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At least 649 records · Page 36Linked to original sources
PubMed2006

Use of abasic site-containing DNA for electrochemical SNPs detection.

In combination with an electrode modified with an abasic site-containing DNA duplex, flavins selectively bind to thymine with a useful electrochemical response, and flavins could be successfully utilized for detection of thymine-related mutations. The abasic site provides hydrophobic microenvironments for the hydrogen bond-forming ligands can recognize the specific target base in the DNA duplex, which is detected by the difference in the electrochemical response.

Biosensing Techniques↗
PubMed2005

Characterization of an analphoid supernumerary marker chromosome derived from 15q25-->qter using high-resolution CGH and multiplex FISH analyses.

Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA are predicted to have a neocentromere and have been referred to as mitotically stable neocentromere marker chromosomes (NMCs). We report the molecular cytogenetic characterization of a new case with analphoid NMC derived from 15q25-->qter using high-resolution comparative genomic hybridization (HR-CGH) and multiplex fluorescence in situ hybridization analyses with various alpha-satellite DNA probes, all-human-centromere probe (AHC), whole chromosome painting probes, and a subtelomere probe. The propositus is a dysmorphic infant who, at age 3 months, showed accelerated growth, partial deafness, and a phenotype similar to that of the eight previously reported cases of distal 15q tetrasomy. Chromosome studies showed that he had a de novo extra SMC in 80% of cells examined. HR-CGH revealed rev ish enh(15)(q25qter). Molecular cytogenetic analysis and molecular DNA polymorphism study demonstrated that this extra SMC is an NMC containing an inverted duplication of the distal long arm of chromosome 15 (tetrasomy 15q25-->qter) which originated paternally, i.e. ish der(15)(qte-->q25::q25[neocen]-->qter)(AHC-, CEP15-, WCP15+, PCP15q++). This case further elucidates the phenotype related to tetrasomy of this specific chromosome segment and represents a new report of a neocentromere on distal chromosome 15q suggesting that this region appears to be susceptible to the formation of neocentromeres.

Abnormalities, Multiple↗
PubMed1993

Functional dissection of the serological DR LYGUE and genotypic DRB1*1303 specificities using a tetanus toxin-specific T-cell clone.

The DRB1 sequence of the homozygous cell line HAG (DR13-DwHAG-DQ7) represents a new DRB allele assigned DRB1*1103, whereas its DRB3 sequence corresponds to the previously described DRB3*0101 (DR52a) allele. The DRB1*1303 gene product is undetectable by current sera used in routine serology typing. We report here direct evidence that the MHC molecule encoded by the DRB1*1303 gene is functional in antigen presentation and in T-cell restriction. We describe a T-cell clone specific for tetanus toxin whose restriction pattern strictly follows the DRB1*1303 allele, as defined by oligonucleotide typing. It also follows the serologic reactivity with the serum LYGUE and also the DwHAG MLC-defined specificity pattern, with one exception. The potential functional sites for the DRB1*1303 gene product involved in T-cell restriction were deduced from sequence comparisons between DRB1*1303 and closely related DRB1 alleles. The relevant as substitutions were located within close proximity to each other on the HLA class II structural model. Our results demonstrate that 1) DRB1*1303 is functional in antigen presentation and T-cell restriction 2) the functional region involved in antigen presentation and T-cell restriction by DRB1*1303 can be defined structurally.

Alleles↗
PubMed1997

Molecular genetic studies on DNA polymorphism of the HLA class II genes associated with human longevity.

Okinawan Japanese are well known for their longevity; the population rate of centenarians in Okinawa is about 3.8 times higher than that of the whole Japan, where the average life expectancies both among men and among women are the highest in the world. In this study, we analyzed HLA class II alleles of Okinawan centenarians by the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method for the purpose of clarifying the presence of primary genetic factors in the major histocompatibility complex (MHC) region associated with human longevity. DRB1*1401, DQB1*0503, DQA1*0101=0104 and DQA1*05 were significantly increased in the centenarians. The significant increase of HLA-DQB1*0503 and/or DQA1*0101=0104 in the centenarians can be explained by a linkage disequilibrium with DRB1*1401, or vice versa. Further, the tendency was observed toward increase with respect to DRB1*0101 and DRB1*1201. These data suggest that several alleles of the HLA-DRB1 and/or HLA-DQ genes are involved in human longevity.

