The DOI matches its Crossref record; 155 of the 157 references it cites were found in a registry or an index.
Repeat instability: mechanisms of dynamic mutations
Abstract
Disease-causing repeat instability is an important and unique form of mutation that is linked to more than 40 neurological, neurodegenerative and neuromuscular disorders. DNA repeat expansion mutations are dynamic and ongoing within tissues and across generations. The patterns of inherited and tissue-specific instability are determined by both gene-specific cis-elements and trans-acting DNA metabolic proteins. Repeat instability probably involves the formation of unusual DNA structures during DNA replication, repair and recombination. Experimental advances towards explaining the mechanisms of repeat instability have broadened our understanding of this mutational process. They have revealed surprising ways in which metabolic pathways can drive or protect from repeat instability.
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“By a process that is poorly understood, a small number of specific normal-length STRs undergo somatic or germline expansion and transition to intermediate, pre-mutation, and mutation (affected) repeat unit tract lengths (Mirkin, 2007; Pearson et al., 2005).”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Pearson et al., 2005
In the citing paper
“Notably, a large number of daSTRs known to undergo paternal instability (McMurray, 2010; Pearson et al., 2005) co-localized to boundaries in mouse sperm and not in mouse oocytes (Du et al., 2017), suggesting that daSTRs could be at boundaries when germ line expansion takes place (Figure S3).”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Pearson et al., 2005
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Items 201–300 of 926
Mason, A. G., Tomé, S., Simard, J. P., Libby, R. T., Bammler, T. K., Beyer, R. P., Morton, A. J., Pearson, C. E., & Spada, A. R. L. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt551 · Cited by 55
“While a set of examples of repeat-associated pathology has been reported in plants and in a canine species, neither of these repeats demonstrates the dramatic repeat instability seen in human patients (2,34).”
BackgroundAdams, R. H. J., Blackmon, H., Reyes‐Velasco, J., Schield, D. R., Card, D. C., Andrew, A. L., Waynewood, N., & Castoe, T. A. (2016) · Genome · doi:10.1139/gen-2015-0124 · Cited by 53
“…have demonstrated microsatellite locus conservation across considerable scales of evolutionary time in specific lineages (FitzSimmons et al. 1995; Pepín et al. 1995; Rico et al. 1996; Schlotteröer et al. 1991), while other studies have noted substantial divergence in microsatellite content even…”
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Postreplication Repair Inhibits CAG · CTG Repeat Expansions in Saccharomyces cerevisiae
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“Expansions of trinucleotide repeats (TNRs) are the genetic basis for at least 15 human neurological diseases, including Huntington’s disease, myotonic dystrophy type 1, and fragile X syndrome (39, 42, 60).”
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“m sh 6 − /− ↑ tr an si ti on s; ↑ ta rg et in g of C :G ↓ ↓ fr eq u en cy [5 2]”
BackgroundInfluentialMismatch Recognition Protein MutSβ Does Not Hijack (CAG) Hairpin Repair in Vitro
Tian, L., Hou, C., Tian, K., Holcomb, N., Gu, L., & Li, G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.c109.014977 · Cited by 56
Trinucleotide Repeats: A Structural Perspective
Almeida, B., Fernandes, S., Abreu, I. A., & Macedo‐Ribeiro, S. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00076 · Cited by 52
“More interestingly, in the brain of patients affected by CAG expansions, differences in repeat instability have been found between specific cell types (Pearson et al., 2005; Gonitel et al., 2008; Lopez Castel et al., 2010).”
BackgroundIncision-dependent and error-free repair of (CAG)n/(CTG)n hairpins in human cell extracts
Hou, C., Chan, N. L. S., Gu, L., & Li, G. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1638 · Cited by 53
“1638" language="eng" relation="no"> Expansion of trinucleotide repeats (TNRs) is tightly associated with at least 15 human familial neurological, neurodegenerative and neuromuscular disorders, including CAG repeat expansion–caused Huntington's disease and CTG repeat expansion–caused myotonic dystroph”
Wang, S., Zhang, L., & Matz, M. V. (2008) · Journal of Heredity · doi:10.1093/jhered/esn100 · Cited by 51
“Although mechanisms of repeat instability are still unclear, it is well known that trinucleotide repeats form the largest component of a broader category of repeat-associated disorders in humans (Pearson et al. 2005).”
