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Point MutationMutation, MissenseMutationFrameshift MutationMolecular Sequence DataBase SequenceGerm-Line MutationPedigreeAmino Acid SequenceDNA Mutational AnalysisExonsPolymerase Chain ReactionAmino Acid SubstitutionMutagenesis, Site-DirectedHeterozygoteMutation RateAllelesPolymorphism, Single-Stranded ConformationalMutagenesisSequence Analysis, DNASequence DeletionHomozygoteProtein Structure, TertiaryDNA PrimersGenotypePhenotypeBinding SitesCell LineCodonModels, MolecularCodon, NonsenseEscherichia coliSequence Homology, Amino AcidDNA-Binding ProteinsGene DeletionCloning, MolecularProtein BindingGenes, DominantDNAGenes, RecessiveSequence AlignmentSuppression, GeneticTranscription FactorsPlasmidsChromosome MappingTransfectionGenes, p53Genetic TestingGenetic Complementation TestDNA, MitochondrialMutant ProteinsSaccharomyces cerevisiaeTranscription, GeneticBacterial ProteinsPromoter Regions, GeneticMembrane ProteinsRecombinant ProteinsIntronsStructure-Activity RelationshipProtein ConformationNuclear ProteinsSyndromeEthylnitrosoureaDNA, NeoplasmRNA, MessengerGenetic VariationPolymorphism, GeneticModels, GeneticPolymorphism, Restriction Fragment LengthCarrier ProteinsGenetic LinkageKineticsRecombinant Fusion ProteinsFounder EffectHeterozygote DetectionMutagenesis, InsertionalGenesRecombination, GeneticConserved SequenceCOS CellsGenes, LethalGenetic Predisposition to DiseaseGenes, BacterialRestriction MappingConsanguinitySignal TransductionRNA SplicingProtein Structure, SecondarySaccharomyces cerevisiae ProteinsProto-Oncogene ProteinsProteinsGenes, SuppressorFamily HealthGene FrequencyDNA, ComplementaryProto-Oncogene Proteins B-rafTemperatureGenes, FungalMutagensExomeCricetinaeEvolution, MolecularCrosses, GeneticCells, CulturedDrug ResistanceMice, Mutant StrainsChromosome DeletionOligonucleotide ProbesFungal ProteinsMicrosatellite RepeatsGenes, BRCA1Amino Acid MotifsCercopithecus aethiopsRNA Splice SitesDNA, BacterialRepressor ProteinsBlotting, SouthernGene Expression RegulationINDEL MutationTumor Suppressor Protein p53Gene ExpressionReverse Transcriptase Polymerase Chain ReactionPhosphorylationHeLa CellsEscherichia coli ProteinsSelection, GeneticEye ProteinsDrug Resistance, MicrobialGenes, rasDrug Resistance, ViralJewsSequence Homology, Nucleic AcidDrosophila ProteinsNucleic Acid ConformationAge of OnsetOligodeoxyribonucleotidesTrans-ActivatorsDNA RepairBlotting, WesternGenetic Diseases, X-LinkedGlycineRetinitis PigmentosaMice, TransgenicRNA, Transfer, LeuAlanineAbnormalities, MultipleCell Transformation, NeoplasticArginineMELAS SyndromeVirus ReplicationPolymorphism, Single NucleotideDNA Transposable ElementsDrosophila melanogasterDimerizationras ProteinsDNA GyraseGene Expression Regulation, BacterialPenetranceDrug Resistance, BacterialGenetic MarkersSerineFibroblastsMitochondrial EncephalomyopathiesX ChromosomeGenes, BRCA2CHO CellsModels, BiologicalLoss of HeterozygosityTumor Cells, CulturedCodon, TerminatorEye AbnormalitiesDNA, ViralEthyl MethanesulfonateProtein TransportMice, Inbred C57BLProtein FoldingCysteineRepetitive Sequences, Nucleic AcidDrosophilaImmunohistochemistryCell NucleusDNA, FungalAdenosine TriphosphatasesHEK293 CellsMitochondrial DiseasesViral ProteinsOperonGenetic HeterogeneityAdaptor Proteins, Signal TransducingCell Line, TumorGenes, RegulatorProtein StabilityPhylogenyMitochondrial MyopathiesAsian Continental Ancestry GroupRNANeoplasm ProteinsProtein-Serine-Threonine KinasesRNA, ViralCharcot-Marie-Tooth DiseaseMosaicism
Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Frameshift Mutation: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Mutation Rate: The number of mutations that occur in a specific sequence, GENE, or GENOME over a specified period of time such as years, CELL DIVISIONS, or generations.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Polymorphism, Single-Stranded Conformational: Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Homozygote: An individual in which both alleles at a given locus are identical.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Codon, Nonsense: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Genes, Recessive: Genes that influence the PHENOTYPE only in the homozygous state.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Suppression, Genetic: Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Bacterial Proteins: Proteins found in any species of bacterium.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Syndrome: A characteristic symptom complex.Ethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.DNA, Neoplasm: DNA present in neoplastic tissue.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Genetic Variation: Genotypic differences observed among individuals in a population.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Kinetics: The rate dynamics in chemical or physical systems.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Founder Effect: A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.Heterozygote Detection: Identification of genetic carriers for a given trait.Mutagenesis, Insertional: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Genes, Lethal: Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Genes, Bacterial: The functional hereditary units of BACTERIA.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Consanguinity: The magnitude of INBREEDING in humans.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Genes, Suppressor: Genes that have a suppressor allele or suppressor mutation (SUPPRESSION, GENETIC) which cancels the effect of a previous mutation, enabling the wild-type phenotype to be maintained or partially restored. For example, amber suppressors cancel the effect of an AMBER NONSENSE MUTATION.Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Proto-Oncogene Proteins B-raf: A raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Genes, Fungal: The functional hereditary units of FUNGI.Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.Exome: That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Crosses, Genetic: Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Chromosome Deletion: Actual loss of portion of a chromosome.Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.Fungal Proteins: Proteins found in any species of fungus.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Genes, BRCA1: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.RNA Splice Sites: Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Blotting, Southern: A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.INDEL Mutation: A mutation named with the blend of insertion and deletion. It refers to a length difference between two ALLELES where it is unknowable if the difference was originally caused by a SEQUENCE INSERTION or by a SEQUENCE DELETION. If the number of nucleotides in the insertion/deletion is not divisible by three, and it occurs in a protein coding region, it is also a FRAMESHIFT MUTATION.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Eye ProteinsDrug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.Drug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Jews: An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Age of Onset: The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Genetic Diseases, X-Linked: Genetic diseases that are linked to gene mutations on the X CHROMOSOME in humans (X CHROMOSOME, HUMAN) or the X CHROMOSOME in other species. Included here are animal models of human X-linked diseases.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.RNA, Transfer, Leu: A transfer RNA which is specific for carrying leucine to sites on the ribosomes in preparation for protein synthesis.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Abnormalities, MultipleCell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Arginine: An essential amino acid that is physiologically active in the L-form.MELAS Syndrome: A mitochondrial disorder characterized by focal or generalized seizures, episodes of transient or persistent neurologic dysfunction resembling strokes, and ragged-red fibers on muscle biopsy. Affected individuals tend to be normal at birth through early childhood, then experience growth failure, episodic vomiting, and recurrent cerebral insults resulting in visual loss and hemiparesis. The cortical lesions tend to occur in the parietal and occipital lobes and are not associated with vascular occlusion. VASCULAR HEADACHE is frequently associated and the disorder tends to be familial. (From Joynt, Clinical Neurology, 1992, Ch56, p117)Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.DNA Transposable Elements: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.DNA Gyrase: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Penetrance: The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Mitochondrial Encephalomyopathies: A heterogenous group of disorders characterized by alterations of mitochondrial metabolism that result in muscle and nervous system dysfunction. These are often multisystemic and vary considerably in age at onset (usually in the first or second decade of life), distribution of affected muscles, severity, and course. (From Adams et al., Principles of Neurology, 6th ed, pp984-5)X Chromosome: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.Genes, BRCA2: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Codon, Terminator: Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.Eye Abnormalities: Congenital absence of or defects in structures of the eye; may also be hereditary.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Ethyl Methanesulfonate: An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Mice, Inbred C57BLProtein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)DNA, Fungal: Deoxyribonucleic acid that makes up the genetic material of fungi.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Mitochondrial Diseases: Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.Viral Proteins: Proteins found in any species of virus.Operon: In bacteria, a group of metabolically related genes, with a common promoter, whose transcription into a single polycistronic MESSENGER RNA is under the control of an OPERATOR REGION.Genetic Heterogeneity: The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesCell Line, Tumor: A cell line derived from cultured tumor cells.Genes, Regulator: Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Mitochondrial Myopathies: A group of muscle diseases associated with abnormal mitochondria function.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.Charcot-Marie-Tooth Disease: A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single ZYGOTE, as opposed to CHIMERISM in which the different cell populations are derived from more than one zygote.

Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation. (1/13935)

The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01). These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma.  (+info)

Cooperative binding of heat shock factor to the yeast HSP82 promoter in vivo and in vitro. (2/13935)

Previous work has shown that heat shock factor (HSF) plays a central role in remodeling the chromatin structure of the yeast HSP82 promoter via constitutive interactions with its high-affinity binding site, heat shock element 1 (HSE1). The HSF-HSE1 interaction is also critical for stimulating both basal (noninduced) and induced transcription. By contrast, the function of the adjacent, inducibly occupied HSE2 and -3 is unknown. In this study, we examined the consequences of mutations in HSE1, HSE2, and HSE3 on HSF binding and transactivation. We provide evidence that in vivo, HSF binds to these three sites cooperatively. This cooperativity is seen both before and after heat shock, is required for full inducibility, and can be recapitulated in vitro on both linear and supercoiled templates. Quantitative in vitro footprinting reveals that occupancy of HSE2 and -3 by Saccharomyces cerevisiae HSF (ScHSF) is enhanced approximately 100-fold through cooperative interactions with the HSF-HSE1 complex. HSE1 point mutants, whose basal transcription is virtually abolished, are functionally compensated by cooperative interactions with HSE2 and -3 following heat shock, resulting in robust inducibility. Using a competition binding assay, we show that the affinity of recombinant HSF for the full-length HSP82 promoter is reduced nearly an order of magnitude by a single-point mutation within HSE1, paralleling the effect of these mutations on noninduced transcript levels. We propose that the remodeled chromatin phenotype previously shown for HSE1 point mutants (and lost in HSE1 deletion mutants) stems from the retention of productive, cooperative interactions between HSF and its target binding sites.  (+info)

The alphaE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells. (3/13935)

The acquisition of invasiveness is a crucial step in the malignant progression of cancer. In cancers of the colon and of other organs the E-cadherin/catenin complex, which is implicated in homotypic cell-cell adhesion as well as in signal transduction, serves as a powerful inhibitor of invasion. We show here that one allele of the alphaE-catenin (CTNNA1) gene is mutated in the human colon cancer cell family HCT-8, which is identical to HCT-15, DLD-1 and HRT-18. Genetic instability, due to mutations in the HMSH6 (also called GTBP) mismatch repair gene, results in the spontaneous occurrence of invasive variants, all carrying either a mutation or exon skipping in the second alphaE-catenin allele. The alphaE-catenin gene is therefore, an invasion-suppressor gene in accordance with the two-hit model of Knudsen for tumour-suppressor genes.  (+info)

Correlation between the status of the p53 gene and survival in patients with stage I non-small cell lung carcinoma. (4/13935)

The association of p53 abnormalities with the prognosis of patients with non-small cell lung carcinoma (NSCLC) has been extensively investigated to date, however, this association is still controversial. Therefore, we investigated the prognostic significance of p53 mutations through exons 2 to 11 and p53 protein expression in 103 cases of stage I NSCLC. p53 mutations were detected in 49 of 103 (48%) tumors. Two separate mutations were detected in four tumors giving a total of 53 unique mutations in 49 tumors. Ten (19%) of mutations occurred outside exons 5-8. Positive immunohistochemical staining of p53 protein was detected in 41 of 103 (40%) tumors. The concordance rate between mutations and protein overexpression was only 69%. p53 mutations, but not expression, were significantly associated with a shortened survival of patients (P<0.001). Furthermore, we investigated the correlation between the types of p53 mutations and prognosis. p53 missense mutations rather than null mutations were associated with poor prognosis (P < 0.001 in missense mutations and P=0.243 in null mutations). These results indicated that p53 mutations, in particular missense mutations, rather than p53 expression could be a useful molecular marker for the prognosis of patients with surgically resected stage I NSCLC.  (+info)

p73 at chromosome 1p36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent. (5/13935)

p73, a novel p53 family member, is a recently identified candidate neuroblastoma (NBL) suppressor gene mapped at chromosome 1p36.33 and was found to inhibit growth and induce apoptosis in cell lines. To test the hypothesis that p73 is a NBL suppressor gene, we analysed the p73 gene in primary human NBLs. Loss of heterozygosity (LOH) for p73 was observed in 19% (28/151) of informative cases which included 92 mass-screening (MS) tumors. The high frequency of p73 LOH was significantly associated with sporadic NBLs (9% vs 34%, P<0.001), N-myc amplification (10% vs 71%, P<0.001), and advanced stage (14% vs 28%, P<0.05). Both p73alpha and p73beta transcripts were detectable in only 46 of 134 (34%) NBLs at low levels by RT-PCR methods, while they were easily detectable in most breast cancers and colorectal cancers under the same conditions. They found no correlation between p73 LOH and its expression levels (P>0.1). We found two mutations out of 140 NBLs, one somatic and one germline, which result in amino acid substitutions in the C-terminal region of p73 which may affect transactivation functions, though, in the same tumor samples, no mutation of the p53 gene was observed as reported previously. These results suggest that allelic loss of the p73 gene may be a later event in NBL tumorigenesis. However, p73 is infrequently mutated in primary NBLs and may hardly function as a tumor suppressor in a classic Knudson's manner.  (+info)

RNA binding by the novel helical domain of the influenza virus NS1 protein requires its dimer structure and a small number of specific basic amino acids. (6/13935)

The RNA-binding/dimerization domain of the NS1 protein of influenza A virus (73 amino acids in length) exhibits a novel dimeric six-helical fold. It is not known how this domain binds to its specific RNA targets, one of which is double-stranded RNA. To elucidate the mode of RNA binding, we introduced single alanine replacements into the NS1 RNA-binding domain at specific positions in the three-dimensional structure. Our results indicate that the dimer structure is essential for RNA binding, because any alanine replacement that causes disruption of the dimer also leads to the loss of RNA-binding activity. Surprisingly, the arginine side chain at position 38, which is in the second helix of each monomer, is the only amino-acid side chain that is absolutely required only for RNA binding and not for dimerization, indicating that this side chain probably interacts directly with the RNA target. This interaction is primarily electrostatic, because replacement of this arginine with lysine had no effect on RNA binding. A second basic amino acid, the lysine at position 41, which is also in helix 2, makes a strong contribution to the affinity of binding. We conclude that helix 2 and helix 2', which are antiparallel and next to each other in the dimer conformation, constitute the interaction face between the NS1 RNA-binding domain and its RNA targets, and that the arginine side chain at position 38 and possibly the lysine side chain at position 41 in each of these antiparallel helices contact the phosphate backbone of the RNA target.  (+info)

A concise promoter region of the heart fatty acid-binding protein gene dictates tissue-appropriate expression. (7/13935)