Adult↗
PubMed2003

Differential transfer and dissemination of hypovirus and nuclear and mitochondrial genomes of a hypovirus-infected Cryphonectria parasitica strain after introduction into a natural population.

Biological control of plant diseases generally requires release of living organisms into the environment. Cryphonectria hypoviruses function as biological control agents for the chestnut blight fungus, Cryphonectria parasitica, and hypovirus-infected C. parasitica strains can be used to treat infected trees. We used naturally occurring molecular marker polymorphisms to examine the persistence and dissemination of the three genomes of a hypovirus-infected C. parasitica strain, namely, the double-stranded RNA genome of Cryphonectria hypovirus 1 (CHV1) and the nuclear and mitochondrial genomes of its fungal host. The hypovirus-infected strain was experimentally introduced into a blight-infested chestnut coppice forest by treating 73 of 246 chestnut blight cankers. Two years after introduction, the hypovirus had disseminated to 36% of the untreated cankers and to 35% of the newly established cankers. Spread of the hypovirus was more frequent within treated sprout clusters than between sprout clusters. Mitochondrial DNA of the introduced fungus also was transferred into the resident C. parasitica population. Concomitant transfer of both the introduced hypovirus and mitochondrial DNA was detected in almost one-half of the treated cankers analyzed. The introduced mitochondrial DNA haplotype also was found in three resident isolates from newly established cankers. The nuclear genome of the introduced strain persisted in the treated cankers but did not spread beyond them.

Ascomycota↗
PubMed2004

Emerging principles of conformation-based prion inheritance.

The prion hypothesis proposes that proteins can act as infectious agents. Originally formulated to explain transmissible spongiform encephalopathies (TSEs), the prion hypothesis has been extended with the finding that several non-Mendelian traits in fungi are due to heritable changes in protein conformation, which may in some cases be beneficial. Although much remains to be learned about the specific role of cellular cofactors, mechanistic parallels between the mammalian and yeast prion phenomena point to universal features of conformation-based infection and inheritance involving propagation of ordered beta-sheet-rich protein aggregates commonly referred to as amyloid. Here we focus on two such features and discuss recent efforts to explain them in terms of the physical properties of amyloid-like aggregates. The first is prion strains, wherein chemically identical infectious particles cause distinct phenotypes. The second is barriers that often prohibit prion transmission between different species. There is increasing evidence suggesting that both of these can be manifestations of the same phenomenon: the ability of a protein to misfold into multiple self-propagating conformations. Even single mutations can change the spectrum of favored misfolded conformations. In turn, changes in amyloid conformation can shift the specificity of propagation and alter strain phenotypes. This model helps explain many common and otherwise puzzling features of prion inheritance as well as aspects of noninfectious diseases involving toxic misfolded proteins.

Amyloid↗
PubMed2003

Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13.

Severe deficiency of the von Willebrand Factor (VWF)-cleaving proteinase, ADAMTS13, is associated with the development of thrombotic thrombocytopenic purpura (TTP). Several mutations spread across the ADAMTS13 gene have been identified in association with a deficiency of VWF-cleaving proteinase activity in patients with congenital TTP. The spread of these dysfunctional mutations and the domain structure of ADAMTS13 are suggestive of a complex interaction between the enzyme and its substrate. We have studied a patient with congenital TTP who is a compound heterozygote for the Thr196Ile mutation in the metalloproteinase domain and a frameshift mutation (4143-4144insA) in the second CUB domain that results in loss of the last 49 amino acids of the protein. The VWF-cleaving proteinase activity of the truncated enzyme was comparable to that of the wild-type enzyme but its secretion from transfected COS-7 cells was about 14% of the wild type.

ADAM Proteins↗
PubMed2003

Fibrinogen--marker or mediator of vascular disease?

