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)

Type I diabetes is strongly associated with the major histocompatibility complex (MHC) class II region (DR and DQ loci), and to a lesser extent the class III region (complement C4 loci). Restriction fragment length polymorphism analysis was employed to investigate the C4 and heat shock protein 70 (HSP70) loci of 176 patients with type I diabetes and 92 healthy controls. In the patient population there was an excess of deletions of the C4A locus (48.5% vs 22.1%, P less than 0.0005). The HSP70 probe in conjunction with the restriction endonuclease Pst I detects two alleles of 9 or 8.5 kilobases (kb). The 8.5 kb allele was significantly increased in the patient group compared to healthy controls (0.569 vs 0.353, respectively, P less than 0.0005). Furthermore, a C4A deletion nearly always occurred with the 8.5 kb HSP70 allele, suggesting that it may be a marker of the HLA-A1,B8,C4A deletion, DR3 extended haplotype.
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PMID:Complement C4 and heat shock protein 70 (HSP70) genotypes and type I diabetes mellitus. 227 64

The high molecular weight genomic DNA from 31 patients with idiopathic membranous nephropathy (IMN) has been digested with a restriction endonuclease Taq I, electrophoresed, blotted and hybridised with probes to the HLA-DRB, -DQA, -DQB, -DPA and -DPB genes. The restriction endonuclease Msp I was also used with the HLA-DPA and -DPB probes. The resulting restriction fragment length polymorphism (RFLP) has been analysed and compared with 55 controls treated in the same way. There was a significant increase in the DRB restriction fragments associated with HLA-DR3 (Fisher's p = 0.011), in particular with a sub-division of DR3 (Fisher's p = 0.0038). These results confirm at the DNA level serological correlations observed for IMN. A 4.5 Kb DQA RFLP was significantly raised in IMN patients (Fisher's p = 0.002) and is proposed as a major disease susceptibility factor.
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PMID:A DQA1 allele is strongly associated with idiopathic membranous nephropathy. 257 74

The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes. C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes, 21-OHA and 21-OHB, and is also remarkable in the high frequency of the 'null' alleles, C4A Q0 and C4B Q0. The molecular basis for the C4A Q0 allele was studied in 26 families through restriction fragment length polymorphism (RFLP) analysis with C4 and 21-OH cDNA probes after digestion of the DNA with the endonuclease HindIII. The individuals expressing the extended haplotype HLA-A1 (of A2) Cw7 B8 C2C BfS C4AQ0B1 DR3 have a large deletion taking off the C4A and 21-OHA genes.
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PMID:Heterogeneity in the structural basis of the human complement C4A null allele (C4A Q0) as revealed by HindIII restriction fragment length polymorphism analysis. 288 19

We investigated the T cell antigen receptor constant (TCR beta) beta-chain genes of patients with Graves' disease using restriction fragment length polymorphism analysis. Genomic DNA from patients and normal subjects was digested with the restriction endonuclease Bg1 II, transferred to nylon membranes using the Southern blot technique, and hybridized with a TCR beta probe. A significant increase in the frequency of the 10.0; 9.2-kilobase heterozygous phenotype was found in GD (68.6%) vs. 42.1% in normal subjects (P = 0.003). Using the complex phenotype TCR homozygote (hetero) DR3 as a reference (odds ratio = 1.00), we found that the risk for Graves' disease was restricted to TCR beta heterozygote/DR3+ individuals (odds ratio = 8.31; chi 2 = 11.82; P = 0.0009); in the absence of TCR beta heterozygosity, DR3 was not significantly associated with the disease. These results suggest that TCR beta chain genes also are associated with susceptibility to GD and that the association is most pronounced in (or restricted to) those individuals who are HLA DR3 positive.
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PMID:Polymorphism of the T cell receptor beta-chain in Graves' disease. 288 83

Polymorphic restriction endonuclease sites within the HLA-DR alpha gene have been defined, localized, and used as genetic markers in the analysis of susceptibility to insulin-dependent diabetes mellitus (IDDM). Hybridization of Bgl II-digested human genomic DNA with a cDNA clone for the HLA-DR alpha chain (pDR alpha-1) has revealed three allelic restriction fragment lengths: 3.8 kilobase pairs (kb), 4.2 kb, and 4.5 kb. Hybridization of EcoRV-digested human genomic DNA with the same probe has revealed two allelic polymorphic restriction fragment lengths: 9.2 kb and 13.0 kb. By analysis of double digests of genomic DNA from individuals homozygous for each of the allelic variants, the polymorphic restriction sites were found to be clustered near the 3' end of the HLA-DR alpha gene. The observed correlations of DR alpha Bgl II restriction site variants with serologically determined DR specificities suggest linkage disequilibrium between the DR alpha and DR beta loci. The 3.8-kb fragment is correlated with the DR1 type (Pc = 4.4 X 10(-4)); and the 4.2-kb fragment, with a subset (B8,DR3) of the DR3 type (Pc = 5.1 X 10(-4)) and with the DR6 type. The segregation pattern of HLA-DR alpha polymorphic Bgl II restriction fragments was analyzed in six IDDM families. The observed association of IDDM with the Bgl II 4.2-kb DR alpha restriction variant is higher than with existing serological markers and supports the utility of this approach in elucidating IDDM inheritance.
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PMID:Polymorphic restriction endonuclease sites linked to the HLA-DR alpha gene: localization and use as genetic markers of insulin-dependent diabetes. 299 92

