PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “deCode Genetics”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1999

Low-salt crystallization of T7 RNA polymerase: a first step towards the transcription bubble complex.

DNA-dependent RNA polymerase is the key enzyme responsible for the biosynthesis of RNA, a process known as transcription. This process, which decodes the genetic information from DNA, is one of the most significant events in a biological system. The crystallization of both native and a chimeric T7/T3 RNAP using high salt conditions has been reported previously but these conditions proved unsuitable for DNA-RNAP complex formation since at high salt concentrations the DNA binding affinity to RNAP is reduced. A search for low-salt crystallization conditions has yielded new low-salt crystals of native T7-RNAP, a chimeric T7-RNAP (T7/T3 RNAP) which contains the T3 promoter recognition sequence, and a T7-RNAP containing an N-terminal histidine tag. The crystals, which are better suited for DNA-RNAP complex formation, belong to space group P3121 with a = 136, c = 156 A, contain a single molecule per asymmetric unit and diffract to 2.7 A resolution. Packing analysis shows that the new low-salt crystals have packing contacts similar to those observed in the high-salt T7-RNAP crystals reported previously. The diffraction anisotropicity observed in crystals of T7 RNAP is explained in term of crystal packing.

Base Sequence↗
PubMed2002

Global gene expression analysis of developing neocortex using SAGE.

The mammalian brain is estimated to contain about a hundred billion neurons, making it the most complex biological structure on earth. Trying to understand the assembly and function of this elaborate organ is a formidable task. Yet the information to build a brain is encoded by no more than a subset of the 80,000 genes present in the genome, a more manageable number. This review describes the use of SAGE technology (Serial Analysis of Gene Expression) to decode the genetic repertoire of genes that are differentially expressed in time and in space during development of the neocortex, the part of the mammalian brain responsible for complex traits. We demonstrate that SAGE is not only powerful for generating comprehensive molecular portraits from the developing cortex but can also assist in discovering new genes.

Animals↗
PubMed2002

[Genetics and arterial hypertension: 3 approaches to decode a complex disease].

Human arterial hypertension is a complex trait, partly determined by genetic factors. From the analysis of familial studies, it has been estimated that approximately 30% of the blood pressure variance within a population was of genetic origin. Three main types of human studies have been undertaken to try to identify susceptibility genes to hypertension. The first one corresponds to the systematic analysis of the so-called candidate genes, i.e. genes encoding proteins, enzymes, receptors, which are known to belong to pathways controlling blood pressure. Up to now, the most interesting results have been obtained on genes encoding the renin angiotensin system, the a adducin, the G protein subunit beta 3, and adrenergic receptors. The genome wide scan approach corresponds to a systematic analysis of evenly spaced markers throughout the genome in sibling pairs or in more complex families. This second strategy has shown that there was not a single locus that was regularly found by several studies, but rather several possible loci which most often have not been replicated from one study to another one. Among those, the long arm of the human chromosome 17 (17q12-q21) is in synteny with a blood pressure locus found in spontaneously hypertensive rats. The third approach, up to now the most successful, corresponds to the identification of major genes involved in rare Mendelian forms of hypertension. For example, genes responsible for Liddle syndrome, glucocorticoid remediable aldosteronism, apparent mineralocorticoid excess have been characterized and have demonstrated the importance of sodium and water homeostasis in blood pressure control.

Animals↗
PubMed2026

AUA codon decoding by preferential use of tRNAIle(UAU) in Lactobacillus casei.

