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STRs: Ancient Architectures of the Genome beyond the Sequence

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Abstract

Short tandem repeats (STRs) are commonly defined as short runs of repetitive nucleotides, consisting of tandemly repeating 2–6- bp motif units, which are ubiquitously distributed throughout genomes. Functional STRs are polymorphic in the population, and their variations influence gene expression, which subsequently may result in pathogenic phenotypes. To understand STR phenotypic effects and their functional roles, we describe four different mutational mechanisms including the unequal crossing-over model, gene conversion, retrotransposition mechanism and replication slippage. Due to the multi-allelic nature, small length, abundance, high variability, codominant inheritance, nearly neutral evolution, extensive genome coverage and simple assaying of STRs, these markers are widely used in various types of biological research, including population genetics studies, genome mapping, molecular epidemiology, paternity analysis and gene flow studies. In this review, we focus on the current knowledge regarding STR genomic distribution, function, mutation and applications.

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The data sets generated and/or analyzed during the study are available from the corresponding author on reasonable request.

References

  • Abdul-Muneer P (2014) Application of microsatellite markers in conservation genetics and fisheries management: recent advances in population structure analysis and conservation strategies. Genetics Research International

  • Abuín M, Martínez P, Sánchez L (1996) Localization of the repetitive telomeric sequence (TTAGGG) n in four salmonid species. Genome 39:1035–1038

    Article  PubMed  Google Scholar 

  • Albanèse V, Biguet NF, Kiefer H, Bayard E, Mallet J, Meloni R (2001) Quantitative effects on gene silencing by allelic variation at a tetranucleotide microsatellite. Hum Mol Genet 10:1785–1792

    Article  PubMed  Google Scholar 

  • Aranda A, Pérez-Ortín JE, Benham CJ, del Olmo ML (1997) Analysis of the structure of a natural alternating d (TA) n sequence in yeast chromatin. Yeast 13:313–326

    Article  CAS  PubMed  Google Scholar 

  • Bagshaw AT (2017) Functional mechanisms of microsatellite DNA in eukaryotic genomes. Genome Biol Evol 9:2428–2443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bahlo M, Bennett MF, Degorski P, Tankard RM, Delatycki MB, Lockhart PJ (2018) Recent advances in the detection of repeat expansions with short-read next-generation sequencing. F1000Research, 7

  • Bapat BV, Madlensky L, Temple LK, Hiruki T, Redston M, Baron DL, Xia L, Marcus VA, Soravia C, Mitri A (1999) Family history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer. Hum Genet 104:167–176

    Article  CAS  PubMed  Google Scholar 

  • Bauer P, Laccone F, Rolfs A, Wüllner U, Bösch S, Peters H, Liebscher S, Scheible M, Epplen J, Weber BH (2004) Trinucleotide repeat expansion in SCA17/TBP in white patients with Huntington’s disease-like phenotype. J Med Genet 41:230–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bayele HK, Peyssonnaux C, Giatromanolaki A, Arrais-Silva WW, Mohamed HS, Collins H, Giorgio S, Koukourakis M, Johnson RS, Blackwell JM (2007) HIF-1 regulates heritable variation and allele expression phenotypes of the macrophage immune response gene SLC11A1 from a Z-DNA–forming microsatellite. Blood 110:3039–3048

    Article  CAS  PubMed  Google Scholar 

  • Behnke JM, Iraqi F, Menge D, Baker R, Gibson J, Wakelin D (2003) Chasing the genes that control resistance to gastrointestinal nematodes. J Helminthol 77:99–109

    Article  CAS  PubMed  Google Scholar 

  • Bell GI, Jurka J (1997) The length distribution of perfect dimer repetitive DNA is consistent with its evolution by an unbiased single-step mutation process. J Mol Evol 44:414–421

    Article  CAS  PubMed  Google Scholar 

  • Benham CJ (1996) Duplex destabilization in superhelical DNA is predicted to occur at specific transcriptional regulatory regions. J Mol Biol 255:425–434

    Article  CAS  PubMed  Google Scholar 

  • Bettencourt C, Santos C, Montiel R, Do Carmo Costa M, Cruz-Morales P, Santos LR, Simões N, Kay T, Vasconcelos J, Maciel P (2010) Increased transcript diversity: novel splicing variants of Machado-Joseph Disease gene (ATXN3). Neurogenetics 11:193–202

    Article  CAS  PubMed  Google Scholar 

  • Biet E, Sun J-S, Dutreix M (1999) Conserved sequence preference in DNA binding among recombination proteins: an effect of ssDNA secondary structure. Nucleic Acids Res 27:596–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brinkmann B, Meyer E, Junge A (1996) Complex mutational events at the HumD21S11 locus. Hum Genet 98:60–64

    Article  CAS  PubMed  Google Scholar 

  • Brown LY, Brown SA (2004) Alanine tracts: the expanding story of human illness and trinucleotide repeats. Trends Genet 20:51–58