Fibrinogen plays a key role in platelet aggregation, the final step of the coagulation cascade, i.e. the formation of fibrin, and it is a major determinant of plasma viscosity and erythrocyte aggregation. It is both constitutively expressed and inducible during an acute phase reaction. Increased plasma fibrinogen levels are associated with an increased risk of coronary heart disease and myocardial infarction. The question as to whether fibrinogen is only a marker of the inflammatory process involved in atherosclerosis or a mediator, i.e. a pathogenic factor, has not yet been answered. Human in vivo studies do not permit a conclusive answer to this question. If it is a pathogenic factor, fibrinogen lowering would be a therapeutic option. Selective fibrinogen-lowering agents do not exist however. All agents that lower fibrinogen also have other cardiovascular effects such as a decrease in cholesterol or inflammation. Newer information stems from molecular biology. Polymorphisms in the human fibrinogen gene with higher fibrinogen levels do not increase the risk for myocardial infarction. Fibrinogen knockout mice crossed with an atherosclerosis-susceptible strain (apoprotein E null mice) did not show a decreased extent of atherosclerosis despite the absence of fibrinogen, and a mouse strain over-expressing fibrinogen did not show an increased degree of atherosclerosis. Thus, fibrinogen seems to be a marker rather than a mediator of vascular disease, which would make selective fibrinogen lowering a useless preventive or therapeutic strategy.

Animals↗
PubMed1986

The molecular mechanisms of two common polymorphisms of drug oxidation--evidence for functional changes in cytochrome P-450 isozymes catalysing bufuralol and mephenytoin oxidation.

Using the stereospecific metabolism of (+)- and (-)-bufuralol and (+)- and (-)-metoprolol as model reactions, we have characterized the enzymic deficiency of the debrisoquine/sparteine-type polymorphism by comparing kinetic data of subjects in vivo with their microsomal activities in vitro and with reconstituted activities of cytochrome P-450 isozymes purified from human liver. The metabolism of bufuralol in liver microsomes of in vivo phenotyped 'poor metabolizers' of debrisoquine and/or sparteine is characterized by a marked increase in Km, a decrease in Vmax and a virtual loss of the stereoselectivity of the reaction. These parameters apparently allow the 'phenotyping' of microsomes in vitro. A structural model of the active site of a cytochrome P-450 for stereospecific metabolism of bufuralol and other polymorphically metabolized substrates was constructed. Two cytochrome P-450 isozymes, P-450 buf I and P-450 buf II, both with MW 50,000 Da, were purified from human liver on the basis of their ability to metabolize bufuralol to 1'-hydroxy-bufuralol. However, P-450 buf I metabolized bufuralol in a highly stereoselective fashion ((-)/(+) ratio 0.16) as compared to P-450 buf II (ratio 0.99) and had a markedly lower Km for bufuralol. Moreover, bufuralol 1'-hydroxylation by P-450 buf I was uniquely characterized by its extreme sensitivity to inhibition by quinidine. Antibodies against P-450 buf I and P-450 buf II inhibited bufuralol metabolism in microsomes and with the reconstituted enzymes. Immunochemical studies with these antibodies with microsomes and translations in vitro of RNA from livers of extensive and poor metabolizers showed no evidence for a decrease in the recognized protein or its mRNA. Because the antibodies do not discriminate between P-450 buf I and P-450 buf II, both a decreased content of P-450 buf I or its functional alteration could explain the polymorphic metabolism in microsomes. The genetically defective stereospecific metabolism of mephenytoin was determined in liver microsomes of extensive and poor metabolizers of mephenytoin phenotyped in vivo. Microsomes of poor metabolizers were characterized by an increased Km and a decreased Vmax for S-mephenytoin hydroxylation as compared to extensive metabolizers and a loss of stereospecificity for the hydroxylation of S-versus R-mephenytoin. A cytochrome P-450 with high activity for mephenytoin 4-hydroxylation was purified from human liver. Immunochemical studies with inhibitory antibodies against this isozyme suggest the presence in poor-metabolizer microsomes of a functionally altered enzyme.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Determination of "hybrids" in simple hybrids of maize by SSR-PCR].

