Disease relevance of Open Reading Frames

• We report here the functional expression in E. coli of the entire single open reading frame of R2Bm and show that it encodes a double-stranded endo-nuclease (integrase) that can specifically cleave the 28S gene at the R2 insertion site [1].
• The mRNAs for the 80 kd adenovirus preterminal protein (pTP) and the 140 kd DNA polymerase (AdPol) contain several exons spliced to the main open reading frames (m-ORFs) located in the early transcription unit E2B [2].
• HPV-16 is actively transcribed in the cancers; the most abundant transcripts map to the E6 and E7 early open reading frames [3].
• Fragile X syndrome is characterized at the molecular level by amplification of a (CGG)n repeat and hypermethylation of a CpG island preceeding the open reading frame of the fragile X gene (FMR-1) located in Xq27 [4].
• We have identified a major gamma-herpesvirus-divergent locus (DL-B) in HHV-8 DNA encoding several HHV-8 unique open reading frames (ORFs), including a homologue of interleukin-6 (IL-6) and two homologues of macrophage inflammatory protein MIP-1 [5].

Psychiatry related information on Open Reading Frames

• A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome [6].
• Huntington's Disease (HD) is caused by expansion of a CAG repeat within a putative open reading frame of a recently identified gene, IT15 [7].
• Complete sequencing of the prion protein open reading frame of a 68-year-old woman affected by a familial form of Creutzfeldt-Jakob disease (CJD) revealed a new mutation at codon 210 resulting in the substitution of isoleucine for valine [8].
• Mutations in the open reading frame of the beta-site APP cleaving enzyme (BACE) locus are not a common cause of Alzheimer's disease [9].
• Nucleotide sequence analysis of the two cDNAs identified known genes not previously associated with the pathogenesis of AIDS dementia, including the neurotrophin receptor tyrosine kinase receptor B (TrkB) and the potassium channel human open rectifyer K+ channel (ORK) homologous open reading frame (HOHO1) [10].

High impact information on Open Reading Frames

• These data indicate that Pol II-associated Set2 methylates H3 providing a transcriptional memory which signals for deacetylation of ORFs by Rpd3S [11].
• We localized jsd to a 272-kb region and resequenced this area to identify the underlying mutation: a frameshift that severely truncates the predicted protein product of a 2.3-kb genomic open reading frame [12].
• In addition to previously identified targets, Abf1, Rap1 and Mig1 bound to 107, 90 and 75 putative new target intergenic regions, respectively, many of which were upstream of previously uncharacterized open reading frames [13].
• NBS1p70 is produced by internal translation initiation within the NBS1 mRNA using an open reading frame generated by the 657del5 frameshift [14].
• Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families [15].

Chemical compound and disease context of Open Reading Frames

• The fourth open reading frame encodes two functional polypeptides, a large precursor of the major envelope glycoprotein and a smaller protein derived from the 3'-terminus long open reading frame analogous to the long open reading frame (lor) product of HTLV-I and -II [16].
• In rats with hereditary hypothalamic diabetes insipidus (Brattleboro rats) the gene for the vasopressin precursor lacks a single G residue in the protein-coding region [17].
• The open reading frame encodes 591 amino acids having a striking degree of similarity to the Escherichia coli structural gene (48% identical amino acids with 76% overall similarity including conservative substitutions) with the glutamine amide transfer domain being particularly conserved [18].
• To test these hypotheses, we have inserted the rp51 intron into the coding region of a hybrid Escherichia coli beta-galactosidase gene, thereby interrupting the open reading frame subsequent to the initiating methionine codon [19].
• The glutamate racemase gene of Pediococcus pentosaceus has a 795-nt open reading frame and encodes 265-amino acid residues, which form a monomeric protein (M(r) 29,000) [20].

