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)

Using a DNA probe for the switch region of immunoglobulin heavy chain genes, together with the restriction endonuclease Sst I, we detected a particular polymorphic DNA pattern in 17 of 28 patients (60.7%) with psoriatic arthropathy but in only 5 of 41 patients (12.2%) with psoriasis alone. Our findings suggest that genes in the immunoglobulin region confer susceptibility to the development of arthropathy in patients with psoriasis.
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PMID:Arthritis in patients with psoriasis is associated with an immunoglobulin gene polymorphism. 283 8

In order to ascertain whether the immunoglobulin heavy chain genes are important in the aetiology of Type 1 diabetes, we have used restriction fragment length polymorphism (RFLP) analysis of genomic DNA to study 148 Caucasoid subjects with Type 1 diabetes and 146 normal Caucasoid subjects. A DNA probe homologous to the switch regions for the IgM (S mu) and IgA1 (S alpha 1) genes when used in conjunction with the restriction endonuclease Sst I detects RFLPs at both these loci. There were no significant differences in phenotype or gene frequencies for the alleles of S mu or S alpha 1 in the patients when compared with control subjects; nor were there significant associations of S mu or S alpha 1 with HLA-DR type or gender.
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PMID:Immunoglobulin heavy chain switch region polymorphisms are not associated with type 1 diabetes. 290 16

The DNA's of 41 patients with various forms of renal disease and of 52 controls were investigated for restriction fragment length polymorphisms (RFLP), using a probe recognising the immunoglobulin Cmu heavy chain gene. With the restriction endonuclease Sst 1, 50 of the controls and 12 of the patients had the expected single 4.3 kilobase (kb) fragment. The remaining 29 patients and 2 controls displayed two patterns of banding, 8 patients and 1 control had a 6.8 kb band in addition to the 4.3 kb, and 21 patients and 1 control had a single band of 5.1 kb. In addition, a significant association between high creatinine levels (greater than 150 mumol/l) and abnormal bands was found (21/25 patients with high levels had abnormal bands compared with only 5/16 patients with normal levels). These results are evidence for an association between the human immunoglobulin heavy chain region and renal disease and they apparently confirm an association already reported at the protein level. However, the new RFLP bands, although reproducible and restricted to renal patients, occur in an area where few polymorphisms would be expected. Further, the association with high creatinine suggests some subtle interaction between the creatinine pathway and this area of the human chromosome.
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PMID:Immunoglobulin C mu gene restriction fragment length polymorphisms associated with chronic renal failure. 298 95

The time of replication during the S phase in a murine erythroleukemia (MEL) cell line was determined for immunoglobulin heavy chain constant region C alpha, C gamma 2b and C mu sequences whose boundaries are defined by EcoR1 restriction endonuclease sites (EcoR1 segments). Logarithmically growing cultures of MEL cells with an S phase of about 7.5 hours were pulse labelled with 20 micrograms/ml of 5-bromodeoxyuridine (BUdR). The cells were then fractionated by centrifugal elutriation into 10-12 distinct populations containing cells in different stages of the cell cycle. Flow microfluorimetric (FMF) analysis of DNA content, measurements of cell volume and autoradiography after 3H-thymidine pulse labelling were used to determine position in the cell cycle. Fractions were pooled to represent four selected intervals of S in which BU-DNA was synthesized for 2.5 hrs or less. Newly replicated DNA which had incorporated BUdR into one strand was isolated, cleaved with EcoR1, and separated on neutral Cs2S04 gradients. Equal amounts of BU-DNA replicated during these four intervals of S were electrophoresed in 0.8% agarose gels, transferred to diazotized aminobenzyloxymethyl paper and hybridized with 32p probes containing the C alpha, C gamma 2b and C mu genes and flanking sequences. The relative amounts of segments replicated were assessed by quantitation of the appropriate bands on the autoradiograms by microdensitometry. The results indicate that the 2.8 kb C alpha, 6.6 kb C gamma 2b and 12 kb C mu EcoR1 segments in these MEL cells replicated during defined intervals of the first half of the S phase. The order of replication of these EcoR1 segments as the cells proceeded through S was C alpha, C gamma 2b, C mu, corresponding to the linear order of the genes determined by restriction endonuclease mapping.
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PMID:The temporal order of replication of murine immunoglobulin heavy chain constant region sequences corresponds to their linear order in the genome. 629 19

