Repeat expansion

In Huntington s disease the polyglutamine repeat expansion in exon 1 of HD leads to a toxic gain of the protein huntingtin (htt). Harper et al. could show that siRNA directed against mutant human htt reduced htt iriRNA and protein expression in cell culture and in HD... 

Davies SW, Beardsall K, Turmaine M, DiFiglia M, Aronin N, Bates GP. Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions Lancet 1998 351 131-133. 

Bates GP, Mangiarini L, Davies SW. Transgenic mice in the study of polyglutamine repeat expansion diseases. Brain Pathol 1998 8 699-714. 

Usdin K, Grabczyk E. DNA repeat expansions and human disease. Cell Mol Life Sci 2000 57[6] 914-931. 

Lieberman AP, Fischbeck KH. Triplet repeat expansion in neuromuscular disease. Muscle Nerve 2000 23[6] 843—850. 

Friedreich s ataxia is caused by an intronic triplet repeat expansion. Friedreich s ataxia is an autosomal recessive disorder characterized by progressive ataxia, nystagmus, distal sensory polyneuropathy and corticospinal tract degeneration. It is caused by an unstable expanded GAA repeat in intron 1 of the frataxin gene on chromosome 9ql3. This diminishes expression of frataxin, a mitochondrial iron-storage protein that participates in free radical metabolism [71]. 

The unusual multisystemic clinical parallels between DM1 and DM2 suggest a similar pathogenic mechanism. The discovery that DM2 mapped to chromosome 3 and not to the DM1 region of chromosome 19 makes it unlikely that specific gene expression defects cause the common clinical features of the disease. The discovery that a CCTG repeat expansion located on chromosome 3... 

Ikeuchi, T., Takano, H., Koide, R. et al Spinocerebellar ataxia type 6 CAG repeat expansion in alA voltage-dependent calcium channel gene and clinical variations in Japanese population. Ann. Neurol 42 879-884,1997. 

David, G., Abbas, N., Stevanin, G. etal Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat. Genet. 17 65-70,1997. 

The energy imparted to the ions depends on the energy of the rf pulse and the duration of the pulse. The energy does not have to be raised in one event but may be absorbed by the ion in small portions. A technique called sustained off-resonance excitation (SORT) (82) uses a low-amplitude rf pulse that is off-resonance to the ion cyclotron frequency. The difference of the cyclotron frequency and the excitation frequency (-500 Hz) causes the ion to experience in- and out-of-phase excitation that has the effect of a repeated expansion and shrinkage of the cyclotron orbit. In this process, the ion undergoes a large number of low-energy collisions and the Ecom slowly increases until the ion dissociates. 

Repeat expansion Nudeotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinudeotide repeat is made up of 3-base-pair sequences, and a tetranudeotide 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. 

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]... 

Triplet repeat expansion Expansions in coding regions cause protein product to be longer than normal and unstable. Disease often shows anticipation in pedigree. 

Mutation in spUce site Trinucleotide repeat expansion i... 

Answer C, PCR primers flanking the mutation, as well as Southern blottii would be needed to detect the extent of the triplet repeat expansion. 

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... 

In fragile X syndrome, triplet repeat expansions are responsible for the majority of cases. It should be noted, however, that any mutation that disrupts the functional activity of the FMRl protein could lead to a similar phenotype. This was in fact established when a patient with severe fragile X syndrome was found who did not have a triplet repeat expansion. Rather, this patient had a point mutation that changed a highly conserved amino acid within the RNA-binding domain of the FMRl protein (De Boulle et al., 1993 Siomi et al., 1994 Musco et... 

Sidransky, E., Burgess, C., Ikeuchi, T., Lindblad, K., Long, R.T., Philibert, R.A., Rapoport, J., Schalling, M., Tsuji, S., and Ginns, E.I. (1998) A triplet repeat on 17q accounts for most expansions detected by the repeat-expansion-detection technique. Am ] Hum Genet 62 1548-1551. 

Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Canizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, DeMichele G, Filla A, DeFrutos R, Palau F, Patel PI, DiDonato S, Mandel JL, Cocozza S, Koenig M, Pandolfo M (1996) Friedreich s ataxia autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271 1423-1427... 

Fragile X families exhibit two types of FMR1 gene mutation. The repeat expansion of more than 230 copies with subsequent methylation of the CpG island is referred to as a full mutation. All males and about half of the females who carry full mutations have mental retardation. Mosaic males with full mutations are almost always affected to the same extent as fully affected males, while mosaic females vary in... 

Fortune MT, Kennedy JL, Vincent JB. 2003. Anticipation and CAG CTG repeat expansion in schizophrenia and bipolar affective disorder. Curr Psychiatry Rep 5(2) 145-154. 

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