, Volume 104, Issue 1, pp 2–13 | Cite as

Mechanisms of DNA expansion

  • Cynthia T. McMurray
Chromosoma Focus


Unstable transmission of repeating segments in genes is now recognized as a new class of mutations causing human disease. Genetic instability observed in disease is termed an “expansion mutation” when the mutation is an increase in the copy number of a repeated unit, commonly a di-or trinucleotide. While the expansion mutation is well characterized in disease, the mechanism by which expansion occurs is not clear. This article focuses on physical properties of expansion at repeating nucleotides that may provide clues to the mechanism. Both biochemical and genetic data indicate that DNA structure is part of the mechanism and the underlying cause for expansion.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aaltonen LA, Peltomäki, Leach FS, Sistonen P, Pylkkänen, Mecklin J-P, Järvinen H, Powell SM, Jen J, Hamilton SR, Petersen GM, Kinzler KW, Vogelstein B, Chapelle Ade la (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260: 812–816Google Scholar
  2. Andrew SE, Goldberg YP, Theilmann J, Zeisler J, Hayden MR (1994) A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing. Hum Mol Genet 3: 65–67Google Scholar
  3. Bates G, Lehrach H (1994) Trinucleotide repeat expansion and human genetic disease. Bioessays. 16: 277–284Google Scholar
  4. Bernstein JA, Richardson CC (1989) Characterization of the helicase and primase activities of the 63-kDa component of the bacteriophage T7 gene 4 product. J Biol Chem 264: 13066–13073Google Scholar
  5. Bouffler S, Silver A, Cox R (1994) The role of DNA repeats and associated secondary structure in genomic instability and neoplasia. Bioessays 15: 409–412Google Scholar
  6. Breslauer KJ, Frank R, Blocker H, Marky LA (1986) Predicting DNA duplex stability from base sequence comparison. Proc Natl Acad Sci USA 83: 3746–3750Google Scholar
  7. Brooks JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion J-P, Hodson T, Sohn R, Lemelman B, Snell RG, Rundle SA, Crow S, Davies J, Shelbourne P, Buxton J, Jones C, Juvonen V, Johnson K, Harper PS, Shaw DJ, Housmans DE (1992) Molecular basis of myotonic dystrophys: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 68: 799–808Google Scholar
  8. Burge C, Campbell AM, Karlin S (1992) Over-and under-representation of short oligonucleotides in DNA sequences. Proc Natl Acad Sci USA 89: 1358–1362Google Scholar
  9. Catasti P, GuptaG, Garcia AE, Ratliff R, Hong L, Yau P, Moyzis RK, Bradbury EM (1994) Unusual structures of the tandem repetitive DNA sequences located at human centromeres. Biochemistry 33:3819–3830Google Scholar
  10. Chalberg MD, Englund PT (1979) The effect of template secondary structure on vaccinia DNA polymerase. J Biol Chem 254: 7820–7826Google Scholar
  11. Chen X, Mariappan SVS, Catasti P, Ratliff R, Moyzis RK, Laayoun A, Smith SS, Bradbury EM, Gupta G (1995) Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications. Proc Natl Acad Sci USA 92: 5199–5203Google Scholar
  12. Chung M, Ranum LPW, Duvick LA, Servadio A, Zoghbi HY Orr HT (1993) Evidence for a mechanism predisposing intergenerational CAG repeat instability in spinocerebellar ataxia type I. Nat Genet 5: 254–258Google Scholar
  13. Cooper DN, Krawczak M (1991) Mechanisms of insertional mutagenesis in human genes causing genetic disease. Hum Genet 87: 409–415Google Scholar
  14. Dayn A, Samadashwily GM, Mirkin SM (1992) Intramolecular DNA triplexes: unusual sequence requirements and influence on DNA polymerization. Proc Natl Acad Sci USA 89: 11406–11410Google Scholar