The heart fatty acid-binding protein (HFABP) is a member of a family of binding proteins with distinct tissue distributions and diverse roles in fatty acid metabolism, trafficking, and signaling. Other members of this family have been shown to possess concise promoter regions that direct appropriate tissue-specific expression. The basis for the specific expression of the HFABP has not been previously evaluated, and the mechanisms governing expression of metabolic genes in the heart are not completely understood. We used transient and permanent transfections in ventricular myocytes, skeletal myocytes, and nonmyocytic cells to map regulatory elements in the HFABP promoter, and audited results in transgenic mice. Appropriate tissue-specific expression in cell culture and in transgenic mice was dictated by 1.2 kb of the 5'-flanking sequence of FABP3, the HFABP gene. Comparison of orthologous murine and human genomic sequences demonstrated multiple regions of near-identity within this promoter region, including a CArG-like element close to the TATA box. Binding and transactivation studies demonstrated that this element can function as an atypical myocyte enhancer-binding factor 2 site. Interactions with adjacent sites are likely to be necessary for fully appropriate, tissue-specific, developmental and metabolic regulation.  (+info)

The DNA binding activity of Translin is mediated by a basic region in the ring-shaped structure conserved in evolution. (8/13935)

DNA binding proteins, for the most part, function as dimers or tetramers which recognize their target sequences. Here we show that Translin, a novel single-stranded DNA end binding protein, forms a ring-shaped structure conserved throughout evolution and that this structure is responsible for its DNA binding activity. Point mutations at Leu184 and Leu191 in the leucine zipper motif of human Translin resulted in loss of the multimeric structure and abrogation of DNA binding. Point mutations at R86, H88, H90 to T86, N88, N90 in one of the basic regions, however, completely inhibited the DNA binding activity without affecting the multimeric structure. These results support the view that the DNA binding domain of Translin is formed in the ring-shaped structure in combination with its basic region (amino acids 86-97) polypeptides.  (+info)

