Trinucleotide Repeat Expansions: Mechanisms and Disease Associations

Jörg T Epplen, Ruhr‐University, Bochum, Germany
Stefan Wieczorek, Ruhr‐University, Bochum, Germany

Published online: September 2007

DOI: 10.1002/9780470015902.a0005067.pub2

Trinucleotide (and selected other) repeat expansions may cause severe neurodegenerative disorders with adult onset. Either elongated polyglutamine/polyalanine blocks, toxic polyglutamine peptides or reduced gene expression are responsible for the differential pathogenesis of this rather novel disease category.

Keywords: DNA expansion; neurodegeneration; dynamic mutation; simple repetitive DNA; trinucleotide repeats

Figure 1. Schematic representation of genes and their trinucleotide blocks involved in selected repeat expansion diseases other than polyglutamine disorders (black bars, protein coding parts). Detailed exon–intron structures of the genes are not shown or have been minimized to demonstrate intronic localization of the repeat blocks. The physiological length ranges of the polymorphic simple repeat tracts are enumerated in the tips of the inverted triangles (grey), whereas the pathological range is annotated in the darkly shaded top portion of each triangle.
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 Further Reading
    Albrecht A and Mundlos S (2005) The other trinucleotide repeat: polyalanine expansion disorders. Current Opinion in Genetics and Development 15(3): 285–293.
    ePath Androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) (AR); LocusID: 367. Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene & cmd=Retrieve & dopt=summary & list_uids=367
    ePath Androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) (AR); MIM number: 313700. OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=313700
    ePath Cystatin B (stefin B) (CSTB); LocusID: 1476. Entrez Gene: www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene & cmd=Retrieve & dopt=summary & list_uids=1476
    ePath Cystatin B (stefin B) (CSTB); MIM number: 601145. OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601145
    ePath Fragile X mental retardation 1 (FMR1); LocusID: 2332. Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene & cmd=Retrieve & dopt=summary & list_uids=2332
    ePath Fragile X mental retardation 1 (FMR1); MIM number: 309550. OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=309550
    ePath Friedreich ataxia (FRDA); LocusID: 2395. Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene & cmd=Retrieve & dopt=summary & list_uids=2395
    ePath Friedreich ataxia (FRDA); MIM number: 606829. OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606829
    Gatchel JR and Zoghbi HY (2005) Diseases of unstable repeat expansion: mechanisms and common principles. Nature Reviews Genetics 6(10): 743–755.
    ePath Spinocerebellar ataxia 8 (SCA8); LocusID: 6315. Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene & cmd=Retrieve & dopt=summary & list_uids=6315
    ePath Spinocerebellar ataxia 8 (SCA8); MIM number: 603680. OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603680

Related Sub-Topics:

Neurobiology of Disease | Neurons | Molecular Genetics of Common and Complex Disease | Genetics of Intelligence and Cognition | Mutational Mechanisms of Genetic Disease | Gene and Genome Structure and Organisation | Chromosomes and Chromatin Modifications | DNA Damage and Repair | Mechanisms of Cell Death, Senescence and Metabolism
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Article Title: Trinucleotide Repeat Expansions: Mechanisms and Disease Associations
 
How to Cite close
Epplen, Jörg T, and Wieczorek, Stefan(Sep 2007) Trinucleotide Repeat Expansions: Mechanisms and Disease Associations. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005067.pub2]