  15. Debyser Z, Tabor S, Richardson CC (1994) Coordination of leading and lagging strand DNA synthesis at the replication fork of bacteriophage T7. Cell 77: 157–166Google Scholar
  16. DePamphilis ML (1993) Origins of DNA replication that function in eukaryotic cells. Curr Opin Cell Biol 5: 434–441Google Scholar
  17. Devys D, Biancalana V, Rousseau F, Baul J, Mandel JL, Oberle I (1992) Analysis of full fragile X mutations in fetal tissue of monozygotic twins indicate that abnormal methylation and some heterogeneity are establised early in development. Am J Med Genet 208–216Google Scholar
  18. Drummond JT, Li GM, Longley MJ, Modrich P (1995) Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells. Science 268: 1909–1912Google Scholar
  19. Eichler EE (1994) Length of uninterrupted CGG repeats determines instability in the FMR-1 gene. Nat Genet 8: 88–95Google Scholar
  20. Fearon ER, Cho KR, Nigro JM, Kern SE, Simons JW, Ruppert JM, Hamilton SR, Preisinger AC, Thomas G, Kinzler KW, Vogelstein B (1990) Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247: 49–56Google Scholar
  21. Fry M, Loeb LA (1994) The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure. Proc Natl Acad Sci USA 91: 4950–4954Google Scholar
  22. Fu YH, Kuhl DPA, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJMH, Holden JJA, Fenwick RGJr, Warren ST, Oostra BA, Nelson DL, Caskey CT (1991) Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67: 1047–1058Google Scholar
  23. Gacy AM, Goellner G, Juranic N, Macura S, McMurray CT (1995) Trinucleotide repeats that expand in human disease form hairpin structures in vitro. Cell 81: 533–540Google Scholar
  24. Goldberg YP, Kremer B, Andrew SE, Theilmann J, Graham RK, Squitieri F, Telenius H, Adam S, Sajoo A, Starr E, Heiberg A, Wolff G, Hayden MR (1993) Molecular analysis of new mutations for Huntington's disease: Intermadiate alleles and sex of origin effects. Nat Genet 5: 174–179Google Scholar
  25. Goldberg YP, McMurray CT, Zeisler J, Almquist E, Sillence D, Richards F, Gacy AM, Buchanan J, Telenius H, Hayden M (1995) Increased instability of intermediate alleles in families with sporadic Huntington's Disease compared to similar sized intermediate alleles in the general population. Hum Mol Genet (in press)Google Scholar
  26. Goldfarb LG, Brown P, McCombie WR, Goldfarber D, Swergold GD, Wills PR, Cervenakova L, Baron H, Gibbs CJJr, Gadjusek DC (1991) Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. Proc Natl Acad Sci USA 88: 10926–10930Google Scholar
  27. Han J, Hsu C, Zhu Z, Longshore JW, Finley WH (1994) Over-representation of the disease associated (CAG) and (CGG) repeats in the human genome. Nucleic Acids Res 22: 1735–1740Google Scholar
  28. Harayama S, Rekik M, Bairoch A, Neidle EL, Ornston LN (1991) Potential DNA slippage structures acquired during evolutionary divergence of Acinetobacter calcoaceticus chromosomal benABC and Pseudomonas putida TOL pWW0 plasmid xylXYZ, genes encoding benzoate dioxygenases. J Bacteriol 173: 7540–7548Google Scholar
  29. Hirst MC, Grewal PK, Davies KE (1994) Precursor arrays for triplet repeat expansion at the fragile X locus. Hum Mol Genet 9: 1553–1560Google Scholar
  30. Hoelzel AR, Lopez JV, Dover GA, O'Brien SJ (1994) Rapid evolution of a heteroplasmic repetitive sequence in the mitochondrial DNA control region of carnivores. J Mol Evol 39: 191–199Google Scholar
  31. Huang CC, Hearst JE (1980) Pauses at positions of secondary structure during in vitro replication of single-stranded fd bacteriophage DNA by T4 DNA polymerase. Anal Biochem 103: 127–139Google Scholar