    Article  CAS  PubMed  Google Scholar 

  • Calkhoven CF, Bouwman PR, Snippe L (1994) Translation start site multiplicity of the CCAAT/enhancer binding protein α mRNA is dictated by a small 5′ open reading frame. Nucleic Acids Res 22:5540–5547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canapa A, Cerioni PN, Barucca M, Olmo E, Caputo V (2002) A centromeric satellite DNA may be involved in heterochromatin compactness in gobiid fishes. Chromosome Res 10:297–304

    Article  CAS  PubMed  Google Scholar 

  • Cen Z, Jiang Z, Chen Y, Zheng X, Xie F, Yang X, Lu X, Ouyang Z, Wu H, Chen S (2018) Intronic pentanucleotide TTTCA repeat insertion in the SAMD12 gene causes familial cortical myoclonic tremor with epilepsy type 1. Brain 141:2280–2288

    Article  PubMed  Google Scholar 

  • Chastain PD, Sinden RR (1998) CTG repeats associated with human genetic disease are inherently flexible. J Mol Biol 275:405–411

    Article  CAS  PubMed  Google Scholar 

  • Chen CM, Sio CP, Lu YL, Chang HT, Hu CH, Pai TW (2014) Identification of conserved and polymorphic STRs for personal genomes. BMC Genomics 15:S3

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen CM, Hou YT, Liu JY, Wu YR, Lin CH, Fung HC, Hsu WC, Hsu Y, Lee SH, Hsieh-Li HM (2009) PPP2R2B CAG repeat length in the Han Chinese in Taiwan: association analyses in neurological and psychiatric disorders and potential functional implications. Am J Med Genet B Neuropsychiatr Genet 150:124–129

    Article  CAS  Google Scholar 

  • Chen HY, Ma SL, Huang W, Ji L, Leung VH, Jiang H, Yao X, Tang NL (2016) The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model. Sci Rep 6:38225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen TM, Kuo PL, Hsu CH, Tsai SJ, Chen MJ, Lin CW, Sun HS (2007) Microsatellite in the 3′ untranslated region of human fibroblast growth factor 9 (FGF9) gene exhibits pleiotropic effect on modulating FGF9 protein expression. Hum Mutat 28:98–98

    Article  PubMed  Google Scholar 

  • Chen X, Temnykh S, Xu Y, Cho Y, McCouch S (1997) Development of a microsatellite framework map providing genome-wide coverage in rice (Oryza sativa L.). Theor Appl Genet 95:553–567

    Article  CAS  Google Scholar 

  • Chen Y, Roxby R (1997) Identification of a functional CT-element in the Phytophthora infestanspiypt1 gene promoter. Gene 198:159–164

    Article  CAS  PubMed  Google Scholar 

  • Chistiakov DA, Hellemans B, Volckaert FA (2006) Microsatellites and their genomic distribution, evolution, function and applications: a review with special reference to fish genetics. Aquaculture 255:1–29

    Article  CAS  Google Scholar 

  • Choi K, Zhao X, Kelly KA, Venn O, Higgins JD, Yelina NE, Hardcastle TJ, Ziolkowski PA, Copenhaver GP, Franklin FCH (2013) Arabidopsis meiotic crossover hot spots overlap with H2A. Z nucleosomes at gene promoters. Nat Gen 45:1327

  • Colak D, Zaninovic N, Cohen MS, Rosenwaks Z, Yang WY, Gerhardt J, Disney MD, Jaffrey SR (2014) Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome. Science (New York, NY) 343:1002

    Article  CAS  Google Scholar 

  • Consortium IHGS (2001) Initial sequencing and analysis of the human genome. Nature 409:860

  • Contente A, Dittmer A, Koch MC, Roth J, Dobbelstein M (2002) A polymorphic microsatellite that mediates induction of PIG3 by p53. Nat Genet 30:315

    Article  PubMed  Google Scholar 

  • Cuppens H, Lin W, Jaspers M, Costes B, Teng H, Vankeerberghen A, Jorissen M, Droogmans G, Reynaert I, Goossens M (1998) Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg) m locus explains the partial penetrance of the T5 polymorphism as a disease mutation. J Clin Investig 101:487–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dashnow H, Lek M, Phipson B, Halman A, Sadedin S, Lonsdale A, Davis M, Lamont P, Clayton JS, Laing NG (2018) STRetch: detecting and discovering pathogenic short tandem repeat expansions. Genome Biol 19:121

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Deelen W, Bakker C, Halley DJ, Oostra BA (1994) Conservation of CGG region in FMR1 gene in mammals. Am J Med Genet 51:513–516

    Article  CAS  PubMed  Google Scholar 

  • Dib C, Fauré S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Kazan J, Seboun E (1996) A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 380:152

    Article  CAS  PubMed  Google Scholar 

  • Dokholyan NV, Buldyrev SV, Havlin S, Stanley HE (2000) Distributions of dimeric tandem repeats in non-coding and coding DNA sequences. J Theor Biol 202:273–282

    Article  CAS  PubMed  Google Scholar 

  • Drinan DP, Kalinowski ST, Vu NV, Shepard BB, Muhlfeld CC, Campbell MR (2011) Genetic variation in westslope cutthroat trout Oncorhynchus clarkii lewisi: implications for conservation. Conserv Genet 12:1513–1523

    Article  Google Scholar 

  • Dumbovic G, Forcales S-V, Perucho M (2017) Emerging roles of macrosatellite repeats in genome organization and disease development. Epigenetics 12:515–526

