Conclusion
As discussed in the present review, many challenging issues regarding the molecular mechanisms of neurodegeneration are associated with investigation of triplet repeat diseases. Since the molecular structures of the causative genes for triplet repeat diseases have been fully elucidated, triplet repeat diseases no doubt offer the best model systems to investigate the pathophysiology of neurodegenerative diseases, and it is strongly expected that creation of animal models of human diseases and development of cell culture systems for investigation of neuronal toxicity caused by triplet repeat expansions will be a crucial step for development of therapeutic measures for triplet repeat diseases.
Similar content being viewed by others
Article PDF
References
Basset ASet al. (1994): Evidence for anticipation in schizophrenia. Am J Hum Genet54: 864–870
Brook JD, McCurrach ME, Harley HGet al. (1992): Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell68: 799–808
Burke JR, Enghild JJ, Martin MEet al. (1996): Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nature Med2: 347–350
Campuzano V, Montermini L, Molto MDet al. (1996): Friedreich's ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science271: 1423–1427
Carey N, Johnson K, Nokelainen Oet al. (1995): Meiotic drive and myotonic dystrophy. (Reply) Nature Genet10: 133
Evans K, Fryer A, Inglehearn C, Young DJet al. (1994): Genetic linkage of cone-rod retinal dystrophy to chromosome 19q and evidence for segregation distortion. Nature Genet6: 210–213
Fu YH, Pizzuti A, Fenwick RG Jret al. (1992): An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science255: 1256–1258
Goldberg YP, Nicholson DW, Rasper DMet al. (1996): Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nature Genet13: 442–449
Gouw LGet al. (1994): Autosomal dominant cerebellar ataxia with retinal degeneration: clinical, neuropathologic, and genetic analysis of a large kindred. Neurology44: 1441–1447
Hunter AGW, Jacob P, O'hoy Ket al. (1993): Decrease in the size of the myotonic dystrophy CTG repeat during transmission from parent to child: Implications for genetic counselling and genetic anticipation. Am J Med Genet45: 401–407
Hurst GDD, Hurst LD, Barrett JA (1995): Meiotic drive and myotonic dystrophy. Nature Genet10: 132–133
Igarashi S, Takiyama Y, Cancel Get al. (1995): Intergenerational instability of the CAG repeat of the gene for Machado-Joseph disease (MJD1) is affected by the genotype of the normal chromosome.-Implication for the molecular mechanism of the instability of the CAG repeat. Hum Mol Genet4: 1137–1146
Ikeda H, Yamaguchi M, Sugai S, Aze Y, Narumiya S, Kakizuka A (1996): Xpanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nature Genet13: 196–202
Ikeuchi T, Igarashi S, Takiyama Yet al. (1966): Non-Mendelian transmission in dentatorubral-pallidoluysian atrophy and Machado-Joseph disease: The mutant allele is preferentially transmitted in male meiosis. Am J Hum Genet58: 730–733
Ikeuchi T, Koide R, Tanaka H (1995a): Dentatorubral-pallidoluysian atrophy (DRPLA): Clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat. Ann Neurol37: 769–775
Ikeuchi T, Onodera O, Oyake Met al. (1995b): Dentatorubral-pallidoluysian atrophy (DRPLA)-Close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation. Semin Cell Biol6: 37–44
Ikeuchi T, Onodera O, Tanaka Het al. (1995c): Dentatorubral-pallidoluysian atrophy (DRPLA). Clin Neurosci3: 23–27
Jarvik GP, Patton MA, Homfray Tet al. (1994): Non-Mendelian transmission in a human developmental disorder: split hand/split foot. Am J Hum Genet55: 710–713
Jeffrey AJ, Tamaki K, MacLeod Aet al. (1994): Complex gene conversion events in germline mutation at human minisatellites. Nature Genet6: 136–145
Kawaguchi Yet al. (1994): CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nature Genet8: 221–227
Koide R,et al. (1994): Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nature Genet6: 9–13
Kremer EJ, Pritchard M, Lynch M, Yu Set al. (1991): Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science252: 1711–1714
