Microsatellites

Abstract

Microsatellites are short, in‐tandem arranged repetitive deoxyribonucleic acid (DNA) elements which are widespread in eukaryotic and prokaryotic genomes. The basic unit lengths of microsatellites (or simple DNA sequence repeats) comprise up to six (or eight) nucleotides, and these motifs are perfectly reiterated from 5 to more than 100 times. Longer and more imperfectly reiterated periodicities border on the definitions of the so‐called minisatellites. Microsatellites have been utilised as markers for population genetic studies, forensic and relatedness testing, investigations on genetic diversity and the identification of genetic traits. However, microsatellite expansions are also involved in human diseases. Lynch syndrome, a hereditary tumour predisposition disease, is characterised by microsatellite instability due to defective mismatch repair, promoting tumourigenesis. Furthermore, microsatellite expansion diseases are rare, but interesting model diseases characterised by diverse pathogenetic pathways. Hence microsatellites exhibit a broad spectrum of biological relevance ranging from neutral or selfish to pathogenic elements.

Key Concepts

  • Microsatellites exhibit perfect tandem repetition of short nucleotide motifs.
  • Microsatellites represent most variable components throughout most genomes.
  • The biological significance of microsatellites ranges from selfishness and molecular marker for a small genome region to disease‐causing mutations when expanded, respectively.

Keywords: microsatellite; simple DNA sequences; DNA marker; repetitive DNA; genomic junk; mutations; polymorphism; hypervariability

Figure 1. CAG repeat expansion underlying Huntington disease (HD). Carriers of intermediate alleles (≥27–35 CAG repeats) usually do not develop symptoms of HD, but repeat lengths may increase during (mainly male) meiosis. The 36–39 CAG repeats are causative for HD, but show reduced penetrance, while repeat lengths of ≥40 CAG repeats lead to HD with full penetrance.
close

References

Bhargava A and Fuentes FF (2010) Mutational dynamics of microsatellites. Molecular Biotechnology 44: 250–266.

Dayalu P and Albin RL (2015) Huntington disease: pathogenesis and treatment. Neurologic Clinics 33: 101–114.

Dion V and Wilson JH (2009) Instability and chromatin structure of expanded trinucleotide repeats. Trends in Genetics 25: 288–297.

Dumache R, Ciocan V, Muresan C and Enache A (2016) Molecular DNA analysis in forensic identification. Clinical Laboratory 62: 245–248.

Eckert KA and Hile SE (2009) Every microsatellite is different: intrinsic DNA features dictate mutagenesis of common microsatellites present in the human genome. Molecular Carcinogenesis 48: 379–388.

Epplen JT, Mäueler W and Santos EJM (1998) On GATAGATA and other ‘junk’ in the barren stretch of genomic desert. Cytogenetics and Cell Genetics 80: 75–82.

Fondon JW and Garner HR (2004) Molecular origins of rapid and continuous morphological evolution. Proceedings of the National Academy of Sciences of the United States of America 101: 18058–18063.

Fondon JW 3rd, Hammock EA, Hannan AJ and King DG (2008) Simple sequence repeats: genetic modulators of brain function and behavior. Trends in Neurosciences 31: 328–334.

Gatalica Z, Vranic S, Xiu J, Swensen J and Reddy S (2016) High microsatellite instability (MSI‐H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine. Familial Cancer 15 (3): 405–412.

International Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921.

Jeffreys AJ, Wilson V and Thein SL (1985) Hypervariable minisatellite regions in human DNA. Nature 314: 67–73.

Ji Y, Eichler EE, Schwartz S and Nicholls RD (2000) Structure of chromosomal duplicons and their role in mediating human genomic disorders. Genome Research 10: 597–610.

Kazazian HH Jr (2004) Mobile elements: drivers of genome evolution. Science 303: 1626–1632.

Leclercq S, Rivals E and Jarne P (2007) Detecting microsatellites within genomes: significant variation among algorithms. BMC Bioinformatics 8: 125.

Meola G and Cardani R (2015) Myotonic dystrophies: an update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochimica et Biophysica Acta 1852: 594–606.

Press MO, Carlson KD and Queitsch C (2014) The overdue promise of short tandem repeat variation for heritability. Trends in Genetics 30: 504–512.

Putman AI and Carbone I (2014) Challenges in analysis and interpretation of microsatellite data for population genetic studies. Ecology and Evolution 4: 4399–4428.

Richard GF, Kerrest A and Dujon B (2008) Comparative genomics and molecular dynamics of DNA repeats in eukaryotes. Microbiology and Molecular Biology Reviews 72: 686–727.

Salehi LB, Bonifazi E, Stasio ED, et al. (2007) Risk prediction for clinical phenotype in myotonic dystrophy type 1: data from 2,650 patients. Genetic Testing 11: 84–90.

Skinner D (1977) Satellite DNAs. Bioscience 27: 790–796.

Tautz D (1993) Notes on the definition and nomenclature of tandemly repetitive DNA sequences. In: Pena SDJ, Chakraborty R, Epplen JT and Jeffreys AJ (eds) DNA Fingerprinting: State of the Science, pp. 21–28. Basel: Birkhäuser.

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

Velho S, Fernandes MS, Leite M, Figueiredo C and Seruca R (2014) Causes and consequences of microsatellite instability in gastric carcinogenesis. World Journal of Gastroenterology 20: 16433–16442.

Warby SC, Graham RK and Hayden MR (2010) Huntington disease. GeneReviews. PMID: 20301482 [Internet].

Weber J and Wong C (1993) Mutation of human short tandem repeats. Human Molecular Genetics 2: 1123–1128.

Yamamoto H and Imai K (2015) Microsatellite instability: an update. Archives of Toxicology 89: 899–921.

Zhang J (2012) Genetic redundancies and their evolutionary maintenance. Advances in Experimental Medicine and Biology 751: 279–300.

Zhao X and Usdin K (2015) The repeat expansion diseases: the dark side of DNA repair. DNA Repair (Amst) 32: 96–105.

Further Reading

Hancock JM (1996) Simple sequences in a ‘minimal’ genome. Nature Genetics 14: 14–15.

Ohno S (1972) Evolutional reason for having so much junk DNA. In: Pfeiffer RA (ed) Modern Aspects of Cytogenetics: Constitutive Heterochromatin in Man, pp. 169–180. Stuttgart: FK Schattauer.

Padeken J, Zeller P and Gasser SM (2015) Repeat DNA in genome organization and stability. Current Opinion in Genetics and Development 31: 12–19.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Hoffjan, Sabine, and Epplen, Jörg T(Aug 2016) Microsatellites. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005911.pub3]