Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed PCR of many DNA fragments of 6-32 nucleotides in length. Some of the fragments expanded into kilobase lengths even in the absence of the complementary strand. The dramatic expansion was observed for (CA)8, (TG)8, (CA)4, (CA)6, (CA)12, (TG)4, (TG)6, (TG)12, (TC)10, (GA)10 and other single strands. Similar expansions were exhibited by related trinucleotide repeats (TTG)5, (CAA)5, (TGG)5, and (CCA)5 as well. However even small perturbations of the strict repetitive nature of the DNA primary structure substantially reduced the expansions. The expansion products had properties characteristic for normal Watson-Crick duplexes. Hence either the Taq polymerase and/or other components of the PCR buffer promote homoduplex formation of the nonselfcomplementary fragments, which is necessary to prime the synthesis of the complementary DNA strand, or the Taq polymerase is able to copy the single-stranded DNA template without any priming effect. The present observations have implications for the evolution of genomic DNA, microsatellite length polymorphism as well as the pathological expansions of trinucleotide repeats in the human genome.
Mol Biol Rep 2003 Sep
PMID:Expansion during PCR of short single-stranded DNA fragments carrying nonselfcomplementary dinucleotide or trinucleotide repeats. 1297 70

Novak et al. [Brain Res. Mol. Brain Res. 107 (2002) 183] reported that a CAA insertion in the 3'-untranslated region of the Nogo gene was associated with schizophrenia. We examined the frequency of this CAA insertion in 57 European American subjects with schizophrenia and 243 controls, and in a smaller group of African American subjects (N=72; 20 with schizophrenia). We found a similar frequency of the CAA insertion for patients and controls in both populations, but a large difference in CAA insertion frequency between the two racial groups.
Brain Res Mol Brain Res 2004 Jan 05
PMID:Nogo 3'-untranslated region CAA insertion: failure to replicate association with schizophrenia and demonstration of marked population difference in frequency of the insertion. 1474 11

Studies show that administration of interferon (IFN)-alpha causes a significant increase in depressive symptoms. The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-alpha-induced depressive symptoms, first by decreasing the TRP availability to the brain and second by the induction of the KYN pathway resulting in the production of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of psychiatric disorders and eligible for IFN-alpha treatment, were recruited. Depressive symptoms were measured using the Montgomery Asberg Depression Rating Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance through the blood-brain barrier, KYN and kynurenic acid (KA), a neuroprotective metabolite, were performed using high-performance liquid chromatography. All assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. The MADRS score significantly increased during IFN-alpha treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA ratio, reflecting the neurotoxic challenge. The TRP/CAA (competing amino acids) ratio, reflecting TRP availability to the brain, did not significantly change during treatment. Total MADRS score was significantly associated over time with the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found that IDO decreases TRP availability to the brain, this study does support a role for IDO activity in the pathophysiology of IFN-alpha-induced depressive symptoms, through its induction of neurotoxic KYN metabolites.
Mol Psychiatry 2005 Jun
PMID:IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. 1549 6

Methods that detect rare base substitutions within populations of DNA molecules are valuable tools for studying the DNA-damaging effects of chemicals and for pool screening for single-nucleotide polymorphisms. Allele-specific competitive blocker-polymerase chain reaction (ACB-PCR) uses a mutant-specific PCR primer with more 3'-terminal mismatches to an abundant or wild-type sequence than to a rare or mutant sequence in order to amplify specifically an allele that differs from the wild-type by a single base pair. ACB-PCR reactions include a blocker primer to reduce the amount of background signal generated from the abundant wild-type template. The nonextendable blocker primer preferentially anneals to the wild-type DNA sequence, thereby excluding the annealing of the extendable mutant-specific primer to the wild-type sequence. Inclusion of single-strand DNA binding protein in the ACB-PCR reaction and use of the Stoffel fragment of Taq DNA polymerase both significantly increase allele discrimination. The concurrent analysis of mutant fraction standards and equivalent PCR products amplified from genomic DNA samples makes ACB-PCR a quantitative method that can detect a base pair substitution in the presence of a 105-fold excess of wild-type DNA. Methods for the ACB-PCR measurement of the mouse H-ras codon 61 CAA --> AAA mutation are presented.
Methods Mol Biol 2005
PMID:Allele-specific competitive blocker-PCR detection of rare base substitution. 1550 27

