373:
negative effect and/or a mix of these mechanisms for the protein hosting the expansion. Translation of these repeat expansions occurs mostly through two mechanisms. First, there may be translation initiated at the usual AUG or a similar (CUG, GUG, UUG, or ACG) start codon. This results in expression of a pathogenic protein encoded by one particular coding frame. Second, a mechanism named "repeat-associated non-AUG (RAN) translation" uses translation initiation that starts directly within the repeat expansion. This potentially results in expression of three different proteins encoded by the three possible reading frames. Usually, one of the three proteins is more toxic than the other two. Typical of these RAN type expansions are those with the trinucleotide repeat CAG. These often are translated into polyglutamine-containing proteins that form inclusions and are toxic to neuronal cells. Examples of the disorders caused by this mechanism include
Huntington's disease and Huntington disease-like 2, spinal-bulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and spinocerebellar ataxia 1–3, 6–8, and 17.
338:
introns, intergenic regions) normally contain trinucleotide sequences, or repeated sequences of one particular nucleotide, or sequences of 2, 4, 5 or 6 nucleotides. Such repetitive sequences occur at a low level that can be regarded as "normal". Sometimes, a person may have more than the usual number of copies of a repeat sequence associated with a gene, but not enough to alter the function of that gene. These individuals are referred to as "premutation carriers". The frequency of carriers worldwide appears to be 1 in 340 individuals. Some carriers, during the formation of eggs or sperm, may give rise to higher levels of repetition of the repeat they carry. The higher level may then be at a "mutation" level and cause symptoms in their offspring.
353:. Such epigenetic alterations can inhibit transcription, causing reduced expression of the associated encoded protein. The epigenetic alterations and their effects are described more fully by Barbé and Finkbeiner These authors cite evidence that the age at which an individual begins to experience symptoms, as well as the severity of disease, is determined both by the size of the repeat and the epigenetic state within the repeat and around the repeat. There is often increased methylation at
1099:
113:
25:
1043:. A parent with 35 repeats would be considered normal and would not exhibit any symptoms of the disease. However, that parent's offspring would be at an increased risk of developing Huntington's compared to the general population, as it would take only the addition of one more CAG codon to cause the production of mHTT (mutant HTT), the protein responsible for disease.
66:
334:, was also identified on the X chromosome, but was found to be the result of an expanded CCG repeat. The discovery that trinucleotide repeats could expand during intergenerational transmission and could cause disease was the first evidence that not all disease-causing mutations are stably transmitted from parent to offspring.
928:
As of 2017, ten neurological and neuromuscular disorders were known to be caused by an increased number of CAG repeats. Although these diseases share the same repeated codon (CAG) and some symptoms, the repeats are found in different, unrelated genes. Except for the CAG repeat expansion in the 5' UTR
1046:
Huntington's very rarely occurs spontaneously; it is almost always the result of inheriting the defective gene from an affected parent. However, sporadic cases of
Huntington's in individuals who have no history of the disease in their families do occur. Among these sporadic cases, there is a higher
1051:
gene, especially those whose repeats approach the number (36) required for the disease to manifest. Each successive generation in a
Huntington's-affected family may add additional CAG repeats, and the higher the number of repeats, the more severe the disease and the earlier its onset. As a result,
953:
do not share any specific symptoms and are unlike the PolyQ diseases. In some of these diseases, such as
Fragile X syndrome, the pathology is caused by lack of the normal function of the protein encoded by the affected gene. In others, such as Myotonic Dystrophy Type 1, the pathology is caused by a
279:
repeats) increase in copy numbers until they cross a threshold above which they cause developmental, neurological or neuromuscular disorders. In addition to the expansions of these trinucleotide repeats, expansions of one tetranucleotide (CCTG), five pentanucleotide (ATTCT, TGGAA, TTTTA, TTTCA, and
1085:
between two DNA strands can take place at multiple points along the sequence. This may lead to the formation of 'loop out' structures during DNA replication or DNA repair synthesis. This may lead to repeated copying of the repeated sequence, expanding the number of repeats. Additional mechanisms
376:
The first main category, the loss of function type with epigenetic contributions, can have repeats located in either a promoter, in 5'untranscribed regions upstream of promoters, or in introns. The second category, toxic RNAs, has repeats located in introns or in a 3' untranslated region of code
368:
The second main category of trinucleotide repeat disorders and related microsatellite disorders involves a toxic RNA gain of function mechanism. In this second type of disorder, large repeat expansions in DNA are transcribed into pathogenic RNAs that form nuclear RNA foci. These foci attract and
372:
The third main category of trinucleotide repeat disorders and related microsatellite disorders is due to the translation of repeat sequenced into pathogenic proteins containing a stretch of repeated amino acids. This results in, variously, a toxic gain of function, a loss of function, a dominant
337:
Trinucleotide repeat disorders and the related microsatellite repeat disorders affect about 1 in 3,000 people worldwide. However, the frequency of occurrence of any one particular repeat sequence disorder varies greatly by ethnic group and geographic location. Many regions of the genome (exons,
322:. Patients carry from 230 to 4000 CGG repeats in the gene that causes fragile X syndrome, while unaffected individuals have up to 50 repeats and carriers of the disease have 60 to 230 repeats. The chromosomal instability resulting from this trinucleotide expansion presents clinically as
1060:
The majority of diseases caused by expansions of simple DNA repeats involve trinucleotide repeats, but tetra-, penta- and dodecanucleotide repeat expansions are also known that cause disease. For any specific hereditary disorder, only one repeat expands in a particular gene.
