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Microsatellite
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===Effects within introns=== Microsatellites within [[intron]]s also influence phenotype, through means that are not currently understood. For example, a GAA triplet expansion in the first intron of the X25 gene appears to interfere with transcription, and causes [[Friedreich's ataxia]].<ref name="Bidichandani 1998">{{cite journal | vauthors = Bidichandani SI, Ashizawa T, Patel PI | title = The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure | journal = American Journal of Human Genetics | volume = 62 | issue = 1 | pages = 111β21 | date = January 1998 | pmid = 9443873 | pmc = 1376805 | doi = 10.1086/301680 }}</ref> Tandem repeats in the first intron of the Asparagine synthetase gene are linked to acute lymphoblastic leukaemia.<ref name="Akagi 2008">{{cite journal | vauthors = Akagi T, Yin D, Kawamata N, Bartram CR, Hofmann WK, Song JH, Miller CW, den Boer ML, Koeffler HP | display-authors = 6 | title = Functional analysis of a novel DNA polymorphism of a tandem repeated sequence in the asparagine synthetase gene in acute lymphoblastic leukemia cells | journal = Leukemia Research | volume = 33 | issue = 7 | pages = 991β6 | date = July 2009 | pmid = 19054556 | pmc = 2731768 | doi = 10.1016/j.leukres.2008.10.022 }}</ref> A repeat polymorphism in the fourth intron of the NOS3 gene is linked to hypertension in a Tunisian population.<ref name="Jemaa 2008">{{cite journal | vauthors = Jemaa R, Ben Ali S, Kallel A, Feki M, Elasmi M, Taieb SH, Sanhaji H, Omar S, Kaabachi N | display-authors = 6 | title = Association of a 27-bp repeat polymorphism in intron 4 of endothelial constitutive nitric oxide synthase gene with hypertension in a Tunisian population | journal = Clinical Biochemistry | volume = 42 | issue = 9 | pages = 852β6 | date = June 2009 | pmid = 19111531 | doi = 10.1016/j.clinbiochem.2008.12.002 }}</ref> Reduced repeat lengths in the EGFR gene are linked with osteosarcomas.<ref name="Kersting 2008">{{cite journal | vauthors = Kersting C, Agelopoulos K, Schmidt H, Korsching E, August C, Gosheger G, Dirksen U, Juergens H, Winkelmann W, Brandt B, Bielack S, Buerger H, Gebert C | display-authors = 6 | title = Biological importance of a polymorphic CA sequence within intron 1 of the epidermal growth factor receptor gene (EGFR) in high grade central osteosarcomas | journal = Genes, Chromosomes & Cancer | volume = 47 | issue = 8 | pages = 657β64 | date = August 2008 | pmid = 18464244 | doi = 10.1002/gcc.20571 | s2cid = 19472307 | doi-access = free }}</ref> An archaic form of splicing preserved in [[zebrafish]] is known to use microsatellite sequences within intronic mRNA for the removal of introns in the absence of U2AF2 and other splicing machinery. It is theorized that these sequences form highly stable [[Cloverleaf model of tRNA|cloverleaf]] configurations that bring the 3' and 5' intron splice sites into close proximity, effectively replacing the [[spliceosome]]. This method of RNA splicing is believed to have diverged from human evolution at the formation of [[tetrapod]]s and to represent an artifact of an [[RNA world]].<ref>{{cite journal | vauthors = Lin CL, Taggart AJ, Lim KH, Cygan KJ, Ferraris L, Creton R, Huang YT, Fairbrother WG | display-authors = 6 | title = RNA structure replaces the need for U2AF2 in splicing | journal = Genome Research | volume = 26 | issue = 1 | pages = 12β23 | date = January 2016 | pmid = 26566657 | pmc = 4691745 | doi = 10.1101/gr.181008.114 }}</ref>
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