BackgroundEnvironmental stress induces trinucleotide repeat mutagenesis in human cells
Chatterjee, N., Lin, Y., Santillan, B. A., Yotnda, P., & Wilson, J. H. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421917112 · Cited by 49
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“Although it is commonly believed that recombination has only a minor influence on microsatellite evolution (Ellegren 2004) it has clearly been demonstrated that recombination can influence microsatellite expansion and stability (Jakupciak and Wells 1999, 2000; Pearson et al. 2005).”
BackgroundCockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo
Kovtun, I. V., Johnson, K. O., & McMurray, C. T. (2011) · Aging · doi:10.18632/aging.100324 · Cited by 52
“In this regard, DNA repair proteins have been the focus of much attention [1-3].”
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FRA2A Is a CGG Repeat Expansion Associated with Silencing of AFF3
Metsu, S., Rooms, L., Rainger, J. K., Taylor, M. S., Bengani, H., Wilson, D. I., Chilamakuri, C. S. R., Morrison, H., Vandeweyer, G., Reyniers, E., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004242 · Cited by 49
“been associated with dynamic mutations [1,2] and at least 40 neurological, neurodegenerative and neuromuscular disorders are known to be caused by these types of mutations [3,4].”
BackgroundPentanucleotide repeats at the spinocerebellar ataxia type 31 (SCA31) locus in Caucasians
Ishikawa, K., Dürr, A., Klopstock, T., Müller, S., de Toffol, B., Vidailhet, M., Vighetto, A., Marelli, C., Wichmann, H. ‐., Illig, T., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e3182377e3a · Cited by 49
The Challenge of Small-Scale Repeats for Indel Discovery
Narzisi, G., & Schatz, M. C. (2015) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2015.00008 · Cited by 50
“Assembly based methods afford the best sensitivity for detecting indel mutations, especially long indels, as they avoid any expectation or dependencies of the reads aligning end-to-end to the reference genome.”
Gray, S. J., Gerhardt, J., Doerfler, W., Small, L. E., & Fanning, E. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01382-06 · Cited by 49
“Through successive generations, as the repeats expand, the symptoms of disease appear and increase in severity (9, 10, 19, 45, 56).”
BackgroundHubert, L., Lin, Y., Dion, V., & Wilson, J. H. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05158-11 · Cited by 52
“In bacteria the link has been ascribed to the effects of negative supercoiling on enhancing the formation of repeat-induced non-B DNA structures (38), which are thought to constitute the key common event leading to changes in repeat-tract length (24, 40, 56).”
BackgroundGenome-wide analysis of simple sequence repeats in the model medicinal mushroom Ganoderma lucidum
Qian, J., Xu, H., Song, J., Xu, J., Zhu, Y., & Chen, S. (2012) · Gene · doi:10.1016/j.gene.2012.09.127 · Cited by 48
Lin, Y., & Wilson, J. H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046807 · Cited by 47
“These processes may vary in their relative importance to repeat instability in different cell types in humans [3,5,13].”
BackgroundTavanez, J. P., Bengoechea, R., Berciano, M. T., Lafarga, M., Carmo‐Fonseca, M., & Enguita, F. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006418 · Cited by 48
“Tandem arrays of simple repeats such as mono-, tri-, and tetranucleotides are common in eukaryotic genomes, and repeat instability is the cause for more than 40 neurological, neurodegenerative and neuromuscular diseases [1].”