1325:
Papp, David; Hernandez, Luis A; Mai, Theresa A; Haanen, Terrance J; O’Donnell, Meghan A; Duran, Ariel T; Hernandez, Sophia M; Narvanto, Jenni E; Arguello, Berenice; Onwukwe, Marvin O; Mirkin, Sergei M; Kim, Jane C (2024-02-07). Rhind, N (ed.).
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The first main category these authors discuss is repeat expansions located within the promoter region of a gene or located close to, but upstream of, a promoter region of a gene. These repeats are able to promote localized DNA
1035:: their severity increases with each successive generation that inherits them. This is likely explained by the addition of CAG repeats in the affected gene as the gene is transmitted from parent to child. For example,
280:
AAGGG), three hexanucleotide (GGCCTG, CCCTCT, and GGGGCC), and one dodecanucleotide (CCCCGCCCCGCG) repeat cause 13 other diseases. Depending on its location, the unstable trinucleotide repeat may cause defects in a
933:
in SCA12, the expanded CAG repeats are translated into an uninterrupted sequence of glutamine residues, forming a polyQ tract, and the accumulation of polyQ proteins damages key cellular functions such as the
377:
beyond the stop codon. The third category, largely producing toxic proteins with polyalanines or polyglutamines, has trinucleotide repeats that occur in the exons of the affected genes.
2941:
369:
alter the location and function of RNA binding proteins. This, in turn, causes multiple RNA processing defects that lead to the diverse clinical manifestations of these diseases.
1328:"Massive contractions of myotonic dystrophy type 2-associated CCTG tetranucleotide repeats occur via double-strand break repair with distinct requirements for DNA helicases"
1681:
Laskaratos A, Breza M, Karadima G, Koutsis G (June 2021). "Wide range of reduced penetrance alleles in spinal and bulbar muscular atrophy: a model-based approach".
130:
38:
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Ramakrishnan S, Gupta V. Trinucleotide Repeat
Disorders. 2023 Aug 22. In: StatPearls . Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID 32644680.
341:
Three categories of trinucleotide repeat disorders and related microsatellite (4, 5, or 6 repeats) disorders are described by Boivin and
Charlet-Berguerand.
2440:
693:
296:, or lead to production of a toxic protein. In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes.
942:, usually affecting people later in life. However different polyQ-containing proteins damage different subsets of neurons, leading to different symptoms.
83:
75:
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3108:
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produced by the expression of the affected gene. In yet others, the pathology is caused by toxic assemblies of RNA in the nuclei of cells.
149:
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447:
44:
156:
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2404:
1967:
214:
196:
52:
3113:
2433:
2247:"Analysis of strand slippage in DNA polymerase expansions of CAG/CTG triplet repeats associated with neurodegenerative disease"
163:
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families that have had
Huntington's for many generations show an earlier age of disease onset and faster disease progression.
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Classification of the trinucleotide repeat, and resulting disease status, depends on the number of CAG repeats in
123:
2950:
2672:
1767:"GGC Repeat Expansion and Exon 1 Methylation of XYLT1 Is a Common Pathogenic Variant in Baratela-Scott Syndrome"
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1907:"Clinical behaviour of spinocerebellar ataxia type 12 and intermediate length abnormal CAG repeats in PPP2R2B"
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750:
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323:
413:. The repeated codons in the remaining disorders do not code for glutamine, and these can be classified as
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Trinucleotide repeat expansion disorders, Triplet repeat expansion disorders or Codon reiteration disorders
170:
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Schoser, Benedikt (1993), Adam, Margaret P.; Feldman, Jerry; Mirzaa, Ghayda M.; Pagon, Roberta A. (eds.),
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2337:"DNA slip-outs cause RNA polymerase II arrest in vitro: potential implications for genetic instability"
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1276:"30 years of repeat expansion disorders: What have we learned and what are the remaining challenges?"
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frequency of individuals with a parent who already has a significant number of CAG repeats in their
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1850:"Myotonic Dystrophy Type 2: An Update on Clinical Aspects, Genetic and Pathomolecular Mechanism"
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LaCroix AJ, Stabley D, Sahraoui R, Adam MP, Mehaffey M, Kernan K, et al. (January 2019).
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Some of the problems in trinucleotide repeat syndromes result from causing alterations in the
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1580:"Genetic and Epigenetic Interplay Define Disease Onset and Severity in Repeat Diseases"
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1985:
1385:"On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability"
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expansion diseases (also known as repeat expansion disorders), are a set of over 30
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occurs when there are more than 35 CAG repeats on the gene coding for the protein
2213:
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1725:
1634:"Proteins Containing Expanded Polyglutamine Tracts and Neurodegenerative Disease"
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1225:"Trinucleotide CGG Repeat Diseases: An Expanding Field of Polyglycine Proteins?"
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synthesis. Because the tandem repeats have identical sequence to one another,
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2023:
2006:
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1817:
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Adegbuyiro A, Sedighi F, Pilkington AW, Groover S, Legleiter J (March 2017).
1528:"DNA methylation has a local effect on transcription and histone acetylation"
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Fan HC, Ho LI, Chi CS, Chen SJ, Peng GS, Chan TM, et al. (May 2014).