  32. Huber HE, Bernstein J, Nakai H, Tabor S, Richardson CC (1988) Interactions of DNA replication proteins of bacteriophage T7. Cancer Cells 6/Eukaryotic DNA replication, 11–17Google Scholar
  33. Jansen G, Willems P, Coerwinkel M, Nillesen W, Smeets H, Vits L, Howeler C, Brunner H, Wieringa B, (1994) Gonosomal mosaicism in myotonic dystrophy patients: involvement of mitotic events in (CTG)n repeat variation and selection against extreme expansion in sperm. Am J Hum Genet 54: 575–585Google Scholar
  34. Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Mishimura M, Akiguchi I, Kimura J, Marumiya S, Kakizuka A (1994) CAG expansions in a novel gene for machado-Joseph disease at chromosome 14q32.1. Nat Genet 8: 221–227Google Scholar
  35. Kelly R, Bulfield G, Collick A, Gibbs M, Jeffreys AJ (1989) Characterization of a highly unstable mouse minisatellite locus: Evidence for somatic mutation during early development. Genomics 5:844–856Google Scholar
  36. Ketterling RP, Liao D, Sommer SS (1995) Microdeletions in the factor IX gene: three recurrences associated with a quasipalindromic sequence. Am J Hum Genet 56: 343–346Google Scholar
  37. Knight SJL, Flannery AV, Hirst MC, Campbell L, Christodoulou Z, Phelps SR, Pointon J, Middleton-Price HR, Barnicoat A, Pembrey ME, Holland J, Oostra BA, Bobrow M, Davies KE (1993) Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell 74: 127–134Google Scholar
  38. Kohwi Y, Wang H, Kohwi-Shigematsu T (1993) A single trinucleotide 5′AGC3′/5′GCT3′, of the triplet-repeat disease genes confers metal ion-induced non-B DNA structure. Nucleic Acids Res 21: 5651–5655Google Scholar
  39. Koide R, Jkeuchi T, Onodera O, Tanaka H, Igarashi S, Endo K, Takahashi H, Kondo R, Ishikawa A, Hayashi T, Saito M, Tomoda A, Miike T, Naito H, Ikuta F, Tsuji S (1994) Unstable expansion of CAG repeat in hereditary dentatorubral-pallido-Juysian atrophy (DRPLA). Nat Genet 6: 9–13Google Scholar
  40. Komure O, Sano A, Nishino N, Yamauchi N, Ueno S, Kondoh K, Sano N, Takahashi M, Murayama N, Kondo I et al. (1995) DNA analysis in hereditary dentatorubral-pallidoluysian atrophy: correlation between CAG repeat length and phenotypic variation and the molecular basis of anticipation. Neurology 45: 143–149Google Scholar
  41. Kremer B, Goldberg P, Andrew SE, Theilmann J, Telenius H, Zeisler J, Squitieri F, Lin B, Bassett A, Almqvist E, Bird TD, Hayden MR (1994) A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 330: 1401–1406Google Scholar
  42. Kremer B, Theilmann J, Almqvist E, Spence N, Telenius H, Goldberg YP, Hayden MR (1995) Sex dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes. Am J Hum Genet (in press)Google Scholar
  43. Kremer EJ, Pritchard M, Lynch M, Yu S, Holman K, Baker E, Warrent ST, Schlessinger D, Sutherland GR, Richards RI (1991) Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science 252: 1711–1714Google Scholar
  44. Kruyer H, Mila M, Glover G, Carbonell P, Ballesta F, Estivill X (1994) Fragile X syndrome and the (CGG)n mutation: two families with discordant MZ twins. Am J Hum Genet 54: 437–432Google Scholar
  45. Kunkel TA (1993) Slippery DNA and diseases. Nature 365: 207–208Google Scholar
  46. Kunst CB, Warren ST (1994) Cryptic and polar variation of the Fragile X repeat could result in predisposing normal alleles. Cell 77: 853–861Google Scholar
  47. Kuryavyi VV, Jovin TM (1995) Triad-DNA: a model for trinucleotide repeats. Nat Genet 9: 339–341Google Scholar