BackgroundAltered Replication in Human Cells Promotes DMPK (CTG) n · (CAG) n Repeat Instability
Liu, G., Chen, X., Gao, Y., Lewis, T., Barthelemy, J., & Leffak, M. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06727-11 · Cited by 49
“In 428-12D DM1 lymphoblasts that have lost ISDMPK on the nonexpanded chromosome, (CTG)n is copied as the leading-strand template from ISSIX5, which is the orientation that preferentially gives rise to expansions (56, 67, 70).”
BackgroundGene correction in patient-specific iPSCs for therapy development and disease modeling
Jang, Y.-Y., & Ye, Z. (2016) · Human Genetics · doi:10.1007/s00439-016-1691-5 · Cited by 48
“This plays a role in several forms of neurodegenerative diseases, such as Huntington’s disease (HD) and fragile X syndrome (Pearson et al. 2005).”
BackgroundFragile X Associated Primary Ovarian Insufficiency (FXPOI): Case Report and Literature Review
Fink, D. A., Nelson, L. M., Pyeritz, R. E., Johnson, J., Sherman, S. L., Cohen, Y., & Elizur, S. E. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00529 · Cited by 47
“to a family of more than 40 disorders characterized by repeat instability on transmission from parent to child (Pearson et al., 2005).”
BackgroundEvolutionary Origins of Pseudogenes and Their Association with Regulatory Sequences in Plants
Xie, J., Li, Y., Liu, X., Zhao, Y., Li, B., Ingvarsson, P. K., & Zhang, D. (2019) · The Plant Cell · doi:10.1105/tpc.18.00601 · Cited by 46
“S -p. Gene and C quantification was conducted using StringTie (Pertea et al., 2016), with parameters -e -G. Identification of lncRNA Catalogs For prediction of lncRNAs in Populus, the clean reads were first aligned to the reference genome using hisat2 v2.”
MethodInfluentialStructures and stability of simple DNA repeats from bacteria
Brázda, V., Fojta, M., & Bowater, R. P. (2020) · Biochemical Journal · doi:10.1042/bcj20190703 · Cited by 47
Complete sequencing of expandedSAMD12repeats by long-read sequencing and Cas9-mediated enrichment
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“It was commonly accepted that Pol a synthesizes a small amount of DNA in comparison to other replicative DNA polymerases – 1/10 of Okazaki fragment, estimated to be from 165 to 250 base pairs, [Waga and Stillman, 1998] [Pearson et al., 2005; Smith and Whitehouse, 2012].”
BackgroundInfluentialCis-acting DNA sequence at a replication origin promotes repeat expansion to fragile X full mutation
Gerhardt, J., Zaninović, N., Zhan, Q., Madireddy, A., Nolin, S. L., Ersalesi, N., Yan, Z., Rosenwaks, Z., & Schildkraut, C. L. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201404157 · Cited by 45
“Expanded repeats are inherited as a result of repeat instability that is thought to occur during germ cell generation and early stages of embryogenesis (Pearson et al., 2005; Mirkin, 2007; López Castel et al., 2010; Rousseau et al., 2011).”
Genome (in)stability at tandem repeats
Balzano, E., Pelliccia, F., & Giunta, S. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.10.003 · Cited by 50
Parent-of-origin differences of mutant HTT CAG repeat instability in Huntington’s disease
Aziz, N. A., van Belzen, M. J., Coops, I. D., Belfroid, R. D. M., & Roos, R. A. C. (2011) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2011.04.002 · Cited by 53
“Also in contrast to postmeiotic male germ cells that virtually lack proteins, arrested oocytes are primed with DNA repair and recombination activities [25].”
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“and other inherited neurological disorders [1,2].”
BackgroundNew insights into repeat instability
McIvor, E., Polak, U., & Напиерала, М. (2010) · RNA Biology · doi:10.4161/rna.7.5.12745 · Cited by 42
“These unusual mutations, termed dynamic mutations due to unstable, progressive character and nonMendelian inheritance occur predominantly at GC-rich repeat sequences.(12) Several cis elements and trans factors that affect repeat instability have been identified thus far, however no comprehensive model explaining the m…”
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“IGF1 contains a polymorphic sequence, composed of multiple cytosine– adenine (CA) dinucleotides repeats, which is located 969 bp upstream of the transcription start site in a region containing regulatory elements that may affect trans-activation [11,12].”
