 10.1046/j.1365-294x.2000.00892.x | bibcode = 2000MolEc...9..421W | s2cid = 46475635 }}</ref> As [[next generation sequencing]] becomes more affordable the use of microsatellites has decreased, however they remain a crucial tool in the field.<ref>{{cite journal | vauthors = Allendorf FW, Hohenlohe PA, Luikart G | title = Genomics and the future of conservation genetics | journal = Nature Reviews. Genetics | volume = 11 | issue = 10 | pages = 697–709 | date = October 2010 | pmid = 20847747 | doi = 10.1038/nrg2844 | s2cid = 10811958 }}</ref>

===Plant breeding===
[[Marker assisted selection]] or marker aided selection (MAS) is an indirect selection process where a [[Trait (biology)|trait]] of interest is selected based on a [[Biological marker|marker]] ([[Morphology (biology)|morphological]], [[biochemical]] or [[DNA]]/[[RNA]] variation) linked to a trait of interest (e.g. productivity, disease resistance, stress tolerance, and quality), rather than on the trait itself. Microsatellites have been proposed to be used as such markers to assist plant breeding.<ref name="Miah2013">{{cite journal | vauthors = Miah G, Rafii MY, Ismail MR, Puteh AB, Rahim HA, Islam K, Latif MA | title = A review of microsatellite markers and their applications in rice breeding programs to improve blast disease resistance | journal = International Journal of Molecular Sciences | volume = 14 | issue = 11 | pages = 22499–528 | date = November 2013 | pmid = 24240810 | pmc = 3856076 | doi = 10.3390/ijms141122499 | doi-access = free }}</ref>