Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “deCode Genetics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 235 records · Page 13Linked to original sources
PubMed2000

Quadruplet codons: implications for code expansion and the specification of translation step size.

One of the requirements for engineering expansion of the genetic code is a unique codon which is available for specifying the new amino acid. The potential of the quadruplet UAGA in Escherichia coli to specify a single amino acid residue in the presence of a mutant tRNA(Leu) molecule containing the extra nucleotide, U, at position 33.5 of its anticodon loop has been examined. With this mRNA-tRNA combination and at least partial inactivation of release factor 1, the UAGA quadruplet specifies a leucine residue with an efficiency of 13 to 26 %. The decoding properties of tRNA(Leu) with U at position 33.5 of its eight-membered anticodon loop, and a counterpart with A at position 33.5, strongly suggest that in both cases their anticodon loop bases stack in alternative conformations. The identity of the codon immediately 5' of the UAGA quadruplet influences the efficiency of quadruplet translation via the properties of its cognate tRNA. When there is the potential for the anticodon of this tRNA to dissociate from pairing with its codon and to re-pair to mRNA at a nearby 3' closely matched codon, the efficiency of quadruplet translation at UAGA is reduced. Evidence is presented which suggests that when there is a purine base at position 32 of this 5' flanking tRNA, it influences decoding of the UAGA quadruplet.

Amino Acid Sequence↗
PubMed2002

Genetics, genomics and gene discovery in the auditory system.

The sounds of silence have forever been broken as genetics and genomics approaches in human and model organisms have provided a powerful and rapid entry into gene discovery in the auditory system. An understanding of the complexities and beauty of the biological process of hearing itself is unfolding as genes underlying hereditary hearing impairment are identified. Genes involved in modifying hearing are also being found, and will be critical to a full comprehension of genotype-phenotype relationships. Investigations in the auditory system will provide important insight into how the nervous system decodes molecular information. Deafness represents a common sensory disorder that can interfere dramatically in the acquisition of speech and language in children, and in the quality of life for a growing aged population. As newborn screening for hearing impairment is being implemented in many birth hospitals, the prospects for precise clinical diagnosis, appropriate genetic counseling and proper medical management for auditory disorders has never been at a more exciting crossroad.

Animals↗
PubMed2026

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes.

OBJECTIVE: To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS: We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS: GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS: Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

Journal Article↗
PubMed1995

From stand-by to decoding site. Adjustment of the mRNA on the 30S ribosomal subunit under the influence of the initiation factors.

The hypothesis of an adjustment of the mRNA in its ribosomal channel under the influence of the initiation factors has been tested by site-directed crosslinking experiments. Complexes containing 30S subunits with bound mRNA having 4-thio-uracil at specific positions were prepared in the presence or absence of initiation factors and/or fMet-tRNA and subjected to UV irradiation to obtain specific crosslinks of the radioactively labeled mRNA with bases of the 16S rRNA and with ribosomal proteins. The subsequent identification of the specific sites of both mRNA and rRNA and individual ribosomal proteins involved in the crosslinking, obtained under different conditions of complex formation, provide direct evidence for the occurrence of a partial relocation of the mRNA on the 30S ribosomal subunits under the influence of the factors. The nature of this mRNA relocation is compatible with our previous proposal of a shift of the template from an initial ribosomal "stand-by site" to a second site closer to that occupied when the initiation triplet of the mRNA is decoded in the P-site.

Base Sequence↗
PubMed1992

Encoded combinatorial chemistry.

The diversity of chemical synthesis and the power of genetics are linked to provide a powerful, versatile method for drug screening. A process of alternating parallel combinatorial synthesis is used to encode individual members of a large library of chemicals with unique nucleotide sequences. After the chemical entity is bound to a target, the genetic tag can be amplified by replication and utilized for enrichment of the bound molecules by serial hybridization to a subset of the library. The nature of the chemical structure bound to the receptor is decoded by sequencing the nucleotide tag.

Amino Acid Sequence↗
PubMed1999

The zebrafish genome contains two distinct selenocysteine tRNA[Ser]sec genes.

