Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification of the base substitution responsible for Ag(x/y) completes the description of the antigen group polymorphisms associated with the apolipoprotein B polypeptide. Surprisingly, all five antigen group polymorphisms alter restriction endonuclease cleavage sites and have associated restriction fragment length polymorphisms, thereby providing a convenient alternative for antigen group phenotyping.
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PMID:Identification of the base substitution responsible for the Ag(x/y) polymorphism of apolipoprotein B-100. 199 55

The antigenic group (Ag) system of homospecific human serum antigens of low density lipoprotein is detected by antiserum from multiply transfused patients. A complex series of common Ag alleles has been described, but the biochemical nature of this polymorphism is uncertain. Here we report that DNA polymorphisms at the human apolipoprotein B (apoB) locus are very closely linked to alleles of the Ag system. We also show a strong association between Ag(x) and a polymorphism detected with the restriction endonuclease Xba I. We conclude that the immunologically determined Ag system represents protein polymorphism of apoB rather than primary genetic differences in posttranslational processing or lipid binding. These studies therefore demonstrate that the Ag locus is located on the short arm of human chromosome 2 in the region p23-p24 to which the apoB gene has been assigned. Since the Ag(x) antigen is associated with altered plasma lipid levels, this determinant may indicate a functionally important domain of apoB.
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PMID:Genetic linkage between the antigenic group (Ag) variation and the apolipoprotein B gene: assignment of the Ag locus. 287 24

Levels of apolipoprotein B, the protein component of low-density lipoproteins, correlate with the risk of coronary heart disease. We examined whether genetic variation in apolipoprotein B is associated with myocardial infarction by studying apolipoprotein B-gene restriction-fragment-length polymorphisms in 84 patients with myocardial infarction and an equal number of matched controls. Southern blot analysis with apolipoprotein B-gene probes, performed after DNA was digested with the endonucleases XbaI and EcoRI, revealed alleles that we designated as X1, X2, and X3 and as R1 and R2, respectively. Similar studies with the endonuclease MspI revealed alleles of many different sizes (the difference was due to an insertion-deletion polymorphism), which we grouped as larger and smaller alleles and designated as ID1 and ID2, respectively. The frequencies of the X1, R1, and ID1 alleles were all significantly higher (P less than 0.01) in the cases than in the controls. None of the alleles, however, was significantly associated with variation in levels of low-density lipoprotein cholesterol or apolipoprotein B, and the functional importance of these alleles is therefore uncertain. Nonetheless, in addition to quantitative variation in apolipoprotein B levels in plasma, genetic variation at the apolipoprotein B locus may be a new and independent risk factor for myocardial infarction.
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PMID:Apolipoprotein B-gene DNA polymorphisms associated with myocardial infarction. 302 2

A strong association has been uncovered between DNA variation at the apolipoprotein B (apoB) locus (detectable with the restriction endonuclease XbaI) and apoB level. The findings are suggestive of associations also between this DNA polymorphism and total cholesterol as well as fasting triglyceride levels, confirming recent results reported by British workers. The data suggest that lipid/apolipoprotein associations with the XbaI polymorphism are primarily caused by an effect on apoB level. In the present and in a previously reported study we found a strong association between the XbaI polymorphism and the homospecific Ag antigenic variation in low density lipoprotein (LDL) which had previously exhibited associations with lipid levels. The present data indicate that the apoB/lipid associations of the Ag and XbaI polymorphisms may reflect the same phenomenon. The associations reported could reflect variation in an apoB domain close to Ag as well as to the XbaI restriction site that is of importance for lipid binding by apoB. Alternatively, the association of apoB level with the XbaI polymorphism (which reflects a silent third base mutation in a threonine codon) could reflect phenomena related to codon usage.
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PMID:DNA polymorphism at the apolipoprotein B locus is associated with lipoprotein level. 350 91

A rapid detection of the Arg3500-->Gln mutation of human apolipoprotein B-100 is of particular interest because of its prevalence in familial forms of hypercholesterolemia. A simple procedure, based on amplification by polymerase chain reaction (PCR) and NlaIII endonuclease restriction cleavage, allows this diagnosis without ambiguity. By using two oligonucleotide primers carrying one mismatch each, two permanent restriction sites were generated in the normal allele, while one of them disappeared in the mutant allele. Thus, the two alleles can be differentiated by their specific N/aIII restriction profile.
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PMID:Application of PCR site-directed mutagenesis for a rapid and accurate detection of mutation 3500 (Arg-->Gln) of human apolipoprotein B-100. 796 2