  48. LaSpada AR, Paulson HL, Fischbeck KH (1994a) Trinucleotide repeat expansion in neurological disease (review). Ann Neurol 36: 814–822Google Scholar
  49. LaSpada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH (1994b) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352: 7–79Google Scholar
  50. Landwehrmeyer GB, McNeil SM, Dure LSIV, Ge P, Aizawa H, Huang Q, Ambrose CM, Duyao MP, Bird ED, Bonilla E, et al. (1995) Huntington's disease gene: regional and cellular expression in brain of normal and affected individuals. Ann Neurol 37: 218–230Google Scholar
  51. Levinson G, Gutman GA (1987) Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol 4: 203–221Google Scholar
  52. Li T, Nicolaou C (1994) Chemical self-replication of palindromic duplex DNA. Nature 369: 218–221Google Scholar
  53. Lindahl T (1994) DNA surveillance defect in cancer cells. Curr Biol 4:249–251Google Scholar
  54. MacDonald ME, Barnes G, Srinidhi J, Duyao MP, Ambrose CM, Myers RH, Gray J, Conneally PM, Young A, Penney J, et al. (1993) Gametic but not somatic instability of CAG repeat length in Huntington's disease. J Med Genet 30: 982–986Google Scholar
  55. Maddox J (1994) Triplet repeat genes raise questions. Nature 368: 685Google Scholar
  56. Mandel J-L (1994) Trinucleotide disease on the rise. Nat Genet 7: 453–455Google Scholar
  57. Marx J (1993) New colon cancer gene discovered. Science 260: 751–752Google Scholar
  58. Mendelman LV, Richardson CC (1991) Requirements for primer synthesis by bacteriophage T7 63-kDa gene 4 protein. J Biol Chem 266: 23240–23250Google Scholar
  59. Mitas M, Yu A, Dill J, Kamp TJ, Chambers EJ, Haworth S (1995) Hairpin properties of single-stranded DNA containing a GC-rich triplet repeat: (CTG)15. Nucl Acids Res 23: 1050–1059Google Scholar
  60. Modrich P (1991) Mechanisms and biological effects of mismatch repair. A Rev Genet 25: 229–253Google Scholar
  61. Modrich P (1991) Mismatch repair, genomic stability and cancer. Science 266: 1959–1960Google Scholar
  62. Nagafuchi S, Yanagisawa H, Sato K, Shirayama T, Ohsaki E, Bundo M, Takeda T, Tadokoro K, Kondo I, Murayama N, Tanaka Y, Kikushima H, Umino K, Kurosawa H, Furukawa T, Nihei K, Inoue T, Sano A, Komure O, Takahashi M, Yoshizawa T, Kanawawa I, Yamada M (1994) Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nat Genet 6: 14–18Google Scholar
  63. Nakai H, Richardson CC (1988) The effect of the T7 and Escherichia coli DNA-binding proteins at the replication fork of bacteriophage T7. J Biol Chem 263: 9831–9839Google Scholar
  64. Nasir J, Floresco SB, O'Kusky JR, Diewert VM, Richman JM, Zeisler J, Borowski A, Marth JD, Phillips AG, Hayden MR (1995) Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 81: 811–823Google Scholar
  65. Nossal N (1992) Protein-protein interactions at a DNA replication fork: bacteriophage T4 as a model. FASEB J 6: 871–878Google Scholar
  66. O'Hoy KL, Tsilfidis C, Mahadevan MS, Neville CE, Barceló J, Hunter AGW, Korneluk RG (1993) Reduction in size of the myotonic dystrophy trinucleotide repeat mutation during transmission. Science 259: 809–811Google Scholar
  67. Orr HT, Chung M, Banfi S, Kwiatkowski TJJr, Servadio A, Beaudet AL, McCall AE, Duvick LA, Ranum LPW, Zoghbi HY (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet 4: 221–226Google Scholar
  68. Owen F, Poulter M, Shah T, Collinge J, Lofthouse R, Baker H, Ridley R, McVey J, Crow TJ (1990) An in frame insertion in the prion gene in familial Creutzfeldt-Jakob disease. Mol Brain Res 7: 272–276Google Scholar
  69. Palombo F, Gallinari P, Iaccarino I, Lettieri T, Hughes M, D'Arrigo A, Truong O, Hsuan JJ, Jiricny J (1995) GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells. Science 268: 1912–1914Google Scholar