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1726:"Microsatellite Expansion Diseases: Repeat Toxicity Found in Translation"
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change in protein expression or function mediated through changes in the
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Genetic disorders due to increases in the number of repeating nucleotides
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938:. A common symptom of polyQ diseases is the progressive degeneration of
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900:
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281:
1479:"Microsatellites in different eukaryotic genomes: survey and analysis"
2898:
1445:. Genetic and Rare Diseases Information Center (GARD). Archived from
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2198:"Repeat instability during DNA repair: Insights from model systems"
2145:
Mirkin SM (June 2007). "Expandable DNA repeats and human disease".
2644:
2335:
Salinas-Rios V, Belotserkovskii BP, Hanawalt PC (September 2011).
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601:
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393:. In over half of these disorders, the repeated trinucleotide, or
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Trinucleotide repeats are a subset of a larger class of unstable
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2422:
2288:"New insights into repeat instability: role of RNA•DNA hybrids"
1954:. Ataxic Disorders. Vol. 103. Elsevier. pp. 535–547.
2048:"Neurodegenerative disease: RNA repeats put a freeze on cells"
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106:
59:
18:
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Orr HT, Zoghbi HY (2007). "Trinucleotide repeat disorders".
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involving hybrid RNA:DNA intermediates have been proposed.
365:. This first category is designated as "loss of function".
2413:
1905:
Srivastava AK, Takkar A, Garg A, Faruq M (January 2017).
1383:
Khristich, Alexandra N.; Mirkin, Sergei M. (March 2020).
2245:
Petruska J, Hartenstine MJ, Goodman MF (February 1998).
2007:"Polyglutamine (PolyQ) diseases: genetics to treatments"
2402:
National
Institute of Neurological Disorders and Stroke
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87:
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Critical
Reviews in Biochemistry and Molecular Biology
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increased expression, and a novel polyglycine product
318:, which has since been mapped to the long arm of the
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1824:, Seattle (WA): University of Washington, Seattle,
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137:. Unsourced material may be challenged and removed.
2102:Walker FO (January 2007). "Huntington's disease".
830:RNA-based; unbalanced DMPK/ZNF9 expression levels
330:in males. The second DNA-triplet repeat disease,
1946:O'Hearn E, Holmes SE, Margolis RL (2012-01-01).
1848:Meola, Giovanni; Cardani, Rosanna (2015-07-22).
389:of the gene, while others are caused by altered
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1274:Depienne, Christel; Mandel, Jean-Louis (2021).
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1031:Trinucleotide repeat disorders generally show
357:near the repeat region, resulting in a closed
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2434:
1948:"Chapter 34 - Spinocerebellar ataxia type 12"
409:. These diseases are commonly referred to as
8:
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2093:
2091:
1526:Irvine RA, Lin IG, Hsieh CL (October 2002).
397:, is CAG. In a coding region, CAG codes for
2196:Usdin K, House NC, Freudenreich CH (2015).
694:Fragile X-associated tremor/ataxia syndrome
53:Learn how and when to remove these messages
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2389:at the U.S. National Library of Medicine
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951:non-coding trinucleotide repeat disorders
636:Non-coding trinucleotide repeat disorders
419:non-coding trinucleotide repeat disorders
215:Learn how and when to remove this message
197:Learn how and when to remove this message
2995:Spinocerebellar ataxia 1, 2, 3, 6, 7, 17
2286:McIvor EI, Polak U, Napierala M (2010).
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1477:Tóth G, Gáspári Z, Jurka J (July 2000).
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2046:Sanders DW, Brangwynne CP (June 2017).
1223:Boivin M, Charlet-Berguerand N (2022).
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2397:GeneReviews/NCBI/NIH/UW entry on DRPLA
1185:10.1146/annurev.neuro.29.051605.113042
7:
2980:Dentatorubral-pallidoluysian atrophy
859:RNA-based; Nuclear RNA accumulation
135:adding citations to reliable sources
88:move details into the article's body
2251:The Journal of Biological Chemistry
1724:Gao FB, Richter JD (January 2017).
326:, distinctive facial features, and
2510:Short tandem repeat/Microsatellite
1960:10.1016/b978-0-444-51892-7.00034-6
1950:. In Subramony SH, Dürr A (eds.).
1771:American Journal of Human Genetics
489:Spinal and bulbar muscular atrophy
448:Dentatorubropallidoluysian atrophy
303:repeats that occur throughout all
14:
1854:Journal of Neuromuscular Diseases
411:polyglutamine (or polyQ) diseases
34:This article has multiple issues.
1544:10.1128/MCB.22.19.6689-6696.2002
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111:
64:
23:
1389:Journal of Biological Chemistry
1069:Triplet expansion is caused by
146:"Trinucleotide repeat disorder"
122:needs additional citations for
42:or discuss these issues on the
3119:Trinucleotide repeat disorders
3109:Genetic disorders by mechanism
2514:Trinucleotide repeat disorders
2387:Trinucleotide+Repeat+Expansion
1952:Handbook of Clinical Neurology
1578:Barbé L, Finkbeiner S (2022).