Biological context of Open Reading Frames

• The breakpoint cluster region within ALL-1 spans 8 kb and encompasses several small exons, most of which begin in the same phase of the open reading frame [21].
• The 856 amino acid open reading frame contains five Krüppel-type zinc finger motifs and proline-rich and acidic regions similar to those of known transcription factors [22].
• Frameshift mutations in the ORFs of the tnpA gene's first intron markedly reduce Spm activity in transgenic tobacco, indicating that intron sequences encode essential gene products [23].
• Molecular analyses of nap and mle mutations indicate that mle+, nap+, and napts activities are encoded by the same open reading frame and suggest that napts is due to a single amino acid substitution [24].
• Intron 4 (14) of the split gene cob in mitochondrial DNA contains a long open reading frame in phase with the preceding exon [25].

Anatomical context of Open Reading Frames

• DMR-N9 transcripts, mainly expressed in brain and testis, possess a single, large open reading frame, but the function of its protein product is unknown [26].
• Membrane fractions of Cos-7 cells transfected with an expression construct containing the open reading frame of HL-5 showed specific LTB4 binding, with a K(d) (0.154nM) comparable to that observed in retinoic acid-differentiated HL-60 cells [27].
• Ribosome occupancy of the yeast CPA1 upstream open reading frame termination codon modulates nonsense-mediated mRNA decay [28].
• After transfection with the CY6 open reading frame, a mouse pre-B cell line exhibited calcium flux and chemotaxis in response to I-309 (EC50 = 2 nM for each), whereas 20 other chemokines were inactive [29].
• The 585 nt open reading frame of this cDNA encodes a polypeptide of about 21.7 kd that is essential for the expression in frog oocytes of omega-conotoxin-sensitive, dihydropyridine-resistant, calcium channels [30].

Associations of Open Reading Frames with chemical compounds

• An open reading frame that contains this cysteine-rich region exists in all other paramyxovirus "P" gene sequences examined, which suggests that it may have important biological significance [31].
• Sequencing of the 5'-noncoding region showed that at -151 there is an open reading frame of 23 codons of which six are for leucine [32].
• The results show that the leader peptide, the product of the upstream open reading frame, plays an essential, negative role in the specific repression of CPA1 by arginine [33].
• The CAG repeat is within the open reading frame and is predicted to encode glutamine in three of the isoforms [34].
• The gene is ubiquitously expressed to form a single 4.5 kb transcript and encoded by an open reading frame of 1184 amino acids (aa), in which a polyglutamine track with variable length starts at aa 484 [35].

Gene context of Open Reading Frames

• The 5' leader of GCN4 mRNA contains four small open-reading-frames [36].
• The 5' region of CPA1 mRNA contains a 25 codon upstream open reading frame [33].
• Here, we report conditions that result in a dramatic transient increase in the rate of GCN4 protein synthesis, which also requires the prior translation of the 5' most proximal open reading frame but is independent of the GCN2 protein [37].
• Gene lamB is followed by molA, an unidentified reading frame corresponding to a 131-amino-acid peptide with the characteristics of an exported protein [38].
• The gene does not contain any significant conserved ORFs and thus does not appear to encode a protein, suggesting that XIST may function as a structural RNA within the nucleus [39].

Analytical, diagnostic and therapeutic context of Open Reading Frames

• Sequence analysis of the smoothened transcription unit reveals a single open reading frame encoding a protein with seven putative transmembrane domains [40].
• The first intron of gene 1 is 4434 nucleotides long and contains two large open reading frames, 2714 bp and 761 bp in size, which hybridize to minor RNA species in Northern blot experiments [41].
• In these conditions, the CYP1 protein is detected by Western blot analysis and has a molecular mass in agreement with the open reading frame sequence [42].
• Also using RT-PCR, the full open reading frame for human PDE1B1 cDNA was cloned from RPMI-8392 cells and it encodes a protein of 536 amino acids with 96% identity to bovine, rat, and mouse species [43].
• We used a DNA microarray containing 97% of the ORFs predicted from this sequence to monitor changes in M. tuberculosis gene expression in response to the antituberculous drug isoniazid [44].

References