Disease relevance of Dinucleotide Repeats

• METHODS: Dinucleotide repeat loci were analyzed by polymerase chain reaction from microdissected adenoma and/or carcinoma stages from formalin-fixed paraffin-embedded HNPCC tumors [1].
• A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology [2].
• These results provide evidence to suggest that there may be an unidentified locus for susceptibility to Parkinson's disease that is in linkage disequilibrium with dinucleotide repeat markers mapping near CYP2D6 on ch22q13 [3].
• Human hormone-sensitive lipase: genetic mapping, identification of a new dinucleotide repeat, and association with obesity and NIDDM [4].
• Whereas colorectal cancers displayed a predominant pattern consisting of instability at the BAT loci (in 89% of tumors), TGF beta RII (73%), dinucleotide repeats (70%), MSH3 (43%), and BAX (30%), no such single pattern was discernible in endometrial cancers [5].

Psychiatry related information on Dinucleotide Repeats

• Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse [6].
• Eighty-four unrelated Caucasian patients with DSM III-R bipolar disorder and 84 Caucasian controls were typed for three markers in MAOA: a dinucleotide repeat in intron 2, a VNTR in intron 1, and an Fnu4HI RFLP in exon 8 [7].
• In a sample of Caucasian male PTSD patients, dinucleotide repeat polymorphisms of the GABA(A) receptor beta 3 subunit gene were compared to scores on the General Health Questionnaire-28 (GHQ) [8].

High impact information on Dinucleotide Repeats

• A yeast strain containing a mutation in the PCNA gene had a strongly elevated mutation rate in a dinucleotide repeat, and the rate was not further elevated in a strain also containing a mutation in MLH1 [9].
• These data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene [10].
• Pima Indians were scored for genotypes at three polymorphic dinucleotide repeat loci (markers) near the gene TNF-alpha at 6p21 [11].
• Association between dinucleotide repeat in non-coding region of interferon-gamma gene and susceptibility to, and severity of, rheumatoid arthritis [12].
• The homopolymeric nucleotide tracts and dinucleotide repeats, which potentially regulate the on- and off-status of the target genes by the strand-slipped mispairing mechanism, are often found in the genes encoding the outer-membrane proteins, in enzymes for lipopolysaccharide synthesis, and within DNA modification/restriction systems [13].

Chemical compound and disease context of Dinucleotide Repeats

• Using a polymorphic dinucleotide repeat, we have investigated the contribution of the gene encoding the beta-subunit of the muscle acetylcholine receptor (CHRNB1), the target autoantigen, to the susceptibility to myasthenia gravis (MG) [14].
• The phospholipase C-gamma1 gene (PLCG1) and lithium-responsive bipolar disorder: re-examination of an intronic dinucleotide repeat polymorphism [15].
• Additionally, a variant number of dinucleotide-repeat sequences in the promotor for uridine 5'-diphosphate glucuronosyltransferase 1A1 influences the glucuronidation of SN-38, the active metabolite of irinotecan, which is associated with severe toxicity, including diarrhea and neutropenia [16].
• We evaluated the association between 3 polymorphisms in the SRD5A2 gene (2 single nucleotide polymorphism: alanine-49 to threonine [A49T] and valine-89 to leucine [V89L], and a (TA)n dinucleotide repeat in the 3' untranslated region), and BPH and prostate cancer within a multiethnic population [17].

Biological context of Dinucleotide Repeats

• We analyzed a set of polymorphic dinucleotide-repeat markers flanking the microdeletion on chromosome 17 in a group of seven unrelated families with a de novo NF1 microdeletion [18].
• We find significant linkage disequilibrium between CLN3 and the dinucleotide repeat marker loci D16S288 (chi 2(7) = 46.5, P < .005), D16S298 (chi 2(6) = 36.6, P < .005), and D16S299 (chi 2(7) = 73.8, P < .005), and also a novel RFLP marker at the D16S272 locus (chi 2(1) = 5.7, P = .02) [19].
• Direct DNA sequence analysis of the (dC-dA)n.(dG-dT)n locus in intron 49 revealed an additional length polymorphism which varies by single-basepair increments, is adjacent to the dinucleotide repeat block, and enhances the polymorphic content of this marker [20].
• A variable dinucleotide repeat in the CFTR gene contributes to phenotype diversity by forming RNA secondary structures that alter splicing [21].
• Using a new assay, we have also discovered that mutations in spel1 decrease the stability of a dinucleotide repeat when it is copied into the site of a double-strand break during gene conversion [22].