    Article  PubMed  PubMed Central  Google Scholar 

  • Ejima Y, Yang L, Sasaki MS (2000) Aberrant splicing of the ATM gene associated with shortening of the intronic mononucleotide tract in human colon tumor cell lines: a novel mutation target of microsatellite instability. Int J Cancer 86:262–268

    Article  CAS  PubMed  Google Scholar 

  • Ellegren H (2004) Microsatellites: simple sequences with complex evolution. Nat Rev Genet 5:435

    Article  CAS  PubMed  Google Scholar 

  • Estoup A, Presa P, Krieg F, Vaiman D, Guyomard R (1993) n and (GT) n microsatellites: a new class of genetic markers for Salmo trutta L.(brown trout). Heredity. 71:488

  • Fan H, Chu J-Y (2007) A brief review of short tandem repeat mutation. Genomics Proteomics Bioinformatics 5:7–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faruq M, Srivastava AK, Singh S, Gupta R, Dada T, Garg A, Behari M, Mukerji M (2015) Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population. Indian J Med Res 141:187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fornoni A, Wang Y, Lenz O, Striker LJ, Striker GE (2002) Association of a decreased number of d (CA) repeats in the matrix metalloproteinase-9 promoter with glomerulosclerosis susceptibility in mice. J Am Soc Nephrol 13:2068–2076

    Article  CAS  PubMed  Google Scholar 

  • Frolov A, Liles JS, Kossenkov AV, Tzeng C-WD, Jhala N, Kulesza P, Varadarajulu S, Eloubeidi M, Heslin MJ, Arnoletti JP (2010) Epidermal growth factor receptor (EGFR) intron 1 polymorphism and clinical outcome in pancreatic adenocarcinoma. Am J Surg 200:398–405

    Article  CAS  PubMed  Google Scholar 

  • Fuda NJ, Guertin MJ, Sharma S, Danko CG, Martins AL, Siepel A, Lis JT (2015) GAGA factor maintains nucleosome-free regions and has a role in RNA polymerase II recruitment to promoters. PLoS Genet 11:e1005108

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fukuda K, Ichiyanagi K, Yamada Y, Go Y, Udono T, Wada S, Maeda T, Soejima H, Saitou N, Ito T (2013) Regional DNA methylation differences between humans and chimpanzees are associated with genetic changes, transcriptional divergence and disease genes. J Hum Genet 58:446

    Article  CAS  PubMed  Google Scholar 

  • Gaĭtskoki V, Patkin E (2000) Satellite DNA and disease–possible mechanisms. Trinucleotide Repeats Genetika 36:869–886

    PubMed  Google Scholar 

  • Gatchel JR, Zoghbi HY (2005) Diseases of unstable repeat expansion: mechanisms and common principles. Nat Rev Genet 6:743

    Article  CAS  PubMed  Google Scholar 

  • Gemayel R, Vinces MD, Legendre M, Verstrepen KJ (2010) Variable tandem repeats accelerate evolution of coding and regulatory sequences. Annu Rev Genet 44:445–477

    Article  CAS  PubMed  Google Scholar 

  • Gendrel C-G, Boulet A, Dutreix M (2000) (CA/GT) n microsatellites affect homologous recombination during yeast meiosis. Genes Dev 14:1261–1268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Groh M, Silva LM, Gromak N (2014) Mechanisms of transcriptional dysregulation in repeat expansion disorders. Biochem Soc Trans 42:1123–1128

    Article  CAS  PubMed  Google Scholar 

  • Hänsel-Hertsch R, Beraldi D, Lensing SV, Marsico G, Zyner K, Parry A, di Antonio M, Pike J, Kimura H, Narita M (2016) G-quadruplex structures mark human regulatory chromatin. Nat Genet 48:1267

    Article  PubMed  CAS  Google Scholar 

  • Hardy OJ, Charbonnel N, Fréville H, Heuertz M (2003) Microsatellite allele sizes: a simple test to assess their significance on genetic differentiation. Genetics 163:1467–1482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herbinger CM, Doyle RW, Pitman ER, Paquet D, Mesa KA, Morris DB, Wright JM, Cook D (1995) DNA fingerprint based analysis of paternal and maternal effects on offspring growth and survival in communally reared rainbow trout. Aquaculture 137:245–256

    Article  Google Scholar 

  • Ho PS, Ellison MJ, Quigley GJ, Rich A (1986) A computer aided thermodynamic approach for predicting the formation of Z-DNA in naturally occurring sequences. EMBO J 5:2737–2744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hodel RG, Segovia-Salcedo MC, Landis JB, Crowl AA, Sun M, Liu X, Gitzendanner MA, Douglas NA, Germain-Aubrey CC, Chen S (2016) The report of my death was an exaggeration: a review for researchers using microsatellites in the 21st century. Appl Plant Sci 4:1600025

    Article  Google Scholar 

  • Huang QY, Xu FH, Shen H, Deng HY, Liu YJ, Liu YZ, Li JL, Recker RR, Deng HW (2002) Mutation patterns at dinucleotide microsatellite loci in humans. The American Journal of Human Genetics 70:625–634