Modified nucleosides at the first (wobble) position of tRNA anticodons play critical roles in accurate decoding of the genetic code. In bacteria, the isoleucine AUA codon is typically decoded by tRNAIle(LAU), in which lysidine (L) at the wobble position of tRNAIle with a CAU anticodon ensures discrimination from the methionine AUG codon. However, some bacteria, such as Mycoplasma mobile, lack tRNAIle(LAU) and instead utilize tRNAIle(UAU). In this organism, the unmodified uridine at the wobble position is thought to enable specific decoding of AUA while avoiding AUG recognition. In our previous study, we identified a lactic acid bacterium in which both tRNAIle(LAU) and tRNAIle(UAU) coexist. Here, we show that tRNAIle(LAU) is scarcely aminoacylated in vivo, whereas tRNAIle(UAU) is efficiently aminoacylated. Notably, the presence of 4-thiouridine (s4U) at position 8 inhibits IleRS-dependent aminoacylation of tRNAIle(UAU) in vitro, suggesting a regulatory role of tRNA modification in this process. Moreover, tRNAIle(LAU) exhibits incomplete discrimination between AUA and AUG codons and binds to AUG in the ribosomal A-site binding assays. In contrast, tRNAIle(UAU) containing N 6-threonylcarbamoyladenosine (t6A) at position 37 showed a tendency toward improved discrimination between AUA and AUG codons and preferentially recognized AUA at the ribosomal A site. These results indicate that AUA decoding is predominantly mediated by preferential use of tRNAIle(UAU) rather than canonical tRNAIle(LAU), revealing an alternative mechanism of codon decoding based on differential utilization of tRNA isoacceptors, and providing an additional layer of translational control in bacteria.

RNA, Transfer, Ile↗
PubMedDate not supplied

[Decoding common mechanisms of cellular genetic-epigenetic control in eukaryotes].

The mechanism of genetic epigenetic operation at genomic and chromosomic levels within the limits of imitation model of eucaryotic cellular compartment is postulated, this compartment including left and right operators. Probable pattern of interactions during reproduction, determination and expression of genes as a manifestation of genetic, epigenetic memory and memory of water is shown. A specific character and rate of transformations of nucleotides and proteins are realized through different operation mechanisms over hierarchic processes directed on the preservation of DNA in the line of cellular generations and also determining dynamics of the genome with DNA variations. The mechanism of programmed provision of genetic-epigenetic interaction lies in the ways of control, regulation, adaptation and modulation of nucleotides and proteins transformations which occur on the basis of specific (complementary, kinetic and tunnel effects) choice of directions, place, time and aim of nucleotide-nucleotide, nucleotide-protein, protein-nucleotide and protein-protein interactions.

DNA↗
PubMed1989

Genetic characterization of frameshift suppressors with new decoding properties.

Suppressor mutants that cause ribosomes to shift reading frame at specific and new sequences are described. Suppressors for trpE91, the only known suppressible -1 frameshift mutant, have been isolated in Escherichia coli and in Salmonella typhimurium. E. coli hopR acts on trpE91 within the 9-base-pair sequence GGA GUG UGA, is dominant, and is located at min 52 on the chromosome. Its Salmonella homolog maps at an equivalent position and arises as a rarer class in that organism as compared with E. coli. The Salmonella suppressor, hopE, believed to be in a duplicate copy of the same gene, maps at min 17. The +1 suppressor, sufT, acts at the nonmonotonous sequence CCGU, is dominant, and maps at min 59 on the Salmonella chromosome.

Base Sequence↗
PubMed2026

Advancing precision tacrolimus therapy: a systems genetics dissection in BXD platform.

BACKGROUND: Tacrolimus is a core immunosuppressant in organ transplantation, but its narrow therapeutic window and significant pharmacokinetic variability hinder precision dosing. Although CYP3A5-guided strategies have established clinical relevance for tacrolimus initial dose adjustment, they do not fully account for the marked interindividual variability in tacrolimus exposure, highlighting the need for complementary models to decode more complex genetic regulation. This study aimed to identify candidate genetic modulators of tacrolimus metabolism and develop an integrated predictive framework for individualized therapy. METHODS: Using 46 BXD recombinant inbred mouse strains, we characterized transcriptomics and machine learning, and validated key genes. We then constructed a clinical model using data from 168 renal transplant recipients. RESULTS: We identified 19 genomic loci associated with tacrolimus pharmacokinetic traits and supported DBP/CYP2A6 as candidate modulators associated with tacrolimus disposition. The clinical prediction model, incorporating these genes and clinical variables, achieved robust AUROC. CONCLUSIONS: These findings support a polygenic contribution to tacrolimus metabolism and provide an experimental and computational framework for identifying candidate modulators relevant to individualized dosing. The BXD mouse platform offers a systems-genetics approach for mechanistic discovery that may inform future translational studies on tacrolimus precision dosing.