Identification of seven novel mutations in LH β-subunit gene by SSCP<...Identification of seven novel mutations in LH β-subunit gene by SSCP<...
TY - JOUR. T1 - Identification of seven novel mutations in LH β-subunit gene by SSCP. AU - Roy, Ashim C.. AU - Liao, Wu Xiang. AU - Chen, Ying. AU - Arulkumaran, Sabaratnam. AU - Ratnam, Shan S.. PY - 1996. Y1 - 1996. N2 - Seven new point mutations have been identified from LH β-subunit gene by PCR-mediated SSCP, and sequencing. One mutation was found changing amino acid from Gln102 to Ser102. The remaining six mutations, which did not change the codings, were in complete linkage disequilibrium. SSCP can be used in the diagnosis of LH-related disorders.. AB - Seven new point mutations have been identified from LH β-subunit gene by PCR-mediated SSCP, and sequencing. One mutation was found changing amino acid from Gln102 to Ser102. The remaining six mutations, which did not change the codings, were in complete linkage disequilibrium. SSCP can be used in the diagnosis of LH-related disorders.. KW - Luteinizing hormone. KW - Mutation. KW - Polymerase chain reaction. KW - Restriction enzyme ...
COVID-19: virus strain dominant worldwide is different from original in Wuhan : Peoples DispatchCOVID-19: virus strain dominant worldwide is different from original in Wuhan : Peoples Dispatch
Viral evolution is a common phenomenon. Among other factors that marks how a virus evolves is what is known as point mutation. A point mutation can either be in a specific location of the DNA or it can give rise to the change in a specific position of a critical viral protein. A change of a single base in the DNA or a single amino acid of a protein - the hallmark of point mutation - can bring in huge change in terms of physiology, infectivity and severity of a microorganism, and for that matter, in any organism. As a result of such point mutations, different strains of a virus evolve.. SARS-CoV-2, the coronavirus that caused the COVID-19 pandemic with devastating consequences, also has undergone such point mutation and hence different strains have emerged. A Cell publication has revealed the viral strain that possibly emerged during April 2020 and has now has become the dominant viral form worldwide. The strain, named D614G, is different from the original one found in Wuhan, China and is more ...
Genomic and Biological Characterization of Exon 4 KRAS Mutations in Human Cancer | Cancer ResearchGenomic and Biological Characterization of Exon 4 KRAS Mutations in Human Cancer | Cancer Research
Several decades have passed since oncogenic RAS was first identified as the transforming factor in the Harvey and Kirsten strains of the Mouse Sarcoma Virus (1, 3-5). Since these discoveries, all three RAS family genes (KRAS, NRAS, and HRAS) have been shown to be somatically mutated in human cancer, most commonly as a result of single point mutations at codons 12, 13, and 61.. Despite overwhelming evidence that oncogenic RAS plays a central role in mediating transformation in human tumors, only recently has limited testing for somatic RAS mutations entered routine clinical practice. Widespread adoption of mutational profiling in the clinic has been delayed for several reasons. First, before recent advances in sequencing technology, RAS mutational testing was expensive and time intensive. Second, until recently, there was no definitive evidence that routine testing for RAS mutations would meaningfully affect clinical practice. This changed with the identification of KRAS mutations as a predictor ...
Developing new method for GBA sequencing and detection of germ-line or somatic point mutations, deletion/insertions, and...Developing new method for GBA sequencing and detection of germ-line or somatic point mutations, deletion/insertions, and...
Study Rationale: Mutations in the GBA gene are the most common genetic cause of Parkinson s disease. This gene has a nearby pseudogene, which is a genetic material that is very similar to the original gene but does not encode a protein. Because of the presence of the pseudogene, it is often difficult to identify mutations in the gene using traditional mutation detection techniques. Furthermore, specific mutations that occur as a result of a recombination between the gene and the pseudogene are often missed by the traditional genetic methods.. Hypothesis:. By using a novel technology called targeted locus amplification (TLA) we hypothesize that we will be able to better discriminate between the gene and its pseudogene, and to identify specific recombinations between GBA and its pseudogene.. Study Design:. First, we will design the TLA methods to match the target gene, GBA, and its pseudogene, and examine if it works using random DNA samples. Then, we will examine if the method works by using DNA ...
Using a constraint-based regression method for relative quantification of somatic mutations in pyrosequencing signals: a case...Using a constraint-based regression method for relative quantification of somatic mutations in pyrosequencing signals: a case...
Pyrosequencing Allele Quantification (AQ) is a cost-effective DNA sequencing method that can be used for detecting somatic mutations in formalin-fixed paraffin-embedded (FFPE) samples. The method displays a low turnaround time and a high sensitivity. Pyrosequencing suffers however from two main drawbacks including (i) low specificity and (ii) difficult signal interpretation when multiple mutations are reported in a hotspot genomic region. Using a constraint-based regression method, the new AdvISER-PYRO-SMQ algorithm was developed in the current study and implemented into an R package. As a proof-of-concept, AdvISER-PYRO-SMQ was used to identify a set of 9 distinct point mutations affecting codon 61 of the NRAS oncogene. In parallel, a pyrosequencing assay using the Qiagen software and its AQ module was used to assess selectively the presence of a single point mutation (NRAS $$c.182A|G$$
Antievolution.org - Antievolution.org Discussion Board -Topic::Evolutionary ComputationAntievolution.org - Antievolution.org Discussion Board -Topic::Evolutionary Computation
Mendels Accountant User Manual: Maximal beneficial mutation effects A realistic upper limit must be placed upon beneficial mutations. This is because a single nucleotide change can expand total biological functionality of an organism only to a limited degree. The larger the genome and the greater the total genomic information, the less a single nucleotide is likely to increase the total. Researchers must make a judgment for themselves of what is a reasonable maximal value for a single base change. The MENDEL default value for this limit is 0.001. This limit implies that a single point mutation can increase total biological functionality by as much as 0.1%. In a genome such as man s, assuming only 10% of the genome is functional, such a maximal impact point mutation might be viewed as equivalent to adding 300,000 new information-bearing base pairs each of which had the genome-wide average fitness contribution. Researchers need to honestly define the upper limit they feel is realistic for their ...
Publications | DR. OSANJO GEORGE OYAMOPublications | DR. OSANJO GEORGE OYAMO
a-Galactosidase AgaB from Bacillus stearothermophilus displays a major a(1~6) and a minor a(1~3) regioselectivity in hydrolysis and transglycosylation. Its corresponding gene, agaB, was subjected to saturation mutagenesis at codon 442 in order to change its regioselectivity. The mutant genes were cloned and expressed in Escherichia coli using pBTac2 as vector. The regioselective activity of the mutants was determined using thin layer chromatography and nuclear magnetic resonance spectroscopy. A single point mutation, G442R, resulted in a mutant displaying an a(1~2) regioselectivity. Other amino acid substitutions at this site also gave mutants with altered regioselectivity and transglycosylation profiles. This is the first demonstration that single point mutations can lead to a strong modification of the regioselectivity of a glycosyl hydrolase. The kinetic parameters of the enzyme variants were determined and a preliminary investigation of possible substrates for condensation reactions ...
Generalized Radial Basis Function-Based High-Dimensional Model Representation Handling Existing Random Data | Journal of...Generalized Radial Basis Function-Based High-Dimensional Model Representation Handling Existing Random Data | Journal of...
The radial basis function-based high-dimensional model representation (RBF-HDMR) is very promising as a metamodel for high dimensional costly simulation-based functions. But in the modeling procedure, it requires well-structured regular points sampled on cut lines and planes. In practice, we usually have some existing random points that do not lie on cut lines or planes. For this case, RBF-HDMR cannot utilize the information of these random points because of its inner regular sampling process. To utilize the existing random points, this article presents two strategies to build a generalized RBF-HDMR (GRBF-HDMR) model. The GRBF-HDMR model using the error model (EM) strategy, called GRBF-HDMREM, constructs an error RBF model based on the prediction errors at all the sampled points to improve the RBF-HDMR predictions. While the GRBF-HDMR model using the error allocation (EA) strategy, called GRBF-HDMREA, employs the virtual regular points projected from the random points and the estimated virtual ...
The variance gene for normal people as the control set compared with TCGA gene mutations for a certain cancer typeThe variance gene for normal people as the control set compared with TCGA gene mutations for a certain cancer type
It is very nice for you to answer my question so specific.. I think my work should be related with the first one. After reading your answer, I still have two questions about it.. 1. According to your answer, the mutations seen in both tumor and matched normal samples are usally germline, so I wonder, do the germline mutations, which can be detected from normal tissues of this patient, are eliminated from the somatic mutations, listed in that publication? (I guess if we check and search mutations in the tumor tissues of one patient, it is impossible to determine whether one mutation is belong to the somatic mutations or germline mutations, inherited from his parents. Unless we make the same analysis to the normal tissues of this patient and find the germline mutations of s/he, can we make sure which is somatic mutation and which is germline mutation.). 2. I just make sure Im clear about what you say. Most of the mutations for samples like TCGA-02-0047-11A-01D-1490-08 are belong to germline ...
2.9 Fixed vs Segregating Mutations2.9 Fixed vs Segregating Mutations
The horizontal axis represents time, and the vertical axis represents a percentage of the population. When a mutation enters the population, it occurs in only one individual and is plotted as a point somewhere on the x axis. If the mutation is passed on, for example to four new offspring, then it will be in a higher percentage of the population at the next time step. Most mutations will soon drop out of the population. Either the individual where the mutation originates will not survive, or if it does survive and mate, by chance it may not pass the mutation to its children. Even then the children may not pass the mutation any further. Mutations that eventually die out show up as inverted ``V shapes in the figure: they are introduced, they are passed on to some proportion of the population in the next few generations, and eventually the percentage drops to 0 as the mutation disappears. Some small percentage of new mutations are passed on successfully. If by chance the mutation continues to ...
13425 (Compute mutation type of a ClusterSeed or ClusterQuiver) - Sage13425 (Compute mutation type of a ClusterSeed or ClusterQuiver) - Sage
sage -t --long devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py ********************************************************************** File "devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py", line 1259, in sage.combinat.cluster_algebra_quiver.mutation_type._mutation_type_test Failed example: _mutation_type_test(2) # long time Expected: True (A, 2) True (A, (1, 1), 1) True (B, 2) True (BC, 1, 1) True (G, 2) Got: True (A, (1, 1), 1) True (A, 2) True (B, 2) True (BC, 1, 1) True (G, 2) ********************************************************************** File "devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py", line 1266, in sage.combinat.cluster_algebra_quiver.mutation_type._mutation_type_test Failed example: _mutation_type_test(3) # long time Expected: True (A, 3) True (A, (2, 1), 1) True (B, 3) True (BB, 2, 1) True (BC, 2, 1) True (C, 3) True (CC, 2, 1) True (G, 2, -1) True (G, 2, 1) Got: True (A, (2, 1), 1) ...
A comparison of ARMS and DNA sequencing for mutation analysis in clinical biopsy samples | Journal of Experimental & Clinical...A comparison of ARMS and DNA sequencing for mutation analysis in clinical biopsy samples | Journal of Experimental & Clinical...
In this study ARMS has been found to be both more sensitive and robust at detecting somatic mutations in clinical material than DNA sequencing. There were no examples where ARMS did not detect an assay-specific mutation that was detected by DNA sequencing. There were 42 mutations detected by ARMS that were not detected by DNA sequencing either due to low quantity or quality DNA causing assay fails or low mutant DNA compared to normal DNA in the sample that was beyond the detection limit of sequencing. They were not believed to be false positive results as they were known mutations, the results were reproducible and adequate controls were analysed in parallel. There were 12 mutations detected by sequencing that were not detected by ARMS because the ARMS assays used were not designed to detect these mutations, either because the mutations were rare (melanoma study) or ARMS assays had not yet been developed to detect these mutations. However, using the larger panel of ARMS assays now available the ...
View Mutations on 3D protein structures (Xena -| MuPIT)View Mutations on 3D protein structures (Xena -| MuPIT)
Figure. Xena Browser link-out to MuPIT 3D mutation view. On the left of the figure is Xena mutation column view of ERBB2 somatic mutations from the TCGA breast cancer cohort (https://xenabrowser.net/heatmap/?bookmark=6098aca9a00041d6271f18f2b471a241). User clicking on the MuPIT link-out menu (similar to how xena links out to Tumor Map), it will send all the mutations genomic positions as well as their recurrence p values to the MuPIT display. On the right side of the figure, MuPIT displays mutations in various size of bright green spheres. Large spheres for recurrent mutations. Size of the mutation spheres are determined by recurrence p values. The MuPIT display shows these ERBB2 somatic mutations cluster around the ERBB2 active site (ATP binding site in blue and proton acceptor site in teal).. ...
Mutation and Cancer: The Antecedents to Our Studies of Adaptive Mutation | GeneticsMutation and Cancer: The Antecedents to Our Studies of Adaptive Mutation | Genetics
LITTLE excuse is needed for still being interested in mutation. We are here thanks to the germline mutations experienced by our ancestors, and, at least in the developed nations of the world, more of us die from somatic mutations than from any other single cause. For the evolutionary biologist, the process of mutation presents no problems. For anyone attempting an overview of cancer research, however, the process has become increasingly obscure. It was this obscurity that prompted my laboratory in the 1980s to look again at the interplay between mutation and selection.. Germline mutation: To some extent, the particular mutational changes that generated the evolutionary tree can be deduced from comparisons of the differences in sequence that distinguish the different branches of the tree. It is not easy, however, to investigate what were the causes of those changes. Perhaps for that reason, it is customary to think of mutation as being driven by chance events attributable to the natural ...
An efficient visualization tool for the analysis of protein mutation matrices | BMC Bioinformatics | Full TextAn efficient visualization tool for the analysis of protein mutation matrices | BMC Bioinformatics | Full Text
Mutation matrices have been frequently used to describe measures of physicochemical similarities among amino acids. Dayhoff et al. initially introduced the use of the mutation matrix, which was constructed from the phylogenetic analysis of 71 proteins with at least 85% pairwise sequence identity [1]. They observed point mutations in the matrices resulting from both the mutation of the gene itself, and the subsequent acceptance of the mutation, possibly as a predominant form. Not all possible replacements for an amino acid are acceptable, and the group of acceptable mutations vary from one protein family to another [1]. The Dayhoff matrix still ranks among the widely-used scoring schemes for generating multiple alignments, although there have been several modifications, such as the use of a larger number of more divergent protein sequences, as well as the generation of separate log-odds matrices for soluble and non-soluble proteins [2].. It remains difficult, however, to evaluate the effects of ...
HTML5 Experiment: A Rotating Solid Cube | codeNtronixHTML5 Experiment: A Rotating Solid Cube | codeNtronix
DOCTYPE html, ,html, ,head, ,title,HTML5 Experiment: A Rotating Solid Cube,/title, ,script type=text/javascript, window.onload = startDemo; function Point3D(x,y,z) { this.x = x; this.y = y; this.z = z; this.rotateX = function(angle) { var rad, cosa, sina, y, z rad = angle * Math.PI / 180 cosa = Math.cos(rad) sina = Math.sin(rad) y = this.y * cosa - this.z * sina z = this.y * sina + this.z * cosa return new Point3D(this.x, y, z) } this.rotateY = function(angle) { var rad, cosa, sina, x, z rad = angle * Math.PI / 180 cosa = Math.cos(rad) sina = Math.sin(rad) z = this.z * cosa - this.x * sina x = this.z * sina + this.x * cosa return new Point3D(x,this.y, z) } this.rotateZ = function(angle) { var rad, cosa, sina, x, y rad = angle * Math.PI / 180 cosa = Math.cos(rad) sina = Math.sin(rad) x = this.x * cosa - this.y * sina y = this.x * sina + this.y * cosa return new Point3D(x, y, this.z) } this.project = function(viewWidth, viewHeight, fov, viewDistance) { var factor, x, y factor = fov / ...
Point Set GraphicsPoint Set Graphics
where. X1 is the x coordinate of new point. Y1 is the y coordinate of the new point. X is the x coordinate of the seed point. Y is the y coordinate of the seed point. The recurrence formula is the heart of this process. By changing these equations, you can begin to create new recursive point sets.. Running The Program. After youve entered the program (and made the appropriate changes if you use tape), RUN it. First youll be asked whether you want to create a new point set, or view a point set which you have saved on tape or disk. If you enter a two, and youre using a disk drive, type in the name of the picture file you wish to see. If you are using tape, push PLAY when the computer beeps.. Since you havent created any point sets yet, enter 1. The recurrence formula (lines 170-190) will be displayed. Type CONT and youll see the points created by the recurrence formula begin to appear on the screen along with their x and y coordinates. The points will continue to be plotted until you take one ...
Mutation found that kills off gene responsible for diabetes | The TechMutation found that kills off gene responsible for diabetes | The Tech
