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in DNA occurs. All of these diseases have neurological symptoms. Prior to the understanding of the genetic mechanism for anticipation, it was debated whether anticipation was a true biological phenomenon or whether the earlier age of diagnosis was related to heightened awareness of disease symptoms
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that increases the number of repeats in offspring inheriting the mutant allele. Once the number of copies reaches over 100, the disease will manifest earlier in life (although the individual will still reach adulthood before the symptoms are evident) and the symptoms will be more severe – including
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For many of the loci, trinucleotide expansion is harmless, but in some areas expansion has detrimental effects that cause symptoms. When the trinucleotide repeat is present within the protein-coding region, the repeat expansion leads to production of a mutant protein with
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In order to have a deleterious effect, the number of repeats must cross a certain threshold. For example, normal individuals have between 5 and 30 CTG repeats within the 3' UTR of
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The mechanism behind the expansion of the triplet repeats is not well understood. One hypothesis is that the increasing number of repeats influences the overall shape of the
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152:. If the number of repeats is between 50 and 100, the person is only mildly affected – perhaps having only cataracts. However, meiotic instability could result in a
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Armanios M., Chen J. L., Chang Y. P., Brodsky R. A., Hawkins A., Griffin C. A., Eshleman J. R., Cohen A. R., Chakravarti A., Hamosh A., Greider C. W. (2005).
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262:"Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita"
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212:– GAA (Note: Friedreich ataxia does not usually exhibit anticipation because it is an autosomal recessive disorder.)
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161:. As the number progresses upwards past 400, the symptoms show themselves during childhood or infancy.
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is a phenomenon whereby as a genetic disorder is passed on to the next generation, the symptoms of the
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Polito, J.M.; Mendeloff, A.I; Harris, M.L; Bayless, T.M; Childs, Barton; Rees, R.C (23 March 1996).
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produced have a greater number of repeats than are found in the somatic tissues.
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Fresko, I; M Soy; V Hamuryudan; S Yurdakul; Ş Yavuz; Z Tümerd; H Yazici (1998).
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347:"Preliminary evidence for genetic anticipation in Crohn's disease"
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85:(e.g. CGG) which is repeated a number of times. During
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57:Trinucleotide repeats are apparent in a number of
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318:: CS1 maint: multiple names: authors list (
28:become apparent at an earlier age with each
396:"Genetic anticipation in Behçet's syndrome"
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449:at the U.S. National Library of Medicine
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165:Examples of diseases showing anticipation
532:Spinocerebellar ataxia 1, 2, 3, 6, 7, 17
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169:Diseases showing anticipation include:
81:'s. They consist of a pattern of three
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104:and thus the expression of the gene.
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517:Dentatorubral-pallidoluysian atrophy
335:, NCBI Bookshelf: Friedreich Ataxia.
199:– TTAGGG (telomere repeat sequence)
53:Trinucleotide repeats and expansion
129:in which the repeat is found (ex.
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646:Genetic disorders by mechanism
148:, the gene that is altered in
34:trinucleotide repeat disorders
1:
364:10.1016/S0140-6736(96)90870-3
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509:Polyglutamine (PolyQ), CAG
133:) or many genes through a
65:. They have been found in
624:Spinocerebellar ataxia 10
606:Myotonic dystrophy type 2
584:Spinocerebellar ataxia 12
570:Myotonic dystrophy type 1
488:Non-Mendelian inheritance
577:Spinocerebellar ataxia 8
451:Medical Subject Headings
266:Proc Natl Acad Sci U S A
230:Without expression type
117:. This is the case for
287:10.1073/pnas.0508124102
180:spinocerebellar ataxias
536:Machado-Joseph disease
197:Dyskeratosis congenita
522:Huntington's disease
447:Genetic+anticipation
185:Huntington's disease
119:Huntington's disease
38:Huntington's disease
563:Friedreich's ataxia
412:10.1136/ard.57.1.45
278:2005PNAS..10215960A
205:Autosomal recessive
556:Fragile X syndrome
223:Fragile X syndrome
191:Myotonic dystrophy
174:Autosomal dominant
150:myotonic dystrophy
139:myotonic dystrophy
108:Disease mechanisms
42:myotonic dystrophy
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357:(9004): 798–800.
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63:human genome
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157:electrical
83:nucleotides
351:The Lancet
247:References
123:expression
91:germ cells
44:, where a
36:, such as
30:generation
333:Link text
131:fragile X
640:Category
381:21921598
306:16247010
218:X-linked
178:Several
159:myotonia
18:genetics
622:ATTCT (
430:9536823
421:1752455
373:8622336
297:1276104
274:Bibcode
125:of the
87:meiosis
67:introns
61:in the
604:CCTG (
453:(MeSH)
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79:3' UTR
582:CAG (
575:CTG (
568:CTG (
561:GAA (
554:CGG (
377:S2CID
225:– CGG
193:– CTG
187:– CAG
71:exons
426:PMID
369:PMID
320:link
302:PMID
146:DMPK
127:gene
73:and
59:loci
40:and
416:PMC
408:doi
359:doi
355:347
292:PMC
282:doi
270:102
141:).
98:DNA
77:or
16:In
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316:}}
312:{{
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