A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes

@article{MacDonald1993ANG,
  title={A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes},
  author={Marcy E. MacDonald and Christine M. Ambrose and Mabel P. Duyao and Richard H. Myers and Carol Lin and Lakshmi Srinidhi and Glenn T. Barnes and Sherryl A. M. Taylor and Marianne F. James and Nicolet Groot and Heather Macfarlane and Barbara Jenkins and Mary Anne Anderson and Nancy S Wexler and James F. Gusella and Gillian P Bates and Sarah Baxendale and Holger Hummerich and Susan F. Kirby and Michael Aidan North and Sandra Youngman and Richard F Mott and G{\"u}nther Zehetner and Zdenek Sedlacek and Annemarie Poustka and A. -M. Frischauf and Hans Lehrach and Alan Buckler and Deanna M. Church and Lynn Doucette‐Stamm and Michael C. O’Donovan and Laura Riba-Ram{\'i}rez and Manish S. Shah and Vincent P Stanton and Scott A. Strobel and Karen M. Draths and Jennifer L. Wales and Peter B. Dervan and David E Housman and Michael Altherr and Rita Shiang and Leslie M. Thompson and Thomas J. Fielder and John J. Wasmuth and Danilo A Tagle and John Valdes and Lon Elmer and Marc Allard and Lucio H Castilla and Manju Swaroop and Kris Blanchard and Francis S. Collins and Russell G. Snell and Tracey Holloway and Kathleen Gillespie and Nicole A Datson and Duncan J. Shaw and P S Harper},
  journal={Cell},
  year={1993},
  volume={72},
  pages={971-983}
}
The Huntington's disease (HD) gene has been mapped in 4p16.3 but has eluded identification. [...] Key Result A (CAG)n repeat longer than the normal range was observed on HD chromosomes from all 75 disease families examined, comprising a variety of ethnic backgrounds and 4p16.3 haplotypes. The (CAG)n repeat appears to be located within the coding sequence of a predicted approximately 348 kd protein that is widely expressed but unrelated to any known gene. Thus, the HD mutation involves an unstable DNA segment…Expand
Mouse Huntington's disease gene homolog (Hdh)
TLDR
The absence of a long CAG repeat in the mouse is consistent with the lack of a spontaneous mouse model of HD, and the information presented concerning the sequence of the mouse gene should facilitate attempts to create such a model. Expand
Structure and expression of the Huntington's disease gene: Evidence against simple inactivation due to an expanded CAG repeat
TLDR
Observations suggest that the dominant HD mutation either confers a new property on the mRNA or alters an interaction at the protein level, suggesting the operation of interacting factors in determining specificity of cell loss. Expand
Trinucleotide repeat expansions and human genetic disease.
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TLDR
The cloning of two regions at which chromosome breakage can be induced has in each case uncovered an unstable CG-rich triplet repeat which becomes methylated when fully expanded, suggesting a common basis to the observed phenotypes. Expand
Analysis of triplet repeats in the huntingtin gene in Japanese families affected with Huntington's disease.
TLDR
Strong linkage disequilibrium was found between the CAG repeat expansion and an allele of (CCG)10 in JapaneseHD chromosomes in Japanese HD chromosomes, distinct from that described previously in western populations. Expand
A novel long and unstable CAG/CTG trinucleotide repeat on chromosome 17q.
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The size of the CAG/CTG repeat of allele L is within the range of the expanded CAG repeat of disease-causing genes, but it did not detect any association of phenotype L with various neurodegenerative diseases, including frontotemporal dementia and parkinsonism. Expand
Genetic Modifiers of CAG.CTG Repeat Instability in Huntington's Disease Mouse Models
TLDR
Significant data have revealed that the absence of proteins from the mismatch repair (MMR) or the base and nucleotide excision repair decreased the pathogenic expansion‐biased somatic mosaicism and/or intergenerational expansions. Expand
Accurate sizing of (CAG)n repeats causing Huntington disease by fluorescent PCR.
TLDR
The mutation mechanism was found to be the expansion of a CAG repeat in the 5′-translated region of the HD gene, which leads to the characteristic clinical symptoms and neuropathology of HD. Expand
Functional characterization of the human Huntington's disease gene promoter.
TLDR
Partial deletion of the evolutionarily conserved part of the promoter significantly reduces the activity in both neuronal and non-neuronal cells indicating that the core promoter activity is located between nucleotides -221 and 4, relative to the +1 translation start site. Expand
Trinucleotide repeat analysis of Huntington's disease gene in Singapore.
TLDR
The range of CAG repeats in the normal and HD alleles in the population is similar to those reported elsewhere. Expand
Normal and Expanded Huntington’s Disease Gene Alleles Produce Distinguishable Proteins Due to Translation Across the CAG Repeat
TLDR
The HD mutation does not eliminate expression of the HD gene but instead produces an altered protein with an expanded polyglutamine stretch near the N terminus, indicating that HD pathogenesis is probably triggered by an effect at the level of huntingtin protein. Expand
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TLDR
Increases in the size of the allele in patients with DM are now shown to be due to an increased number of trinucleotide CTG repeats in the 3' untranslated region of a DM candidate gene. Expand
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TLDR
The results argue against a telomeric location for HD and suggest that the HD mutation in this family is either associated with DNA predisposed to double recombination and/or gene conversion within the 6-Mb region or is in a gene that is outside this region and that is different from that mutated in most other families with HD. Expand
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Nucleotide sequence analysis of a cDNA clone derived from the HD gene region has revealed that it encodes a member of the fibroblast growth factor subfamily of tyrosine kinase receptors, some members of which are known to be involved in the differentiation and survival of certain cell types within the central nervous system. Expand
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Comparison of closely spaced marker pairs on normal and HD chromosomes, as well as analysis of haplotypes across the HD region, suggest that simple recombination subsequent to a single original HD mutation cannot easily explain the pool of HD chromosomes seen today. Expand
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TLDR
Eight new DNA polymorphisms spanning the Huntington's disease candidate region should prove valuable for analysis of recombination and linkage disequilibrium inHD, as well as for preclinical diagnosis of the disorder. Expand
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A fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes is identified and localization of the brain-expressed FMR-1 gene to this EcoRI fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome. Expand
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TLDR
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TLDR
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TLDR
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