Trinucleotide Repeats

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

La Spada, A. R., Roling, D. B., Harding, A. E. et al. Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. Nat. Genet. 2 301-304,1992. 

Dentatorubalpallidoluysian atrophy (DRPLA) Autosomal dominant CAG trinucleotide repeat... 

Huntington s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington s disease chromosomes. Cell 72 971-983,1993. 

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]... 

Trinucleotide Repeats Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes, [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... 

Answer A. The presence of an expanded trinucleotide repeat in 5 untranslated region of the gene is an accurate test for fragile X syndrome. 

T. Nenguke, M. I. Aladjem, J. F. Gusella, N. S. Wexler, and N. Arnheim, Candidate DNA replication initiation regions at human trinucleotide repeat disease loci. Hum. Mol. Genet. 12, 1021-1028 (2003). 

Trinucleotide repeat disorders. Annual Revieiv of Neuroscience, 30, 575-621. 

Protein NMR Techniques, Second Edition, edited by A. Kristina Downing, 2004 277. Trinucleotide Repeat Protocols, edited by... 

Slipped mispairing at the replication fork can cause repeated copying of some sequences within the tract and thus lead to expansion of trinucleotide repeat (TNR) tracts at the 5 ends of certain genes. 

Examp 1 es of genetic diseases that show anticipation are Huntington disease, Fragile X syndrome, and other disorders that arise from trinucleotide repeat... 

Disease symptoms occur only when the length of the trinucleotide repeat region exceeds a threshold. 

Cummings CJ, Zoghbi HY. Fourteen and counting unraveling trinucleotide repeat diseases. Hum Mol Genet 2000 9 909 -916. 

Repeat expansion Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated. This type of mutation can cause the resulting protein to function improperly. 

Warren, S. (1996) The expanding world of trinucleotide repeats. Science 271 1374-1375. 

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