La Spada AR, Wilson EM, Lubahn DB (1991): Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature352: 77–79
Lang AE, Rogaeva EA, Tsuda Tet al. (1994): Homozygous inheritance of the Machado-Joseph disease gene. Ann Neurol36: 443–447
Li X-J, Li S-H, Sharp AHet al. (1995): A huntingtin-associated protein enriched in brain with implications for pathology. Nature378: 398–402
Lyttle TW (1993): Cheaters sometimes prosper: distortion of Mendelian segregation by meiotic drive. Trends Genet9: 205–210
Mahadevan M, Tsilfidis C, Sabourin L (1992): Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science255: 1253–1255
Mclnnis MG, McInnis MG, McMahon FJ, Chase GA, Simpson SG, Ross CA, DePaulo JRet al. (1993): Anticipation in bipolar affective disorder. Am J Hum Genet53: 385–390
Munier F, Spence MA, Pescica Get al. (1992): Paternal selection favoring mutant alleles of the retinoblastoma susceptibility gene. Hum Genet89: 508–512
Nagafuchi Set al. (1994a): Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nature Genet6: 14–18
Nagafuchi Set al. (1994b): Structural and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA). Nature Genet8: 177–181
Naito N, Oyanagi S (1982): Familial myoclonus epilepsy and choreoathetosis; Hereditary dentatorubral-pallidoluysian atrophy. Neurology32: 789–817
Oberle I, Rousseau F, Heitz Det al. (1991): Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science252: 1097–1102
O'Hoy KL, Tsilfidis C, Mahadevan MSet al. (1993): Reduction in size of the myotonic dystrophy trinucleotide repeat mutation during transmission. Science259: 809–812
Onodera Oet al. (1995): Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of the expanded alleles in the CNS. Am J Hum Genet57: 1050–1060
Orr HTet al. (1993): Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nature Genet4: 221–226
Raju NB, Perkins DD (1991): Expression of meiotic drive elements spore killer 2 and spre killer 3 in asci of neurospora tetrasperma. Genetics129: 25–37
Ranum LPWet al. (1994): Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. Nature Genet8: 280–284
Sato K, Kashihara K, Okada Sea al. (1995): Does homozygous type CAG trinucleotide repeat expansion advance the onset of dentatorubral-pallidoluysian atrophy? Neurology45: 1934–1936
Silver LM (1993): The peculiar journey of a selfish chromosome: mouse t haplotypes and meiotic drive. Trends Genet9: 250–254
Takano H, Onodera Oet al. (1996): Somatic mosaicism of expanded CAG arrays in brain of dentatorubral-pallidoluysian atrophy (DRPLA): Age-and cellular population-dependent dynamics of mitotic instability. Am J Hum Genet58: 1212–1222
Takiyama Y, Igarashi S, Rogaeva EAet al. (1995): Evidence for inter-generational instability in the CAG repeat on the MJD1 gene and for conserved haplotypes at flanking markers amongst Japanese and Caucasian subjects with Machado-Joseph disease. Hum Mol Genet4: 1137–1146
Telenius H, Kremer B, Goldberg YPet al. (1994): Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nature Genet6: 409–414
The Huntington's Disease Collaborative Research Group (1993): A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell72: 971–983
Ueno S, Kondoh K, Kotani Yet al. (1995): Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA). Hum Mol Genet4: 663–666
Verkerk AJ, Pieretti M, Sutcliffe JSet al. (1991): Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile syndrome. Cell65: 905–914
Wexler NS, Young AB, Tanzi REet al. (1987): Homozygotes for Huntington's disease. Nature326: 194–197
Yu S, Pritchard M, Kremer Eet al. (1991): Fragile X genotype characterized by an unstable region of DNA. Science252: 1179–1181
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tsuji, S. Unstable expansion of triplet repeats as a new disease mechanism for neurodegenerative diseases. Jap J Human Genet 41, 279–290 (1996). https://doi.org/10.1007/BF01913170
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01913170
Keywords
This article is cited by
-
Human genetics: Past, present, and future, with special reference to major trends in Japan
Japanese Journal of Human Genetics (1997)