A new study based on genetic testing of 150,000 people has found a rare mutation that protects even fat people from getting Type 2 diabetes. The effect is so pronounced - the mutation reduces risk by two-thirds - that it provides a promising new target for developing a drug to mimic the mutations effect.. The mutation destroys a gene used by pancreas cells where insulin is made. Those with the mutation seem to make slightly more insulin and have slightly lower blood glucose levels for their entire lives.. Already Pfizer, which helped finance the study, and Amgen, which owns a company whose data played a key role in the research, are starting programs aimed at developing drugs that act like the mutation, the companies said.. But Timothy Rolph, a Pfizer vice president, cautioned it can take 10 to 20 years to get a drug to market after discovering something new about human genetics and disease.. The study, published Sunday in Nature Genetics, involved a mutation so rare that finding it was only ...
Re: Mutation events replacement from Jonas Sicking on 2011-07-22 (public-webapps@w3.org from July to September 2011)Re: Mutation events replacement from Jonas Sicking on 2011-07-22 ([email protected] from July to September 2011)
On Fri, Jul 22, 2011 at 2:08 AM, Dave Raggett ,[email protected], wrote: , On 22/07/11 02:26, Adam Klein wrote: ,, ,, This is only complex because youre coalescing the mutations, right? ,, In Rafaels original proposal, each mutation would result in a single ,, immutable mutation record, so the semantics would be to deliver (by ,, appending to a queue associated with each observer) a mutation record ,, to any currently-registered observers. ,, ,, Or is there some other concern with beginning notifications partway ,, through a task? , , I would suggest avoiding coalescing mutations altogether! , , But if you are going to, *dont* coalesce mutations when the resulting DOM , tree is dependent on the order in which those mutations took place. This is , critical to distributed editing applications. The DOM should have no such behavior. The only exception to this rule that I know of is ,script, elements. They execute their contained script the first time they are inserted into a Document, but dont undo ...
3rd+Week+Presentation - C7 == 4 free points Dont need to turn prelab back in Small numbers in the report are points you got...3rd+Week+Presentation - C7 == 4 free points Don't need to turn prelab back in Small numbers in the report are points you got...
View Notes - 3rd+Week+Presentation from CHEM 1310 at Georgia Tech. C7 == 4 free points Dont need to turn prelab back in Small numbers in the report are points you got…number in lower left hand
Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive...Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive...
Figure 2. FGFR point mutations confer resistance to BGJ398 and other FGFR inhibitors. A, In silico model of BGJ398 in binding pocket of FGFR2, demonstrating steric clash in the context of a V564F mutation. B and C, Mutagenesis screen in BaF3 cells that were engineered to express a TEL-FGFR3 fusion protein and subjected to increasing doses of BGJ398. The bar graph in B indicates the number of BGJ398-resistant clones isolated with indicated FGFR3 point mutations, with higher doses of BGJ398 resulting exclusively in colonies harboring the V555M gatekeeper mutation. Proliferation was quantified in C after 3 days with Alamar blue. Corresponding FGFR2 amino acids are indicated after the slash. D, IC50 values for BaF3 cells expressing the indicated constructs and treated with a variety of inhibitors. E and F, Proliferation assays with BaF3 cells expressing the FGFR2 V564F constructs and treated with increasing doses of either BGJ398 (E) or LY287445 (F). G, Phospho-FGFR2 ELISA demonstrating that FGFR2 ...
Detection of 11 germline inactivating TP53 mutations and absence of TP63 andHCHK2 mutations in 17 French families with Li...Detection of 11 germline inactivating TP53 mutations and absence of TP63 andHCHK2 mutations in 17 French families with Li...
In the six families without detectable TP53germline mutation (fig 2), we then analysed theTP63 gene. To screen for inactivatingTP63 mutations, we performed a functional assay in yeast. Transformation of the pCI51 plasmid18containing the wild type coding region corresponding to the isoform γ of TP63 into the yIG397-RGC yeast reporter strain resulted in white colonies. Transformation of two mutant pCI51 plasmids (with the mutation Leu264Ser or Cys269Ser generated by PCR induced mutagenesis), used as controls, resulted only in red colonies. In four index cases, for whom mRNA was available, the TP63 cDNA was PCR amplified from lymphocytes between codons 18 and 434, cloned by homologous recombination into the gapped expression vector pCI51 linearised between codons 30 and 420, and transformed into yIG397-RGC; the percentage of red colonies (table 1) suggested the absence of heterozygous inactivating mutations. We also sequenced in the six families without detectable TP53 mutation exons 2 to 15 of ...
Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemiaPoint mutations in the RUNX1/AML1 gene: another actor in RUNX leukemia
The RUNX1/AML1 gene is the most frequent target for chromosomal translocation in leukemia. In addition, recent studies have demonstrated point mutations in the RUNX1 gene as another mode of genetic alteration in development of leukemia. Monoallelic germline mutations in RUNX1 result in familial plat …
pr.probability - Minimum separation among $m$ random points on an $n$-dimensional unit sphere - MathOverflowpr.probability - Minimum separation among $m$ random points on an $n$-dimensional unit sphere - MathOverflow
If the angle between the vectors $v_i$ and $v_j$ is denoted by $\theta_{ij}$, then using cosine rule we have $$\rho = 2 \min_{i,j \in\{1,2,\dots,m\}}\sin({\theta_{ij}}/{2})$$ Assuming that $m$ is a large number, then minimum will occur for a very small value of $\theta_{ij}$. Hence, $$\rho \approx \min_{i,j \in\{1,2,\dots,m\}} \theta_{ij}$$ Since the points are distributed uniformly, It is not difficult to find the distribution of $\theta_{ij}$ and then find the expectation and variance of $\rho$. This I guess will give a pretty good estimate of the actual value of expectation and variance of $\rho$.. ...
Absence of point mutation in the third intracellular loop of...Absence of point mutation in the third intracellular loop of...
[Absence of point mutation in the third intracellular loop of alpha 1B- and alpha 1D adrenergic receptor in the aortae of spontaneously hypertensive rats].: Our
Mutations and Their Consequences - Causative AgentMutations and Their Consequences - Causative Agent
Because of mutations, the concept that all cells arising from a single cell are identical is not strictly true, since every large population contains mutants. Even the cells in a single colony that contains about 1 million cells are not completely identical because of random mutations. These mutations provide a mechanism by which organisms, with their altered characteristics, can respond to a changing environment. This is the process of natural selection. The environment, however, does not cause the mutation but rather selects those cells that can grow under its conditions. Thus, a spontaneous mutation to antimicrobial resistance, though rare, will result in the mutants becoming the dominant organisms in a hospital environment where the antimicrobial medication is present, because only the resistant cells can survive. The antimicrobial kills the sensitive cells and thereby allows the resistant cells to take over the population.. Since genes mutate independently of one another, the chance that ...
BIS101 HW6 F08 Engebrecht - Deletions x Point mutations 1 2 3 4 5 1 2 3 4 5 1 a 2 b 3 c 4 d 5 e 2 The following DNA is part of...BIS101 HW6 F08 Engebrecht - Deletions x Point mutations 1 2 3 4 5 1 2 3 4 5 1 a 2 b 3 c 4 d 5 e 2 The following DNA is part of...
View Notes - BIS101 HW6 F08 Engebrecht from BIS 101 at UC Davis. Deletions x Point mutations 1 2 3 4 5 1 2 3 4 5 1 - - - - + a + - - + + 2 - - + + b + + - + - 3 - - - c - + - - + 4 - + d - - - + + 5
Sequence-based mutation analysis BCKDHA - BioinformatikpediaSequence-based mutation analysis BCKDHA - Bioinformatikpedia
For position 29 only BLOSSUM62 says that this mutation is not likely. The 9 other sources show that this mutation wont have a damaging influence on the function or structure of the protein. This is perspicuous since the conservation of this position is not very high. The amino acid on position 125 is quite good conserved with 96%. SNAP and SIFT says that this mutation will have an influence on the protein whereas Polyphen2 says that this mutation is ether not (HumVar) or hardly damaging (HumDiv). Since this position is quite good conserved it is more likely that this mutation will have an influence on the function or structure of the protein. back to Maple_syrup_urine_disease main page go back to Task 5 Mapping SNPs ...
CRISPR Point Mutation Cell Line Service | Applied StemCellCRISPR Point Mutation Cell Line Service | Applied StemCell
Utilizing the precision of CRISPR/Cas9 technology, we can generate cell lines with a point mutation in your gene of interest. Click here to learn more!
A point mutation in KINDLIN3 ablates activation of three integ...A point mutation in KINDLIN3 ablates activation of three integ...
A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans.: Monogenic deficiency diseases provide unique opportunities to define t
dom] Mutation Observers from Anne van Kesteren on 2011-12-05 (public-webapps@w3.org from October to December 2011)dom] Mutation Observers from Anne van Kesteren on 2011-12-05 ([email protected] from October to December 2011)
As discussed mutation observers would be best defined in the DOM. The DOM is discussed on [email protected]: http://lists.w3.org/Archives/Public/www-dom/ (I bccd public-webapps just in case anyone missed this.) I think I now defined the last hook needed for mutation observers, replace all. The hooks related to tree mutations are defined here: http://dvcs.w3.org/hg/domcore/raw-file/tip/Overview.html#mutation-algorithms To illustrate: * appendChild(node) maps to the append algorithm, which invokes pre-insert, which eventually does insert. * setting textContent maps to the replace all algorithm, which invokes remove (for each child node) followed by a single append * setting innerHTML can be defined just like textContent, using a DocumentFragment for the nodes to be inserted Whether separate pre-insert and insert is really necessary depends on how we end up defining mutation observers. Im not sure what the current status of mutation observers is, but one open question was whether ...
IDH Inhibitor idhinhibitor.comIDH Inhibitor idhinhibitor.com
Rkin and, in unique, to the initial RING domain.It has been suggested that point mutations may lead to a greater all round loss of function than entire exonic
CiNii 論文 - A Novel Somatic Point Mutation of the RET Proto-oncogene in Tumor Tissues of Small...CiNii 論文 - A Novel Somatic Point Mutation of the RET Proto-oncogene in Tumor Tissues of Small...
YOSHIMOTO Katsuhiko , TANAKA Chisato , MORITANI Maki , SHIMIZU Eiji , YAMAOKA Takashi , YAMADA Shozo , SANO Toshiaki , ITAKURA Mitsuo Endocrine journal 46(1), 199-207, 1999-02 医中誌Web 参考文献26件 ...
Biology-Online • View topic - Polymorphism and MutationBiology-Online • View topic - Polymorphism and Mutation
Just about numbers. A mutation is a change to a single individual that may or may not be propagated. For example a single point mutation where a base is replaced or deleted from a strand of DNA. This may cause the individual some discomfort or problems but is normally isolated to the individual ...
Mutation Detection - R. G. H. Cotton; E. Edkins; S. Forrest - Oxford University PressMutation Detection - R. G. H. Cotton; E. Edkins; S. Forrest - Oxford University Press
Mutation detection is increasingly undertaken in a wide spectrum of research areas: in medicine it is fundamental in isolating disease genes and diagnosis, and is especially important in cancer research; in biology, commercially important genes can be identified by the mutations they contain. But mutation detection is time-consuming and expensive.
Controversial double points rule for final F1 Grand Prix of season here to stay // F1 News // James Allen on F1 - The official...Controversial double points rule for final F1 Grand Prix of season here to stay // F1 News // James Allen on F1 - The official...
The controversial rule to award double points at the final race of the season is set to go ahead after a meeting in Geneva on Wednesday between Formula 1 team
Remnantmods • View topic - Mutation Src + Halo 2 idbRemnantmods • View topic - Mutation Src + Halo 2 idb
In this rar are the contents of the hdd mutation sits on. It contains the current (non-functioning) source code as well as multiple source backups I had made throughout its development. The current source code is capable of importing tags from other projects, but when I last touched it I was in the middle of writing code to explode the sound_diagnostics tag at decompile time, and rebuilding it at compile time from the sound tags. So in its current state it will not work for anything, if it even compiles without errors. I would check the last source backup to see if it can import tags, since it could prove useful to some people. I would also like to say that this project is the result of many years of work, coding styles, and ideas. It is a mess and does not reflect my current coding ability. My only request is that if you choose to do anything to Mutation and release it, please release it under another name with credit to the mutation source code. I have a vision in my head of what Mutation ...
ARITHMETIC APPARATUS, ELLIPTIC SCALAR MULTIPLICATION METHOD OF ARITHMETIC APPARATUS, ELLIPTIC SCALAR MULTIPLICATION PROGRAM...ARITHMETIC APPARATUS, ELLIPTIC SCALAR MULTIPLICATION METHOD OF ARITHMETIC APPARATUS, ELLIPTIC SCALAR MULTIPLICATION PROGRAM...
13. An arithmetic apparatus that calculates a coordinate value kG obtained by scalar multiplication of a coordinate value G of a specific point included in an elliptic curve by a multiplier value k represented by a t-bit bit sequence, the arithmetic apparatus comprising: a constant storage unit that pre-stores a coordinate value 2.sup.tG obtained by scalar multiplication of the coordinate value G of the specific point by 2 to a power oft; an initial setting unit that sets the coordinate value G of the specific point in a scalar multiplication variable R; a scalar multiplication unit that references the t-bit bit sequence representing the multiplier value k in units of a predetermined number of bits from a most significant bit, and each time the predetermined number of bits of the bit sequence are referenced, sets in a zeroth work variable R[0] a coordinate value obtained by doubling the scalar multiplication variable R, sets in a first work variable R[1] a coordinate value obtained by adding a ...
Mutation overview page PRL - p.L199= ( Substitution - coding silent)Mutation overview page PRL - p.L199= ( Substitution - coding silent)
These are internal identifiers that are unique to a mutation on a particular transcript and are displayed in the URL of the mutation pages. Therefore, several of these internal ids could be associated with a single genomic COSV id where the mutation has been mapped to all overlapping genes and transcripts. Similarly, since every COSM id is mapped to one COSV id (where genomic coordinates are known), each COSM id can also be associated with several alternative (internal) identifiers. These ids are expected to change between assemblies (GRCh37 and GRCh38) and between the releases ...
Mutation overview page FGFR1 ENST00000341462 - p.? ( Unknown)Mutation overview page FGFR1 ENST00000341462 - p.? ( Unknown)
These are internal identifiers that are unique to a mutation on a particular transcript and are displayed in the URL of the mutation pages. Therefore, several of these internal ids could be associated with a single genomic COSV id where the mutation has been mapped to all overlapping genes and transcripts. Similarly, since every COSM id is mapped to one COSV id (where genomic coordinates are known), each COSM id can also be associated with several alternative (internal) identifiers. These ids are expected to change between assemblies (GRCh37 and GRCh38) and between the releases ...
Are there any tools to simulate mutations?Are there any tools to simulate mutations?
I am working on a gene mutation method. I am trying to test my tool using 1000 genome vcf file (multigenome vcf file). I am using only one chromosome(as that should be enough to test my algorithm). I now want to simulate mutations in ~10 samples of 1K genome project vcf file. Can someone please suggest me a tool that can be used to simulate mutation in a multgenome vcf file?. ...
Guide to Mutation DetectionGuide to Mutation Detection
... | As genomic science and potential gene therapies continue to develop, the detection of mutations plays an increasingly central role in diverse areas of biology. With innumerable detection techniques available spanning multiple disciplines, the choice of the best method for a particular study can prove exceedingly difficult.
Applying mutation analysis for object-oriented programs using a reflective approach - IEEE Conference PublicationApplying mutation analysis for object-oriented programs using a reflective approach - IEEE Conference Publication
This paper presents a mutation analysis tool based on a reflective macro system. Mutation analysis is a powerful and computationally expensive technique th
Probability help pleaseProbability help please
Suppose we choose a random point in the interval (-2, 1) and denote the distance to 0 by X. Prove that X is a continuous random variable.
Emergence of fluoroquinolone-resistant Streptococcus pyogenes in Japan by a point mutation leading to a new amino acid...Emergence of fluoroquinolone-resistant Streptococcus pyogenes in Japan by a point mutation leading to a new amino acid...
TY - JOUR. T1 - Emergence of fluoroquinolone-resistant Streptococcus pyogenes in Japan by a point mutation leading to a new amino acid substitution. AU - Arai, Kazuaki. AU - Hirakata, Yoichi. AU - Yano, Hisakazu. AU - Kanamori, Hajime. AU - Endo, Shiro. AU - Hirotani, Ayako. AU - Abe, Yuko. AU - Nagasawa, Mitsuaki. AU - Kitagawa, Miho. AU - Aoyagi, Tetsuji. AU - Hatta, Masumitsu. AU - Yamada, Mitsuhiro. AU - Nishimaki, Katsushi. AU - Takayama, Yoko. AU - Yamamoto, Natsuo. AU - Kunishima, Hiroyuki. AU - Kaku, Mitsuo. PY - 2011/3/1. Y1 - 2011/3/1. N2 - Objectives: Streptococcus pyogenes causes various diseases in humans. While the prevalence of fluoroquinolone-resistant S. pyogenes isolates has been increasing since 2000 in the USA and Europe, it has remained very low in Japan. We isolated a fluoroquinolone-resistant S. pyogenes strain and analysed its genetics. Methods: TU-296, a strain of S. pyogenes resistant to levofloxacin (MIC 16 mg/L), was isolated from the throat of a patient in their ...
Current Studies | The Colleen Giblin Research Laboratories for Pediatric NeurologyCurrent Studies | The Colleen Giblin Research Laboratories for Pediatric Neurology
Open for Enrollment. Mitochondrial and Mental Retardation: Investigations of Clinical Syndromes Associated with MtDNA Point Mutations. The Natural History Study is an ongoing study that involves participants that have point mutations in mitochondrial DNA (mtDNA). These mutations affect the genetic material contained in the mitochondria of the cell. Mitochondria, often called the "powerhouse" of the cell, are small structures within cells that provide the energy necessary to power growth and change over time. The purpose of this study is to better characterize mitochondrial disorders as they present over time in participants. Through this study we hope to determine whether mtDNA point mutations produce any measurable disturbances of thinking, attention, intelligence, behavior, or neurological functioning. Eligible participants must have a proven mitochondrial point mutation. Some or all participants may represent members of a single family because mtDNA point mutations are inherited from ones ...
Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and...Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and...
In this study, we describe the clinical features and provide experimental analyses of a novel point mutation affecting the penultimate nucleotide of the first exon of the HBA2 (HBA2: c.94A,G) gene identified in a 26-year-old female who also carries a heterozygous Hb E (HBB: c.79G,A) variant. The aim of the study was to investigate the impact of this point mutation on the transcriptional activity of the HBA2 gene using a combination of an initial in silico prediction followed by in vitro mutagenesis and transcriptional activity assessment. The analyses revealed that the HBA2: c.94A,G point mutation causes the activation of a cryptic splice site located 49bp upstream of the exon1-intron1 boundary in both HBA2 long and short isoforms, thus generating a frameshift and a premature termination codon between codons 48 and 49 in the second exon. A rapid degradation of the aberrantly spliced transcripts by the nonsense mediated decay (NMD) surveillance system is highly indicative of an a-thalassemia ...
Modulation of erbB kinase activity and oncogenic potential by single point mutations in the glycine loop of the catalytic...Modulation of erbB kinase activity and oncogenic potential by single point mutations in the glycine loop of the catalytic...
TY - JOUR. T1 - Modulation of erbB kinase activity and oncogenic potential by single point mutations in the glycine loop of the catalytic domain. AU - Shu, Hui Kuo G.. AU - Chang, Chi Ming. AU - Ravi, Lakshmeswari. AU - Ling, Lei. AU - Castellano, Chris M.. AU - Walter, Elizabeth. AU - Pelley, Robert J.. AU - Kung, Hsing Jien. PY - 1994/1/1. Y1 - 1994/1/1. N2 - Avian c-erbB is activated to a leukemia oncogene following truncation of its amino-terminal ligand-binding domain by retroviral insertion. The insertionally activated transcripts encode protein products which have constitutive tyrosine kinase activity and can induce erythroleukemia but not sarcomas. We have previously found that a valine-to-isoleucine point mutation at position 157 (V157I mutant) within the tyrosine kinase domain of this truncated erbB can dramatically activate the sarcomagenic potential of the oncogene and increase the kinase activity of this oncoprotein. This mutation lies at position 157 of the insertionally activated ...
Error-Prone Polymerase, DNA Polymerase IV, Is Responsible for Transient Hypermutation during Adaptive Mutation in Escherichia...Error-Prone Polymerase, DNA Polymerase IV, Is Responsible for Transient Hypermutation during Adaptive Mutation in Escherichia...
When populations of microorganisms are exposed to nonlethal selections, mutations that relieve the selective pressure arise (7), a phenomenon called adaptive mutation (6). Although it originally seemed that only useful mutations appeared (7), it is now clear that selected mutations are accompanied by nonselected mutations, i.e., the process is not directed to useful genes (12).. Most research on adaptive mutation has focused on a strain of Escherichia coli, called FC40, that cannot utilize lactose (Lac−) but that readily reverts to lactose utilization (Lac+) when lactose is its only carbon source (6). The process that produces adaptive Lac+ mutations is not the same as that which produces Lac+ mutations during normal growth. Unlike growth-dependent mutations, almost all adaptive Lac+ mutations are dependent on recombination functions (6, 10, 24). While several different types of sequence changes revert the Lac− allele during growth, adaptive Lac+ mutations are almost all −1-bp frameshifts ...
An Allelic Series of Mutations in the Kit ligand Gene of Mice. I. Identification of Point Mutations in Seven Ethylnitrosourea...An Allelic Series of Mutations in the Kit ligand Gene of Mice. I. Identification of Point Mutations in Seven Ethylnitrosourea...
In this report we describe the molecular genetic alterations in eight KitlSl mutant alleles that arose from ENU mutagenesis. One of these alleles (KitlSl-25R) contains an intragenic rearrangement or deletion; however, it is not clear whether that alteration was induced by ENU treatment or resulted from a coincidental, spontaneous mutation in an ENU-treated mouse. Point mutations were found in seven of the eight KitlSl alleles and were of five types: two A/T → G/C transitions (KitlSl-22R and KitlSl-42R); two G/C → A/T transitions (KitlSl-31R and KitlSl-39R); an A/T → T/A transversion (KitlSl-28R); an A/T → C/G transversion (KitlSl-30R); and a G/C → T/A transversion (KitlSl-36R). Such molecular diversity is somewhat surprising considering that 82% of the previously characterized ENU-induced germline mutations in the mouse were either A/T → G/C transitions or A/T → T/A transversions (Noveroskeet al. 2000). The only previously reported ENU-induced KitlSl mutation was an A/T → T/A ...
COMUS: Clinician-Oriented locus-specific MUtation detection and deposition System | BMC Genomics | Full TextCOMUS: Clinician-Oriented locus-specific MUtation detection and deposition System | BMC Genomics | Full Text
Genetic mutations have two major types: large mutation (deletion, insertion, duplication, and inversion) and point mutation (nonsense, missense, and frame shift). Some mutations can induce DNA transcription and translation errors eventually causing protein dysfunction that leads to disease [1, 2]. Currently, many whole genome scale association studies between disease and variation are being published [3]. However, medical researchers have had to go through mutations in patient DNA to detect mutations that may be the cause of a disease [4, 5].. There are many human disease gene databases that contain disease-causing mutation information as locus-specific databases (LSDBs). Also, large databases, such as Online Mendelian Inheritance in Man (OMIM) [6] and the Human Gene Mutation Database (HGMD) [7], collect and describe comprehensively all disease-related genes. In contrast, LSDBs usually describe variations in a small number of genes. The LSDBs aim to provide particular genetic mutation ...
Evolution - A-Z - MutationEvolution - A-Z - Mutation
A mutation is any change occurring in the message that a gene carries. Mutations mainly arise as copy errors when DNA is replicated at mitosis and meiosis. Darwinian evolution requires a constant supply of variation: much of it is supplied by mutation, and a mutation-selection balance can maintain a genetic polymorphism. The first major geneticist to study mutation was H.J. Muller, who demonstrated it can be induced by X-rays. He also recognized that the rate of mutation in nature is extremely low, and that they are almost always deleterious to the fitness of the organism. The accumulation of deleterious mutations places a mutational load on the population. Mutations can occur at single base level or at chromosomal level. The effects of mutation can occasionally be very dramatic: some of these fruitflies have suffered mutations which alter the number of wings that develop... Is mutation directed?. ...
Mutations in 115-Year-Old Provide Perspective for Personal Genome Sequencing | DNA Science BlogMutations in 115-Year-Old Provide Perspective for Personal Genome Sequencing | DNA Science Blog
Mutations are generally regarded as bad. Ive covered several on this blog, from the curious genetics of werewolves to homeotic mutations that turn arms into legs to the sad tales of neurologic disease and hereditary blindness.. But some mutations are good. Perhaps the best is the CCR5 mutation that keeps HIV out of our cells, a genetic glitch that drugs and gene therapy are trying to imitate. Most mutations, it seems, are neither evil nor beneficial, but neutral. After all, Henny lived in good health for 115 years, yet her blood cells still accrued 450 mutations.. DNA Science blog always tries to find a different perspective to genetics news, and for the case of Henny, it is the fact that mutations need not signal doom. Dr. Holstege had the idea to look at Hennys genome because of the role of somatic mutations in causing cancer. But another view is that many mutations do nothing at all.. Neutral mutations will impact the application of DNA sequencing in health care decision-making. The Nature ...
Gradual selection of a cellular clone presenting a mutation at codon 179 of the p53 gene during establishment of the...Gradual selection of a cellular clone presenting a mutation at codon 179 of the p53 gene during establishment of the...
We studied the occurrence of a p53 mutation along passages stored as frozen vials during establishment of a nontumorigenic human mammary epithelial cell line HMT-3522. Mutations were identified by a PCR-SSCP approach using DNA as a template. The mutation, a nonconservative nucleotide substitution at codon 179 changing a histidine into an asparagine, appeared between passages 51 and 63 and was concommitant to a change in growth conditions. Cells were no longer grown on collagen coat and cell growth was not responsive to insulin, transferrin, or hydrocortisone anymore. To assess if the mutation was an early or a late event during cell line evolution we put a vial of cells frozen at passage 30 back into culture and tested for the appearance of a p53 mutation along newly produced passages. The same mutation (His to Asp at codon 179), as previously identified, reemerged between passages 48 and 52, thus indicating that the mutation was preexisting in passage 30 and gradually selected out because of ...
Somatic mutation identification and verification - QIAGENSomatic mutation identification and verification - QIAGEN
Mutation assays can then be grouped together into PCR arrays based off common themes to enable users to profile a focused set of mutations. The mutations on an array are selected based on a commonality, such as being from the same gene, signaling pathway, or cancer type. For example, users could profile the most common 84 mutations in breast cancer or the 44 most common mutations in APC. The Custom qBiomarker Somatic Mutation PCR Arrays allow users to select the mutations that they wish to profile. Together, the qBiomarker Somatic Mutation products facilitate sensitive detection and profiling of mutations in cancer cells or tumor samples ...
Team:Calgary/Project/OSCAR/Desulfurization - 2012.igem.orgTeam:Calgary/Project/OSCAR/Desulfurization - 2012.igem.org
dszA has four PstI cut sites. dszB has a PstI and a NotI cut site. dszC has two PstI cut sites. In order to be able to use these parts in construction, we had to eliminate these cut sites. Stratagene site directed mutagenesis was used for this purpose. During this procedure, two primers are designed for each mutation. Primers are complementary to the DNA strands except for one base pair. Therefore after the PCR, the whole plasmid is amplified with a point mutation. The base pair was chosen in a way so that it eliminates the cut site but the codon it belongs to still codes for the same amino acid (a silent mutation). We also used the same method to perform the Y63F mutagenesis in dszB (rationale will be explained). In this case the primers also introduce a point mutation. The point mutation causes the codon to code for Phe instead of Tyr. We also did this in a way so that the site of the mutation turns into a hpyAV cut site so we can confirm the mutagenesis by cutting the plamid with ...
Biology-Online • View topic - What makes dominant allele dominant?Biology-Online • View topic - What makes dominant allele dominant?
2) its not only about expression. The difference can be anywhere from transcription to protein post-translational modifications. There can be mutation in the promotor changing significantly expression. If the binding of ribosome will be impaired, there will be much less of protein made. Single point mutations can lead to differences in binding of miRNAs. On the protein level, there are several options, you can have premature STOP codon and the resulting peptide is too short to do its work. Or you can have change of a crucial residue to turn off your protein, like in case of Asp to Asn mutations in receptor which impair its ability to transfer phosphates and thus signal the binding. Or you could change the post-translational modification and thus mis-localizing the protein or impairing its binding to partners or simply changing its activity ...
Teleomechanist: 2008Teleomechanist: 2008
The genetic code has the remarkable property of error minimization, whereby the arrangement of amino acids to codons is highly efficient at reducing the deleterious effects of random point mutations and transcriptional and translational errors. Whether this property has been explicitly selected for is unclear. Here, three scenarios of genetic code evolution are examined, and their effects on error minimization assessed. First, a simple model of random stepwise addition of physicochemically similar amino acids to the code is demonstrated to result in substantial error minimization. Second, a model of random addition of physicochemically similar amino acids in a codon expansion scheme derived from the Ambiguity Reduction Model results in improved error minimization over the first model. Finally, a recently introduced 213 Model of genetic code evolution is examined by the random addition of physicochemically similar amino acids to a primordial core of four amino acids. Under certain conditions, 22% ...
Teleomechanist: November 2008Teleomechanist: November 2008
The genetic code has the remarkable property of error minimization, whereby the arrangement of amino acids to codons is highly efficient at reducing the deleterious effects of random point mutations and transcriptional and translational errors. Whether this property has been explicitly selected for is unclear. Here, three scenarios of genetic code evolution are examined, and their effects on error minimization assessed. First, a simple model of random stepwise addition of physicochemically similar amino acids to the code is demonstrated to result in substantial error minimization. Second, a model of random addition of physicochemically similar amino acids in a codon expansion scheme derived from the Ambiguity Reduction Model results in improved error minimization over the first model. Finally, a recently introduced 213 Model of genetic code evolution is examined by the random addition of physicochemically similar amino acids to a primordial core of four amino acids. Under certain conditions, 22% ...
Two novel point mutations of the XLRS1 g - pestfile siteTwo novel point mutations of the XLRS1 g - pestfile site
The high correlation in metabolic efficiency within twin pairs in response to therapeutic weight loss suggests a strong genetic contribution. Unexpected effects of a whole body irradiation on cialis prices 5mg the mortality rate of baby mice after an experimental infection with the vesicular stomatitis virus (VSV) Experimental evidence also shows that in many cases the protein achieves partial sequence specificity by indirect recognition, i.e., by recognizing structural properties of the DNA. Spatial mapping of city-wide PBDE levels using an exponential decay model. We have, therefore, reassigned the name GST omega to this new alpha-class anionic GST of human liver. In contrast, in adrenal medullary-transplanted animals, epibatidine elevated responses to acute noxious stimuli and markedly suppressed phase 2 formalin responses in a dose-related fashion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Therefore, ...
Thousands of rare mutations linked with cancer revealed in new analysisThousands of rare mutations linked with cancer revealed in new analysis
Cancer arises when genetic mutations in a cell cause abnormal growth that leads to a tumour.. Some cancer drugs exploit this to attack tumour cells by targeting proteins that are mutated from their usual form because of mutations in the genes that encode them.. However, only a fraction of all the mutations that contribute significantly to cancer have been identified.. Thomas Peterson, at the University of Maryland, and colleagues developed a new statistical analysis approach that uses genetic data from cancer patients to find cancer-causing mutations.. Unlike previous studies that focused on mutations in individual genes, the new approach addresses similar mutations shared by families of related proteins.. Specifically, the new method focuses on mutations in sub-components of proteins known as protein domains.. Even though different genes encode them, different proteins can share common protein domains.. The new strategy draws on existing knowledge of protein domain structure and function to ...
Mutations and Drug Resistance | Frontiers Research TopicMutations and Drug Resistance | Frontiers Research Topic
A drug must interact with its target(s) to achieve the therapeutic effects. Mutation in drug target is a critical mechanism that results in drug resistance. The aim of this topic is to highlight clinically-relevant mutations in drug targets that lead to resistance to anticancer or antivirus agents as well as current strategies in overcoming these resistances. There are several scenarios under which a mutation could lead to drug resistance. Mutations could reduce the binding affinity of a drug to its target or render the target constitutively active. Worse yet, mutations could turn a drug from an antagonist into an agonist. For example, current therapeutic strategy for advanced prostate cancer is to inhibit the androgen receptor (AR) signaling. However, the W741C mutation in the AR was found to convert bicalutamide from an antagonist of the wild type AR into an agonist of the W741C AR mutant, which actually promotes tumor growth. Whats more, multiple resistant mutations in AR could be
Mutations in gene Tmem161b as cause for cardiac arrhythmias - UMC UtrechtMutations in gene Tmem161b as cause for cardiac arrhythmias - UMC Utrecht
In their new paper, published in PNAS, the researchers show that the Tmem161b protein plays an important role in the regulation of the cardiac rhythm in at least two species: the zebrafish and the mouse. The researchers observed a disturbed cardiac rhythm in a group of zebrafish embryos and the cause was traced back to a mutation in Tmem161b. Likewise, mice that carried a mutation in this gene displayed abnormalities in heart function. Homozygous mutations - that is, mutations that occur on both copies of the gene - are incompatible with life; animals with this double mutation in Tmem161b die prematurely. This also appears to be the case in humans. Animals with a heterozygous mutation - a mutation on one copy of the gene - mature, but then appear more susceptible to developing cardiac arrythmias. "We do not know yet whether this is also the case in humans. Further research is necessary to elucidate this," says Lotte Koopman, researcher on the project ...
T Helper and B Cell Escape Mutations within the HBc Gene in Patients with Asymptomatic HBV Infection: A Study From the...T Helper and B Cell Escape Mutations within the HBc Gene in Patients with Asymptomatic HBV Infection: A Study From the...