Prior studies have established that the expression of the human apolipoprotein B (apoB) gene in the intestine is dependent on DNA sequences located a great distance from the structural gene. To identify the location of those sequences, we used recA-assisted restriction endonuclease (RARE) cleavage to truncate the 5'- or 3'-flanking sequences from a 145-kilobase (kb) bacterial artificial chromosome spanning the entire human apoB gene. Seven RARE cleavage- modified bacterial artificial chromosomes with different lengths of flanking sequences were used to generate transgenic mice. An analysis of those mice revealed that as little as 1.5 kb of 3' sequences or 5 kb of 5' sequences were sufficient to confer apoB expression in the liver. In contrast, apoB gene expression in the intestine required DNA sequences 54-62 kb 5' to the structural gene. Those sequences retained their ability to direct apoB expression in the intestine when they were moved closer to the gene. These studies demonstrate that the intestinal expression of the apoB gene is dependent on DNA sequences located an extraordinary distance from the structural gene and that the RARE cleavage/transgenic expression strategy is a powerful approach for analyzing distant gene-regulatory sequences.
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PMID:Apolipoprotein B gene expression in a series of human apolipoprotein B transgenic mice generated with recA-assisted restriction endonuclease cleavage-modified bacterial artificial chromosomes. An intestine-specific enhancer element is located between 54 and 62 kilobases 5' to the structural gene. 970 18

During the last years several genetic markers have appeared which were extensively studied for their clinical consequences and impact. Therefore, we developed 14 new genetic tests using the TaqMan technology. The new test systems detect the alpha1-antitrypsin, ACE, apolipoprotein B-100, apolipoprotein E, factor V Leiden, prothrombin, HFE, MTHFR, COL1A1, VDR and HLA-B27 mutations. These new kits were compared to the established endonuclease restriction digestion and flow cytometry, respectively. The results showed, that the allelic discrimination assays (TaqMan method) were in 100% concordance with the formerly used digestion method. Flow cytometry revealed a lower specificity in contrast to the TaqMan PCR system. Thus, it could be demonstrated that the new TaqMan assays are robust, rapid and automated methods for high throughput applications which avoid time consuming (and therefore expensive) and difficult post-PCR steps.
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PMID:A highly reproducible and economically competitive SNP analysis of several well characterized human mutations. 1520 39

MicroRNAs (miRNAs) are a group of recently discovered small RNAs produced by the cell using a unique process, involving RNA polymerase II, Microprocessor protein complex, and the RNAase III/Dicer endonuclease complex, and subsequently sequestered in an miRNA ribonucleoprotein complex. The biological functions of miRNAs depend on their ability to silence gene expression, primarily via degradation of the target mRNA and/or translational suppression, mediated by the RNA-induced silencing complex (RISC). First discovered in Caenorhabditis elegans (lin-4), miRNAs have now been identified in a wide array of organisms, including plants, zebrafish, Drosophila, and mammals. The expression of miRNAs in multicellular organisms exhibits spatiotemporal, and tissue- and cell-specificity, suggesting their involvement in tissue morphogenesis and cell differentiation. More than 200 miRNAs have been identified or predicted in mammalian cells. Recent studies have demonstrated the importance of miRNAs in embryonic stem cell differentiation, limb development, adipogenesis, myogenesis, angiogenesis and hematopoiesis, neurogenesis, and epithelial morphogenesis. Overexpression (gain-of-function) and inactivation (loss-of-function) are currently the primary approaches to studying miRNA functions. Another family of small RNAs related to miRNAs is the small interfering RNAs (siRNAs), generated by Dicer from long double-stranded RNAs (dsRNAs), and produced from an induced transgene, a viral intruder, or a rogue genetic element. siRNAs silence genes via either mRNA degradation, using the RISC, or DNA methylation. siRNAs are actively being applied in basic, functional genetic studies, particularly in the generation of gene knockdown animals, as well as in gene knockdown studies of cultured cells. These studies have provided invaluable information on the specific function(s) of individual genes. siRNA technology also presents exciting potential as a therapeutic approach in disease prevention and treatment, as suggested by a recent study targeting apolipoprotein B (ApoB) in primates. Further elucidation of how miRNAs and other small RNAs interact with known and yet-to-be identified gene regulatory pathways in the cell should provide us with a more in-depth understanding of the mechanisms regulating cellular function and differentiation, and facilitate the application of small RNA technology in disease control and treatment.
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PMID:MicroRNAs and cell differentiation in mammalian development. 1684 91