    Article  CAS  PubMed  Google Scholar 

  • Hui J, Stangl K, Lane WS, Bindereif A (2003) HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats. Nat Struct Mol Biol 10:33

    Article  CAS  Google Scholar 

  • Iyer V, Struhl K (1995) Poly (dA: dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. EMBO J 14:2570–2579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jasinska A, Michlewski G, de Mezer M, Sobczak K, Kozlowski P, Napierala M, Krzyzosiak WJ (2003) Structures of trinucleotide repeats in human transcripts and their functional implications. Nucleic Acids Res 31:5463–5468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jenkins BG, Andreassen OA, Dedeoglu A, Leavitt B, Hayden M, Borchelt D, Ross CA, Ferrante RJ, Beal MF (2005) Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington’s disease. J Neurochem 95:553–562

    Article  CAS  PubMed  Google Scholar 

  • Jiang B, Yap MK, Leung KH, Ng PW, Fung WY, Lam WW, Gu Y-S, Yip SP (2011) PAX6 haplotypes are associated with high myopia in Han Chinese. PLoS One 6:e19587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jobling MA, Hurles M, Tyler-Smith C (2013) Human evolutionary genetics: origins, peoples and disease. Garland Science

  • Jodice C, Mantuano E, Veneziano L, Trettel F, Sabbadini G, Calandriello L, Francia A, Spadaro M, Pierelli F, Salvi F (1997) Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p. Hum Mol Genet 6:1973–1978

    Article  CAS  PubMed  Google Scholar 

  • Karakousis A, Barr AR, Chalmers KJ, Ablett GA, Holton TA, Henry RJ, Lim P, Langridge P (2003) Potential of SSR markers for plant breeding and variety identification in Australian barley germplasm. Aust J Agric Res 54:1197–1210

    Article  CAS  Google Scholar 

  • Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M, Tohyama J, Akasaka N, Hayasaka K (2007) A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome). Am J Hum Genet 81:361–366

    Article  CAS  PubMed  Google Scholar 

  • Koob MD, Moseley ML, Schut LJ, Benzow KA, Bird TD, Day JW, Ranum LP (1999) An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 21:379

    Article  CAS  PubMed  Google Scholar 

  • Kramer M, Sponholz C, Slaba M, Wissuwa B, Claus RA, Menzel U, Huse K, Platzer M, Bauer M (2013) Alternative 5’untranslated regions are involved in expression regulation of human heme oxygenase-1. PLoS One 8:e77224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar RP, Krishnan J, Singh NP, Singh L, Mishra RK (2013) GATA simple sequence repeats function as enhancer blocker boundaries. Nat Commun 4:1844

    Article  PubMed  CAS  Google Scholar 

  • Li Y-C, Korol AB, Fahima T, Nevo E (2004) Microsatellites within genes: structure, function, and evolution. Mol Biol Evol 21:991–1007

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Seidel K, Marschall P, Klein M, Hope A, Schacherl J, Schmitz J, Menk M, Schefe JH, Reinemund J (2012) A polymorphic microsatellite repeat within the ECE-1c promoter is involved in transcriptional start site determination, human evolution, and Alzheimer’s disease. J Neurosci 32:16807–16820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li YC, Korol AB, Fahima T, Beiles A, Nevo E (2002) Microsatellites: genomic distribution, putative functions and mutational mechanisms: a review. Mol Ecol 11:2453–2465

    Article  CAS  PubMed  Google Scholar 

  • Lin JX, Ishikawa K, Sakamoto M, Tsunemi T, Ishiguro T, Amino T, Toru S, Kondo I, Mizusawa H (2008) Direct and accurate measurement of CAG repeat configuration in the ataxin-1 (ATXN-1) gene by “dual-fluorescence labeled PCR-restriction fragment length analysis.” J Hum Genet 53:287

    Article  CAS  PubMed  Google Scholar 

  • Liquori CL, Ricker K, Moseley ML, Jacobsen JF, Kress W, Naylor SL, Day JW, Ranum LP (2001) Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 293:864–867

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Mulholland N, Fu H, Zhao K (2006) Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling. Mol Cell Biol 26:2550–2559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Q, Teare JM, Granok H, Swede MJ, Xu J, Elgin SC (2003) The capacity to form H-DNA cannot substitute for GAGA factor binding to a (CT) n·(GA) n regulatory site. Nucleic Acids Res 31:2483–2494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma J, Defrances MC, Zou C, Johnson C, Ferrell R, Zarnegar R (2009) Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer. J Clin Investig 119:478–491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin P, Makepeace K, Hill SA, Hood DW, Moxon ER (2005) Microsatellite instability regulates transcription factor binding and gene expression. Proc Natl Acad Sci 102:3800–3804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matilla-Duenas A (2012) The ever expanding spinocerebellar ataxias. Editorial the Cerebellum 11:821–827

    Article  PubMed  Google Scholar 

  • Mcmurray CT (1995) Mechanisms of DNA expansion. Chromosoma 104:2–13

    CAS  PubMed  Google Scholar 

  • McNeil JA, Smith KP, Hall LL, Lawrence JB (2006) Word frequency analysis reveals enrichment of dinucleotide repeats on the human X chromosome and [GATA] n in the X escape region. Genome Res 16:477–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Messier W, Li SH, Stewart C-B (1996) The birth of microsatellites. Nature 381:483

