Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset

Human Molecular Genetics

Volumn 18, Issue 16, 2009, Pages 3039-3047

  Swami, Meera ^a   Hendricks, Audrey E ^b   Gillis, Tammy ^a   Massood, Tiffany ^b   Mysore, Jayalakshmi ^a   Myers, Richard H ^b   Wheeler, Vanessa C ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENINE; CYTOSINE; GUANINE;

ARTICLE; BRAIN CORTEX; CONTROLLED STUDY; DISEASE DURATION; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOMIC INSTABILITY; HUMAN; HUMAN TISSUE; HUNTINGTON CHOREA; NEUROPATHOLOGY; ONSET AGE; PHENOTYPE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROGNOSIS; QUANTITATIVE ANALYSIS; SOMATIC MUTATION; TRINUCLEOTIDE REPEAT;

ADULT; AGE OF ONSET; AGED; AGED, 80 AND OVER; BRAIN; FEMALE; HUMANS; HUNTINGTON DISEASE; MALE; MIDDLE AGED; TRINUCLEOTIDE REPEAT EXPANSION; YOUNG ADULT;

EID: 68049113685     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddp242     Document Type: Article

References (47)

1. Harper, P.S. (1999) Huntington's disease: A clinical, genetic and molecular model for polyglutamine repeat disorders. Philos. Trans. R. Soc. Lond. B, Biol. Sci., 354, 957-961.
2. Huntington's disease collaborative research group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 72, 971-983.
3. Vonsattel, J.P., Myers, R.H., Stevens, T.J., Ferrante, R.J., Bird, E.D. and Richardson, E.P. (1985) Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol., 44, 559-577.
4. Duyao, M., Ambrose, C., Myers, R., Novelletto, A., Persichetti, F., Frontali, M., Folstein, S., Ross, C., Franz, M., Abbott, M. et al. (1993) Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat. Genet., 4, 387-392.
5. Andrew, S.E., Goldberg, Y.P., Kremer, B., Telenius, H., Theilmann, J., Adam, S., Starr, E., Squitieri, F., Lin, B., Kalchman, M.A. et al. (1993) The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat. Genet., 4, 398-403.
6. Snell, R.G., MacMillan, J.C., Cheadle, J.P., Fenton, I., Lazarou, L.P., Davies, P., MacDonald, M.E., Gusella, J.F., Harper, P.S. et al. (1993) Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nat. Genet., 4 393-397.
7. Stine, O.C., Pleasant, N., Franz, M.L., Abbott, M.H., Folstein, S.E. and Ross, C.A. (1993) Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum. Mol. Genet., 2, 1547-1549.
8. Gusella, J.F.,McNeil, S., Persichetti, F., Srinidhi, J., Novelletto, A., Bird, E., Faber, P., Vonsattel, J.P., Myers, R.H. and MacDonald, M.E. (1996) Huntington's disease. Cold Spring Harb. Symp. Quant. Biol., 61, 615-626.
9. Myers, R., Marans, K.S. and MacDonald, M. (1998) Huntington's disease. In Wells, R.D. and Warren, S.T. (eds), Genetic Instabilities and Hereditary Neurological Diseases. Academic Press, San Diego, CA, USA, pp. 301-323.
10. Li, J.L., Hayden, M.R., Almqvist, E.W., Brinkman, R.R., Durr, A., Dode, C., Morrison, P.J., Suchowersky, O., Ross, C.A., Margolis, R.L. et al. (2003) A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS Study. Am. J. Hum. Genet., 73, 682-687.
11. Wexler, N.S., Lorimer, J., Porter, J., Gomez, F., Moskowitz, C., Shackell, E., Marder, K., Penchaszadeh, G., Roberts, S.A., Gayan, J. et al. (2004) Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc. Natl. Acad. Sci. USA, 101, 3498-3503.
12. Rubinsztein, D.C., Leggo, J., Chiano, M., Dodge, A., Norbury, G., Rosser, E. and Craufurd, D. (1997) Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease. Proc. Natl. Acad. Sci. USA, 94, 3872-3876.
13. MacDonald, M.E., Vonsattel, J.P., Shrinidhi, J., Couropmitree, N.N., Cupples, L.A., Bird, E.D., Gusella, J.F. and Myers, R.H. (1999) Evidence for the GluR6 gene associated with younger onset age of Huntington's disease. Neurology, 53, 1330-1332.