The Nogo gene was putatively implicated in schizophrenia based on gene expression and genetic association data. In this study, we attempt to replicate the possible association of the CAA insertion and a nearby TATC deletion with schizophrenia in 204 complete and incomplete triads and in a sample of 462 unrelated cases and 153 controls, all of Caucasian origin. Our genotyping results indicated that neither the trinucleotide insertion polymorphism (CAAins; 43.4% vs. 41.8%, p>0.5) nor the polymorphism-TATC deletion (TATCdel; 49.8% vs. 49.3%, p>0.1) allele frequency is significantly different in patients compared to controls. The homozygous CAAins frequency is not significantly different between patients and controls either (18.0% vs. 15.0%, chi2=0.985, p>0.1). Furthermore, neither CAAins/TATCdel individually, nor the haplotype carrying both CAAins and TATCdel is preferentially transmitted to affected offspring.
Brain Res Mol Brain Res 2005 Jan 05
PMID:CAA insertion polymorphism in the 3'UTR of Nogo gene on 2p14 is not associated with schizophrenia. 1566 75

A substantial body of evidence supports the identity of polyglutamine as the pathogenic agent in a variety of human neurodegenerative disorders where the mutation is an expanded CAG repeat. However, in apparent contradiction to this, there are several human neurodegenerative diseases (some of which are clinically indistinguishable from the 'polyglutamine' diseases) that are due to expanded repeats that cannot encode polyglutamine. As polyglutamine cannot be the pathogenic agent in these diseases, either the different disorders have distinct pathogenic pathways or some other common agent is toxic in all of the expanded repeat diseases. Recently, evidence has been presented in support of RNA as the pathogenic agent in Fragile X-associated tremor/ataxia syndrome (FXTAS), caused by expanded CGG repeats at the FRAXA locus. A Drosophila model of FXTAS, in which 90 copies of the CGG repeat are expressed in an untranslated region of RNA, exhibits both neurodegeneration and similar molecular pathology to the 'polyglutamine' diseases. We have, therefore, explored the identity of the pathogenic agent, and specifically the role of RNA, in a Drosophila model of the polyglutamine diseases by the expression of various repeat constructs. These include expanded CAA and CAG repeats and an untranslated CAG repeat. Our data support the identity of polyglutamine as the pathogenic agent in the Drosophila models of expanded CAG repeat neurodegenerative diseases.
Hum Mol Genet 2005 Apr 15
PMID:The pathogenic agent in Drosophila models of 'polyglutamine' diseases. 1575 76

The utility of liver H-ras codon 61 CAA to AAA mutant fraction as a biomarker of liver tumor development was investigated using neonatal male mice treated with 4-aminobiphenyl (4-ABP). Treatment with 0.1, 0.3, or 1.0 mumol 4-ABP produced dose-dependent increases in liver DNA adducts in B6C3F(1) and C57BL/6N mice. Eight months after treatment with 0.3 mumol 4-ABP or the DMSO vehicle, H-ras codon 61 CAA to AAA mutant fraction was measured in liver DNA samples (n = 12) by allele-specific competitive blocker-polymerase chain reaction (ACB-PCR). A significant increase in average mutant fraction was found in DNA of 4-ABP-treated mice, with an increase from 1.3 x 10(-5) (control) to 44.9 x 10(-5) (treated) in B6C3F(1) mice and from 1.4 x 10(-5) to 7.0 x 10(-5) in C57BL/6N mice. Compared with C57BL/6N mutant fractions, B6C3F(1) mutant fractions were more variable and included some particularly high mutant fractions, consistent with the more rapid development of liver foci expected in B6C3F(1) mouse liver. Twelve months after treatment, liver tumors developed in 79.2% of 4-ABP-treated and 22.2% of control B6C3F(1) mice; thus measurement of H-ras mutant fraction correlated with subsequent tumor development. This study demonstrates that ACB-PCR can directly measure background levels of somatic oncogene mutation and detect a carcinogen-induced increase in such mutation.
Mol Carcinog 2005 Apr
PMID:Levels of 4-aminobiphenyl-induced somatic H-ras mutation in mouse liver DNA correlate with potential for liver tumor development. 1576 37