425:Polyglutamine (PolyQ) diseases
265:trinucleotide repeat expansion
253:trinucleotide repeat disorders
1:
2501:Variable number tandem repeat
2116:10.1016/S0140-6736(07)60111-1
1695:10.1136/jmedgenet-2020-106963
1173:Annual Review of Neuroscience
723:Fragile XE mental retardation
576:Spinocerebellar ataxia Type 6
509:Spinocerebellar ataxia Type 1
290:regulation of gene expression
233:Trinucleotide repeat disorder
2214:10.3109/10409238.2014.999192
1743:10.1016/j.neuron.2017.01.001
1332:G3: Genes, Genomes, Genetics
1056:Non-trinucleotide expansions
917:effect on promoter function
312:trinucleotide repeat disease
1818:"Myotonic Dystrophy Type 2"
1683:Journal of Medical Genetics
1650:10.1021/acs.biochem.6b00936
936:ubiquitin-proteasome system
3135:
2972:Polyglutamine (PolyQ), CAG
1784:10.1016/j.ajhg.2018.11.005
1293:10.1016/j.ajhg.2021.03.011
271:in which repeats of three
3087:Spinocerebellar ataxia 10
3069:Myotonic dystrophy type 2
3047:Spinocerebellar ataxia 12
3033:Myotonic dystrophy type 1
2951:Non-Mendelian inheritance
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1597:10.3389/fnagi.2022.750629
1402:10.1074/jbc.rev119.007678
1344:10.1093/g3journal/jkad257
1242:10.3389/fgene.2022.843014
441:Pathogenic PolyQ repeats
3040:Spinocerebellar ataxia 8
2391:Medical Subject Headings
2024:10.3727/096368914X678454
351:methylation of cytosines
2414:Genetics Home Reference
801:impaired transcription
751:Baratela-Scott syndrome
324:intellectual disability
2999:Machado-Joseph disease
2909:Protein tandem repeats
2837:Tandemly arrayed genes
2341:Nucleic Acids Research
2264:10.1074/jbc.273.9.5204
1106:This section is empty.
895:Spinocerebellar ataxia
866:Spinocerebellar ataxia
616:Spinocerebellar ataxia
596:Spinocerebellar ataxia
553:Machado-Joseph disease
549:Spinocerebellar ataxia
529:Spinocerebellar ataxia
405:result in an expanded
2304:10.4161/rna.7.5.12745
1443:"Fragile XE syndrome"
772:abnormal methylation
745:abnormal methylation
687:abnormal methylation
314:to be identified was
3114:Huntington's disease
2985:Huntington's disease
2882:Pathogenicity island
2011:Cell Transplantation
1924:10.1093/brain/aww269
1860:(Suppl 2): S59–S71.
1584:Front Aging Neurosci
1037:Huntington's disease
1033:genetic anticipation
969:Huntington's disease
469:Huntington's disease
438:Normal PolyQ repeats
332:fragile X-E syndrome
131:improve this article
3026:Friedreich's ataxia
2167:10.1038/nature05977
2159:2007Natur.447..932M
2073:10.1038/nature22503
2064:2017Natur.546..215S
1495:10.1101/gr.10.7.967
1011:Reduced-penetrance
971:
779:Friedreich's ataxia
407:polyglutamine tract
363:gene downregulation
3019:Fragile X syndrome
2832:Gene amplification
2407:2016-12-15 at the
2353:10.1093/nar/gkr429
1866:10.3233/JND-150088
966:
947:non-polyQ diseases
924:Symptoms and signs
837:Myotonic dystrophy
808:Myotonic dystrophy
665:Fragile X syndrome
316:fragile X syndrome
292:; produce a toxic
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2454:repeated sequence
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1721:
1715:
1714:
1678:
1672:
1671:
1661:
1644:(9): 1199–1217.
1629:
1620:
1619:
1609:
1599:
1575:
1566:
1565:
1555:
1523:
1517:
1516:
1506:
1474:
1468:
1465:
1459:
1458:
1456:
1454:
1439:
1433:
1432:
1422:
1404:
1380:
1374:
1373:
1363:
1322:
1316:
1315:
1305:
1295:
1271:
1265:
1264:
1254:
1244:
1220:
1197:
1196:
1168:
1121:
1118:
1108:You can help by
1101:
1094:
1022:Full-penetrance
1014:May be affected
972:
640:
429:
349:changes such as
230:
220:
213:
202:
195:
191:
188:
182:
180:
139:
115:
107:
100:
97:
91:
82:Please read the
68:
67:
60:
49:
27:
26:
19:
3134:
3133:
3129:
3128:
3127:
3125:
3124:
3123:
3099:
3098:
3097:
3092:
3079:Pentanucleotide
3074:
3061:Tetranucleotide
3052:
3004:
2990:Kennedy disease
2957:
2948:
2918:
2913:
2865:
2814:
2682:
2654:
2631:
2605:Retrotransposon
2586:
2577:Inverted repeat
2565:
2550:DNA transposon
2546:Retrotransposon
2541:Gene conversion
2532:
2525:
2522:
2473:
2464:
2447:
2409:Wayback Machine
2383:
2378:
2334:
2333:
2329:
2285:
2284:
2280:
2244:
2243:
2239:
2195:
2194:
2190:
2144:
2143:
2139:
2101:
2100:
2089:
2045:
2044:
2040:
2004:
2003:
1999:
1990:
1988:
1970:
1945:
1944:
1940:
1904:
1903:
1899:
1847:
1846:
1842:
1834:
1832:
1815:
1814:
1810:
1764:
1763:
1759:
1723:
1722:
1718:
1680:
1679:
1675:
1631:
1630:
1623:
1577:
1576:
1569:
1538:(19): 6689–96.