14. Holbert, S., Denghien, I., Kiechle, T., Rosenblatt, A., Wellington, C., Hayden, M.R., Margolis, R.L., Ross, C.A., Dausset, J., Ferrante, R.J. et al. (2001) The G1n-Ala repeat transcriptional activator CA150 interacts with huntingtin: Neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis. Proc. Natl. Acad. Sci. USA 98, 1811-1816.
15. Naze, P., Vuillaume, I., Destee, A., Pasquier, F. and Sablonniere, B. (2002) Mutation analysis and association studies of the ubiquitin carboxy-terminal hydrolase L1 gene in Huntington's disease. Neurosci. Lett., 328, 1-4.
16. Chattopadhyay, B., Ghosh, S., Gangopadhyay, P.K., Das, S.K., Roy, T., Sinha, K.K., Jha, D.K., Mukherjee, S.C., Chakraborty, A., Singhal, B.S. et al. (2003) Modulation of age at onset in Huntington's disease and spinocerebellar ataxia type 2 patients originated from eastern India. Neurosci. Lett., 345, 93-96.
17. Djousse, L., Knowlton, B., Hayden, M.R., Almqvist, E.W., Brinkman, R.R., Ross, C.A., Margolis, R.L., Rosenblatt, A., Durr, A., Dode, C. et al. (2004) Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16. Neurogenetics, 5, 109-114.
18. Metzger, S., Bauer, P., Tomiuk, J., Laccone, F., Didonato, S., Gellera, C., Soliveri, P., Lange, H.W., Weirich-Schwaiger, H., Wenning, G.K. et al. (2006) The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington's disease. Neurogenetics, 7, 27-30.
19. Li, J.L., Hayden, M.R., Warby, S.C., Durr, A., Morrison, P.J., Nance, M., Ross, C.A., Margolis, R.L., Rosenblatt, A., Squitieri, F. et al. (2006) Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: The HD MAPS study. BMC Med. Genet., 7, 71.
20. Andresen, J.M., Gayan, J., Cherny, S.S., Brocklebank, D., Alkorta-Aranburu, G., Addis, E.A., Cardon, L.R., Housman, D.E. and Wexler, N.S. (2007) Replication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds. J. Med. Genet., 44, 44-50.
21. Metzger, S., Rong, J., Nguyen, H.P., Cape, A., Tomiuk, J., Soehn, A.S., Propping, P., Freudenberg-Hua, Y., Freudenberg, J., Tong, L. et al. (2008) Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease. Hum. Mol. Genet., 17, 1137-1146.
22. Gayan, J., Brocklebank, D., Andresen, J.M., Alkorta-Aranburu, G., Zameel Cader, M., Roberts, S.A., Cherny, S.S., Wexler, N.S., Cardon, L.R. and Housman, D.E. (2008) Genomewide linkage scan reveals novel loci modifying age of onset of Huntington's disease in the Venezuelan HD kindreds. Genet. Epidemiol., 32, 445-453.
23. Telenius, H., Kremer, B., Goldberg, Y.P., Theilmann, J., Andrew, S.E., Zeisler, J., Adam, S., Greenberg, C., Ives, E.J. and Clarke, L.A. (1994) Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nat. Genet., 6, 409-414.
24. De Rooij, K.E., De Koning Gans, P.A., Roos, R.A., Van Ommen, G.J. and Den Dunnen, J.T. (1995) Somatic expansion of the (CAG)n repeat in Huntington disease brains. Hum. Genet., 95, 270-274.
25. Wheeler, V.C., Auerbach, W., White, J.K., Srinidhi, J., Auerbach, A., Ryan, A., Duyao, M.P., Vrbanac, V., Weaver, M., Gusella, J.F. et al. (1999) Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse. Hum. Mol. Genet., 8, 115-122.
26. Kennedy, L. and Shelbourne, P.F. (2000) Dramatic mutation instability in HD mouse striatum: Does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease? Hum. Mol. Genet., 9, 2539-2544.
27. Kennedy, L., Evans, E., Chen, C., Craven, L., Detloff, P., Ennis, M. and Shelbourne, P. (2003) Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis. Hum. Mol. Genet., 12, 3359-3367.
28. Shelbourne, P.F., Keller-McGandy, C., Bi, W.L., Yoon, S.R., Dubeau, L., Veitch, N.J., Vonsattel, J.P., Wexler, N.S., Arnheim, N. and Augood, S.J. (2007) Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain. Hum. Mol. Genet., 16, 1133-1142.
29. Gonitel, R., Moffitt, H., Sathasivam, K., Woodman, B., Detloff, P.J., Faull, R.L. and Bates, G.P. (2008) DNA instability in postmitotic neurons. Proc. Natl Acad. Sci. USA, 105, 3467-3472.