The zebrafish is widely used as a model system for studying mammalian developmental genetics and more recently, as a model system for carcinogenesis. Since there is mounting evidence that selenium can prevent cancer in mammals, including humans, we characterized the selenocysteine tRNA[Ser]sec gene and its product in zebrafish. Two genes for this tRNA were isolated and sequenced and were found to map at different loci within the zebrafish genome. The encoding sequences of both are identical and their flanking sequences are highly homologous for several hundred bases in both directions. The two genes likely arose from gene duplication which is a common phenomenon among many genes in this species. In addition, zebrafish tRNA[Ser]sec was isolated from the total tRNA population and shown to decode UGA in a ribosomal binding assay.

Animals↗
PubMedDate not supplied

How mitochondria redefine the code.

Annotated, complete DNA sequences are available for 213 mitochondrial genomes from 132 species. These provide an extensive sample of evolutionary adjustment of codon usage and meaning spanning the history of this organelle. Because most known coding changes are mitochondrial, such data bear on the general mechanism of codon reassignment. Coding changes have been attributed variously to loss of codons due to changes in directional mutation affecting the genome GC content (Osawa and Jukes 1988), to pressure to reduce the number of mitochondrial tRNAs to minimize the genome size (Anderson and Kurland 1991), and to the existence of transitional coding mechanisms in which translation is ambiguous (Schultz and Yarus 1994a). We find that a succession of such steps explains existing reassignments well. In particular, (1) Genomic variation in the prevalence of a codon's third-position nucleotide predicts relative mitochondrial codon usage well, though GC content does not. This is because A and T, and G and C, are uncorrelated in mitochondrial genomes. (2) Codons predicted to reach zero usage (disappear) do so more often than expected by chance, and codons that do disappear are disproportionately likely to be reassigned. However, codons predicted to disappear are not significantly more likely to be reassigned. Therefore, low codon frequencies can be related to codon reassignment, but appear to be neither necessary nor sufficient for reassignment. (3) Changes in the genetic code are not more likely to accompany smaller numbers of tRNA genes and are not more frequent in smaller genomes. Thus, mitochondrial codons are not reassigned during demonstrable selection for decreased genome size. Instead, the data suggest that both codon disappearance and codon reassignment depend on at least one other event. This mitochondrial event (leading to reassignment) occurs more frequently when a codon has disappeared, and produces only a small subset of possible reassignments. We suggest that coding ambiguity, the extension of a tRNA's decoding capacity beyond its original set of codons, is the second event. Ambiguity can act alone but often acts in concert with codon disappearance, which promotes codon reassignment.

Base Composition↗
PubMed2026

Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.

Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.

Humans↗
PubMed1995

The involvement of two distinct regions of 23 S ribosomal RNA in tRNA selection.

The role of ribosomal RNA in maintaining the accuracy of translation has been investigated genetically by selecting for rRNA mutations that promoted frameshifting at a specific site in a reporter gene in Escherichia coli. Mutations were recovered in two different regions of 23 S rRNA and each promoted readthrough of stop codons as well as increasing the levels of frameshifting. The first group of mutations was in a small stem loop (the 1916 loop) in domain IV of 23 S rRNA. This stem-loop has been mapped to the subunit interface of the ribosome, close to the decoding center on the 30 S subunit. The second group of mutations was in helix 89, one of the helices emerging from the central loop of domain V. Helix 89 has been implicated in subunit-subunit interactions and peptidyltransferase activity, and it is proposed that mutations in helix 89 influence the accuracy of decoding by affecting the interaction of the CCA end of the tRNA with the peptidyltransferase center.

Base Sequence↗
PubMed1997

Multiple von Neumann computers: an evolutionary approach to functional emergence.

A novel system composed of multiple von Neumann computers and an appropriate problem environment is proposed and simulated. Each computer has a memory to store the machine instruction program, and when a program is executed, a series of machine codes in the memory is sequentially decoded, leading to register operations in the central processing unit (CPU). By means of these operations, the computer not only can handle its generally used registers but also can read and write the environmental database. Simulation is driven by genetic algorithms (GAs) performed on the population of program memories. Mutation and crossover create program diversity in the memory, and selection facilitates the reproduction of appropriate programs. Through these evolutionary operations, advantageous combinations of machine codes are created and fixed in the population one by one, and the higher function, which enables the computer to calculate an appropriate number from the environment, finally emerges in the program memory. In the latter half of the article, the performance of GAs on this system is studied. Under different sets of parameters, the evolutionary speed, which is determined by the time until the domination of the final program, is examined and the conditions for faster evolution are clarified. At an intermediate mutation rate and at an intermediate population size, crossover helps create novel advantageous sets of machine codes and evidently accelerates optimization by GAs.

