Dynamic mutations in human genes: A review of trinucleotide repeat diseases

1996 ◽  
Vol 75 (2) ◽  
pp. 193-217 ◽  
Author(s):  
John W. Longshore ◽  
Jack Tarleton

2003 ◽  
Vol 18 (9) ◽  
pp. 1041-1044 ◽  
Author(s):  
Ruth H. Walker ◽  
Paul F. Good ◽  
P. Shashidharan




1996 ◽  
Vol 42 (10) ◽  
pp. 1582-1588 ◽  
Author(s):  
R C McGlennen

Abstract Routine clinical molecular testing of diseases associated with unstable or dynamic trinucleotide repeat syndromes poses unique technical, medical, and ethical challenges to the laboratory. Although the pathophysiology of these disorders is to date still largely undefined, the uniformity of their genetics has led to the development of highly informative diagnostic tests. In general, amplification techniques, such as the polymerase chain reaction (PCR), are used to determine the size of alleles within the genes linked to these disorders. Technically, these assays require empirical optimization so that the PCR reactions are both robust and reproducible, and occasionally other methods must be used to confirm diagnoses. Beyond execution of the test, however, the molecular diagnostics laboratory needs also to be fundamentally involved in the process of interpreting these tests in the correct clinical context and in setting policy as to how these data are presented to patients.



2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammadmersad Ghorbani ◽  
Simon J. E. Taylor ◽  
Mark A. Pook ◽  
Annette Payne

Previous studies have examined DNA methylation in different trinucleotide repeat diseases. We have combined this data and used a pattern searching algorithm to identify motifs in the DNA surrounding aberrantly methylated CpGs found in the DNA of patients with one of the three trinucleotide repeat (TNR) expansion diseases: fragile X syndrome (FRAXA), myotonic dystrophy type I (DM1), or Friedreich’s ataxia (FRDA). We examined sequences surrounding both the variably methylated (VM) CpGs, which are hypermethylated in patients compared with unaffected controls, and the nonvariably methylated CpGs which remain either always methylated (AM) or never methylated (NM) in both patients and controls. Using the J48 algorithm of WEKA analysis, we identified that two patterns are all that is necessary to classify our three regions CCGG* which is found in VM and not in AM regions and AATT* which distinguished between NM and VM + AM using proportional frequency. Furthermore, comparing our software with MEME software, we have demonstrated that our software identifies more patterns than MEME in these short DNA sequences. Thus, we present evidence that the DNA sequence surrounding CpG can influence its susceptibility to bede novomethylated in a disease state associated with a trinucleotide repeat.



2020 ◽  
Vol 1 (337) ◽  
pp. 25-32 ◽  
Author(s):  
Belkozhayev A.M. ◽  
Niyazova R.Ye.

Trinucleotide repeat expansion disorders constitute a group of dominantly inherited neurological diseases that are incurable and ultimately fatal. In the present work, miRNA binding sites were predicted by the MirTarget program. It was given characteristics of miRNAs binding sites in 5' and 3' UTR mRNAs genes of non-polyglutamine trinucleotide disorders with CGG, GCC, CUG repeats. Binding sites of 2567 miRNAs with mRNAs of 17494 human genes were determined. 206 genes with nucleotide repeats, mRNAs of which are bind with miRNA in the 5'UTR and 3'UTR, were observed. From thus, 2668 miRNAs binding sites are located in the 5'UTR, 3853 – in the 3'UTR with ΔG/ΔGm values equal to 85 % and more. It was found that 34 gene’s mRNA having trinucleotide (CGG\GCC\CUG) repeats were targets for miR-4258, miR-3960 miR-211-3p and miR-3155b. miR-4258 binds to mRNA of ADARB1, C11orf87 and CBFB genes with free binding energy - 93 kJ/mole and ΔG/ΔGm 91%, to mRNA of ARHGEF7, BCR, BRSK2 and C9orf91 genes with free binding energy - 91 kJ/mole and ΔG/ΔGm 89%. miR-3960 binds in GCC repeats to mRNA of ABCC1 and BLMH genes with free binding energy - 116 kJ/mole. miR-211-3p and miR-3155b interact with mRNA of ACACA and ANKRD13D genes in 5’-3’untranslated regions. Studying binding characteristics of miRNA and genes will help identify association of miRNAs with genes with trinucleotide repeats for recommending for the diagnosis of nucleotide repeat expansion disorders.



2018 ◽  
Vol 42 (12) ◽  
pp. 9757-9763 ◽  
Author(s):  
Yalan Liu ◽  
Jiao Li ◽  
Gang Chang ◽  
Ruizhi Zhu ◽  
Hanping He ◽  
...  

The combination of SPCE and magnetic beads simplifies the experimental procedure, which is useful for early diagnosis of trinucleotide repeat diseases.





1998 ◽  
Vol 8 (3) ◽  
pp. 321-330 ◽  
Author(s):  
Christopher E Pearson ◽  
Richard R Sinden




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