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

HLA class II antigens are transmembrane glycosylated heterodimers composed of an alpha and a beta chain. Several of these chains are highly polymorphic. The structural bases of the polymorphism are nucleotide acid substitutions which are situated in the first domain (exon II) of alpha and beta genes. Specific sequences of these domains can be obtained by amplification of genomic DNA using the polymerase chain reaction. Polymorphic sites are recognized by restriction endonuclease treatment and separation of the DNA fragments by polyacrylamide gel electrophoresis. The resulting fragments of different lengths are used to identify different alleles. We used the above technique for typing the HLA-DQA1 alleles in 41 Tunisian diabetic patients. The frequency of DQA1*0301 was greatly increased compared with the control group. This was in agreement with previously published data in Caucasian and Japanese insulin-dependent diabetes mellitus (IDDM) patients, while the significant increase in the frequency of the DQA1*0501 allele was comparable with that of Caucasian IDDM patients but contrasted with a decrease in this allele in Japanese IDDM patients. Our results provide confirmation of the contribution of the DQA1*0301 allele to disease susceptibility in a Tunisian population.
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PMID:Association of type 1 diabetes mellitus with the HLA-DQA1*0301 allele in a Tunisian population. 168 Feb 41

HLA class II molecules are surface heterodimers which are essential in the initiation of immune responses. The amount of polymorphism expressed by the different class II molecules is largely dependent on the polymorphic structure of their beta chains. Cross-hybridization between class II beta genes frequently hampered restriction fragment length polymorphism analysis of donor genomic DNA. In this report we show that the cross-hybridization between human class II beta genes is mediated by a region of high homology, rich in C and G residues, between the first domain encoding sequences of DP, DQ, and DR genes. The removal of the DNA segment containing this region from the fragments used as labeled probes against the corresponding fragments of the genes at other loci or against endonuclease digested genomic DNA completely eliminated or drastically reduced the cross-hybridization. Also, the RFLP patterns generated with the shortened probes were more informative and much simpler to interpret than were these generated with probes made from the original genes.
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PMID:First domain encoding sequence mediates human class II beta-chain gene cross-hybridization. 290 Aug 11

Human transplantation antigens encoded in the major histocompatibility complex (MHC) region play a key role in regulating the immune responses. Here, we will describe the summary of our analyses on the structure and function of the human MHC molecules, HLA antigens as follows. 1) The genomic organization of the HLA antigen region was examined by cosmid cloning and pulsed-field gel electrophoresis technique. The HLA antigen region spans over at least 3,000 kb, and constitutes a multigene family. 2) Genetic polymorphisms in the HLA gene region were analyzed by Southern hybridization with restriction endonuclease digested genomic DNA using the class II cDNAs as probes (RFLP) and found to be tightly associated with each allo specificity. 3) The functional expression of the HLA class II gene product were observed after transfer of their cloned genes into the mouse fibroblast and human lymphocytes. 4) Narcolepsy is completely associated with HLA-DR2 Dw2, but no difference in the sequence of the DQ beta 1 domain could be found between narcoleptic and healthy individuals. This fact suggests that narcolepsy is not caused by mutation in the DQ beta gene. Based on results, it was inferred that one or both of the two Asps within the second variable region in the first domain of the DR beta chain is directly correlated with predisposition to narcolepsy.
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PMID:[Structure and function of human transplantation antigens]. 290 88

Restriction endonuclease digestion of genomic DNA from 24 lymphoblastoid cell lines homozygous for the HLA class II specificity DQw3, followed by hybridization with a DQ beta-chain cDNA probe, identified a genomic polymorphism with variable BamHI and HindIII recognition sites. This restriction fragment pattern was found for several haplotypes associated with the DQw3 specificity, including some haplotypes positive for the HLA-DR specificities DR4, DR5, DRw8, and DRw12. The variant fragment pattern corresponds precisely with the reactivity of a monoclonal antibody, A-10-83, previously shown to define a serologic split of DQw3. Serologic detection of the specific DQw3.1 genomic polymorphism indicated that the corresponding DQ beta-chain variants are expressed. This polymorphic restriction fragment pattern, then, represents a selective marker for DQ beta-chain genes that appear to define a DQ beta-chain-associated specificity, here called DQw3.1.
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PMID:Identification of a polymorphic variant associated with HLA-DQw3 and characterized by specific restriction sites within the DQ beta-chain gene. 299 95