BackgroundNucleoporins and chromatin metabolism
Ptak, C. P., & Wozniak, R. W. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.03.024 · Cited by 44
DNA Polymorphisms: DNA-Based Molecular Markers and Their Application in Medicine
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“The extra CAG repeats that causes extra glutamine is produced [9] and there are more than 40 neurological diseases in humans, such as spinocerebellar ataxia with polyglutamine tracts, which are caused by microsatellite motif length changes in trinucleotide arrays [39].”
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Lévesque, S., Dombrowski, C., Morel, M., Réhel, R., Côté, J., Bussières, J., Morgan, K., & Rousseau, F. (2009) · Clinical Genetics · doi:10.1111/j.1399-0004.2009.01237.x · Cited by 44
“This reinforces the hypothesis of a cis-acting genomic element influencing FMR1 instability other than the tripletrepeats themselves (36) since the vast majority of such alleles have two AGG interruptions in the FMR1 triplet array (7, 37).”
BackgroundRepeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders
Usdin, K., Hayward, B. E., Kumari, D., Lokanga, R. A., Sciascia, N., & Zhao, X.-N. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00226 · Cited by 45
“…the repeats during normal genomic replication and others that suggest that expansion occurs as a result of aberrant repair of the secondary structures formed by the repeats perhaps during transcription or as a result of DNA damage (see Pearson et al., 2005; Mirkin, 2007 for comprehensive reviews).”
BackgroundThe GH1/IGF-1 axis polymorphisms and their impact on breast cancer development
Wagner, K., Hemminki, K., & Försti, A. (2006) · Breast Cancer Research and Treatment · doi:10.1007/s10549-006-9411-9 · Cited by 43
“Furthermore, with an increasing repeat length, the DNA becomes more unstable since the replication fork pauses at the repeats and is more prone to involve slippage events or doublestrand breaks [68].”
BackgroundYang, J. H., & Freudenreich, C. H. (2007) · Gene · doi:10.1016/j.gene.2007.01.025 · Cited by 43
“The myotonic dystrophy locus, where CTG tracts larger than 150 repeats are often observed, exhibits instability in proliferating cell types that are presumably undergoing Fen1-dependent flap processing during replication (Fortune et al., 2000;Pearson et al., 2005).”
BackgroundInfluentialNon-canonical actions of mismatch repair
Crouse, G. F. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.11.020 · Cited by 43
“However, in the case of trinucleotide repeats (CAG/CTG, CGG/CCG, and GAA/TTC) the opposite is true; MMR proteins, including MutSβ, MutLα and possibly MutLγ, have been shown to enhance the expansions of the repeats [66].”
BackgroundTomé, S., & Gourdon, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020457 · Cited by 43
Annear, D. J., Vandeweyer, G., Elinck, E., Sanchis‐Juan, A., French, C. E., Raymond, F. L., & Kooy, R. F. (2021) · Scientific Reports · doi:10.1038/s41598-021-82050-5 · Cited by 43
Non-LTR retrotransposons and microsatellites
Grandi, F. C., & An, W. (2013) · Mobile Genetic Elements · doi:10.4161/mge.25674 · Cited by 42
Searching for Non‐B DNA‐Forming Motifs Using nBMST (Non‐B DNA Motif Search Tool)
Cer, R. Z., Bruce, K. H., Donohue, D. E., Temiz, N. A., Mudunuri, U. S., Yi, M., Volfovsky, N., Bacolla, A., Luke, B. T., Collins, J., et al. (2012) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg1807s73 · Cited by 41
“…from "pre-mutation" (generally longer than normal) alleles (Brouwer et al., 2009) by mechanisms involving the formation of non-canonical DNA structures, such as hairpins (Pearson et al., 2005; Wells et al., 2005; Mirkin, 2007), and their processing by DNA repair enzymes, leading to expansion.”