  70. Papadopoulos N, Nicolaides NC, Liu B, Parsons R, Lengauer C, Palombo F, D'Arrigo A, Markowitz S, Willson JKV, Kinzler KW, Jiricny J, Vogelstein B (1995) Mutations of GTBP in genetically unstable cells. Science 268: 1915–1919Google Scholar
  71. Petronis A, Kennedy JL (1995) Unstable genes-unstable mind? Am J Psychiatry 152: 164–172Google Scholar
  72. Plassart E, Fontaine B (1994) Genes with triplet repeats: a new class of mutations causing neurological diseases (review). 48: 191–197Google Scholar
  73. Ranum LP, Chung MY, Banfi S, Bryer A, Schut LJ, Ramesar R, Duvick LA, McCall A, Subramony SH, Goldfarb L, et al. (1994) Molecular and clinical correlations in spinocerebellar ataxia type I: evidence for familial effects on the age at onset. Am J Hum Genet 55: 244–252Google Scholar
  74. Reiss AL, Kazazian HHJr, Krebs CM, McAughan A, Boehm CD, Abrams MT, Nelson DL (1994) Frequency and stability of the fragile X premutation. Hum Mol Genet 3: 393–398Google Scholar
  75. Reyniers E, Vits L, DeBoulle K, VanRoy B VanVelzen D, Graaff Ede, Verkerk AJMH, Jorens HZJ, Darby JK, Oostra B, Willems PJ (1993) The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm. Nat Genet 4: 107–108Google Scholar
  76. Richards RI, Sutherland GR (1992) Dynamic mutations: a new class of mutations causing human disease. Cell 70: 709–712Google Scholar
  77. Ross CA, McInnis MG, Margolis RL, Li S-H (1993) Genes with triplet repeats: candidate mediators of neuropsychiatric disorders. Trends Neurosci 16: 254–260Google Scholar
  78. Rousseau F, Heitz D, Oberlé I, Mandel J-L (1991) Selection in blood from female carriers of the fragile X syndrome: inverse correlation between age and proportion of active X chromosomes carrying the full mutation. Am J Med Genet 28: 830–386Google Scholar
  79. Rubinsztein DC, Barton DE, Davison BCC, Ferguson-Smith MA (1993) Analysis of the Huntington gene reveals a trinucleotide-length polymorphism in the region of the gene that contains two CCG-rich stretches and a correlation between decreased age of onset of Huntington's disease and CAG repeat number. Hum Mol Genet 2: 1713–1715Google Scholar
  80. Schalling M, Hudson TJ, Buetow KH, Housman DE (1993) Direct detection of novel expanded trinucleotide repeats in the human genome. Nat Genet 4: 135–139Google Scholar
  81. Shelbourne P, Winqvist R, Kunert E, Davies J, Leisti J, Thiele H, Bachmann H, Buxton J, Williams B, Johnson K (1992) Unstable DNA may be responsible for the incomplete penetrance of the myotonic dystrophy phenotype. Hum Mol Genet 1: 467–473Google Scholar
  82. Sherman LA, Gefter ML (1976) Studies on the mechanism, of enzymatic DNA elongation by Escherichia coli DNA polymerase II. J Mol Biol 103: 61–76Google Scholar
  83. Snow K, Doud LK, Hagerman R, Pergolizzi RG, Erster SH, Thibodeau SN (1993) Analysis of a CGG sequence at the FMR-I locus in Fragile X families and in the general population. Am J Hum Genet 53: 1217–1228Google Scholar
  84. Snow K, Tester DJ, Kruckeberg KE, Schaid DJ, Thibodeau SN (1994) Sequence analysis of the Fragile X trinucleotide repeat: Implications for the origin of the Fragile X mutation. Hum Mol Genet 3: 1543–1551Google Scholar
  85. Stine OC, Pleasant N, Franz ML, Abbott MH, Folstein SE, Ross CA (1993) Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum Mol Genet 2: 1547–1549Google Scholar
  86. Strand M, Prolla TA, Liskay RM, Petes TD (1993) Destabilization of a simple repetitive DNA in yeast by mutations affecting mismatched repair. Nature 365: 274–276Google Scholar