Algorithms↗
PubMed1982

Origin of life: a hypothesis for the origin of adaptor-mediated ordered synthesis of proteins and an explanation for the choice of terminating codons in the genetic code.

Life can be defined as a system of self-sustained chemical processes springing from the ordered synthesis of proteins directed by nucleic acids. To the notoriously difficult problem of the origin of this basic process of nucleic acid-directed protein synthesis, we give a solution of molecular interactions between pentanucleotides and amino acids. A particular conformation of a pentanucleotide forms a double sided template, with its 'inside' capable of nestling an amino acid while the 'outside' acts as an adaptor to a 'codon' triplet on long-chain nucleic acids. This serves as a primitive decoding system. An important aspect of our postulate is that a dynamic interaction is triggered, by this decoding system, through which amino acids are brought to juxtaposition facilitating peptide bond formation. Almost all the important and unique features of contemporary protein-synthesizing machinery are seen to be a direct and natural consequence of our postulate. The emergence of the termination codons also fits in, as a natural consequence of this molecular mechanism.

Animals↗
PubMed2026

Integrative proteogenomic and observational analysis identifies potential biomarkers for latent autoimmune diabetes in adults.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) shares core genetic and immunological features with type 1 diabetes (T1D) but is frequently misdiagnosed as type 2 diabetes (T2D). With few biomarkers for its timely diagnosis and management, this study integrated proteome-wide Mendelian randomisation (MR) and observational clinical analysis to identify potential LADA biomarkers. METHODS: We performed proteome-wide MR using cis-protein quantitative trait loci (cis-pQTLs) for 1,389 plasma proteins from the deCODE study (n = 35,559) and genome-wide association study (GWAS) data for LADA (2,634 cases and 5,947 controls, European ancestry). Robustness was enhanced via multiple sensitivity analyses. Pathway enrichment analysis, druggability evaluation, phenome-wide MR, and interaction analyses were performed to investigate the clinical relevance and biological context of candidate proteins. Candidate proteins were further evaluated using enzyme-linked immunosorbent assays in a matched Chinese clinical study (n = 241) to assess their discriminative ability for LADA. RESULTS: Proteome-wide MR and colocalisation analyses indicated associations between genetically predicted plasma levels of C-X-C motif chemokine ligand 10 (CXCL10; OR [95% CI] per 1-SD increase in protein levels: 5.49 [1.74,17.32]), serum amyloid A1 (SAA1; 1.28 [1.14,1.45]), and SAA2 (1.22 [1.11,1.34]) with LADA risk. Replication, multi-tissue eQTL, and multivariable MR supported CXCL10's association. Druggability evaluation suggested CXCL10 as a drug target under investigation, and phenome-wide MR of 1,006 diseases and traits indicated no major safety concerns for CXCL10 as a potential biomarker. In the observational clinical study, CXCL10 differentiated LADA from healthy controls (area under the receiver operating characteristic curve [ROC-AUC]: 0.889; precision-recall area under the curve [PR-AUC]: 0.919) and T2D (ROC-AUC: 0.838; PR-AUC: 0.921), with both models showing adequate calibration. CONCLUSIONS: This study suggests that CXCL10 is a putative biomarker associated with LADA, demonstrating discriminative ability to distinguish LADA from T2D in an observational clinical cohort. These findings contribute to understanding the autoimmune molecular aetiology of LADA and support its diagnostic potential in resolving the clinical ambiguity between LADA and T2D.

Humans↗
PubMed2026

Characterizing the impact of plasma protein levels on human brain structure and disorders leveraging integrative multi-omics analysis.