BackgroundStudy of the Genetic Etiology of Primary Ovarian Insufficiency: FMR1 Gene
Barasoain, M., Barrenetxea, G., Huerta, I., Télez, M., Criado, M. B., & Arrieta, I. (2016) · Genes · doi:10.3390/genes7120123 · Cited by 45
“[51], the repeat mutation process is dynamic, with products that continue to mutate within tissues and across generations.”
BackgroundGenerating somatic mosaicism with a Cre recombinase–microsatellite sequence transgene
Akyol, A., Hinoi, T., Feng, Y., Bommer, G. T., Glaser, T. M., & Fearon, E. R. (2008) · Nature Methods · doi:10.1038/nmeth.1182 · Cited by 42
Mrc1, Tof1 and Csm3 inhibit CAG·CTG repeat instability by at least two mechanisms
Razidlo, D. F., & Lahue, R. S. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.01.009 · Cited by 42
“These findings are entirely consistent with the structure-forming requirement of pathogenic TNRs as a major part of accepted models of instability [1,2].”
BackgroundMethodResultInfluentialMéndez-Bermúdez, A., Hills, M., Pickett, H. A., Phan, A. T., Mergny, J., Riou, J., & Royle, N. J. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp629 · Cited by 44
“Telomeric DNA sequences are tandem repeat arrays that share some properties with other microsatellite or simple tandem repeat (STRs) sequences (e.g. di-, tri-, tetra- and penta-nucleotide repeat arrays) within the human genome.”
BackgroundInfluentialThe distribution of microsatellites in the Nasonia parasitoid wasp genome
Pannebakker, B. A., Niehuis, O., Hedley, A., Gadau, J., & Shuker, D. M. (2010) · Insect Molecular Biology · doi:10.1111/j.1365-2583.2009.00915.x · Cited by 41
“Moreover, microsatellite loci have also been implicated in a number of human diseases, including several cancers (Ashley & Warren, 1995; Oda et al., 2005; Pearson et al., 2005), with disease associated with microsatellite expansion or instability.”
BackgroundThe hidden side of unstable DNA repeats: Mutagenesis at a distance
Shah, K., & Mirkin, S. M. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.04.020 · Cited by 42
“[3–5]).”
Viterbo, D., Michoud, G., Mosbach, V., Dujon, B., & Richard, G. (2016) · DNA repair · doi:10.1016/j.dnarep.2016.03.002 · Cited by 39
“Trinucleotide repeat expansions are involved in more than two dozen human neurological disorders [1,2].”
BackgroundTomé, S., Dandelot, E., Dogan, C., Bertrand, A., Geneviève, D., Péréon, Y., DM contraction study group, Simon, M., Bonnefont, J., Bassez, G., et al. (2018) · Human Mutation · doi:10.1002/humu.23531 · Cited by 45
Konopka, A., & Atkin, J. D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103137 · Cited by 41
“The ability of nucleic acids to form unusual secondary structures is also related to the instability of repeat sequences [126].”
BackgroundA game of hide and seq: Identification of parallel Y-STR evolution in deep-rooting pedigrees
Claerhout, S., der Haegen, M. V., Vangeel, L., Larmuseau, M., & Decorte, R. (2018) · European Journal of Human Genetics · doi:10.1038/s41431-018-0312-2 · Cited by 41
Maternal germline-specific effect of DNA ligase I on CTG/CAG instability
Tomé, S., Panigrahi, G. B., Castel, A. L., Foiry, L., Melton, D. W., Gourdon, G., & Pearson, C. E. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr099 · Cited by 44
“A role for DNA replication, repair or recombination has been proposed to contribute to repeat expansion (1,9).”