The organization of mouse immunoglobulin heavy chain genes has been investigated by hybridization with cloned mu and alpha cDNA probes. Restriction endonuclease fragments bearing mu and alpha constant region genes and two types of variable region (VH) genes were compared in BALB/c embryos, liver and nine plasmacytomas synthesizing IgM, IgA, IgG1, IgG2a, IgG2b and IgG3. Embryo DNA was found to contain a single copy of the C mu gene per haploid genome. In contrast, one VH probe (HPC 76) detected at least six related VH genes, while the other (S107) detected a separate set of at least four genes, indicating that the germline contains distinct sets of multiple related VH genes. Most VH genes within the two subsets remained in germline context in different plasmacytomas, providing no evidence for somatic reassortment of VH genes. One plasmacytoma was devoid of specific VH genes, including some related to the expressed VH sequence. This may mean that the translocation event creating an active heavy chain gene involves deletion of the DNA between the expressed VH and CH sequences. The context of C mu sequences in DNA from a plasmacytoma secreting IgM differed from that in embryo DNA, as did C alpha sequences in two IgA- and several IgG-secreting plasmacytomas. Unlike heavy chain expression, rearrangement was not confined to one allele and often took different forms within a single cell line, presumably varying on different homologous chromosomes. Each rearrangement, whether resulting in an active C gene or not, appeared to change sequences upstream but not downstream from the CH gene. Significantly, the eight IgG and IgA plasmacytomas examined had undergone deletions of at least half and often all C mu sequences while retaining the embryo level of C alpha sequences. Hence a deletion mechanism may be responsible for the switch in expression from one CH gene to another which occurs during differentiation of a lymphocyte clone.
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PMID:Deletions are associated with somatic rearrangement of immunoglobulin heavy chain genes. 676 10

To elucidate the structure of the gene for the constant region of immunoglobulin mu chains, we have cloned a 9.9-kilobase-pair fragment of mouse DNA bearing a gene for the constant region of the mu chain (C mu gene) from an IgM-secreting mouse plasmacytoma. The sequence around this gene has apparently undergone somatic rearrangement; the gene occurs in an EcoRI restriction endonuclease fragment of a different size from that in embryo or liver DNA and no C mu-bearing fragment of embryo size remains in the plasmacytoma. The cloned sequence lacks a variable region gene; hence, if this C mu gene is active, its position within the clone indicates that the gene for the variable region of a heavy chain (VH gene) must be more than 3.7 kilobase pairs away. The C mu gene is divided by three intervening sequences into four coding segments, each of which encodes one of the domains (homology units) of the polypeptide. The nucleotide sequence coding for amino acids near the V-C junction is not present within the C mu clone or clones bearing homologous embryonic VH genes. This suggests that an immunoglobulin heavy chain, in common with light chains, is encoded not only by a V and C gene, but also by an independent joining region (JH) gene.
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PMID:Intervening sequences divide the gene for the constant region of mouse immunoglobulin mu chains into segments, each encoding a domain. 676 39

Immunoglobulin heavy chain class switching has been observed in vitro. In the IgG2b-producing MPC-11 mouse myeloma cell line, IgG2a-producing cells arise at a high frequency. In some cases, switch variants producing normal-sized (Mr 55,000) gamma 2a heavy chains have arisen spontaneously from a mutagen-induced "intermediate" (ICR 9.7.1) that produces an unusually large (Mr 75,000) heavy chain. Other switch variants have been isolated directly from the parent cell line. The expressed and unexpressed gamma 2b genes of MPC-11 can be distinguished in restriction endonuclease digests of total genomic DNA so that DNA rearrangements detected in MPC-11 variants can be directly associated with one or the other of these two genes. We describe here DNA rearrangements occurring on the expressed heavy chain chromosome of several MPC-11 gamma 2a switch variants and on the expressed chromosome of the ICR 9.7.1 intermediate. Our data indicate that all of these variants express the parental heavy chain variable region (VH) gene, supporting previous protein studies. We provide mapping data for the expressed gene of both ICR 9.7.1 and one of the IgG2a-producing variant cell lines (ICR 9.9.2.1) derived from it and discuss the advantages of an in vitro switching system for examining the dynamics of the immunoglobulin heavy chain class switch.
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PMID:DNA rearrangements in MPC-11 immunoglobulin heavy chain class-switch variants. 680 22