    Article  CAS  PubMed  Google Scholar 

  • Metzgar D, Bytof J, Wills C (2000) Selection against frameshift mutations limits microsatellite expansion in coding DNA. Genome Res 10:72–80

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mirkin SM (2008) Discovery of alternative DNA structures: a heroic decade (1979–1989). Front Biosci 13:1064–1071

    Article  CAS  PubMed  Google Scholar 

  • Muneer PA, Gopalakrishnan A, Musammilu K, Basheer V, Mohindra V, Lal K, Padmakumar K, Ponniah A (2012) Comparative assessment of genetic variability in the populations of endemic and endangered Yellow Catfish, Horabagrus brachysoma (Teleostei: Horabagridae), based on allozyme, RAPD, and microsatellite markers. Biochem Genet 50:192–212

    Article  PubMed  CAS  Google Scholar 

  • Muneer PA, Gopalakrishnan A, Musammilu K, Mohindra V, Lal KK, Basheer V, Lakra W (2009) Genetic variation and population structure of endemic yellow catfish, Horabagrusbrachysoma (Bagridae) among three populations of Western Ghat region using RAPD and microsatellite markers. Mol Biol Rep 36:1779–1791

    Article  PubMed  CAS  Google Scholar 

  • Murat P, Balasubramanian S (2014) Existence and consequences of G-quadruplex structures in DNA. Curr Opin Genet Dev 25:22–29

    Article  CAS  PubMed  Google Scholar 

  • Nadir E, Margalit H, Gallily T, Ben-Sasson SA (1996) Microsatellite spreading in the human genome: evolutionary mechanisms and structural implications. Proc Natl Acad Sci 93:6470–6475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakano M, Okumura N, Nakagawa H, Koizumi N, Ikeda Y, Ueno M, Yoshii K, Adachi H, Aleff RA, Butz ML (2015) Trinucleotide repeat expansion in the TCF4 gene in Fuchs’ endothelial corneal dystrophy in Japanese. Invest Ophthalmol Vis Sci 56:4865–4869

    Article  CAS  PubMed  Google Scholar 

  • Nelson HC, Finch JT, Luisi BF, Klug A (1987) The structure of an oligo (dA)· oligo (dT) tract and its biological implications. Nature 330:221

    Article  CAS  PubMed  Google Scholar 

  • Ng TK, Lam CY, Lam DSC, Chiang SWY, Tam POS, Wang DY, Fan BJ, Yam GH-F, Fan DSP, Pang CP (2009) AC and AG dinucleotide repeats in the PAX6 P1 promoter are associated with high myopia. Mol Vis 15:2239

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nikitina T, Nazarenko S (2004) Human microsatellites: mutation and evolution. Russ J Genet 40:1065–1079

    Article  CAS  Google Scholar 

  • Nikkhah M, Rezazadeh M, Khorshid HK, Biglarian A, Ohadi M (2016) An exceptionally long CA-repeat in the core promoter of SCGB2B2 links with the evolution of apes and Old World monkeys. Gene 576:109–114

    Article  CAS  PubMed  Google Scholar 

  • Obayashi M, Stevanin G, Synofzik M, Monin M-L, Duyckaerts C, Sato N, Streichenberger N, Vighetto A, Desestret V, Tesson C (2015) Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion. J Neurol Neurosurg Psychiatry 86:986–995

    Article  PubMed  Google Scholar 

  • Ogloblina A, Bannikova V, Khristich A, Oretskaya T, Yakubovskaya M, Dolinnaya N (2015) Parallel G-quadruplexes formed by guanine-rich microsatellite repeats inhibit human topoisomerase I. Biochem Mosc 80:1026–1038

    Article  CAS  Google Scholar 

  • Ohadi M, Valipour E, Ghadimi-Haddadan S, Namdar-Aligoodarzi P, Bagheri A, Kowsari A, Rezazadeh M, Darvish H, Kazeminasab S (2015) Core promoter short tandem repeats as evolutionary switch codes for primate speciation. Am J Primatol 77:34–43

    Article  CAS  PubMed  Google Scholar 

  • Okuda H, Kajii E (2002) The evolution and formation of RH genes. Leg Med 4:139–155

    Article  CAS  Google Scholar 

  • Okuda H, Suganuma H, Kamesaki T, Kumada M, Tsudo N, Omi T, Iwamoto S, Kajii E (2000) The analysis of nucleotide substitutions, gaps, and recombination events between RHD and RHCE genes through complete sequencing. Biochem Biophys Res Commun 274:670–683

    Article  CAS  PubMed  Google Scholar 

  • Oliveira EJ, Pádua JG, Zucchi MI, Vencovsky R, Vieira MLC (2006) Origin, evolution and genome distribution of microsatellites. Genet Mol Biol 29:294–307

    Article  CAS  Google Scholar 

  • Orr HT, Zoghbi HY (2007) Trinucleotide repeat disorders. Annu Rev Neurosci 30:575–621