The results of SSRP-analysis of molecular-genetic polymorphism in maize inbred lines and simple hybrids are presented. Character of inheritance of amplicons obtained by SSR-PCR-method was investigated. Test-system for determination of hybridity of simple maize hybrids was proposed, which showed high probability of exclusion of unrelative male forms.

Alleles↗
PubMed2003

[Physiology of immune response genes].

In addition to performing its major physiological function--a control of the immune response, the major gene complex: HLA system, also maintains a human genetic diversity. The latter provides optimal conditions for survival of human being as species. We submit modern data on genome and proteome mechanisms which are principal for maintenance of these functions.

Animals↗
PubMed2003

[Serotonin dysfunctions in the background of the seven deadly sins].

The symbolic characters of the Seven Deadly Sins can be traced from time to time in the cultural history of human mankind, being directly specified in certain artistic products. Such are, among others, the painting entitled "The Seven Deadly Sins and the Four Lost Things" by Hieronymus Bosch and the poems Divina Commedia and The Foerie Queene by Dante Alighieri and Edmund Spenser, respectively. However, there are several paragraphs referring to these behaviours of the Seven Deadly Sins in the Bible and in the dramas of William Shakespeare. The objective of the present review is to propose that dysfunctions in the central serotonergic system might be involved in the neurobiology of these 'sinful' behaviour patterns. Evidences indicate that behaviour traits such as Accidia (Sloth), Luxuria (Lust, Lechery), Superbia (Pride), Ira (Wrath, Anger), Invidia (Envy), Avaritia (Greed, Avarice), and Gula (Gluttony) can relate to the functional alterations of serotonin in the brain. Results of biochemical and molecular genetic (polymorphism) studies on the human serotonergic system (receptor, transporter, enzyme), findings of functional imaging techniques, effects of depletion (or supplementation) of the serotonin precursor tryptophan, data of challenge probe investigations directed to testing central serotonergic functions, alterations in the peripheral serotonin measures (platelet), and the changes in the CSF 5-hydroxy-indoleacetic acid content indicate such serotonergic involvement. Furthermore, results of animal experiments on behaviour change (aggressive, dominant or submissive, appetite, alcohol preference) attributed to serotonin status modification and the clinically evidenced therapeutic efficacy of pharmacological interventions, based on the modulation and perturbation of the serotonergic system (e.g. selective serotonin reuptake inhibitors), in treating the 'sinful' behaviour forms and analogous pathological states reaching the severity of psychiatric disorders (depression, sexual disturbances, social phobia, impulsivity-aggression, obsessive-compulsive and related spectrum disorders, paranoid jealousy, eating disorders) all strongly suggest the possibility that brain serotonin dysfunctions might underlie the neurophysiology of the Seven Deadly Sins.

Behavior↗
PubMed2004

Molecular genetic data at two tetranucleotide repeat loci (D12S66 and D12S67) in two Indian tribal populations.

Molecular genetic polymorphism study was undertaken in two tribal population groups of India at two tetranucleotide repeat loci on chromosome 12 (D12S66 and D12S67). The two tribal groups studied were Bison Horn Maria and Muria, belonging to Bastar district of Madhya Pradesh in Central India. For this study, 75 random, unrelated individuals were analyzed for D12S66 locus, whereas 76 individuals were analyzed for D12S67 locus.

DNA Fingerprinting↗
PubMed2004

Molecular genetic analysis of TPO and CD4 loci among two endogamous ethnic groups of Maharashtra in Western India.

Molecular genetic polymorphism study was undertaken in two endogamous ethnic groups of Maharashtra in Western India at two microsatellites i.e., TPO, a tetranucleotide repeat locus and CD4, a pentanucleotide repeat locus. The two ethnic groups studied were Konkanastha Brahmins and Marathas belonging to Indo-European language family. Eighty-two random, unrelated individuals were genotyped for the locus TPO, whereas for CD4 locus, 79 individuals were genotyped.

DNA Fingerprinting↗