Stimulation with IL-4 plus CD40 mAb is known to induce production of IgE and IgG4. In this study, we determined the IgG subclass specificity of IL-4 plus CD40 mAb stimulation for human purified B cells. We determined true in vitro switching by the generation of switch circular DNA (S gamma/S mu) representing primary S mu/S gamma events and production of gamma subclass-specific germ-line transcripts by a combination of reverse transcription-PCR and restriction endonuclease digestion. We simultaneously measured changes in the levels of IgG subclass proteins produced. Forty-two clones of circular switch DNA were identified and sequenced. The IgG subclass of S gamma fragment in the S gamma/S mu chimeric PCR products was determined by analyzing key S gamma nucleotides. The switch-deleted clones were found to consist of S gamma 1/S mu, S gamma 3/S mu, and S gamma 4/S mu chimeric switch sequences, showing that such switching had occurred. No S gamma 2/S mu chimeric switch sequences were found. While a consensus sequence was not identified at the S gamma/S mu breakpoints, four contiguous guanines (GGGG) were noticeably present in the S gamma region near the breakpoint. The induction of gamma 1, gamma 3, and gamma 4 switch circles in human purified B cells was accompanied by enhanced production of IgG1, IgG3, and IgG4 but not IgG2. Similarly, stimulation with IL-4 alone induced gamma 1, gamma 3, and gamma 4 but not gamma 2 germ-line transcripts. These results demonstrate that IL-4 plus CD40 mAb induces Ig isotype switch from mu to gamma 1, gamma 3, and gamma 4 but not to gamma 2.
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PMID:IL-4 plus CD40 monoclonal antibody induces human B cells gamma subclass-specific isotype switch: switching to gamma 1, gamma 3, and gamma 4, but not gamma 2. 754 71

We examined restriction fragment length polymorphisms (RFLPs) of the switch region genes of the IgM (S mu) and IgA1 (S alpha 1) heavy chain in 78 Japanese children with IgA nephropathy and 88 normal Japanese controls. Genomic DNA obtained from patients and controls was digested with the restriction endonuclease SacI, transferred to nylon membrane using Southern blot procedure, and hybridized with a DNA probe homologous to S mu. This probe detects RFLPs at the S mu and S alpha 1 loci by enhanced chemiluminescence. The genotypic frequency of the S mu and S alpha 1 alleles in patients with IgA nephropathy was similar to normal controls. However, there was a significant association of genotypes with the pathological severity. There was a decreased frequency of the 2.6/2.1 kb S mu heterozygous genotype in patients showing diffuse mesangial proliferation compared to controls or patients showing minimal or focal mesangial proliferation. Our results suggest that immunoglobulin heavy chain switch region genes may not influence susceptibility to IgA nephropathy in children, but may influence the pathological expression of childhood IgA nephropathy.
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PMID:Polymorphism of immunoglobulin heavy chain switch region gene in children with severe IgA nephropathy. 760 74

The development of a reliable polymerase chain reaction (PCR) technique for the routine detection of clonal immunoglobulin heavy chain (IgH) gene rearrangements would represent an attractive alternative to Southern hybridization analysis because of the relative simplicity of PCR protocols, and because the requirements for both quality and quantity of DNA would be considerably less stringent. To assess the utility of PCR for the routine detection of clonal IgH gene rearrangements, samples from 123 adult patients were evaluated and analysis by PCR amplification using IgH Framework 1 or Framework 3 variable region consensus primers was compared with analysis by restriction endonuclease digestion and Southern hybridization with genomic, IgH probes. The authors found that 90% of IgH genes found to be rearranged by Southern hybridization are detected by the PCR technique. An additional 9 patient samples had clonal IgH gene rearrangements that were detectable by PCR alone. Eight of these nine patients had a history of a clonal hematopoietic process at either the morphologic or molecular level, and six had a history of a B-cell malignancy. It is likely that these specimens contained clonal lymphoid populations undetected by the Southern hybridization technique. Thus, the diagnostic sensitivity and specificity of the PCR method for the detection of B-cell tumors were 91% and 95%, respectively. The combination of improved analytical sensitivity and specimen flexibility of the IgH PCR assay could make it the method of choice for the routine detection of clonal IgH gene rearrangements, if minor improvements in the diagnostic sensitivity of the assay can be achieved.
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PMID:Comparison of PCR with southern hybridization for the routine detection of immunoglobulin heavy chain gene rearrangements. 785 59


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