1525:
1524:
1520:
1476:
1475:
1471:
1466:
1462:
1452:
1450:
1449:on 9 March 2013
1441:
1440:
1436:
1382:
1381:
1377:
1324:
1323:
1319:
1273:
1272:
1268:
1222:
1221:
1200:
1170:
1169:
1152:
1148:
1140:RAN translation
1131:
1122:
1116:
1113:
1092:
1075:DNA replication
1067:
1058:
981:Disease status
978:Classification
964:
926:
638:
427:
391:gene regulation
383:
361:state, causing
228:
221:
210:
209:
208:
203:
192:
186:
183:
140:
138:
128:
116:
101:
95:
92:
81:
78:may be too long
73:This article's
69:
65:
28:
24:
17:
12:
11:
5:
3132:
3130:
3122:
3121:
3116:
3111:
3101:
3100:
3094:
3093:
3091:
3090:
3082:
3080:
3076:
3075:
3073:
3072:
3064:
3062:
3058:
3057:
3054:
3053:
3051:
3050:
3043:
3036:
3029:
3022:
3014:
3012:
3006:
3005:
3003:
3002:
2992:
2987:
2982:
2976:
2974:
2965:
2959:
2958:
2949:
2947:
2946:
2939:
2932:
2924:
2915:
2914:
2912:
2911:
2906:
2901:
2896:
2891:
2890:
2889:
2884:
2877:Genomic island
2873:
2871:
2867:
2866:
2864:
2863:
2858:
2857:
2856:
2846:
2845:
2844:
2834:
2828:
2826:
2820:
2819:
2816:
2815:
2813:
2812:
2807:
2802:
2797:
2792:
2787:
2782:
2777:
2772:
2767:
2762:
2757:
2752:
2747:
2742:
2737:
2732:
2727:
2722:
2717:
2712:
2707:
2702:
2696:
2694:
2692:DNA transposon
2688:
2687:
2684:
2683:
2681:
2680:
2675:
2670:
2664:
2662:
2656:
2655:
2653:
2652:
2647:
2641:
2639:
2633:
2632:
2630:
2629:
2624:
2618:
2616:
2607:
2598:
2592:
2591:
2588:
2587:
2585:
2584:
2579:
2573:
2571:
2567:
2566:
2564:
2563:
2562:
2561:
2556:
2548:
2543:
2537:
2535:
2527:
2526:
2524:
2523:
2520:Macrosatellite
2517:
2507:
2498:
2492:
2490:
2488:Tandem repeats
2481:
2475:
2474:
2469:
2466:
2465:
2448:
2446:
2445:
2438:
2431:
2423:
2417:
2416:
2411:
2399:
2394:
2382:
2381:External links
2379:
2377:
2376:
2327:
2298:(5): 551–558.
2278:
2237:
2208:(2): 142–167.
2188:
2137:
2087:
2038:
1997:
1968:
1938:
1897:
1840:
1808:
1757:
1736:(2): 249–251.
1716:
1689:(6): 385–391.
1673:
1621:
1567:
1518:
1469:
1460:
1434:
1375:
1317:
1286:(5): 764–785.
1280:Am J Hum Genet
1266:
1198:
1179:(1): 575–621.
1149:
1147:
1144:
1143:
1142:
1137:
1130:
1127:
1124:
1123:
1117:September 2021
1104:
1102:
1091:
1088:
1066:
1063:
1057:
1054:
1027:
1026:
1023:
1020:
1016:
1015:
1012:
1009:
1005:
1004:
1001:
998:
994:
993:
990:
987:
983:
982:
979:
976:
963:
960:
925:
922:
919:
918:
915:
912:
909:
903:
898:
890:
889:
886:
883:
880:
874:
869:
861:
860:
857:
854:
851:
845:
840:
832:
831:
828:
825:
822:
816:
811:
803:
802:
799:
796:
793:
787:
782:
774:
773:
770:
767:
764:
758:
753:
747:
746:
743:
740:
737:
731:
726:
718:
717:
714:
711:
708:
702:
697:
689:
688:
685:
682:
679:
673:
668:
660:
659:
656:
653:
650:
647:
644:
637:
634:
631:
630:
627:
624:
619:
611:
610:
607:
604:
599:
591:
590:
587:
584:
579:
568:
567:
564:
561:
556:
544:
543:
540:
537:
532:
524:
523:
520:
517:
512:
504:
503:
500:
497:
492:
484:
483:
480:
477:
472:
464:
463:
460:
457:
451:
443:
442:
439:
436:
433:
426:
423:
382:
379:
328:macroorchidism
301:microsatellite
257:microsatellite