Human genomic DNA digested with restriction endonuclease Taq I was hybridized with cDNA probes for DR beta and DQ beta, for correlation of restriction fragment length polymorphisms with HLA-DR specificities. DR beta Taq I RFLPs were distinctive for DR serological types 1 to w9, with the exception of DR3 and w6, and were markedly consistent within DR specificity. Some common variants in RFLPs did emerge within serological type; DR3, e.g., was associated with two different fragment patterns, one of which occurred on the A1.B8.DR3 haplotype and was linked with a DR alpha Bgl II variant, and the other on the B18.DR3 haplotype. In the Pacific specimens examined, RFLPs were, with few exceptions, similar to those seen in Caucasoids sharing the same DR specificity. This study indicates that genomic hybridization is a useful adjunct to serological and cellular class II typing and should be particularly informative in identifying new HLA-DR alleles in populations serologically less well-defined than Caucasoids.
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PMID:HLA-DR beta gene DNA polymorphisms revealed by Taq I correlate with HLA-DR specificities. 300 5

The human major histocompatibility complex includes the DP, DQ, and DR subregions, each of which contains at least one alpha chain gene and two beta chain genes. The products of the alpha chain gene and a beta chain gene from a given subregion combine to form a heterodimer which is found predominantly on the surface of immunocompetent cells, and is essential for effective cell-cell interactions and the generation of an immune response. The beta chain of the DR molecule is highly polymorphic, and it is this polymorphism which is thought to be ultimately responsible for the specific immune responsiveness and disease predisposition conferred by different DR molecules. While the sequences of DR beta chains of the homozygous DR1 cells, homozygous DR2, homozygous DR4, DR3/w6 cells and DR4/w6 genotypes have been partially or completely characterized, no sequence is yet available for the DR beta chain from a homozygous DR5 cell. A cDNA library was therefore constructed from the Swei cell line homozygous for the DR5 haplotype. A beta chain clone was isolated, characterized, and sequenced. Comparison with previously published DR beta chain restriction endonuclease maps and nucleotide sequences demonstrated that this clone was a DR beta chain clone. Comparison of the deduced amino acid sequence with other DR beta chain amino acid sequences shows three regions of variability in the first external domain, corresponding to amino acid residues 9-13, 26-38, and 67-74. The sequence of each of these variable regions in the beta chain from DR5 cells was identical or nearly identical to the sequences of variable regions found in the beta chains of other DR haplotypes, supporting the notion of gene conversion as an evolutionary mechanism generating polymorphism. The second external domain, and transmembrane and intracytoplasmic regions show a high degree of sequence conservation.
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PMID:Complete characterization and sequence of an HLA class II DR beta chain cDNA from the DR5 haplotype. 345 44

HLA-DRB1 and -DRB3 alleles of DR52-associated (DR52ass) HLA-DR antigens were genotyped by a polymerase chain reaction (PCR) - based simple and practical method. Genomic DNAs from two hundred Japanese panels were subjected to PCR with two pairs of primers to separately amplify the DR52ass-DRB1 (DR3, 5, 6, and 8) alleles and DRB3 (DR52) alleles. The specific amplification revealed that 128 and 76 panels possessed DR52ass alleles and DRB3 alleles, respectively. PCR products from these panels were heat-denatured, electrophoresed in a non-denaturing polyacrylamide gel, and visualized by silver staining. Electrophoretic mobilities of the DNA samples were compared with those of the typing standards with known genotypes of DR52ass-DRB1 and DRB3 alleles. This method, designated PCR-DNA conformation polymorphism (DCP) analysis, allowed genotyping of the DR52ass-DRB1 and DRB3 alleles of panels without any sequence-specific oligonucleotide probe (SSOP) or restriction endonuclease, and the entire process after PCR could be completed within a few hours. Because the DR52ass-DRB1 and DRB3 alleles assigned by this method were shown to be identical to those determined by the PCR-SSOP method, PCR-DCP analysis was suggested to be a simple and practical HLA genotyping method.
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PMID:DNA conformation polymorphism analysis of DR52 associated HLA-DR antigens by polymerase chain reaction: a simple, economical and rapid examination for HLA matching in transplantation. 800 42

We have studied the genotypic, haplotypic, and allelic distribution of germline Restriction Fragment Length Polymorphism (RFLP) of T-cell receptor (Tcr) alpha, gamma, and delta loci in 75 insulin-dependent diabetes mellitus (IDDM) patients and 84 healthy blood donors as control population. The restriction endonuclease PvuII produces three allelic fragments of Tcr C gamma (TcrCG) gene segment of 16, 13, and 11.3 Kb respectively. Our observations revealed that PvuII/TcrCG RFLP allelic distributions were not significantly different in the IDDM and the control group. However, 85% of IDDM patients carried HLA DR3 and/or DR4 haplotypes, and when comparing these patients with a second group of HLA DR3+ and/or DR4+ healthy individuals, the 11.3 Kb/PvuII fragment of TcrCG gene was found to be associated with IDDM patients (chi 2 = 11.4, P = 0.003). 54.9% of IDDM patients carried at least one 11.3 Kb allele vs. 21% in controls (chi 2 = 10.77, P = 0.004). No significant association was found between RFLP in Tcr, C alpha, C delta, V gamma 9 loci and IDDM.
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PMID:T-cell receptor alpha, delta, and gamma chain genes in insulin-dependent diabetes mellitus. 909