Anatomical context of Dinucleotide Repeats

• Mismatch repair (MMR)-proficient HCT116+chr3 and MMR-deficient HCT116 cells were transfected with pCMV-(CA)13-EGFP, a plasmid that contains a (CA)13 dinucleotide repeat, which disrupts the reading frame of the downstream enhanced green fluorescent protein gene [23].
• Glucose induces clonal selection and reversible dinucleotide repeat expansion in mesangial cells isolated from glomerulosclerosis-prone mice [24].
• To analyze AtMSH2 effects on germ line DNA fidelity, we measured insertion-deletion mutation of dinucleotide-repeat sequences (microsatellite instability) at nine loci in 16 or more progeny of two to four different wild-type or AtMSH2-deficient plants [25].
• This YAC includes two highly polymorphic dinucleotide repeat sequences that will facilitate genetic studies of the contribution of ADCYAP1R1 in disease states of the central nervous and neuroendocrine systems [26].
• Loss of heterozygosity of the NOS3 dinucleotide repeat marker in atherosclerotic plaques of human carotid arteries [27].

Associations of Dinucleotide Repeats with chemical compounds

• We demonstrate further that 3 alpha, 5 beta, 17 beta-dipyrandenium bound to poly(dA-dT) at low binding ratios induces a switch to the dinucleotide repeat conformation at adjacent steroid-free duplex regions [28].
• Right-handed alternating DNA conformation: poly(dA-dT) adopts the same dinucleotide repeat with cesium, tetraalkylammonium, and 3 alpha, 5 beta, 17 beta-dipyrrolidinium steroid dimethiodide cations in aqueous solution [28].
• Each internal eliminated sequence (IES) is bounded by 5'-TA-3' dinucleotide repeats, a feature common to some classes of DNA transposons [29].
• We have identified a compound dinucleotide repeat within intron 7 of the human erythroid 5-aminolevulinate synthase (ALAS2) gene with a minimum of 9 alleles and heterozygosity of 78% [30].
• From this we conclude that poly (rG-m5dC).poly (rG-m5dC) is in a regular A conformation in Tris buffer at low Na+ levels, shifting to an alternating A conformation with a dinucleotide repeat at intermediate salt concentrations [31].

Gene context of Dinucleotide Repeats

• We have used highly informative dinucleotide repeat markers mapping between D16S148 and D16S150 to refine the localization of CLN3 and to test for linkage to CLN2 [19].
• Like msh2 mutants in other species, we find that flies lacking the spel1 gene suffer a highly increased rate of instability in long runs of dinucleotide repeats when analyzed after 10-12 fly generations [22].
• Two polymorphic markers, one located in intron 8 and another, a dinucleotide repeat marker, AFMa086wg9, located within intron 2, were analyzed in paired blood-tumor DNA samples to assess hemizygous deletions of PTEN [32].
• Furthermore, a functional polymorphic dinucleotide repeat (TCTCT(TC)(n)) 500 bp upstream of the ATG translational start codon was found to regulate strongly the human HMGA2 promoter with an activation pattern that correlates to its TC-repeat length [33].
• We performed linkage analysis using chromosome 17q polymorphisms at D17S74, SCN4A, and GH1, two chromosome 7q31 restriction fragment length polymorphisms, and a dinucleotide repeat polymorphism within the CFTR gene (CFTR-DNR), in three pedigrees with ADMC [34].

Analytical, diagnostic and therapeutic context of Dinucleotide Repeats

• PCR detection of a dinucleotide repeat in the human histidine-rich glycoprotein (HRG) gene [35].
• After balloon angioplasty, carriers of the short length (<25 GT) dinucleotide repeats had a lower postintervention CRP at 24 h (p = 0.009) and 48 h (p < 0.001) and a reduced risk for restenosis (adjusted relative risk 0.43, 95% confidence interval: 0.24 to 0.71, p < 0.001) compared with patients with longer alleles [36].
• Linkage mapping of the human gene for the alpha 1 subunit of the cardiac DHP-sensitive Ca2+ channel (CACNL1A1) to chromosome 12p13.2-pter using a dinucleotide repeat [37].
• Use of a polymorphic dinucleotide repeat sequence to detect non-blastomeric contamination of the polymerase chain reaction in biopsy samples for preimplantation diagnosis [38].
• The transmission/disequilibrium test revealed increased transmission of the (AT)8 (dinucleotide repeat) and A (exon 1) alleles of CTLA-4 gene from heterozygous parents to affected offspring (87.5% and 83.5%) with type 1 AIH, compared with unaffected offspring (50.0% for both, p = 0.009 and 0.02, respectively) [39].

References