Background: Escape mutations potentially allow viruses to avoid detection and clearance by the host immune sys-tem and may represent a mechanism through which infections may persist in some patients. The association of the mutations in the HBcAg gene with Hepatitis B asymptomatic carriers (ASC) has not been studied adequately. The current study was aimed to investigate HBcAg18-27 CTL epitope mutations in ASC patients in the South-Eastern region of Iran. Methods: 100 ASC patients were selected for this study and screened for HLA-A2 using flow cytometry. HBV-DNA was extracted from the HLA-A2 positive patients and the HBc gene was amplified using PCR. Direct double sequencing was performed to analyse mutations in the HBc gene of HBV isolates from patients with ASC. Results: Overall, 25 (25%) of individuals were HLA-A2 positive. Direct double sequencing indicated no mutations in the HBcAg18-27 epitope. However, four mutations within the T helper and three mutations within the B cell epitopes of ASC ...
PPT - Mutations PowerPoint Presentation - ID:1277847PPT - Mutations PowerPoint Presentation - ID:1277847
Mutations . Section 12-4 This section describes and compares gene mutations and chromosomal mutations. Mutations. What are mutations? Mutations are changes in the DNA sequence that affect genetic information. Mutations. Is the following sentence true or false? Slideshow 1277847 by Patman
Sandwalk: One Protein - Two FoldsSandwalk: One Protein - Two Folds
This is an interesting and important finding because it is (so far) the only example of a protein adopting two completely different stable folds with no hydrogen bonds in common at equilibrium. Trivially, natively disordered proteins adopt multiple conformations under physiological solution conditions, and many proteins alter their conformations in response to ligand binding while keeping most of their hydrogen bond network intact. In this case, however, an existing network of stabilizing bonds is completely disrupted in order to form a new fold with a totally different function. Ive already discussed some of the implications of this with respect to protein folding, and in regards to the recent transitive homology studies out of the Cordes group. Lymphotactin offers lessons and ideas for protein folding and evolution that must be taken into account. In particular, the fact that point mutations can significantly stabilize one or the other of these structures implies that there may be previously ...
3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets | Genome Medicine | Full Text3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets | Genome Medicine | Full Text
Many mutations in cancer are of unknown functional significance. Standard methods use statistically significant recurrence of mutations in tumor samples as an indicator of functional impact. We extend such analyses into the long tail of rare mutations by considering recurrence of mutations in clusters of spatially close residues in protein structures. Analyzing 10,000 tumor exomes, we identify more than 3000 rarely mutated residues in proteins as potentially functional and experimentally validate several in RAC1 and MAP2K1. These potential driver mutations (web resources: 3dhotspots.org and cBioPortal.org) can extend the scope of genomically informed clinical trials and of personalized choice of therapy.
Exploiting the Mutanome for Tumor Vaccination | Cancer ResearchExploiting the Mutanome for Tumor Vaccination | Cancer Research
Our study was motivated by the hypothesis that mutations provide a rich source for novel vaccine targets. Although immunogenic mutations have been reported in mouse and man, there is a complete lack of knowledge about the fraction of nonsynonymous mutations processed and presented in an immunologic relevant manner. To address this question, we carried out the first mouse tumor exome capture study, identifying B16F10 somatic point mutations, followed by testing of mutations for their capability to elicit T-cell immunogenicity. Our result is the first map of the B16F10 "T-cell-druggable mutanome.". The B16 melanoma cell line originated spontaneously in a C57BL/6 mouse in 1954 and was propagated by the Jackson Memorial Laboratory in Bar Harbor. In vivo passage of B16 cells resulted in formation of the highly metastatic daughter clone B16F10 (34). B16 cells express melanoma differentiation antigens and present MHC class I restricted epitopes from gp100, MART1 (35), tyrosinase (36), TRP1 (37) and ...
Plus itPlus it
Cancer cells often acquire resistance to therapy due to genetic mutations. However, without drug selection, these mutations would likely have a fitness cost to cancer cells and we hypothesize that the severity of this fitness cost is correlated with the effectiveness of drug treatment, with more effective treatments leading to more drastic genetic lesions. The size of a genetic lesion often correlates with its fitness cost - point mutation having little cost, aneuploidy having a large cost. However, aneuploidy is fast because the search space is only 46 gains or losses, while point mutations are slow with billions of base pairs to search before finding the right mutations. We designed experimental and computational systems to understand the selection pressures that would lead to resistance by these different genetic mechanisms. Mice were implanted with xenograft tumors from the HT1080 fibrosarcoma cell line that were heterozygous for DR5 (TNFRSF10B) and extremely sensitive to treatment with a ...
What is the principle for qBiomarker Somatic Mutation PCR Array data analysis? - QIAGENWhat is the principle for qBiomarker Somatic Mutation PCR Array data analysis? - QIAGEN
The basic principle behind the data analysis is that we compare the Ct value of a mutation assay in a test sample with the Ct value of the same assay in a wildtype sample. When there is a significant difference (a preset value of 4 Cts) between the Ct values, the test sample is concluded to contain the mutation. The Ct values used for comparison can either be raw Ct (in average Ct method) or normalized Ct (in delta delta Ct case). When the Ct difference falls between 3 and 4, we give a borderline mutation call, which means that the mutation may be present at low percentage. When the Ct difference is smaller than 3, we give a negative mutation call (i.e. the mutation percentage is beyond the detection limit of the array). The wildtype sample can be either a genuine wildtype sample that is tested in the same experiment, or it could be a "virtual" wildtype sample that is computed from all test samples. For detailed description of the data analysis principle, refer to (link to white paper ...
Age of father linked to increased mutations in children | Behavioral Healthcare ExecutiveAge of father linked to increased mutations in children | Behavioral Healthcare Executive
A recent study published in Nature has found that the age at which a father has children will determine how many mutations his offspring inherit. Pioneering geneticist J. B. S. Haldane in the 1930s, had worked years before the structure of DNA was determined, but according to Nature, he was correct about why fathers pass on more mutations than mothers. "Sperm is continually being generated by dividing precursor cells, which acquire new mutations with each division. By contrast, women are born with their lifelong complement of egg cells," according to the article. The study found that fathers passed on nearly four times as many new mutations as mothers: on average, 55 versus 14.. Stefánssons team also found that the older a man gets, the more new mutations are passed on. "A 36-year-old will pass on twice as many mutations to his child as a man of 20, and a 70-year-old eight times as many," his team estimated.. Since the average age of childbearing is rising, the study suggests that more ...
All Things Beautiful: DIY Zombie- Apocalyptic Summer Learning Camp, Phase I, part B: Zombies and MutationsAll Things Beautiful: DIY Zombie- Apocalyptic Summer Learning Camp, Phase I, part B: Zombies and Mutations
A gene mutation is a permanent alteration in the DNA sequence that makes up a gene, making the sequence differ from what is found in most people. Mutations can affect anywhere from a single DNA building block (base pair) to a large segment of a chromosome that includes multiple genes. There are two types of gene mutations. Hereditary mutations are inherited from a parent and are present throughout a persons life in virtually every cell in the body. Acquired mutations, sometimes called somatic mutations, occur at some time during a persons life and are present only in certain cells. These changes can be caused by environmental factors or can occur if a mistake is made as DNA copies itself during cell division. ...
Presence of gene mutation helps guide thyroid cancer... ( A specific gene mutation may be usef...)Presence of gene mutation helps guide thyroid cancer... ( A specific gene mutation may be usef...)
...A specific gene mutation may be useful in predicting the level of aggr...The mutation called BRAF V600E is a genetic alteration in the BRAF o...Past studies have shown that the mutation frequently occurs in the mos...The findings come at an important time as both the incidence of thyroi...,Presence,of,gene,mutation,helps,guide,thyroid,cancer,treatment,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
Specified Life: Non-inherited genetic diseaseSpecified Life: Non-inherited genetic disease
A significant but unquantified portion of genetic diseases is non-inherited; occurring from de novo (new) mutations in the the germ cells of the affected individuals. In humans, point mutations (i.e., mutations that occur in a single nucleotide base within the genome) occur with a frequency of about 1 to 3 x 10-8 per base (1), (2). There are many types of mutational alterations other than point mutations (e.g., mutations in microsatellites) (3). Our knowledge of the likelihood of other types of mutation most of these alternate types of mutation is limited. In many cases de novo mutations cause lethal genetic diseases that occur in children, through the action of a dominant gene (i.e., one gene copy that produces the disease). Such diseases are seldom inherited because they cannot be conserved in the population; those with the gene die early in life, without passing the gene to progeny. Sometimes, non-inheritance accounts for some proportion of cases that would otherwise occur as dominant gene ...
New Mutations for Gamma World | Steve KensonNew Mutations for Gamma World | Steve Kenson
The following mutations are based on material from earlier editions of Gamma World, adapted for the Alternity edition. The gamemaster can extend the mutation tables or allow the new mutations to be substituted for some existing mutations, if they are being determined randomly. Physical Mutations Burning Hands Good, Activated, WIL The mutant can emit heat from his hands…
Links Between Blood Cell Mutation and Heart Disease Identified | School of MedicineLinks Between Blood Cell Mutation and Heart Disease Identified | School of Medicine
A new study provides some of the first links between relatively common mutations in the blood cells of the elderly and atherosclerosis.. Though cardiovascular disease, which is characterized in part by atherosclerosis, or plaque build-up, is a leading cause of death in the elderly, almost 60 percent of elderly patients with atherosclerotic cardiovascular disease (CVD) exhibit no conventional risk factors, or just one. This and other data suggest that age-dependent risk factors that havent yet been identified may contribute to CVD.. Scientists know that accumulation of somatic DNA mutations is a feature of aging, though little data exists on the role of such mutations in age-associated disorders beyond cancer. Meanwhile, recent human studies indicate that aging is associated with an increase in somatic mutations in the hematopoietic system, which gives rise to blood cells; these mutations provide a competitive growth advantage to the mutant hematopoietic cells, allowing for their clonal ...
Nonsense mutationNonsense mutation
... In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the
PIT Tests, a Mutation TestingPIT Tests, a Mutation Testing
While wondering over internet, I just come across the "mutation testing" and here I blog about it. The blog largely said about one such framework "PIT tests".. When we say my code coverage is 80%, that only mean, in simple term, your unit tests cover 80% of your code base. Do they really tell you what your tests are really testing? - No. To answer this, there is a thing that called as "mutation testing". The framework I am talking about is PIT tests; they said its like automation tests for your tests. Cool!. How does it work?. Well in plain simple language, it mutate (modify the byte code at runtime) some logical part, decision taking part of your code and then run tests against such modified code, if your test fail (called as mutation killed), your test is OK, if its passed (called mutation survived), beware, there might be some bug hidden there. So, more the mutation killed more good your tests are.. Example:. The simplest example might be ...
Books: mouse modelBooks: mouse model
P53: The Gene That Cracked the Cancer Code by Sue Armstrong Amazon: amazon.com - amazon.co.uk - amazon.de - amazon.fr Asilomar, discovery of DNA, discovery of penicillin, double helix, mouse model, stem cell, trade route And if youre going to generate a mouse for the first time you dont want a mutant thats kind of wimpy. Meanwhile, at MIT in Boston, Tyler Jacks - renowned for creating one of the two first p53 knock-out mice in 1992 - was on the same track. His lab was busy generating two different mouse models that mimicked LFS - one with the same point mutation as Lozanos mice, corresponding to human R175H, and another corresponding to R273H. The two groups published their findings in the same edition of Cell in December 2004. What distinguished their mouse models from others designed to test the activity of mutant p53 was that here the gene was being switched on naturally in response to signals from the cells environment. In most other models, the gene was switched on artificially by ...
Minimization Using Simulated Annealing AlgorithmMinimization Using Simulated Annealing Algorithm
Simulated annealing mimics the annealing process to solve an optimization problem. It uses a temperature parameter that controls the search. The temperature parameter typically starts off high and is slowly "cooled" or lowered in every iteration. At each iteration a new point is generated and its distance from the current point is proportional to the temperature. If the new point has a better function value it replaces the current point and iteration counter is incremented. It is possible to accept and move forward with a worse point. The probability of doing so is directly dependent on the temperature. This unintuitive step sometime helps identify a new search region in hope of finding a better minimum.. ...
iTWire - TO THE POINT: Google rewards users with Google Play Points in new points programiTWire - TO THE POINT: Google rewards users with Google Play Points in new points program
In what is clearly not a pointless move, Google wants to make a real point of its new Google Play Points program that lets you earn points and rewards...
Updated mutation overview - VU Medicinal Chemistry - Tools & DownloadsUpdated mutation overview - VU Medicinal Chemistry - Tools & Downloads
For our British Journal of Pharmacology publication regarding the structural chemogenomics analysis of aminergic GPCRs (publication) we created a comprehensive overview of all site-directed mutagenesis studies performed against HRH1, HRH2, HRH3, HRH4, DRD3, ACM2, ACM3, ADRB1 and ADRB2 (aminergic GPCRs). In total 1420 reported single-point mutations were registered (including their effect on the binding affinity of reported ligands) at 128 individual B&W positions. ...
Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy]Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy]
MYH7 mutations were present in 10% of our families. Mutations were more frequent in patients with a family history of sudden death and in those with severe hypertrophy. Most mutations had been described previously. Some appeared in several families. For some mutations, the correlation between genoty …
Mutation services, Point mutations deletion mutations. 100% sequence guarantee - From BioneerMutation services, Point mutations deletion mutations. 100% sequence guarantee - From Bioneer
Gene synthesis is the most cost effective way to enhance your research. In as little as 2 weeks, you can have your gene cloned in hand and 100% sequence guaranteed. And with Bioneers great pricing it can cost less to order a synthetic gene from us than to buy all the kits and reagents necessary to PCR, ligate, clone, grow, purify and sequence your gene of interest. If you like, our free codon optimization will increase protein expression rates and can enhance protein function. In addition our optimization can make previously un-clonable sections of DNA easy to work with. Send us your sequence, gene ID or an accession number. Let us know what you need and we will deliver! Bioneer also offers Mutagenesis as well as cloning and subcloning services. Bioneer strives to provide the highest quality synthetic genes at a great price. Our goal is to always provide you with the best value for your research dollar. 유전자 설계와 올리고 합성, 클로닝 및 시퀀싱에 이르는 전 과정을
L4D2 EMS/Creating a Simple Mutation - Valve Developer CommunityL4D2 EMS/Creating a Simple Mutation - Valve Developer Community
We also need to provide a way for the Director to know what to do next. In the Mutation System, that is done with a function called GetNextStage(). Were going to use it to control when zombies spawn, when there are delays in attacks and when to display the win results. Think of it as the main loop of the mutation. Its helpful to understand what is meant by the term stage: A stage is a phase of gameplay. In Left4Dead2, some example stages are: PANIC, when huge mobs of infected are attacking and CLEAROUT, wherein the game is waiting for the Survivors to finish off any remaining infected before going on to the next stage. The Suvivors will go through many stages per map. Each time the game finishes a stage (all the zombies get killed, the cooldown ends, etc.) it will call back into your Mutation VScript code asking what to do next. Our Mutations response will be to change some fields in the SessionOptions table to reflect the type of stage wed like to start next. In addition to choosing a ...
Rev Henry Morris Falsehood Explained: Mutations in OrganismsRev Henry Morris' Falsehood Explained: Mutations in Organisms
Yet more lies from Rev Gish. Scientists do not consider mutations beneficial. They observe that the majority of mutations are neutral. The majority of the rest are harmful to the organism. The rest of the mutations are beneficial. It is the latter tiny fraction of mutations that produce new variation and diversity in a populations geneom, from which natural selection works. Rev Gish knows these facts. He just cannot help lying about it ...
iA - Chair of Information Architecture » Blog Archive » Urban Mutations PlatformiA - Chair of Information Architecture » Blog Archive » Urban Mutations Platform
An interactive platform for the identification of catalysing mutations in city generation, assembly and development. In this project we develop a comprehensive urban theory, which identifies so-called mutations in a city: alterations in the citys genetic code, which can be beneficial or harmful, with local or global effect and can drastically affect the citys development. The user can digitally create a city out of several non-specific structural subunits and then apply mutations, represented by structural and functional city elements that signify an explicit change within an otherwise generic city subunit. Mutations distort the city grid and quantify on the city level parameters such as: the type of disturbances caused; the gravity of each disturbance; the size of the affected area. ...