30. Aronin, N., Chase, K., Young, C., Sapp, E., Schwarz, C., Matta, N., Kornreich, R., Landwehrmeyer, B., Bird, E. and Beal, M.F. (1995) CAG expansion affects the expression of mutant Huntingtin in the Huntington's disease brain. Neuron, 15, 1193-1201.
31. Wheeler, V.C., Lebel, L.A., Vrbanac, V., Teed, A., Te Riele, H. and MacDonald, M.E. (2003) Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatum. Hum. Mol. Genet., 12, 273-281.
32. Dragileva, E., Hendricks, A., Teed, A., Gillis, T., Lopez, E.T., Friedberg, E.C., Kucherlapati, R., Edelmann, W., Lunetta, K.L., Macdonald, M.E. et al. (2009) Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes. Neurobiol. Dis., 33, 37-47.
33. Gomes-Pereira, M., Bidichandani, S.I. and Monckton, D.G. (2004) Analysis of unstable triplet repeats using small-pool polymerase chain reaction. Methods Mol. Biol., 277, 61-76.
34. Veitch, N.J., Ennis, M., McAbney, J.P., Shelbourne, P.F. and Monckton, D.G. (2007) Inherited CAG.CTG allele length is a major modifier of somatic mutation length variability in Huntington disease. DNA Repair 6, 789-796.
35. Jung, J. and Bonini, N. (2007) CREB-binding protein modulates repeat instability in a Drosophila model for polyQ disease. Science, 315, 1857-1859.
36. Fortune, M.T., Vassilopoulos, C., Coolbaugh, M.I., Siciliano, M.J. and Monckton, D.G. (2000) Dramatic, expansion-biased, age-dependent, tissue-specific somatic mosaicism in a transgenic mouse model of triplet repeat instability. Hum. Mol. Genet., 9, 439-445.
37. Watase, K., Venken, K.J., Sun, Y., Orr, H.T. and Zoghbi, H.Y. (2003) Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1. Hum. Mol. Genet., 12, 2789-2795.
38. Kaplan, S., Itzkovitz, S. and Shapiro, E. (2007) A universal mechanism ties genotype to phenotype in trinucleotide diseases. PLoS Comput. Biol., 3, e235.
39. Cannella, M., Maglione, V., Martino, T., Ragona, G., Frati, L., Li, G. and Squitieri, F. (2009) DNA instability in replicating Huntington's disease lymphoblasts. BMC Med. Genet., 10, 11.
40. Verny, C., Allain, P., Prudean, A., Malinge, M.C., Gohier, B., Scherer, C., Bonneau, D., Dubas, F. and Le Gall, D. (2007) Cognitive changes in asymptomatic carriers of the Huntington disease mutation gene. Eur. J. Neurol., 14, 1344-1350.
41. Paulsen, J.S., Langbehn, D.R., Stout, J.C., Aylward, E., Ross, C.A., Nance, M., Guttman, M., Johnson, S., MacDonald, M., Beglinger, L.J. et al. (2008) Detection of Huntington's disease decades before diagnosis: The Predict-HD study. J. Neurol. Neurosurg. Psychiatr., 79, 874-880.
42. Rosas, H.D., Salat, D.H., Lee, S.Y., Zaleta, A.K., Pappu, V., Fischl, B., Greve, D., Hevelone, N. and Hersch, S.M. (2008) Cerebral cortex and the clinical expression of Huntington's disease: Complexity and heterogeneity. Brain, 131, 1057-1068.
43. Ashizawa, T., Dubel, J.R. and Harati, Y. (1993) Somatic instability of CTG repeat in myotonic dystrophy. Neurology, 43, 2674-2678.
44. Owen, B.A., Yang, Z., Lai, M., Gajek, M., Badger, J.D. 2nd, Hayes, J.J., Edelmann, W., Kucherlapati, R., Wilson, T.M. and McMurray, C.T. (2005) (CAG)(n)-hairpin DNA binds to Msh2-Msh3 and changes properties of mismatch recognition. Nat. Struct. Mol. Biol., 12, 663-670.
45. Kovtun, I.V., Liu, Y., Bjoras, M., Klungland, A., Wilson, S.H. and McMurray, C.T. (2007) OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature, 447, 447-452.
46. Manley, K., Shirley, T.L., Flaherty, L. and Messer, A. (1999) Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice. Nat. Genet., 23, 471-473.
47. Warner, J.P., Barron, L.H. and Brock, D.J. (1993) A new polymerase chain reaction (PCR) assay for the trinucleotide repeat that is unstable and expanded on Huntington's disease chromosomes. Mol. Cell Probes, 7, 235-239.