255:, a subset of
243:
242:
239:
235:
234:
226:
223:
222:
205:
204:
119:
117:
110:
103:
102:
72:
70:
63:
58:
32:
31:
29:
22:
15:
13:
10:
9:
6:
4:
3:
2:
3131:
3120:
3117:
3115:
3112:
3110:
3107:
3106:
3104:
3088:
3084:
3083:
3081:
3077:
3070:
3066:
3065:
3063:
3059:
3048:
3044:
3041:
3037:
3034:
3030:
3027:
3023:
3020:
3016:
3015:
3013:
3011:
3007:
3000:
2996:
2993:
2991:
2988:
2986:
2983:
2981:
2978:
2977:
2975:
2973:
2969:
2966:
2964:
2963:Trinucleotide
2960:
2956:
2952:
2945:
2940:
2938:
2933:
2931:
2926:
2925:
2922:
2910:
2907:
2905:
2902:
2900:
2897:
2895:
2892:
2888:
2885:
2883:
2880:
2879:
2878:
2875:
2874:
2872:
2868:
2862:
2859:
2855:
2852:
2851:
2850:
2847:
2843:
2842:Ribosomal DNA
2840:
2839:
2838:
2835:
2833:
2830:
2829:
2827:
2825:
2821:
2811:
2808:
2806:
2803:
2801:
2798:
2796:
2793:
2791:
2788:
2786:
2783:
2781:
2778:
2776:
2773:
2771:
2768:
2766:
2763:
2761:
2758:
2756:
2753:
2751:
2748:
2746:
2743:
2741:
2738:
2736:
2733:
2731:
2728:
2726:
2723:
2721:
2718:
2716:
2713:
2711:
2708:
2706:
2703:
2701:
2698:
2697:
2695:
2693:
2689:
2679:
2676:
2674:
2671:
2669:
2666:
2665:
2663:
2661:
2657:
2651:
2648:
2646:
2643:
2642:
2640:
2638:
2634:
2628:
2625:
2623:
2620:
2619:
2617:
2615:
2611:
2608:
2606:
2602:
2599:
2597:
2593:
2583:
2582:Direct repeat
2580:
2578:
2575:
2574:
2572:
2568:
2560:
2557:
2555:
2552:
2551:
2549:
2547:
2544:
2542:
2539:
2538:
2536:
2534:
2528:
2521:
2518:
2515:
2511:
2508:
2506:
2505:Minisatellite
2502:
2499:
2497:
2496:Satellite DNA
2494:
2493:
2491:
2489:
2485:
2482:
2480:
2476:
2472:
2467:
2463:
2459:
2455:
2451:
2444:
2439:
2437:
2432:
2430:
2425:
2424:
2421:
2415:
2412:
2410:
2406:
2403:
2400:
2398:
2395:
2392:
2388:
2385:
2384:
2380:
2372:
2368:
2363:
2358:
2354:
2350:
2346:
2342:
2338:
2331:
2328:
2323:
2319:
2314:
2309:
2305:
2301:
2297:
2293:
2289:
2282:
2279:
2274:
2270:
2265:
2260:
2256:
2252:
2248:
2241:
2238:
2233:
2229:
2224:
2219:
2215:
2211:
2207:
2203:
2199:
2192:
2189:
2184:
2180:
2176:
2172:
2168:
2164:
2160:
2156:
2152:
2148:
2141:
2138:
2133:
2129:
2125:
2121:
2117:
2113:
2109:
2105:
2098:
2096:
2094:
2092:
2088:
2083:
2079:
2074:
2069:
2065:
2061:
2057:
2053:
2049:
2042:
2039:
2034:
2030:
2025:
2020:
2016:
2012:
2008:
2001:
1998:
1987:
1983:
1979:
1975:
1971:
1969:9780444518927
1965:
1961:
1957:
1953:
1949:
1942:
1939:
1934:
1930:
1925:
1920:
1916:
1912:
1908:
1901:
1898:
1893:
1889:
1884:
1879:
1875:
1871:
1867:
1863:
1859:
1855:
1851:
1844:
1841:
1831:
1827:
1823:
1819:
1812:
1809:
1804:
1800:
1795:
1790:
1785:
1780:
1776:
1772:
1768:
1761:
1758:
1753:
1749:
1744:
1739:
1735:
1731:
1727:
1720:
1717:
1712:
1708:
1704:
1700:
1696:
1692:
1688:
1684:
1677:
1674:
1669:
1665:
1660:
1655:
1651:
1647:
1643:
1639:
1635:
1628:
1626:
1622:
1617:
1613:
1608:
1603:
1598:
1593:
1589:
1585:
1581:
1574:
1572:
1568:
1563:
1559:
1554:
1549:
1545:
1541:
1537:
1533:
1532:Mol Cell Biol
1529:
1522:
1519:
1514:
1510:
1505:
1500:
1496:
1492:
1489:(7): 967–81.