Evolution, Mutation and Misconceptions | evolution n designEvolution, Mutation and Misconceptions | evolution 'n design
A common objection to the Evolutionary model is the idea that Mutations are a driving force for change. It is seen all over Creationist literature that mutations destroy information, and never add anything, or have any benefits. -- For example, the Muslim Creationist Harun Yahya claims, The direct effect of mutations is harmful. The changes effected by mutations…
jira] [Assigned] (CASSANDRA-7047) TriggerExecutor should group mutations by row keyjira] [Assigned] (CASSANDRA-7047) TriggerExecutor should group mutations by row key
https://issues.apache.org/jira/browse/CASSANDRA-7047?page=com.atlassian.jira.plugin.system.issuetabpanels:all-tabpanel ] Aleksey Yeschenko reassigned CASSANDRA-7047: -------------------------------------------- Assignee: Aleksey Yeschenko (was: Sergio Bossa) , TriggerExecutor should group mutations by row key , ------------------------------------------------- , , Key: CASSANDRA-7047 , URL: https://issues.apache.org/jira/browse/CASSANDRA-7047 , Project: Cassandra , Issue Type: Improvement , Components: Core , Reporter: Sergio Bossa , Assignee: Aleksey Yeschenko , Fix For: 2.0.8, 2.1 beta2 , , Attachments: 7047-v2.txt, 7047-v3.txt, 7047-v4.txt, CASSANDRA-7047.patch , , , TriggerExecutor doesnt currently group mutations returned by triggers even if belonging to the same row key: while harmless per se (at least, I think so), this is definitely a performance problem, because each mutation is a *cluster* mutation, generating more network traffic, more disk IO and more index calls (if present). -- ...
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Plus itPlus it
Success with molecular-based targeted drugs in the treatment of cancers has ignited extensive research efforts within the field of personalised therapeutics. However, successful application of such therapies is dependent on the presence or absence of mutations within the patients tumor that can confer clinical efficacy or drug resistance. Building on these findings, we developed a high throughput mutation panel for the identification of frequently occurring and clinically-relevant mutations in melanoma. An extensive literature search and interrogation of the Catalogue of Somatic Mutations in Cancer (COSMIC) database identified over 1000 melanoma mutations. Applying a filtering strategy to focus on mutations amenable to the development of targeted drugs, we initially screened 120 different known mutations in 271 samples using the Sequenom MassARRAY® system. A total of 252 mutations were detected in 17 genes. The highest frequency mutations occurred in BRAF (n=154, 57%), NRAS (n=55, 20%), CDK4 ...
TATA boxTATA box
SNP genotypingSNP genotyping
BLOSUMBLOSUM
TUBA1ATUBA1A
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome EditingNo-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing
Blue cone monochromacyBlue cone monochromacy
IndelIndel
Animal model of schizophreniaAnimal model of schizophrenia
The Phoenix FilesThe Phoenix Files
GermacreneGermacrene
Germacrene-A synthaseGermacrene-A synthase
Pinot blancPinot blanc
Ethyl methanesulfonateEthyl methanesulfonate
CEBPACEBPA
Short stature homeobox geneShort stature homeobox gene
Kell antigen systemKell antigen system
DemethylaseDemethylase
AMPD3AMPD3
ThyroglobulinThyroglobulin
5-Bromouracil5-Bromouracil
Neurofibromatosis type IINeurofibromatosis type II
ACTH receptorACTH receptor
Glucocorticoid deficiency 1Glucocorticoid deficiency 1
Gamma-Aminobutyric acidGamma-Aminobutyric acid
EndonucleaseEndonuclease
Mutant proteinMutant protein
Fbx15Fbx15
Fibroblast growth factor receptorFibroblast growth factor receptor
Coagulation factor XIII, A1 polypeptideCoagulation factor XIII, A1 polypeptide
Factor XIFactor XI
CraniosynostosisCraniosynostosis
IndinavirIndinavir
CateninCatenin
Quantitative trait locusQuantitative trait locus
Elastina - Wikipédia, a enciclopédia livreElastina - Wikipédia, a enciclopédia livre
MallardMallard
Chloroplast DNAChloroplast DNA
OctopusOctopus
Category:DNA - Simple English Wikipedia, the free encyclopediaCategory:DNA - Simple English Wikipedia, the free encyclopedia
PAX8PAX8
Evolution of biological complexityEvolution of biological complexity
AndrogenAndrogen
AntiandrogenAntiandrogen
Inferno (Marvel Comics)Inferno (Marvel Comics)
Alpha-1 antitrypsinAlpha-1 antitrypsin
InbreedingInbreeding
PleiotropyPleiotropy
Yellow feverYellow fever
PSEN1PSEN1
Benzo(a)pyreneBenzo(a)pyrene
Hyperimmunoglobulin E syndromeHyperimmunoglobulin E syndrome
PicornavirusPicornavirus
Cav1.2Cav1.2
ArchaeaArchaea
AveragenessAverageness
HistoneHistone
Cold Spring Harbor LaboratoryCold Spring Harbor Laboratory
Codon degeneracyCodon degeneracy
HADHBHADHB
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesDisciplines and OccupationsInformation ScienceNamed GroupsHealth Care
Point MutationMutation, MissenseMutationFrameshift MutationMolecular Sequence DataBase SequenceGerm-Line MutationPedigreeAmino Acid SequenceDNA Mutational AnalysisExonsPolymerase Chain ReactionAmino Acid SubstitutionMutagenesis, Site-DirectedHeterozygoteMutation RateAllelesPolymorphism, Single-Stranded ConformationalMutagenesisSequence Analysis, DNASequence DeletionHomozygoteProtein Structure, TertiaryDNA PrimersGenotypePhenotypeBinding SitesCell LineCodonModels, MolecularCodon, NonsenseEscherichia coliSequence Homology, Amino AcidDNA-Binding ProteinsGene DeletionCloning, MolecularProtein BindingGenes, DominantDNAGenes, RecessiveSequence AlignmentSuppression, GeneticTranscription FactorsPlasmidsChromosome MappingTransfectionGenes, p53Genetic TestingGenetic Complementation TestDNA, MitochondrialMutant ProteinsSaccharomyces cerevisiaeTranscription, GeneticBacterial ProteinsPromoter Regions, GeneticMembrane ProteinsRecombinant ProteinsIntronsStructure-Activity RelationshipProtein ConformationNuclear ProteinsSyndromeEthylnitrosoureaDNA, NeoplasmRNA, MessengerGenetic VariationPolymorphism, GeneticModels, GeneticPolymorphism, Restriction Fragment LengthCarrier ProteinsGenetic LinkageKineticsRecombinant Fusion ProteinsFounder EffectHeterozygote DetectionMutagenesis, InsertionalGenesRecombination, GeneticConserved SequenceCOS CellsGenes, LethalGenetic Predisposition to DiseaseGenes, BacterialRestriction MappingConsanguinitySignal TransductionRNA SplicingProtein Structure, SecondarySaccharomyces cerevisiae ProteinsProto-Oncogene ProteinsProteinsGenes, SuppressorFamily HealthGene FrequencyDNA, ComplementaryProto-Oncogene Proteins B-rafTemperatureGenes, FungalMutagensExomeCricetinaeEvolution, MolecularCrosses, GeneticCells, CulturedDrug ResistanceMice, Mutant StrainsChromosome DeletionOligonucleotide ProbesFungal ProteinsMicrosatellite RepeatsGenes, BRCA1Amino Acid MotifsCercopithecus aethiopsRNA Splice SitesDNA, BacterialRepressor ProteinsBlotting, SouthernGene Expression RegulationINDEL MutationTumor Suppressor Protein p53Gene ExpressionReverse Transcriptase Polymerase Chain ReactionPhosphorylationHeLa CellsEscherichia coli ProteinsSelection, GeneticEye ProteinsDrug Resistance, MicrobialGenes, rasDrug Resistance, ViralJewsSequence Homology, Nucleic AcidDrosophila ProteinsNucleic Acid ConformationAge of OnsetOligodeoxyribonucleotidesTrans-ActivatorsDNA RepairBlotting, WesternGenetic Diseases, X-LinkedGlycineRetinitis PigmentosaMice, TransgenicRNA, Transfer, LeuAlanineAbnormalities, MultipleCell Transformation, NeoplasticArginineMELAS SyndromeVirus ReplicationPolymorphism, Single NucleotideDNA Transposable ElementsDrosophila melanogasterDimerizationras ProteinsDNA GyraseGene Expression Regulation, BacterialPenetranceDrug Resistance, BacterialGenetic MarkersSerineFibroblastsMitochondrial EncephalomyopathiesX ChromosomeGenes, BRCA2CHO CellsModels, BiologicalLoss of HeterozygosityTumor Cells, CulturedCodon, TerminatorEye AbnormalitiesDNA, ViralEthyl MethanesulfonateProtein TransportMice, Inbred C57BLProtein FoldingCysteineRepetitive Sequences, Nucleic AcidDrosophilaImmunohistochemistryCell NucleusDNA, FungalAdenosine TriphosphatasesHEK293 CellsMitochondrial DiseasesViral ProteinsOperonGenetic HeterogeneityAdaptor Proteins, Signal TransducingCell Line, TumorGenes, RegulatorProtein StabilityPhylogenyMitochondrial MyopathiesAsian Continental Ancestry GroupRNANeoplasm ProteinsProtein-Serine-Threonine KinasesRNA, ViralCharcot-Marie-Tooth DiseaseMosaicism
CiNii 論文 - A Novel Somatic Point Mutation of the RET Proto-oncogene in Tumor Tissues of Small...CiNii 論文 - A Novel Somatic Point Mutation of the RET Proto-oncogene in Tumor Tissues of Small...
Developing new method for GBA sequencing and detection of germ-line or somatic point mutations, deletion/insertions, and...Developing new method for GBA sequencing and detection of germ-line or somatic point mutations, deletion/insertions, and...
BIS101 HW6 F08 Engebrecht - Deletions x Point mutations 1 2 3 4 5 1 2 3 4 5 1 a 2 b 3 c 4 d 5 e 2 The following DNA is part of...BIS101 HW6 F08 Engebrecht - Deletions x Point mutations 1 2 3 4 5 1 2 3 4 5 1 a 2 b 3 c 4 d 5 e 2 The following DNA is part of...
What are the advantages of mutation? - AnswersWhat are the advantages of mutation? - Answers
A point mutation in KINDLIN3 ablates activation of three integ...A point mutation in KINDLIN3 ablates activation of three integ...
Absence of point mutation in the third intracellular loop of...Absence of point mutation in the third intracellular loop of...
mutation: Point Mutations | FactMonstermutation: Point Mutations | FactMonster
Point mutation - WikipediaPoint mutation - Wikipedia
Tissue P Systems with Point Mutation Rules | SpringerLinkTissue P Systems with Point Mutation Rules | SpringerLink
Point Mutation | Journal of Clinical MicrobiologyPoint Mutation | Journal of Clinical Microbiology
Point accepted mutation - WikipediaPoint accepted mutation - Wikipedia
Familial Parkinsons point mutation abolishes multiple system atrophy prion replication | PNASFamilial Parkinson's point mutation abolishes multiple system atrophy prion replication | PNAS
The point mutation which made humanityThe point mutation which made humanity
Gene mutation analysis may point to imprinting in newborn lung diseaseGene mutation analysis may point to imprinting in newborn lung disease
MAESTRO--multi agent stability prediction upon point mutations. - PubMed - NCBIMAESTRO--multi agent stability prediction upon point mutations. - PubMed - NCBI
Structural Consequences of Point Mutations in Nine Human HPRT Variants | SpringerLinkStructural Consequences of Point Mutations in Nine Human HPRT Variants | SpringerLink
Multipyrene Tandem Probes for Point Mutations Detection in DNAMultipyrene Tandem Probes for Point Mutations Detection in DNA
Calmodulin Point Mutations Affect Drosophila Development and Behavior | GeneticsCalmodulin Point Mutations Affect Drosophila Development and Behavior | Genetics
A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. - PubMed - NCBIA point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. - PubMed - NCBI
Factor V Leiden Mutation and PT 20210 Mutation: The TestFactor V Leiden Mutation and PT 20210 Mutation: The Test
Dynamic Harmony Search with Polynomial Mutation Algorithm for Valve-Point Economic Load DispatchDynamic Harmony Search with Polynomial Mutation Algorithm for Valve-Point Economic Load Dispatch
Fig. 1: Timing clonal copy number gains using allele frequencies of point mutations. | NatureFig. 1: Timing clonal copy number gains using allele frequencies of point mutations. | Nature
A point mutation of mitochondrial ATPase 6 gene in Leigh syndromeA point mutation of mitochondrial ATPase 6 gene in Leigh syndrome
The spectra of point mutations in vertebrate genomesThe spectra of point mutations in vertebrate genomes
Single Point Mutation In Listeria Monocytogenes Identified | Science 2.0Single Point Mutation In Listeria Monocytogenes Identified | Science 2.0
A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency | PNASA point mutation in the HIV-1 Tat responsive element is associated with postintegration latency | PNAS
TNO Repository search for: subject:point mutationTNO Repository search for: subject:'point mutation'
Near point-of-care, point-mutation test to detect drug resis... : AIDSNear point-of-care, point-mutation test to detect drug resis... : AIDS
DNA From Cystic Fibrosis Patients With And Without Chronic Infections Points To Unsuspected MutationDNA From Cystic Fibrosis Patients With And Without Chronic Infections Points To Unsuspected Mutation
Multiple point mutations - Molecular BiologyMultiple point mutations - Molecular Biology
RCSB PDB - 4L1H: Bence-Jones immunoglobulin REI variable portion with seven point mutationsRCSB PDB - 4L1H: Bence-Jones immunoglobulin REI variable portion with seven point mutations
Cerebral Palsy Genomic Study Points to Rare Damaging Mutations as Disease Contributors | GenomeWebCerebral Palsy Genomic Study Points to Rare Damaging Mutations as Disease Contributors | GenomeWeb
BRCA1 Mutation Prevalent Among Hispanic, Younger B... ( New ethnic findings point out that al...)BRCA1 Mutation Prevalent Among Hispanic, Younger B... ( New ethnic findings point out that al...)
Point Mutation of Ornithine Decarboxylase Gene in Human Hepatocellular Carcinoma | Cancer ResearchPoint Mutation of Ornithine Decarboxylase Gene in Human Hepatocellular Carcinoma | Cancer Research
A Methylated Neurospora 5S rRNA Pseudogene Contains a Transposable Element Inactivated by Repeat-Induced Point Mutation |...A Methylated Neurospora 5S rRNA Pseudogene Contains a Transposable Element Inactivated by Repeat-Induced Point Mutation |...
Turning Point Therapeutics Kinase Inhibitors Show High Potency against Targeted Oncogene Drivers and Their Mutations |...Turning Point Therapeutics' Kinase Inhibitors Show High Potency against Targeted Oncogene Drivers and Their Mutations |...
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesDisciplines and OccupationsInformation ScienceNamed GroupsHealth Care
Point MutationMutation, MissenseMutationFrameshift MutationMolecular Sequence DataBase SequenceGerm-Line MutationPedigreeAmino Acid SequenceDNA Mutational AnalysisExonsPolymerase Chain ReactionAmino Acid SubstitutionMutagenesis, Site-DirectedHeterozygoteMutation RateAllelesPolymorphism, Single-Stranded ConformationalMutagenesisSequence Analysis, DNASequence DeletionHomozygoteProtein Structure, TertiaryDNA PrimersGenotypePhenotypeBinding SitesCell LineCodonModels, MolecularCodon, NonsenseEscherichia coliSequence Homology, Amino AcidDNA-Binding ProteinsGene DeletionCloning, MolecularProtein BindingGenes, DominantDNAGenes, RecessiveSequence AlignmentSuppression, GeneticTranscription FactorsPlasmidsChromosome MappingTransfectionGenes, p53Genetic TestingGenetic Complementation TestDNA, MitochondrialMutant ProteinsSaccharomyces cerevisiaeTranscription, GeneticBacterial ProteinsPromoter Regions, GeneticMembrane ProteinsRecombinant ProteinsIntronsStructure-Activity RelationshipProtein ConformationNuclear ProteinsSyndromeEthylnitrosoureaDNA, NeoplasmRNA, MessengerGenetic VariationPolymorphism, GeneticModels, GeneticPolymorphism, Restriction Fragment LengthCarrier ProteinsGenetic LinkageKineticsRecombinant Fusion ProteinsFounder EffectHeterozygote DetectionMutagenesis, InsertionalGenesRecombination, GeneticConserved SequenceCOS CellsGenes, LethalGenetic Predisposition to DiseaseGenes, BacterialRestriction MappingConsanguinitySignal TransductionRNA SplicingProtein Structure, SecondarySaccharomyces cerevisiae ProteinsProto-Oncogene ProteinsProteinsGenes, SuppressorFamily HealthGene FrequencyDNA, ComplementaryProto-Oncogene Proteins B-rafTemperatureGenes, FungalMutagensExomeCricetinaeEvolution, MolecularCrosses, GeneticCells, CulturedDrug ResistanceMice, Mutant StrainsChromosome DeletionOligonucleotide ProbesFungal ProteinsMicrosatellite RepeatsGenes, BRCA1Amino Acid MotifsCercopithecus aethiopsRNA Splice SitesDNA, BacterialRepressor ProteinsBlotting, SouthernGene Expression RegulationINDEL MutationTumor Suppressor Protein p53Gene ExpressionReverse Transcriptase Polymerase Chain ReactionPhosphorylationHeLa CellsEscherichia coli ProteinsSelection, GeneticEye ProteinsDrug Resistance, MicrobialGenes, rasDrug Resistance, ViralJewsSequence Homology, Nucleic AcidDrosophila ProteinsNucleic Acid ConformationAge of OnsetOligodeoxyribonucleotidesTrans-ActivatorsDNA RepairBlotting, WesternGenetic Diseases, X-LinkedGlycineRetinitis PigmentosaMice, TransgenicRNA, Transfer, LeuAlanineAbnormalities, MultipleCell Transformation, NeoplasticArginineMELAS SyndromeVirus ReplicationPolymorphism, Single NucleotideDNA Transposable ElementsDrosophila melanogasterDimerizationras ProteinsDNA GyraseGene Expression Regulation, BacterialPenetranceDrug Resistance, BacterialGenetic MarkersSerineFibroblastsMitochondrial EncephalomyopathiesX ChromosomeGenes, BRCA2CHO CellsModels, BiologicalLoss of HeterozygosityTumor Cells, CulturedCodon, TerminatorEye AbnormalitiesDNA, ViralEthyl MethanesulfonateProtein TransportMice, Inbred C57BLProtein FoldingCysteineRepetitive Sequences, Nucleic AcidDrosophilaImmunohistochemistryCell NucleusDNA, FungalAdenosine TriphosphatasesHEK293 CellsMitochondrial DiseasesViral ProteinsOperonGenetic HeterogeneityAdaptor Proteins, Signal TransducingCell Line, TumorGenes, RegulatorProtein StabilityPhylogenyMitochondrial MyopathiesAsian Continental Ancestry GroupRNANeoplasm ProteinsProtein-Serine-Threonine KinasesRNA, ViralCharcot-Marie-Tooth DiseaseMosaicism
DeletionGene mutationsGenesDeletionsSequencesOccurLocusProteinIdentify mutationsOrganismAllelesNucleotidesSingle-point mutationParkinson'sSpontaneous mutationClinicalOccursAbstractNucleotideDetectionTypes of point mutationsProteinsNonsynonymous coding muVariantsShow that both mutationsConsequencesCaused by a single point mutationCompound mutationsEscherichiaSomatic mutationsFrameshift mutationsChromosomalSpecific mutationsHeterozygous or homozygousMutantsEffects of mutationsMitochondrialSequenceAlleleGenetic mutationsPossible mutationsResistanceHomozygousTumorResearchersPhenotypeSubsetSingle pointAssaysHereditarySubunitVitroPatientsPotential to induceMolecularCodonsInhibitorsMutantStrainsDeletionsPredictionSecretionChromosome 16Strain
Deletion1
Gene mutations1
Genes4
Deletions4
Sequences1
Occur3
Locus1
  • When a mutation is fixed, it is automatically passed on to every succeeding generation with probability 1.0 (unless there is a ``back mutation'' that changes the locus back to its original form, but this is a very rare event). (ornl.gov)
Protein3
  • According to the constitutive activity hypothesis for G-protein coupling receptors, we inferred that point mutations might possibly exsit in the third intracellular loop of alpha 1B- and/or alpha 1D-adrenergic receptor (AR), the main subtypes of alpha 1-AR mediating phosphatidylinositol hydrolysis in SHR aortae. (mysciencework.com)
  • A point mutation can either be in a specific location of the DNA or it can give rise to the change in a specific position of a critical viral protein. (peoplesdispatch.org)
  • A change of a single base in the DNA or a single amino acid of a protein - the hallmark of point mutation - can bring in huge change in terms of physiology, infectivity and severity of a microorganism, and for that matter, in any organism. (peoplesdispatch.org)
Identify mutations1
Organism3
Alleles1
  • that is, both alleles are mutant, but in spite of previous reports it remains debatable irrespective of whether a heterozygous mutation can cause or improve the danger of PD .In , Hedrich et al. (idhinhibitor.com)
Nucleotides1
Single-point mutation1