With recent advances in high-throughput proteomic technologies, population-scale plasma proteomics datasets, often linked to extensive genetic and phenotypic information, have become increasingly accessible. Yet the relationships between circulating protein levels, brain imaging phenotypes, and risk for neurological and psychiatric disorders remain largely unexplored. Proteome-wide association studies offer a promising approach for elucidating biological mechanisms that connect genetic variation to complex brain-related traits and diseases. In this study, we integrated protein quantitative trait loci (pQTLs) from the two largest plasma proteomic resources (the UK Biobank Pharma Proteomics Project [UKB-PPP] and Ferkingstad et al. [deCODE]) with genome-wide association studies of brain imaging-derived phenotypes in UK Biobank using Mendelian randomization and colocalization analyses. We identified 120 cis and 20 trans associations between plasma proteins and imaging phenotypes and validated these findings using brain tissue-derived proteomic and transcriptomic datasets. Multivariable Mendelian randomization revealed eleven plasma proteins (coding genes APOE, ARL3, MICB, NSF, RHOC, RSPO3, ENPP2, BTN2A1, EIF2AK3, MRVI1, and OPLAH) with significant direct effects on the risk of Alzheimer's disease, Parkinson's disease, multiple sclerosis, bipolar disorder, and schizophrenia. Single-cell expression and pathway enrichment analyses further revealed cell-type-specific effects and distinct biological processes underlying these protein-disease associations. Together, these findings demonstrate robust links between plasma protein variation and brain structure, delineate protein-disease pathways, and highlight the cellular and molecular mechanisms that contribute to neurobiological diversity and pathology.

Journal Article↗
PubMed1998

Toward a new natural medicine.

Treatments summarized under the term "natural medicine," i.e., those offered as an alternative or in addition to conventional medicine, have enjoyed a surge in popularity in recent years. The "natural" descriptor employed in connection with these healing methods is frequently misunderstood, leading to underestimation of the risks arising from incorrect use. However, the essential principle underlying traditional natural medicine, mobilization of the body's own forces against disease, is increasingly being employed in a new, rational form of medicine: molecular medicine. A range of natural endogenous substances for medical use are already available. Human proteins such as erythropoietin can now be produced as medicines in highly pure form with the aid of genetic engineering techniques. Our increasing understanding of the function of our genes and the resulting descriptions of molecular mechanisms underlying disease are also helping us to utilize the body's own construction set. New techniques such as gene therapy will in future enable us to reproduce the natural conditions in the healthy body with increasing specificity in our attempts to cure illnesses. One such application will be the activation of the immune system to combat cancer. The complete decoding of the human genome will not only allow illnesses to be described, and possibly prevented, at an earlier stage. Illnesses will also be able to described more precisely and individually at the molecular level, opening up the possibility of targeted, patient-specific cures.

Amino Acid Sequence↗
PubMedDate not supplied

"Decoding" informed consent. Insights from women regarding breast cancer susceptibility testing.

Cancer susceptibility testing is likely to become routine in medical practice, despite many limitations and unanswered questions. These uncertainties greatly complicate the process of informed consent, creating an excellent opportunity to reconsider exactly how it should be conducted. Research with women's reactions to the availability of genetic susceptibility testing for breast cancer dramatically underscores that informed consent ought to be highly individualized, taking care to discern what patients believe about the disease and its causes and what role they want their physician to play.

Attitude to Health↗
PubMed2000

DNA sequence analysis of the complete mitochondrial genome of the green alga Scenedesmus obliquus: evidence for UAG being a leucine and UCA being a non-sense codon.

The complete DNA sequence of the mitochondrial genome of the chlorophyceen alga Scenedesmus obliquus was determined. The circular genome of 42781bp contains a basic set of 13 mitochondrial genes, which are conserved among plant or algal chondriomes. In addition, two scrambled rRNA and 27 tRNA genes are present, together with four intronic sequences (group I and II) and five open reading frames (ORFs), which show no significant homology to other ORFs from organellar genomes. The comparison with deduced amino acid sequences from 13 conserved mitochondrial genes gives rise to the conclusion that two deviations from the standard genetic code must be present in S. obliquus mitochondria: (i) UAG codes for leucine as was already found in some other algal mitochondria; (ii) UCA is a stop codon, which seems unique for mitochondrial genomes. This was supported by our finding that a tRNA-Leu gene possesses a UCA anticodon and by a missing tRNA-serine, able to decode the UCA codon. Consistent with these data is the absence of any UCA codon from conserved mitochondrial ORFs. This codon occurs only close to the end of all ORFs, while UAA or UGA codons are found at some distance from any conserved ORF. Codon changes by RNA editing can be excluded, since RT-PCR analysis does not reveal any evidence for post-transcriptional RNA modifications of the primary transcript.

Algal Proteins↗