Nogo is a myelin-associated protein associated with neurite outgrowth and regeneration. A previous study has reported an association between an insertion/deletion polymorphism in schizophrenia. We tested for the distribution of the polymorphism and haplotypes of this and another insertion/deletion polymorphism in our population. We have also developed an assay combining allele-specific polymerase chain reaction (AS-PCR) and restriction fragment length polymorphism (RFLP) to simultaneously type these two insertion/deletion polymorphisms. There was a statistically significant difference at the allelic level for both the CAA (chi2 = 4.378, df = 1, P value = 0.036) and TATC (chi2 = 5.807, df = 1, P = 0.016) polymorphisms in the female subgroup, but not in males. With our genotyping method, we also determined the molecular haplotype. Within the female gender, odds ratio is at 1.57 (95% CI 1.05-2.37) for CAACAA-TATC and 1.40 (95% CI 0.55-3.60) for CAA-TATC, the two at-risk haplotypes. Odds ratio is 0.63 (95% CI 0.42-0.93) for the protective wildtype haplotype CAA-TATCTATC. Further study of these two polymorphisms to investigate functional significance and confirm gender-specific association should be carried out.
Brain Res Mol Brain Res 2005 Oct 03
PMID:Gender-specific association of insertion/deletion polymorphisms in the nogo gene and chronic schizophrenia. 1595 57

The Dictyostelium discoideum genome has been sequenced, assembled and annotated to a high degree of reliability. The parts-list of proteins and RNA encoded by the six chromosomes can now be accessed and analyzed. One of the initial surprises was the remarkably large number of genes that are shared with plants, animals, and fungi that must have been present in their common progenitor over a billion years ago. The genome encodes a total of about 10,300 proteins including protein families involved in cytoskeletal control, posttranslational protein modification, detoxification, secondary metabolism, cell adhesion, and signal transduction. The genome has a higher proportion of homopolymeric tracts and simple sequence repeats, such as [CAA]n, than most other genomes. Triplet repeats in translated regions produce the highest known proportion of polyglutamine tracts in any known proteome. Phylogenetic analyses based on complete proteomes confirm that the amoebozoa are a sister group to the animals and fungi, distinct from plants and early diverging species such as Leishmania, Plasmodium, or Giardia. The completed Dictyostelium sequence opens the door to large-scale functional exploration of its genome.
Methods Mol Biol 2006
PMID:The Genome of Dictyostelium discoideum. 1695 82

Southern corn rust (SCR) is a fungal disease caused by Puccinia polysora Underw, which can infect maize and may result in substantial yield losses in maize production. The maize inbred line Qi319 carries the SCR resistance gene RppQ. In order to identify molecular markers linked to the RppQ gene, several techniques were utilized including random amplified polymorphic DNA (RAPD), simple sequence repeat (SSR), and amplified fragment length polymorphism (AFLP). In addition, sequence characterized amplified region (SCAR) techniques combined with bulked segregant analysis (BSA) were used. Seven RAPD markers, eight SSR markers, and sixty-three AFLP primer combinations amplified polymorphisms between two parents and two bulk populations. A large F2 population was used for genetic analysis and for fine mapping of the RppQ gene region. One AFLP polymorphic band, M-CAA/E-AGC 324, was converted to a SCAR marker, MA7, which was mapped to a position 0.46 cM from RppQ. Finally, the RppQ gene was mapped between the SCAR marker MA7 and the AFLP marker M-CCG/E-AGA 157 with distances of 0.46 and 1.71 cM, respectively.
Mol Genet Genomics 2007 Dec
PMID:Characterization and fine mapping of RppQ, a resistance gene to southern corn rust in maize. 1794 Aug 1


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