Trinucleotide Repeat Expansion

Trinucleotide Repeat Expansion DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats, [nih]... 

Mutation in spUce site Trinucleotide repeat expansion i... 

Diseases caused by trinucleotide repeat expansion that niay show anticipation in a pedigree ... 

Thi autosomal dominant disorder, which affects approximately 1 in 8,000 individuals, is characterized by progressive muscle deterioration, cardiac arrhythmia, testicular atrophy, frontal baldness, and cataraas. As noted above, most cases are caused by a trinucleotide repeat expansion in the 3 UTR of a gene that encodes a protein kinase. Larger repeat numbers lead to earlier and more severe expression of the disease (anticipation). Especially large expansions sometimes occur in maternal transmission of the trinucleotide repeat, resulting in a severe neonatal form of the disorder. 

A. Genetic test for a trinucleotide repeat expansion in the fir ile X gene... 

Margolis RL, Mclnnis MG, Rosenblatt A, Ross CA. 1999. Trinucleotide repeat expansion and neuropsychiatric disease. Arch Gen Psychiatry 56(11) 1019-1031. 

Huntingtin (htt) a causative gene of Huntington s Disease (HD), with its N-terminal CAG trinucleotide repeat expansion correlated with the onset of the disease. Predicted to function as a scaffolding molecule for multiple transporting/transcrip-tional molecules in cytoplasm and nucleus. Inclusion of htt and/or its N-terminal polyglutamine tract have been proposed as a potential mechanism of neurodegeneration in HD. 

The remaining mutations are mostly larger lesions and comprise only 7% of human mutations. These include whole gene duplications and deletions, SSR expansions (e.g., trinucleotide repeat expansions), gene rearrangements (e.g., B-and T-cell gene rearrangements), and complex polymorphic loci related to health and disease (e.g., HLA). 

Lazarou LP, Davies P, et al. Relationship between trinucleotide repeat expansion and phenotypic variation in Huntingtons disease. Nat Gent 1993 4 393-7. 

Trinucleotide repeat expansion Amplification from one generation to the next of three nucleotide repeats in the coding or noncoding regions of DNA. The mechanism may arise from DNA complimentary strand slippage. This is associated with fragile X syndrome and myotonic dystrophy. 

Brooks, B.P. and Fischbeck, K.H. (1995) Spinal and bulbar muscular atrophy a trinucleotide-repeat expansion neurodegenerative disease. Trends in Neurosciences, 18, 459-461. 

Feng, Y., et al.. Translational suppression by trinucleotide repeat expansion at FMRI. Science, 1995.268(5211) p. 731-4. 

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