  87. Telenius H, Kremer B, Goldberg YP, Theilmann J, Andrew SE, Zeisler J, Adam S, Greenberg C, Ives EJ, Clarke LA, Hayden MR (1994) Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nature Genet 6: 409–414Google Scholar
  88. The Huntington's Diseases Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72: 971–983Google Scholar
  89. Thibodeau SN, Bren G, Shaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260: 816–819Google Scholar
  90. Trinh TQ, Sinden RR (1993) The influence of primary and secondary DNA structure in deletion and duplication between direct repeats in Escherichia coli. Genetics 134: 409–422Google Scholar
  91. Trinh TQ, Sinden RR (1994) Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli. Nature 352: 544–547Google Scholar
  92. Umar A, Boyer JC, Kunkel TA (1994) DNA loop repair by human cell extracts. Science 266: 814–816Google Scholar
  93. Veaute X, Fuchs RPP (1994) Greater strand susceptibility to mutations in lagging strand of DNA replication in Escherichia coli than in leading strand. Science 261: 598–600Google Scholar
  94. Verkerk AJMH, Pieretti M, Sutcliffe JS, Fu Y-H, Kuhl DPA, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang F, Eussen BW, vanOmmen G-JB, Blonden LAJ, Riggins GJ, Chastain JL, Kunst CB, Galjaard H, Caskey CT, Nelson DL, Oostra BA, Warren ST (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65: 905–914Google Scholar
  95. Vits L, DeBoulle K, Reyniers E, Handig T, Darby JK, Oostra B, Willems PJ (1994) Apparent regression of the CGG repeat in FMR1 to an allele of normal size. Hum Genet 94: 523–526Google Scholar
  96. Warren ST, Nelson DL (1993) Tri-nucleotide repeat expansions in neurological disease. Curr Opin Neurobiol 3: 752–759Google Scholar
  97. Weaver DT, DePamphilis ML (1982) Specific sequences in native DNA that arrest synthesis by DNA polymerase alpha. J Biol Chem 257: 2075–2086Google Scholar
  98. Willems PJ (1994) Dynamic mutations hit double figures. Nat Genet 8: 213–215Google Scholar
  99. Wöhrle D, Hennig I, Vogel W, Steinbach P (1992) Mitotic stability of fragile X mutations in differentiated cells indicateds early post-conceptional trinucleotide repeat expansion. Hum Genet 89: 114–116Google Scholar
  100. Wolff RK, Plaetke R, Jeffreys AJ, White R (1989) Unequal crossing over between homologous chromosomes is not the major mechanism involved in the generation of new alleles at VNTR loci. Genomics 5: 382–384Google Scholar
  101. Wong L-JC, Ashizawa T, Monckton DG, Caskey CT, Richards CS (1995) Somatic heterogeneity of the CTG repeat in myotonic dystrophy is age and size dependent. Am J Hum Genet 56: 114–122Google Scholar
  102. Zhang L, Leeflang EP, Yu J, Arnheim N (1994) Studying human mutations by sperm typing: instability of CAG trinucleotide repeats in the human androgen receptor gene. Nat Genet 7: 531–535Google Scholar
  103. Zheng CJ, Byers B, Moolgavkar SH (1993) Allelic instability in mitosis: a unified model for dominant disorders. Proc Natl Acad Sci USA 90: 10178–10182Google Scholar
  104. Zühlke C, Riess O, Bockel B, Lange H, Thies U (1993) Mitotic stability and meiotic variability of the (CAG)n repeat in the Huntington disease gene. Hum Mol Genet 2: 2063–2067Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Cynthia T. McMurray
    • 1
    • 2
  1. 1.Department of Biochemistry and Molecular BiologyMayo Foundation and Graduate SchoolRochesterUSA
  2. 2.Department of Pharmacology, Molecular Neuroscience ProgramMayo Foundation and Graduate SchoolRochesterUSA

Personalised recommendations