Animals↗
PubMed2003

Decoding property of C5 uridine modification at the wobble position of tRNA anticodon.

Post-transcriptional modification at the first (wobble) position of the tRNA anticodon participates in precise decoding of the genetic code. We recently identified a novel taurine-containing modified uridine (tau m5U; 5-taurinomethyluridine) at the wobble position of mammalian mitochondrial tRNAs and found lack of this modification in mutant mitochondrial tRNAs from human pathogenic cells of the mitochondrial encephalomyopathies, investigate molecular pathogenesis of the diseases, decoding activity of wobble uridines with or without C5 modification was measured using E. coli cell-free translation system. It has been revealed that C5 modification has a functional role for stabilizing U:G wobble base pair.

Amino Acid Sequence↗
PubMed1993

cDNA analyses in the human genome project.

The ultimate goal of the human genome project is to decode all the genetic information carried in the genome. Towards this goal, the physical structure of the genome, as well as the functional aspects of the genome, must be understood. We initiated a cDNA project to collect the 'expression profiles' of all human genes, a database with which to describe which genes are expressed, and to what extent, in any given human cell at a particular time. Single-cycle sequencing of randomly selected members from a 3'-directed cDNA library is most appropriate for this purpose: the sequence data serve as a 'gene signature' to identify the expressing gene, and the frequency of appearance of the gene signature reflects the activity of the gene. The compiled data, which usually cover some 1000 sequencing results per sample, are referred to as an 'expression profile.' We applied this analysis to HepG2 (a cell line derived from a hepatocellular carcinoma), liver cells and lung cells. The expression profiles shed some light upon the unique features of gene expression in the cell or tissue tested. A comparison of the expression profiles among different cells has allowed active genes to be classified as housekeepers or those with cell-specific functions. A significant fraction of the abundantly expressed genes include those that are unique to the cell. In addition, the resulting collection of thousands of gene signatures is a useful source of probes for mapping and for isolating full-size cDNAs.

Animals↗
PubMed1993

Identification of new genes by systematic analysis of cDNAs and database construction.

The large-scale collection of partial cDNA sequences is becoming a powerful tool in biology. Similarity or motif searches in DNA databases using these partial cDNA sequences have facilitated the discovery of new genes of interest. By collecting and registering large numbers of partial sequences with a well designed non-biased cDNA library, an expression profile of active genes in a particular tissue can be obtained. Tissue-specific or stage-specific genes can be discovered by comparing the profiles from different tissues or from a tissue at different stages of development, respectively. The compilation of such expression profiles enables genes to be mapped to the tissue(s) where they are actively transcribed. The large-scale collation of gene sequences actively expressed in the body into databases complements efforts directed towards the structural analysis of the genome, with the ultimate aim of decoding all the genetic information carried in the human genome. This cDNA strategy is also being widely applied to organisms other than man.

Animals↗
PubMed1983

Inhibition of adenovirus early region IV transcription in vitro by a purified viral DNA binding protein.

Adenoviruses depend on cellular mechanisms for the decoding of their genetic information, and so provide a useful and simple model system for the investigation of mammalian gene expression. The five regions transcribed early in adenovirus infection are termed EIa, EIb, EII, EIII and EIV. We report here that the primary product of the EII region, a 72,000 molecular weight DNA-binding protein (DBP), specifically represses transcription from the EIV promoter in an in vitro transcription system. Single-stranded DNA binds to the DBP with high affinity, and as a result inhibits its repressor activity. Our data extend previous genetic evidence that the DBP represses EIV transcription in vivo, and suggest that it acts directly by suppressing transcription from the EIV promoter.

Adenoviridae↗
PubMed2002

Age, body mass index and glucose tolerance in 11 European population-based surveys.

