CTG Triplet Repeats from Human Hereditary Diseases Are Dominant Genetic Expansion Products in Escherichia coli(*)

The relative ability of the 10 triplet repeat sequences to be expanded in Escherichia coli was determined. Surprisingly, CTG tracts are expanded at least 8 times more frequently than any of the other nine triplets. Low levels of expansion were found also for CGG, GTG, and GTC. Thus, the structure of the CTG repeats and/or their utilization by the DNA synthetic systems in vivo must be quite different from the other triplets. These data further validate this genetically defined system for elucidating molecular mechanisms of expansion and may explain why most triplet repeat hereditary neuromuscular and neurodegenerative disease genes contain CTG repeats.

[1]  C. Amemiya,et al.  Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. , 1992, Science.

[2]  Darryl Shibata,et al.  Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis , 1993, Nature.

[3]  H. Zoghbi,et al.  Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I , 1993, Nature Genetics.

[4]  M. Pericak-Vance,et al.  The Haw River Syndrome: Dentatorubropallidoluysian atrophy (DRPLA) in an African–American family , 1994, Nature Genetics.

[5]  J. Weber Informativeness of human (dC-dA)n.(dG-dT)n polymorphisms. , 1990, Genomics.

[6]  J. Weber,et al.  Survey of human and rat microsatellites. , 1992, Genomics.

[7]  T. Kamp,et al.  Hairpin properties of single-stranded DNA containing a GC-rich triplet repeat: (CTG)15. , 1995, Nucleic acids research.

[8]  K. Fischbeck,et al.  Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy , 1991, Nature.

[9]  M. Stratton,et al.  Instability of short tandem repeats (microsatellites) in human cancers , 1994, Nature Genetics.

[10]  J. Sutcliffe,et al.  Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome , 1991, Cell.

[11]  A. Sano,et al.  Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p , 1994, Nature Genetics.

[12]  W. J. Dower,et al.  High efficiency transformation of E. coli by high voltage electroporation , 1988, Nucleic Acids Res..

[13]  O. Onodera,et al.  Unstable expansion of CAG repeat in hereditary dentatorubral–pallidoluysian atrophy (DRPLA) , 1994, Nature Genetics.

[14]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.

[15]  K. Kinzler,et al.  Clues to the pathogenesis of familial colorectal cancer. , 1993, Science.

[16]  T. Ashizawa,et al.  An unstable triplet repeat in a gene related to myotonic muscular dystrophy. , 1992, Science.

[17]  S N Thibodeau,et al.  Microsatellite instability in cancer of the proximal colon. , 1993, Science.

[18]  R. Wells,et al.  Preferential nucleosome assembly at DNA triplet repeats from the myotonic dystrophy gene. , 1994, Science.

[19]  I. Haworth,et al.  The trinucleotide repeat sequence d(GTC)15 adopts a hairpin conformation. , 1995, Nucleic acids research.

[20]  E. Eichler,et al.  Anomalous rapid electrophoretic mobility of DNA containing triplet repeats associated with human disease genes. , 1995, Biochemistry.

[21]  Peter Beighton,et al.  de la Chapelle, A. , 1997 .

[22]  Huda Y. Zoghbi,et al.  Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1 , 1993, Nature Genetics.

[23]  E. Eichler,et al.  Length of uninterrupted CGG repeats determines instability in the FMR1 gene , 1994, Nature Genetics.

[24]  A. Marquis Gacy,et al.  Trinucleotide repeats that expand in human disease form hairpin structures in vitro , 1995, Cell.

[25]  J. Longshore,et al.  Over-representation of the disease associated (CAG) and (CGG) repeats in the human genome. , 1994, Nucleic acids research.

[26]  K. Davies,et al.  Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation , 1993, Cell.

[27]  G. Fox,et al.  DNA CTG triplet repeats involved in dynamic mutations of neurologically related gene sequences form stable duplexes. , 1995, Nucleic acids research.

[28]  Shigenobu Nakamura,et al.  CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1 , 1994, Nature Genetics.

[29]  R. Sinden,et al.  Mismatch repair in Escherichia coli enhances instability of (CTG)n triplet repeats from human hereditary diseases. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Keiichi Ohshima,et al.  Expansion and deletion of CTG repeats from human disease genes are determined by the direction of replication in E. coli , 1995, Nature Genetics.

[31]  R. Wells,et al.  Pausing of DNA Synthesis in Vitro at Specific Loci in CTG and CGG Triplet Repeats from Human Hereditary Disease Genes (*) , 1995, The Journal of Biological Chemistry.

[32]  K. Lindblad,et al.  Growing triplet repeats , 1994, Nature Genetics.