BackgroundHydrostatic pressure prevents chondrocyte differentiation through heterochromatin remodeling
Maki, K., Nava, M. M., Villeneuve, C., Chang, M., Furukawa, K. S., Ushida, T., & Wickström, S. A. (2020) · Journal of Cell Science · doi:10.1242/jcs.247643 · Cited by 38
“A possible explanation of this predisposition of heterochromatin to replication stress could stem from the higher repeat content of heterochromatic regions, resulting in stable secondary structures inhibitory to fork progression (Branzei and Foiani, 2010; Pearson et al., 2005; Zhao et al., 2010) that require additiona…”
BackgroundSequencing technologies and tools for short tandem repeat variation detection
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“The length variability of STRs is phenotypic variation in many species, exemplified by (cid:2) 40 genetic diseases in humans and a handful of disorders in other species [2–9]. disorders are commonly caused by repeat expansion.”
BackgroundIennaco, R., Formenti, G., Trovesi, C., Rossi, R. L., Zuccato, C., Lischetti, T., Bocchi, V. D., Scolz, A., Martínez‐Labarga, C., Rickards, O., et al. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-021-00914-9 · Cited by 42
Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae
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“Failure to maintain genome stability is associated with a large variety of diseases, including not only sporadic and inherited cancers but also several neurological, neurodegenerative, neuromuscular, and aging disorders (Hanahan and Weinberg, 2000; Hasty et al., 2003; Pearson et al., 2005).”
Molecular therapy in myotonic dystrophy: focus on RNA gain-of-function
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“Repetitive sequences have a higher propensity to form non-B DNA structures and can promote the formation of DNA nicks, DSBs or stall replication forks inducing chromosomal rearrangements (38,39).”
BackgroundMartins, S., Pearson, C. E., Coutinho, P., Provost, S., Amorim, A., Dubé, M., Sequeiros, J., & Rouleau, G. A. (2014) · Human Genetics · doi:10.1007/s00439-014-1467-8 · Cited by 38
“, an earlier age-of-onset and increased disease severity in successive generations (Pearson et al. 2005).”
BackgroundTranscription-induced DNA toxicity at trinucleotide repeats
Lin, Y., & Wilson, J. H. (2011) · Cell Cycle · doi:10.4161/cc.10.4.14729 · Cited by 41
Derivation, culture, and characterization of VUB hESC lines
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Population Genetics of Plasmodium vivax in Four Rural Communities in Central Vietnam
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Reduced Penetrance in a Brazilian Family With Spinocerebellar Ataxia Type 10
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“However, the unusual stability of the approximately 850-repeat allele in our described family through 3 generations is compatible with highly interrupted repeat sequences because it is well established that interrupted repeats are more stable than uninterrupted repeats for most microsatellite repeats.(10) Our data for…”
BackgroundMcGinty, R. J., Rubinstein, R. G., Neil, A. J., Dominska, M., Kiktev, D. A., Petes, T. D., & Mirkin, S. M. (2017) · Genome Research · doi:10.1101/gr.228148.117 · Cited by 39
“A par-ticularclass of repetitive sequences called trinucleotide repeats was implicated in hereditary human diseases known as repeat-expan-sion diseases, such as Huntington ’ s disease, fragile X syndrome, and Friedreich ’ s ataxia (Pearson et al. 2005; Mirkin 2007; Orr and Zoghbi 2007).”
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“Several inherited neuromuscular diseases are caused by abnormal expansion of triplet-repeat sequences (1).”
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“TNR expansions often are linked to genetic disorders (Pearson et al., 2005), but consequence of gain or loss of a Ala in the N-terminus of the O.”
BackgroundIs Friedreich ataxia an epigenetic disorder?
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“The basis of the underlying expansion mutation responsible for these disorders is unknown, and problems with DNA replication, recombination and repair have all been suggested as possible mechanisms [6].”
BackgroundInsertions and Deletions (Indels)
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“into two categories, based on molecular events involved in (i) DNA replication or (ii) DNA repair and recombination [28].”
BackgroundDementia and mild cognitive impairment in patients with Parkinson's disease.
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“The process of instability also reveals targets for repeat modulation: DNA replication, DNA repair, and epigenetics all contribute to repeat expansion [13], so a greater understanding of these processes may provide future possibilities to modulate expansion.”