AIMS: To describe the variation in the estimated prevalence of diabetes and impaired glucose regulation (IGR) within Europe in relation to age and body mass index (BMI). METHODS: Cross-sectional data from European population-based studies with both fasting and 2-h glucose after a standard 75-g oral glucose tolerance test were included (9449 men, 7752 women). RESULTS: There was a large variation in the estimated prevalence of diabetes and impaired glucose regulation among 11 European centres, ranging from 2% to 24% for diabetes and 5% to 43% for IGR. In cross-sectional analysis the estimated prevalence of diabetes and IGR increased with age and BMI. The impact of age did not differ between centres with similar age range, and the impact of BMI was similar in most centres. CONCLUSIONS: Differences in age and BMI within Europe partly explained the variation in estimates of the IGR and diabetes prevalence. The impact of age and BMI did not differ between centres. Variations in prevalence must therefore be due to other factors that we could not adjust for, such as methodology, differences in diet, physical activity and genetic predisposition.

Adult↗
PubMed2025

Integrative proteomic analysis provides novel therapeutic insights for etiological subtypes of diabetes.

AIMS: Type 2 diabetes (T2D) is a highly heterogeneous disease characterised by subtypes with variations in aetiology, disease progression, and risk of complications. However, potential drug targets for these subtypes have not been explored. This study aims to investigate potential drug targets by integrating proteomics. MATERIALS AND METHODS: Summary-level data of circulating proteins were extracted from the UK Biobank and the deCODE Health Study. Genetic associations with five diabetes subtypes were obtained from Swedish All New Diabetics in Scania and Malmö Diet and Cancer cohort, including severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). The associations between circulating proteins and diabetes subtypes were assessed through Mendelian randomisation, followed by multiple sensitivity and colocalization analyses. Additionally, tissue-specific, pathway and functional enrichment analysis, assessment of protein druggability, and the protein-protein interaction (PPI) networks were used to further explore biological mechanisms and therapeutic potential. RESULTS: Genetically predicted levels of 2, 2, 9, 3, and 5 circulating proteins were associated with SIRD, SIDD, MARD, MOD, and SAID, respectively. Colocalization analyses further revealed links between GRN with MARD/SIRD, LILRB5 with SIDD/MARD, CR1 with MARD, TNFSF12 with MOD, and DAPK2 with SAID. Enrichment analysis suggested that these proteins were mainly enriched in blood and adipose tissues and involved in immune and inflammatory related pathways. PPI analysis revealed GRN, TNFSF12, and DAPK2 are associated with known T2D targets. CONCLUSIONS: Our study identified several potential drug targets for different subtypes of diabetes using an integrated genetic approach, yielding new insights for precision medicine of diabetes.

Humans↗
PubMed1996

The human genome efforts and the cDNA project.

Molecular biology has been moving swiftly toward clarifying the entire genome of organisms, including human. The human genome efforts that promote this transaction are characterized by the large-scale, high throughput production of data about the structure of the genome of the molecular level and its computer-assisted management. In addition, functional analyses of the genome have become important for decoding the entire genetic information carried in the human genome. In the functional analyses of the genome, the large-scale collection of partial cDNA sequences, the cDNA project, is becoming important, because it allows researchers to register genes active in any given tissue, on one hand, and, on the other hand, it allows for quantitative description of gene activities in tissues. Tissue-specific or stage-specific genes can be discovered by comparing expression profiles from different tissues or from a tissue at different stages of development, respectively.

DNA, Complementary↗
PubMedDate not supplied

[First class transcription termination factors--functional analogs of aminoacyl tRNA].

Reviewed and discussed are the recent data demonstrating profound functional similarity between class-1 translation termination factors (RF1 and RF2 in prokaryotes, aRF1 and eRF1 in Archaea and eukaryotes, respectively) and aminoacyl-tRNA as regards their roles in the course of translation on the ribosome. Functional analogy of these two components of the cell protein-synthesizing machinery was suggested long ago; however, numerous experimental proofs have been obtained only recently. This similarity implies that decoding of the genetic information by the ribosomal machine is performed similarly at all stages of translation, though tRNA plays the main role at initiation and elongation, while the protein is most important for termination. Earlier it was found that nucleic acids (ribozymes) can operate like the protein enzymes, and now we have got evidence for the reverse: a protein (translation termination factor) can act like a nucleic acid (tRNA). Thus one can speak of "exchange" of molecular functions between proteins and nucleic acids. Therefore, the profound chemical difference between proteins and nucleic acids is not an insuperable barrier to their mutual functional replacement in certain situations.

Animals↗