1488:
1484:
1480:
1473:
1470:
1464:
1461:
1448:
1444:
1438:
1435:
1430:
1426:
1421:
1416:
1412:
1408:
1403:
1398:
1394:
1390:
1386:
1379:
1376:
1371:
1367:
1362:
1357:
1353:
1349:
1345:
1341:
1337:
1333:
1329:
1321:
1318:
1313:
1309:
1304:
1299:
1294:
1289:
1285:
1281:
1277:
1270:
1267:
1262:
1258:
1253:
1248:
1243:
1238:
1234:
1230:
1226:
1219:
1217:
1215:
1213:
1211:
1209:
1207:
1205:
1203:
1199:
1194:
1190:
1186:
1182:
1178:
1174:
1167:
1165:
1163:
1161:
1159:
1157:
1155:
1151:
1145:
1141:
1138:
1136:
1133:
1132:
1128:
1120:
1111:
1107:
1103:
1100:
1096:
1095:
1089:
1087:
1084:
1080:
1076:
1072:
1064:
1062:
1055:
1053:
1050:
1044:
1042:
1038:
1034:
1024:
1021:
1018:
1017:
1013:
1010:
1007:
1006:
1002:
1000:Intermediate
999:
996:
995:
991:
988:
985:
984:
980:
977:
975:Repeat count
974:
973:
970:
961:
959:
957:
956:messenger RNA
952:
948:
943:
941:
937:
932:
923:
916:
913:
910:
907:
904:
902:
899:
896:
892:
891:
887:
884:
881:
878:
875:
873:
870:
867:
863:
862:
858:
855:
852:
849:
846:
844:
841:
838:
834:
833:
829:
826:
823:
820:
817:
815:
812:
809:
805:
804:
800:
797:
794:
791:
788:
786:
783:
780:
776:
775:
771:
768:
765:
762:
759:
757:
754:
752:
749:
748:
744:
741:
738:
735:
732:
730:
727:
724:
720:
719:
715:
712:
709:
706:
703:
701:
698:
695:
691:
690:
686:
683:
680:
677:
674:
672:
669:
666:
662:
661:
657:
654:
651:
648:
645:
642:
641:
635:
628:
625:
623:
620:
617:
613:
612:
608:
605:
603:
600:
597:
593:
592:
588:
585:
583:
580:
577:
573:
570:
569:
565:
562:
560:
557:
554:
550:
546:
545:
541:
538:
536:
533:
530:
526:
525:
521:
518:
516:
513:
510:
506:
505:
501:
498:
496:
493:
490:
486:
485:
481:
478:
476:
473:
470:
466:
465:
461:
458:
455:
452:
449:
445:
444:
440:
437:
434:
431:
430:
424:
422:
420:
416:
412:
408:
404:
400:
396:
392:
388:
387:coding region
380:
378:
374:
370:
366:
364:
360:
356:
352:
348:
342:
339:
335:
333:
329:
325:
321:
317:
313:
308:
306:
302:
297:
295:
291:
288:; change the
287:
284:encoded by a
283:
278:
277:trinucleotide
274:
270:
266:
262:
258:
254:
250:
240:
236:
231:
219:
216:
201:
198:
190:
187:December 2020
179:
176:
172:
169:
165:
162:
158:
155:
151:
148: –
147:
143:
142:Find sources:
136:
132:
126:
125:
120:This article
118:
114:
109:
108:
99:
96:November 2023
89:
85:
79:
77:
71:
62:
61:
56:
54:
47:
46:
41:
40:
35:
30:
21:
20:
2962:
2955:anticipation
2854:Gene cluster
2622:Alu sequence
2531:Interspersed
2513:
2344:
2340:
2330:
2295:
2291:
2281:
2254:
2250:
2240:
2205:
2201:
2191:
2150:
2146:
2140:
2107:
2103:
2055:
2051:
2041:
2014:
2010:
2000:
1989:. Retrieved
1951:
1941:
1917:(1): 27–36.
1914:
1910:
1900:
1857:
1853:
1843:
1833:, retrieved
1822:GeneReviews®
1821:
1811:
1777:(1): 35–44.
1774:
1770:
1760:
1733:
1729:
1719:
1686:
1682:
1676:
1641:
1638:Biochemistry
1637:
1587:
1583:
1535:
1531:
1521:
1486:
1482:
1472:
1463:
1453:14 September
1451:. Retrieved
1447:the original
1437:
1392:
1388:
1378:
1335:
1331:
1320:
1283:
1279:
1269:
1232:
1228:
1176:
1172:
1114:
1110:adding to it
1105:
1083:base pairing
1070:
1068:
1059:
1048:
1045:
1030:
950:
946:
944:
930:
927:
905:
876:
847:
818:
789:
760:
733:
704:
675:
418:
414:
410:
402:
384:
375:
371:
367:
343:
340:
336:
320:X chromosome
309:
298:
267:, a kind of
252:
246:
211:
193:
184:
174:
167:
160:
153:
141:
129:Please help
124:verification
121:
93:
76:lead section
74:
50:
43:
37:
36:Please help
33:
2849:Gene family
2760:Tc1/mariner
2715:EnSpm/CACTA
2292:RNA Biology
1229:Front Genet
1003:Unaffected
992:Unaffected
940:nerve cells
403:CAG repeats
355:CpG islands
273:nucleotides
238:Other names
3103:Categories
2861:Pseudogene
2678:retroposon
2596:Transposon
2458:transposon
1991:2022-12-07
1835:2024-07-02
1590:: 750629.
1483:Genome Res
1235:: 843014.