    Article  CAS  PubMed  Google Scholar 

  • Ouyang Q, Zhao X, Feng H, Tian Y, Li D, Li M, Tan Z (2012) High GC content of simple sequence repeats in Herpes simplex virus type 1 genome. Gene 499:37–40

    Article  CAS  PubMed  Google Scholar 

  • Paetkau D (1999) Microsatellites obtained using strand extension: an enrichment protocol. Biotechniques 26:690–697

    Article  CAS  PubMed  Google Scholar 

  • Palsbøll PJ, Bérubé M, Jørgensen H (1999) Multiple levels of single-strand slippage at cetacean tri-and tetranucleotide repeat microsatellite loci. Genetics 151:285–296

    Article  PubMed  PubMed Central  Google Scholar 

  • Palumbo SL, Memmott RM, Uribe DJ, Krotova-Khan Y, Hurley LH, Ebbinghaus SW (2008) A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity. Nucleic Acids Res 36:1755–1769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panyutin I, Kovalsky O, Budowsky E (1989) Magnesium-dependent supercoiling-induced transition in (dG) n·(dC) n stretches and formation of a new G-structure by (dG) n strand. Nucleic Acids Res 17:8257–8271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pathak R, Mamillapalli A, Rangaraj N, Kumar R, Vasanthi D, Mishra K, Mishra RK (2013) AAGAG repeat RNA is an essential component of nuclear matrix in Drosophila. RNA Biol 10:564–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pearson CE, Edamura KN, Cleary JD (2005) Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet 6:729

    Article  CAS  PubMed  Google Scholar 

  • Potaman V, Oussatcheva E, Lyubchenko YL, Shlyakhtenko L, Bidichandani S, Ashizawa T, Sinden R (2004) Length-dependent structure formation in Friedreich ataxia (GAA) n·(TTC) n repeats at neutral pH. Nucleic Acids Res 32:1224–1231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Presneau N, Manderson EN, Tonin PN (2003) The quest for a tumor suppressor gene phenotype. Curr Mol Med 3:605–629

    Article  CAS  PubMed  Google Scholar 

  • Pupko T, Graur D (1999) Evolution of microsatellites in the yeast Saccharomyces cerevisiae: role of length and number of repeated units. J Mol Evol 48:313–316

    Article  CAS  PubMed  Google Scholar 

  • Quilez J, Guilmatre A, Garg P, Highnam G, Gymrek M, Erlich Y, Joshi RS, Mittelman D, Sharp AJ (2016) Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans. Nucleic Acids Res 44:3750–3762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reif A, Kiive E, Kurrikoff T, Paaver M, Herterich S, Konstabel K, Tulviste T, Lesch K-P, Harro J (2011) A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional impulsivity. Psychopharmacology 214:239–248

    Article  CAS  PubMed  Google Scholar 

  • Rezazadeh M, Gharesouran J, Mirabzadeh A, Khorshid HK, Biglarian A, Ohadi M (2015a) A primate-specific functional GTTT-repeat in the core promoter of CYTH4 is linked to bipolar disorder in human. Prog Neuropsychopharmacol Biol Psychiatry 56:161–167

    Article  CAS  PubMed  Google Scholar 

  • Rezazadeh M, Gharesouran J, Movafagh A, Taheri M, Darvish H, Emamalizadeh B, Shahmohammadibeni N, Khorshid HK, Behmanesh M, Sahraian M (2015b) Dominant and protective role of the CYTH4 primate-specific GTTT-repeat longer alleles against neurodegeneration. J Mol Neurosci 56:593–596

    Article  CAS  PubMed  Google Scholar 

  • Rife T, Rasoul B, Pullen N, Mitchell D, Grathwol K, Kurth J (2009) The effect of a promoter polymorphism on the transcription of nitric oxide synthase 1 and its relevance to Parkinson’s disease. J Neurosci Res 87:2319–2325

    Article  CAS  PubMed  Google Scholar 

  • Robinson DO, Hammans SR, Read SP, Sillibourne J (2005) Oculopharyngeal muscular dystrophy (OPMD): analysis of the PABPN1 gene expansion sequence in 86 patients reveals 13 different expansion types and further evidence for unequal recombination as the mutational mechanism. Hum Genet 116:267–271

    Article  CAS  PubMed  Google Scholar 

  • Rothenburg S, Koch-Nolte F, Rich A, Haag F (2001) A polymorphic dinucleotide repeat in the rat nucleolin gene forms Z-DNA and inhibits promoter activity. Proc Natl Acad Sci 98:8985–8990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakamoto N, Ohshima K, Montermini L, Pandolfo M, Wells RD (2001) Sticky DNA, a self-associated complex formed at long GAA· TTC repeats in intron 1 of the frataxin gene, inhibits transcription. J Biol Chem 276:27171–27177

    Article  CAS  PubMed  Google Scholar 

  • Sandaltzopolus R, Mitchelmore C, Bonte E, Wal G, Becker PB (1995) Dual regulation of the Drosophilla hsp26 promoter in vitro. Nucleic Acids Res 23:2479–2487

    Article  Google Scholar 

  • Sawaya SM, Bagshaw AT, Buschiazzo E, Gemmell NJ (2012) Promoter microsatellites as modulators of human gene expression. Springer, Tandem Repeat Polymorphisms