BackgroundCastillo-Lizardo, M., Henneke, G., & Viguera, E. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00403 · Cited by 40
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Genome-wide distribution and organization of microsatellites in six species of birds
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Substrate‐induced DNA strand misalignment during catalytic cycling by DNA polymerase λ
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“…the mechanisms by which simple nucleotide insertion–deletion mutations (‘indels’) are avoided, such as those occurring at microbial contingency loci (Moxon et al, 2006) or those that mutate genes relevant to survival, cancer (Peltomaki, 2003) or degenerative diseases (Pearson et al, 2005).”
BackgroundPolyglutamine Repeats Are Associated to Specific Sequence Biases That Are Conserved among Eukaryotes
Ramazzotti, M., Monsellier, É., Kamoun, C., Degl’Innocenti, D., & Melki, R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030824 · Cited by 35
“its propensity to expand or not during replication [49,51,52].”
BackgroundEimer, H., Sureshkumar, S., Yadav, A. S., Kraupner-Taylor, C. A., Bandaranayake, C., Seleznev, A., Thomason, T., Fletcher, S. J., Gordon, S. F., Carroll, B. S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.044 · Cited by 34
“Disease-associated repeat expansions can be found both in coding and non-coding regions of the affected genes (Gatchel and Zoghbi, 2005; Pearson et al., 2005).”
InfluentialLi, J., Nakamori, M., Matsumoto, J., Murata, A., Dohno, C., Kiliszek, A., Taylor, K., Sobczak, K., & Nakatani, K. (2018) · Chemistry - A European Journal · doi:10.1002/chem.201804368 · Cited by 35
Targeting translesion synthesis (TLS) to expose replication gaps, a unique cancer vulnerability
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“These sites are considered to be difficult to replicate, causing arrest of replication forks or even fork breakage [30–35].”
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Epigenetic changes and non-coding expanded repeats
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“When these mutations were initially discovered it quickly became apparent that they exhibit an unprecedented degree of genetic instability (reviewed by Pearson et al. (2005)).”
BackgroundEnfermedades raras, un paradigma emergente en la medicina del siglo XXI
Palau, F. (2009) · Medicina Clínica · doi:10.1016/j.medcli.2009.06.038 · Cited by 35
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“TNR expansion is associated with more than 40 neurodegenerative diseases such as Huntington’s disease (21,28,29).”
BackgroundGenome-wide scan for analysis of simple and imperfect microsatellites in diverse carlaviruses
Alam, C. M., Singh, A. K., Sharfuddin, C., & Ali, S. (2013) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2013.11.018 · Cited by 34
A genome-wide view of mutation rate co-variation using multivariate analyses
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“Notably, while a number of studies have documented regional variation and co-variation of rates of mutations of several types, they have mostly relied on correlation and univariate regression analyses, which relate mutation rates only in a pair-wise fashion, and attempt to explain their variation (as a function of gen…”
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Metadata
- Authors
- Pearson, C. E., Edamura, K. N., & Cleary, J. D.
- Affiliations
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Corresponding author
- Pearson, Christopher E.
- Venue
- Nature Reviews Genetics
- Published
- 2005-10
- Volume
- 6
- Issue
- 10
- Pages
- 729-742
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W2087505473
- Cited by
- 924
- References
- 157
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 45 · 2023: 29 · 2022: 25 · 2021: 54 · 2020: 27 · 2019: 38 · 2018: 53 · 2017: 45 · 2016: 58 · 2015: 41 · 2014: 55 · 2013: 46 · 2012: 56
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- repeat instability, dynamic mutation, trinucleotide repeat disorders, neurodegenerative diseases, neuromuscular disorders, cis-regulatory elements, trans-acting proteins, DNA replication, DNA repair, DNA recombination, DNA secondary structure
- MeSH terms
- DNA Repair, DNA Replication, Humans, Models, Genetic, Mutation, Recombination, Genetic, Trinucleotide Repeat Expansion, Heredodegenerative Disorders, Nervous System, DNA Repeat Expansion, Genomic Instability
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