1146:References
1079:DNA repair
1077:or during
658:Mechanism
655:Pathogenic
551:Type 3 or
347:epigenetic
310:The first
263:caused by
157:newspapers
39:improve it
2780:P element
2730:Harbinger
2471:Repeatome
1874:2214-3599
1711:219991108
1411:0021-9258
1352:2160-1836
1090:Diagnosis
1065:Mechanism
1025:Affected
908:(5' UTR)
897:Type 12)
885:110 - 250
609:38 - 120
482:36 - 250
415:non-polyQ
399:glutamine
359:chromatin
86:and help
45:talk page
2904:Telomere
2870:See also
2810:Zisupton
2790:Polinton
2785:PiggyBac
2740:Helitron
2559:Helitron
2554:Polinton
2450:Genetics
2405:Archived
2371:21666257
2322:20729633
2232:25608779
2175:17581576
2132:46151626
2124:17240289
2082:28562583
2033:24816443
1986:25745894
1978:21827912
1933:27864267
1892:27858759
1830:20301639
1803:30554721
1752:28103472
1703:32571900
1668:28170216
1616:35592702
1562:12215526
1513:10899146
1429:32060097
1370:37950892
1361:10849350
1312:33811808
1261:35295941
1193:17417937
1129:See also
1071:slippage
962:Genetics
914:55 - 78
850:(3' UTR)
821:(3' UTR)
792:(Intron)
763:(5' UTR)
736:(5' UTR)
707:(5' UTR)
678:(5' UTR)
629:47 - 63
618:Type 17)
589:21 - 30
566:55 - 86
542:33 - 77
522:49 - 88
502:35 - 72
462:49 - 88
456:or DRPLA
401:(Q), so
269:mutation
249:genetics
3085:ATTCT (
2800:Transib
2775:Novosib
2755:Kolobok
2725:Ginger2
2720:Ginger1
2705:Crypton
2362:3177194
2313:3073251
2273:9478975
2223:4454471
2183:4397592
2155:Bibcode
2060:Bibcode
1883:5240594
1794:6323552
1659:5727916
1607:9110800
1420:7105313
1303:8205997
1252:8918734
1135:C9orf72
1073:during
1019:>40
989:Normal
986:<28
931:PPP2R2B
911:7 - 28
901:PPP2R2B
893:SCA12 (
882:16 - 37
868:Type 8)
853:11 - 26
839:Type 2)
810:Type 1)
721:FRAXE (
692:FXTAS (
663:FRAXA (
626:25 - 42
614:SCA17 (
598:Type 7)
582:CACNA1A
563:12 - 40
539:14 - 32
531:Type 2)
446:DRPLA (
305:genomes
282:protein
171:scholar
3067:CCTG (
2899:CRISPR
2765:Merlin
2750:ISL2EU
2700:Academ
2533:repeat
2393:(MeSH)
2369:
2359:
2320:
2310:
2271:
2230:
2220:
2181:
2173:
2147:Nature
2130:
2122:
2104:Lancet
2080:
2052:Nature
2031:
1984:
1976:
1966:
1931:
1890:
1880:
1872:
1828:
1801:
1791:
1750:
1730:Neuron
1709:
1701:
1666:
1656:
1614:
1604:
1560:
1553:134040
1550:
1511:
1504:310925
1501:
1427:
1417:
1409:
1368:
1358:
1350:
1310:
1300:
1259:
1249:
1191:
1008:36–40
997:28–35
888:? RNA
864:SCA8 (
824:5 - 34
795:7 - 34
777:FRDA (
766:6 - 35
739:6 - 35
713:55-200
710:6 - 53
681:6 - 53
652:Normal
606:7 - 17
594:SCA7 (
586:4 - 18
547:SCA3 (
527:SCA2 (
519:6 - 35
507:SCA1 (
499:4 - 34
487:SBMA (
479:6 - 35
459:6 - 35
173:
166:
159:
152:
144:
3045:CAG (
3038:CTG (
3031:CTG (
3024:GAA (
3017:CGG (
2805:Zator
2745:IS3EU
2650:LINE2
2645:LINE1
2637:LINEs
2614:SINEs
2570:Other
2179:S2CID
2128:S2CID
1982:S2CID
1911:Brain
1707:S2CID
1338:(2).
879:(RNA)
835:DM2 (
806:DM1 (
756:XYLT1
649:Codon
602:ATXN7
559:ATXN3
535:ATXN2
515:ATXN1
395:codon
381:Types
178:JSTOR
164:books
2795:Sola
2770:MuDR
2710:Dada
2673:MER4
2668:HERV
2660:LTRs
2367:PMID
2318:PMID
2269:PMID
2228:PMID
2171:PMID
2120:PMID
2078:PMID
2029:PMID
1974:PMID
1964:ISBN
1929:PMID
1888:PMID
1870:ISSN
1826:PMID
1799:PMID
1748:PMID
1699:PMID
1664:PMID
1612:PMID
1558:PMID
1509:PMID
1455:2012
1425:PMID
1407:ISSN
1366:PMID
1348:ISSN
1308:PMID
1257:PMID
1189:PMID
945:The
872:SCA8
848:CCTG
843:CNBP
814:DMPK
798:100+
769:200+
742:200+
729:AFF2
700:FMR1
684:230+
671:FMR1
646:Gene
643:Type
572:SCA6
467:HD (
454:ATN1
435:Gene
432:Type
286:gene
150:news
2735:hAT
2627:MIR
2357:PMC
2349:doi
2308:PMC
2300:doi
2259:doi
2255:273
2218:PMC
2210:doi
2163:doi
2151:447
2112:doi
2108:369
2068:doi
2056:546
2019:doi
1956:doi
1919:doi
1915:140
1878:PMC
1862:doi
1789:PMC
1779:doi
1775:104
1738:doi
1691:doi
1654:PMC
1646:doi
1602:PMC
1592:doi
1548:PMC
1540:doi
1499:PMC
1491:doi
1415:PMC
1397:doi
1393:295
1356:PMC
1340:doi
1298:PMC
1288:doi
1284:108
1247:PMC
1237:doi
1181:doi
1112:.
1049:HTT
1041:HTT
949:or
929:of
906:CAG
877:CTG
856:75+
827:50+
819:CTG
790:GAA
785:FXN
761:GGC
734:CCG
705:CGG
676:CGG
622:TBP
475:HTT
417:or
294:RNA
247:In
133:by
3105::
2953::
2460:,
2456:,
2452::
2365:.
2355:.
2345:39
2343:.
2339:.
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2306:.
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