    Book  Google Scholar 

  • Schlötterer C (1998) Genome evolution: are microsatellites really simple sequences? Curr Biol 8:R132–R134

    Article  PubMed  Google Scholar 

  • Schneider PM, Bender K, Mayr WR, Parson W, Hoste B, Decorte R, Cordonnier J, Vanek D, Morling N, Karjalainen M (2004) STR analysis of artificially degraded DNA—results of a collaborative European exercise. Forensic Sci Int 139:123–134

    Article  CAS  PubMed  Google Scholar 

  • Searle S, Blackwell JM (1999) Evidence for a functional repeat polymorphism in the promoter of the human NRAMP1 gene that correlates with autoimmune versus infectious disease susceptibility. J Med Genet 36:295–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seixas AI, Loureiro JR, Costa C, Ordóñez-Ugalde A, Marcelino H, Oliveira CL, Loureiro JL, Dhingra A, Brandão E, Cruz VT (2017) A pentanucleotide ATTTC repeat insertion in the non-coding region of DAB1, mapping to SCA37, causes spinocerebellar ataxia. Am J Hum Genet 101:87–103

    Article  CAS  PubMed  Google Scholar 

  • Shamjana U, Bharadwaj T, Grace T (2015) Microsatellites: a versatile marker for genetic/evolutionary/ecological studies. Int J Adv Biol Res 5:86–95

    CAS  Google Scholar 

  • Shilo S, Melamed-Bessudo C, Dorone Y, Barkai N, Levy AA (2015) DNA crossover motifs associated with epigenetic modifications delineate open chromatin regions in Arabidopsis. Plant Cell 27:2427–2436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva AM, Brown JM, Buckle VJ, Wade-Martins R, Lufino MM (2015) Expanded GAA repeats impair FXN gene expression and reposition the FXN locus to the nuclear lamina in single cells. Hum Mol Genet 24:3457–3471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh L, Wadhwa R, Naidu S, Nagaraj R, Ganesan M (1994) Sex-and tissue-specific Bkm (GATA)-binding protein in the germ cells of heterogametic sex. J Biol Chem 269:25321–25327

    Article  CAS  PubMed  Google Scholar 

  • Steinbach P, Gläser D, Vogel W, Wolf M, Schwemmle S (1998) The DMPK gene of severely affected myotonic dystrophy patients is hypermethylated proximal to the largely expanded CTG repeat. Am J Hum Genet 62:278–285

    Article  CAS  PubMed  Google Scholar 

  • Streelman JT, Kocher TD (2002) Microsatellite variation associated with prolactin expression and growth of salt-challenged tilapia. Physiol Genomics 9:1–4

    Article  CAS  PubMed  Google Scholar 

  • Subramanian S, Mishra RK, Singh L (2003a) Genome-wide analysis of Bkm sequences (GATA repeats): predominant association with sex chromosomes and potential role in higher order chromatin organization and function. Bioinformatics 19:681–685

    Article  CAS  PubMed  Google Scholar 

  • Subramanian S, Mishra RK, Singh L (2003b) Genome-wide analysis of microsatellite repeats in humans: their abundance and density in specific genomic regions. Genome Biol 4:R13

    Article  PubMed  PubMed Central  Google Scholar 

  • Tassone F, Beilina A, Carosi C, Albertosi S, Bagni C, Li L, Glover K, Bentley D, Hagerman PJ (2007) Elevated FMR1 mRNA in premutation carriers is due to increased transcription. RNA 13:555–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tee SH, Quek A (2013) Mono-, di-, tri-nucleotide tandem repeats and mutation profile of peptidoglycan stimulated NOD2-encoding Card15. In 2013 IEEE Business Engineering and Industrial Applications Colloquium (BEIAC) (pp. 878-882). IEEE

  • Tóth G, Gáspári Z, Jurka J (2000) Microsatellites in different eukaryotic genomes: survey and analysis. Genome Res 10:967–981

    Article  PubMed  PubMed Central  Google Scholar 

  • Toutenhoofd SL, Garcia F, Zacharias DA, Wilson RA, Strehler EE (1998) Minimum CAG repeat in the human calmodulin-1 gene 5′ untranslated region is required for full expression. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression 1398(3), 315-320

  • Tseng SH, Cheng CY, Huang MZ, Chung MY, Su TS (2013) Modulation of formation of the 3’-end of the human argininosuccinate synthetase mRNA by GT-repeat polymorphism. Int J Biochem Mol Biol 4:179

    PubMed  PubMed Central  Google Scholar 

  • Uhlemann AC, Szleza/k NA, Reinhard V, Tomiuk J, Emmer SA, Lell B, Kremsner PG, Kun JF (2004) DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91phox subunit of NADPH oxidase and mediates protection against severe malaria. J Infect Dis 189:2227–2234

    Article  CAS  PubMed  Google Scholar 

  • Urquhart A, Kimpton C, Downes T, Gill P (1994) Variation in short tandem repeat sequences—a survey of twelve microsatellite loci for use as forensic identification markers. Int J Legal Med 107:13–20