Two variants of the serologically defined HLA-DR2 specificity have been reported: DR2 long and DR2 short. Distinct HLA-DR2-associated Dw subtypes have been described at the cellular level. In the Israeli population, DR2 individuals may be grouped into three clusters: DR2/Dw2, DR2/Dw12, and DR2/Dw"AZH". A new approach for the study of the polymorphism of HLA class II genes is to investigate restriction endonuclease fragments obtained from genomic DNA with specific class II cDNA probes. Previous analysis of DQ beta restriction endonuclease fragments subdivided the DR2 haplotypes into two subsets: a DQR1-positive subset and a DQR2.6-positive subset. These two subsets behave in the population as alleles that split HLA DQw1. In the present study, we have analyzed class II DQ alpha, DQ beta, and DR beta restriction fragment length polymorphism (RFLP) in HLA-DR2/Dw-typed healthy, unrelated Israeli individuals, as well as in 11 French HLA-DR2 insulin-dependent diabetes mellitus (IDDM) patients and 11 French DR-matched controls. Three DQ beta allelic clusters (DQR2.6, DQR1, and DQR12) were observed among the DR2 haplotypes and clearly correlated with Dw2, Dw"AZH", and Dw12, respectively. The vast majority of the DR2 IDDM patients (9 out of 11) fit into the DQR1 cluster which correlates with Dw"AZH", while only two patients (2 out of 11) belong to the DQR2.6 cluster (Dw2-like). In contrast, among 11 DR-matched healthy controls, 9 belonged to the DQR2.6 cluster and only 2 belonged to the DQR1 cluster. These studies establish the correlation between the DR2-associated Dw subtypes with specific RFLPs, and indicate that the frequency of the DQR1 subset which correlates with Dw"AZH" is increased in DR2 IDDM patients.
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PMID:HLA-DR2-associated Dw subtypes correlate with RFLP clusters: most DR2 IDDM patients belong to one of these clusters. 300 44

HLA class II polymorphisms have been analyzed on the genomic level by two oligonucleotide probes corresponding to the DNA sequence coding for the amino acids 23-30 in the first domain of the beta chain of DQw3.1 and DQw3.2. Specific hybridization to single endonuclease fragments of DNA from some HLA homozygous cells was detected. Here we report the distribution of these DNA exon sequences among different DQ alleles, and demonstrate that the probes may be used to type for DQw3.1 and DQw3.2 respectively.
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PMID:HLA-DQw3.1 and DQw3.2 associated exon polymorphisms detected by oligonucleotide probes. 340 34

A molecular analysis of HLA class II genes was undertaken in order to characterize the previously reported association between HLA-DR2 and glomerulonephritis caused by antibodies to glomerular basement membrane (Goodpasture's disease). Genomic DNA was prepared from 53 patients with Goodpasture's disease and analysed by: (i) Southern blotting using cDNA probes to DRB, DQA and DQB genes, after digestion with TaqI endonuclease; (ii) allele-specific oligonucleotide probing of specifically amplified DNA; and (iii) nucleotide sequencing of relevant alleles. The patients had a greatly increased frequency of DRw15 (a subspecificity of DR2) which was present in 75.5% of patients and 31% of controls (p < 0.0001). The frequency of DR4 was also increased, especially in patients without DRw15. Overall, 90.5% of the patients had either DRw15 or DR4. In contrast, the frequency of DR1 was significantly reduced (patients 5.6%, controls 20.7%, p < 0.01). Differences in the frequencies of DQA and DQB alleles could all be explained by linkage disequilibrium. Nucleotide sequences of relevant alleles were identical to those previously published. Comparison of derived amino acid sequences of expressed DR beta chains showed that the DR beta chains of DRw15 and DR4 shared a six-amino-acid motif from positions 26-31, that included four polymorphic amino acids none of which are shared with DR1. A sequence-specific oligonucleotide detected this amino-acid motif in 45/49 (91.8%) patients tested. Thus, this particular motif, which lies on the floor of the antigen binding groove, has a stronger association with Goodpasture's disease than any individual allele, and may be of pathogenic significance.
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PMID:Molecular analysis of HLA class II genes in Goodpasture's disease. 770 68