    Article  CAS  PubMed  Google Scholar 

  • Valipour E, Kowsari A, Bayat H, Banan M, Kazeminasab S, Mohammadparast S, Ohadi M (2013) Polymorphic core promoter GA-repeats alter gene expression of the early embryonic developmental genes. Gene 531:175–179

    Article  CAS  PubMed  Google Scholar 

  • van Belkum A, Scherer S, van Alphen L, Verbrugh H (1998) Short-sequence DNA repeats in prokaryotic genomes. Microbiol Mol Biol Rev 62:275–293

    Article  PubMed  PubMed Central  Google Scholar 

  • van Damme P, Veldink JH, van Blitterswijk M, Corveleyn A, van Vught PW, Thijs V, Dubois B, Matthijs G, van den Berg LH, Robberecht W (2011) Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2. Neurology 76:2066–2072

    Article  PubMed  CAS  Google Scholar 

  • Veneziano L, Frontali M (2016) Drpla. GeneReviews®[Internet]. University of Washington, Seattle

  • Vinces MD, Legendre M, Caldara M, Hagihara M, Verstrepen KJ (2009) Unstable tandem repeats in promoters confer transcriptional evolvability. Science 324:1213–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang G, Vasquez KM (2007) Z-DNA, an active element in the genome. Front Biosci 12:38

    Article  Google Scholar 

  • Wang X-B, Kakoulidou M, Giscombe R, Qiu Q, Huang D, Pirskanen R, Lefvert AK (2002) Abnormal expression of CTLA-4 by T cells from patients with myasthenia gravis: effect of an AT-rich gene sequence. J Neuroimmunol 130:224–232

    Article  CAS  PubMed  Google Scholar 

  • Weldon C, Behm-Ansmant I, Hurley LH, Burley GA, Branlant C, Eperon IC, Dominguez C (2017) Identification of G-quadruplexes in long functional RNAs using 7-deazaguanine RNA. Nat Chem Biol 13:18

    Article  CAS  PubMed  Google Scholar 

  • Wilburn B, Rudnicki DD, Zhao J, Weitz TM, Cheng Y, Gu X, Greiner E, Park CS, Wang N, Sopher BL (2011) An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington’s disease-like 2 mice. Neuron 70:427–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willems T, Gymrek M, Highnam G, Mittelman D, Erlich Y (2014) The landscape of human STR variation. Genome Res 24:1894–1904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong B, Chen S, Kwon JA, Rich A (2007) Characterization of Z-DNA as a nucleosome-boundary element in yeast Saccharomyces cerevisiae. Proc Natl Acad Sci 104:2229–2234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu G, Goodridge AG (1998) A CT repeat in the promoter of the chicken malic enzyme gene is essential for function at an alternative transcription start site. Arch Biochem Biophys 358:83–91

    Article  CAS  PubMed  Google Scholar 

  • Zajac P, Öberg C, Ahmadian A (2009) Analysis of short tandem repeats by parallel DNA threading. PLoS One 4:e7823

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zardoya R, Vollmer DM, Craddock C, Streelman JT, Karl S, Meyer A (1996) Evolutionary conservation of microsatellite flanking regions and their use in resolving the phylogeny of cichlid fishes (Pisces: Perciformes). Proc R Soc Lond Ser B Biol Sci 263:1589–1598

  • Zhang J, Ohta T, Maruyama A, Hosoya T, Nishikawa K, Maher JM, Shibahara S, Itoh K, Yamamoto M (2006a) BRG1 interacts with Nrf2 to selectively mediate HO-1 induction in response to oxidative stress. Mol Cell Biol 26:7942–7952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Zuo K, Zhang F, Cao Y, Wang J, Zhang Y, Sun X, Tang K (2006b) Conservation of noncoding microsatellites in plants: implication for gene regulation. BMC Genomics 7:323

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zheng R, Shen Z, Tripathi V, Xuan Z, Freier SM, Bennett CF, Prasanth SG, Prasanth KV (2010) Polypurine-repeat-containing RNAs: a novel class of long non-coding RNA in mammalian cells. J Cell Sci 123:3734–3744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The current study was supported by a grant from Shahid Beheshti University of Medical Sciences.

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Authors and Affiliations

  1. Molecular Genetics Division, GMG center, Tabriz, Iran

    Jalal Gharesouran & Hassan Hosseinzadeh

  2. Division of Medical Genetics, Tabriz Childrens Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

    Jalal Gharesouran, Hassan Hosseinzadeh & Maryam Rezazadeh

  3. Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Soudeh Ghafouri-Fard

  4. Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Taheri

  5. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Jalal Gharesouran, Hassan Hosseinzadeh & Maryam Rezazadeh

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Contributions

MT, HH and SGF wrote the draft and revised it. JG and MR performed the data collection and designed the tables and figures. All authors contributed equally and have fully approved this submission.

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Correspondence to Mohammad Taheri or Maryam Rezazadeh.

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Gharesouran, J., Hosseinzadeh, H., Ghafouri-Fard, S. et al. STRs: Ancient Architectures of the Genome beyond the Sequence. J Mol Neurosci 71, 2441–2455 (2021). https://doi.org/10.1007/s12031-021-01850-6

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