  • A single point mutation, G442R, resulted in a mutant displaying an a(1~2) regioselectivity. (ac.ke)
Parkinson's2
  • Most scientists who study brain conditions such as Parkinson's naturally focus on the brain, but new research from the Van Andel Research Institute in Michigan shows that the obvious starting point is not the only way to go. (parkinsonsnewstoday.com)
  • In the study "Enrichment of risk SNPs in regulatory regions implicate diverse tissues in Parkinson's disease etiology," published in the journal Scientific Report s, scientists now say that collections of small DNA mutations, linked to the risk of Parkinson's, can be found in liver, fat, immune, and developmental cells. (parkinsonsnewstoday.com)
Spontaneous mutation1
Clinical1
  • It can be a useful tool for other research groups, and could be especially important for recruitment of patients with GBA mutations to clinical trials, because this method, unlike other methods, will be able to identify all forms of GBA mutations. (michaeljfox.org)
Occurs2
  • When a mutation enters the population, it occurs in only one individual and is plotted as a point somewhere on the x axis. (ornl.gov)
  • If by chance the mutation continues to spread in each successive generation, it may reach a point when it occurs in every individual, i.e. it becomes fixed. (ornl.gov)
Abstract1
  • Lundin, Erik;Tang, Po-Cheng;Guy, Lionel;Näsvall, Joakim;Andersson, Dan I 2018-03-01 00:00:00 Abstract The distribution of fitness effects of mutations is a factor of fundamental importance in evolutionary biology. (deepdyve.com)
Nucleotide9
Detection11
Types of point mutations1
Proteins9
Nonsynonymous coding mu1
  • Using the MMRF CoMMpass (NCT0145429) study (IA13), we determined the frequency of nonsynonymous coding mutations in the BCL2 family. (bloodjournal.org)
Variants6
Show that both mutations1
  • Voets, together with his colleague Joris Vriens (KU Leuven) and their team at the Laboratory for Ion Channel Research, could show that both mutations affect TRPM3 channel gating. (vib.be)
Consequences4
  • Comparisons with other Drosophila mutant phenotypes suggests potential CAM targets that may mediate these developmental and behavioral effects, and analysis of the CAM crystal structure suggests the structural consequences of the individual mutations. (genetics.org)
  • This study indicates that mutations in obligate symbionts can have major consequences for host fitness and geographic distributions. (pubmedcentralcanada.ca)
  • Since the functional consequences of the mutations remained elusive, we set out to understand how disturbances of this particular ion channel can cause intellectual disability and epileptic seizures. (vib.be)
  • We here investigated, in vitro and in silico, the biophysical consequences of clinically-observed Wilson disease mutations, G85V in MBD1 and G591D in MBD6, incorporated in domain 4. (diva-portal.org)
Caused by a single point mutation1
Compound mutations1
  • Two studies highlighted the higher potency of repotrectinib as compared to other proxy investigational and the currently approved ROS1 and TRK tyrosine kinase inhibitors (TKIs), Xalkori and Vitrakvi, against fusion ROS1s, wildtype TRK, and many resistance mutations, including solvent front, gatekeeper, and compound mutations. (businesswire.com)
Escherichia1
Somatic mutations1
  • Specifically, Dr. Russell described the QuantStudio™ 3D rare mutation analysis solution's subset of 38 wet lab-validated TaqMan ® SNP Genotyping Assays for use in detecting and quantifying rare somatic mutations, e.g. (thermofisher.com)
Frameshift mutations1
Chromosomal2
Specific mutations2
  • Understanding the specific mutations that trigger signals in cell receptors to stimulate cell growth will help us identify biomarkers for specific subtypes of neuroblastoma," said study co-leader Mark A. Lemmon, PhD, professor and chair of Biochemistry and Biophysics at Penn. (oncologynurseadvisor.com)
  • Furthermore, specific mutations that occur as a result of a recombination between the gene and the pseudogene are often missed by the traditional genetic methods. (michaeljfox.org)
Heterozygous or homozygous3
Mutants7
  • Whereas the individual effects of both mutations differ, both can be considered as strong gain-of-function mutants, with increased activity, both under basal conditions and when stimulated," says Voets. (vib.be)
  • This study was aimed at analyzing the functional relevance of these two ABCB4 mutations: MDR3 expression and lipid content in the culture supernatant were evaluated in cell lines stably transfected with the ABCB4 wild-type clone and corresponding mutants. (uniprot.org)
  • Moreover, antibodies reactive with antigenic region F (aa 235 to 242) of VP7 might also be involved since cross-reactivity to serotype G3 was decreased in double mutants carrying an additional mutation, which creates a potential glycosylation site at position 238. (asm.org)
  • We determined the distribution of fitness effects of 510 mutants that each carried between 1 and 10 mutations (synonymous and nonsynonymous) in the hisA gene, encoding an essential enzyme in the l-histidine biosynthesis pathway of Salmonella enterica. (deepdyve.com)
  • For the full set of mutants, the distribution was bimodal with many apparently neutral mutations and many lethal mutations. (deepdyve.com)
  • For a subset of 81 single, nonsynonymous mutants most mutations appeared neutral at high expression levels, whereas at low expression levels only a few mutations were neutral. (deepdyve.com)
  • Three different class I LamB missense mutants (mutations at sites 247, 245, and 148) were used to select 11 independent, new, one-step host range mutants (lambda h phages). (pasteur.fr)
Effects of mutations1
  • and (iv) no single sequence-based predictor could confidently predict the fitness effects of mutations in HisA, but a combination of multiple predictors could predict the effect with a SD of 0.04 resulting in 80% of the mutations predicted within 12% of their observed selection coefficients. (deepdyve.com)
Mitochondrial5
Sequence6
Allele3
Genetic mutations4
  • Whatever your ethnicity or your race, if you have a high-risk profile -- that is, early breast cancer -- it predicts the likelihood of genetic mutations across all ethnicities and races," said Dr. Jeffrey N. Weitzel, director of the department of clinical cancer genetics at the City of Hope Comprehensive Cancer Center, in Duarte, Calif. (bio-medicine.org)
  • Mayo Clinic researchers are using precision genomics to search for undiscovered, inheritable genetic mutations that cause accelerated aging. (laboratoryequipment.com)
  • Not to destroy, but to zero in on genetic mutations that may be linked with short telomere and other inherited bone marrow failure syndromes, providing unique insights into their disease biology. (laboratoryequipment.com)
  • Certain genetic mutations are known to be associated with short telomeres. (laboratoryequipment.com)
Possible mutations1
  • 2015). Fitness landscapes are vast and have as many dimensions as there are possible mutations in a system (de Visser and Krug 2014). (deepdyve.com)
Resistance10
  • However, from a synthetic biology point of view, such a boosted-stress resistance gene represents a useful BioBrick (or building block) for the design of more physiologically robust probiotics or, indeed, plants that are more resistant to cold arid conditions. (science20.com)
  • Ouabain-resistance test detecting mutations in the Na + /K + ATPase was used to investigate the effect of BCR/ABL kinase-mediated inhibition of MMR on mutagenesis. (aacrjournals.org)
  • overall, point mutations in the kinase domain of BCR/ABL have been detected in 50% to 90% of patients with acquired resistance to imatinib, including ∼23% of the imatinib-naive patients ( 3 ). (aacrjournals.org)
  • High-level Cip r (MIC ≥ 64 μg/ml) due to point mutations in the quinolone resistance-determining region was unique to a distinct hospital-adapted genetic complex in E. faecium , previously designated CC17. (asm.org)
  • Acquisition of mutations in parC and gyrA , leading to high-level Cip r , is, in addition to ampicillin resistance and the presence of a putative pathogenicity island, another cumulative step in hospital adaptation of CC17. (asm.org)
  • In the present study, we report a Thai female with a de novo mutation in thyroid hormone receptor-beta (TRbeta) gene causing resistance to thyroid hormone (RTH). (eurekamag.com)
  • Background - Point mutations in the BCR-ABL kinase domain are associated with resistance to TKI therapy. (linkos.cz)
  • Assessing in how many CML patients with failure and warning mutations can be identified, especially now that more sensitive NGS-based mutation screening methods are available, would advance our knowledge of the biology of TKI resistance as well as contribute useful data to revise the ELN recommendations as to when and how BCR-ABL mutation analysis should be performed. (linkos.cz)
  • The counter-selection system takes advantage of the fact that mutations within rpsL leading to streptomycin resistance are recessive in a merodiploid strain. (biomedcentral.com)
  • LamB missense mutations yielding resistance to lambda group in two classes. (pasteur.fr)
Homozygous6
Tumor5
  • This mutation impaired Tat responsiveness of the LTR in transient transfection assays, and the measured defect was complemented in cells that had been treated with tetradecanoyl phorbol acetate or tumor necrosis factor type alpha (TNF-alpha). (pnas.org)
  • In the ongoing TRIDENT-1 clinical trial repotrectinib was active against the solvent front mutation ETV6-TRKC G623E in an entrectinib-resistant patient with a salivary gland tumor (-82%, confirmed partial response, RECIST v1.1). (businesswire.com)
  • In the second tumor, 6139B-PRO, both alleles of the L26 gene have point mutations, and each encodes a different tumor-specific CD4 + T cell-recognized antigen. (rupress.org)
  • In some instances, a somatic mutation encoding a tumor-specific antigen is believed to contribute to the development of cancer ( 4 )( 6 )( 7 )( 8 ). (rupress.org)
  • On the other hand, it is also known that the p53 tumor suppressor gene plays an important role in restriction of abnormal cell proliferation and that loss of this safeguard function induced by its mutation may be a key factor in carcinogenesis. (aacrjournals.org)
Researchers14
  • An international group of researchers led by those at Baylor College of Medicine has analyzed the 42 mutations in FOXF1 in DNA from infants with the disorder and in a report that appears in the journal Human Mutation recommends that genetic testing be considered in infants with persistent pulmonary arterial hypertension with no known cause. (bcm.edu)
  • The researchers have identified a single point mutation (out of a total of 3 million or so nucleotides that constitute the entire listerial genome), which dramatically improves the growth of the pathogen in the refrigerator. (science20.com)
  • WEDNESDAY, Dec. 26 (HealthDay News) -- The gene mutation BRCA1, which is known to increase the risk of breast cancer, is prevalent among Hispanics and young black women with breast cancer, researchers report. (bio-medicine.org)
  • The mutation is known to heighten the risk for Ashkenazi Jews, so the new ethnic findings are something of a surprise, the California researchers noted. (bio-medicine.org)
  • The researchers found that Ashkenazi women with breast cancer had the highest rate of the BRCA1 mutation, at 8.3 percent. (bio-medicine.org)
  • The researchers speculate that Sephardic Jews, who settled in Spain, could have shared the mutation with Ashkenazi Jews, who settled in central and Eastern Europe. (bio-medicine.org)
  • Researchers have now elucidated how both independent mutations affect the channel's function: by making it overly active and highly sensitive to stimulation. (vib.be)
  • Researchers are now able to detect low-frequency mutations by combining TaqMan™ fluorogenic 5' nuclease chemistry with dPCR methodology using the QuantStudio™ 3D Digital PCR System . (thermofisher.com)
  • Researchers analyzed pretreatment GIST samples for mutations from 377 patients in the trial. (cancernetwork.com)
  • The researchers also investigated which ALK mutations were more sensitive to crizotinib in cell cultures. (oncologynurseadvisor.com)
  • Boston, MA - Researchers say they have discovered a gene mutation that slows the metabolism of sugar in the gut, giving people who have the mutation a distinct advantage over those who do not. (mindzilla.com)
  • The researchers say their finding could provide the basis for drug therapies that could mimic the workings of this gene mutation, offering a potential benefit for the millions of people who suffer with diabetes, heart disease, and obesity. (mindzilla.com)
  • In the study, the researchers analyzed the relationship between SGLT-1 mutations and cardiometabolic disease using genetic data obtained from 8,478 participants in the Atherosclerosis Risk In Communities (ARIC) study. (mindzilla.com)
  • The researchers found that about 6 percent of the subjects carried a mutation in SGLT-1 that causes limited impairment of glucose absorption. (mindzilla.com)
Phenotype5
  • One of these mutations produces a striking pupal lethal phenotype involving failure of head eversion. (genetics.org)
  • BCR/ABL-positive cells surviving the treatment with MNNG displayed ∼15-fold higher mutation frequency than parental counterparts and predominantly G:C→A:T and A:T→G:C mutator phenotype typical for MNNG-induced unrepaired lesions. (aacrjournals.org)
  • These two mutations also provide the first genetic evidence that link TRPM3 to a pain phenotype in humans," adds Vriens. (vib.be)
  • Mutations T1031A and T1040C in one of the WD40 repeats of Eed, which account for the hypomorphic and lethal phenotype of eed in mouse development, blocked binding of Ezh2 to Eed in a two-hybrid interaction in yeast and in mammalian cells. (asm.org)
  • Recombination experiments confirmed that in the cases tested, the mutations identified were indeed responsible for the extended host range phenotype. (pasteur.fr)
Subset1
Single point13
  • The predictive power of MAESTRO for single point mutations and stabilizing disulfide bonds is comparable to similar methods. (nih.gov)
  • The prediction error is defined as the absolute difference between the experimental determined Δ Δ G and the predicted Δ Δ G. Data are given for the three main single point mutation sets (SP1, SP3, SP4) as well as the multi-point mutation set (MP). (nih.gov)
  • from a food safety perspective, a single point mutation with the potential to induce such dramatic shifts in cell growth and survival at low temperatures-making an already dangerous pathogen even more formidable-raises significant food-safety concerns which need to be addressed. (science20.com)
  • The paper, "A single point mutation in the listerial betL σA-dependent promoter leads to improved osmo- and chill-tolerance and a morphological shift at elevated osmolarity," will be published in the November/December 2013 issue of Bioengineered but is available open access now . (science20.com)
  • A single-point mutation, V328A, turn the (S)-selective omega-transaminase into an (R)-selective enzyme. (diva-portal.org)
  • Single point mutations may affect the serotype reactivity of serotype G11 porcine rotavirus strains: a widening spectrum? (asm.org)
  • 1. "We used a series of regional replacements and single-point mutations, coupled with functional analyses, to demonstrate that two single-point mutations located in the transmembrane regions of the molecule together determine their ligand selectivity. (elifesciences.org)
  • 1. "Its ortholog HarmOr14b is specific for Z9-14:Ald in H. armigera and we further demonstrate that two single-point mutations, F232I and T355I, located in the transmembrane domains of the receptor, together determine the functional shift between orthologs in the two closely related species. (elifesciences.org)
  • 4. "We systematically identify two single-point mutations, F232I and T355I, located in the transmembrane regions of HassOr14b that together determine the functional shift to its ortholog, HarmOr14b, in H. armigera . (elifesciences.org)
  • A single point mutation of the negatively charged pore loop (P-loop) glutamate (E342) to either a positively charged lysine or arginine resulted in functional channels, which consistently responded to cGMP, although the currents were generally extremely small. (rupress.org)
  • We used Red ® /ET ® Recombination in combination with rpsL counter-selection to introduce a single point mutation into the E. coli MG1655 genome, one of the widely used bacterial model strains in systems biology. (biomedcentral.com)
  • We used rpsL counter-selection in combination with Red ® /ET ® Recombination to introduce a single point mutation into the kdpA gene locus of the MG1655 strain genome. (biomedcentral.com)
  • Introduction of a single point mutation into kdpA was chosen to demonstrate rpsL based counter-selection in combination with Red ® /ET ® Recombination on the E. coli chromosome. (biomedcentral.com)
Assays3
  • Together with TaqMan ® SNP Genotyping Assays , the resulting QuantStudio™ 3D rare mutation analysis solution helps achieve the high levels of performance required to detect and absolutely quantify mutations present at a very low frequency. (thermofisher.com)
  • Dr. Iain Russell, Sr. Product Manager for TaqMan ® Assays , spoke of the most recent QuantStudio™ 3D enhancements to benefit rare mutation analysis in an interview at the American Society for Human Genetics (ASHG) 2014 annual meeting. (thermofisher.com)
  • Functional studies, including chondrogenesis assays with primary mesenchymal cells, luciferase reporter gene assays and Surface Plasmon Resonance analysis, of the GDF5 W-414R variant in comparison to other GDF5 mutations associated with isolated BDA1 (p.R399C) or SYNS2 (p.E491K) revealed a dual pathomechanism characterized by a gain-and loss-of-function at the same time. (uni-wuerzburg.de)
Hereditary4
  • We recently described a family with neurological findings similar to HSAN (Hereditary sensory and autonomic neuropathy) type V having a point mutation in the Nerve growth factor beta (NGFB) gene. (bmj.com)
  • Point mutations affecting PMP22 can cause hereditary demyelinating and dysmyelinating peripheral neuropathies. (uzh.ch)
  • CGH analysis and VHL mutation analysis of sporadic and hereditary hemangioblastomas point to genetic heterogeneity. (ru.nl)
  • The importance of the TRPV4 channel for human physiology has been highlighted in recent years with the identification of an increasing number of hereditary diseases associated with mutations of this channel. (kuleuven.be)
Subunit1
  • Using gene-targeting technology, we generated mice harboring a subtle point mutation (N265M) in the second transmembrane region of the beta3 subunit of the GABA(A) receptor. (uzh.ch)
Vitro2
  • Coexpression of the A53T and E46K mutations was unable to rescue MSA prion infection in vitro, establishing that MSA α-synuclein prions are conformationally distinct from the misfolded α-synuclein in PD patients. (pnas.org)
  • A male infertility-linked human PLCζ (phospholipase Cζ) mutation introduced into mouse PLCζ completely abolishes both in vitro PIP 2 (phosphatidylinositol 4,5-bisphosphate) hydrolysis activity and the ability to trigger in vivo Ca 2+ oscillations in mouse eggs. (portlandpress.com)
Patients15
  • In the exhaustive study of 42 new FOXF1 mutations in patients with this disorder, most were sporadic and not inherited from parents. (bcm.edu)
  • DGGE screening of 32 apparently unrelated heterozygous FH patients revealed 16 unique different aberrant DGGE patterns in 27 patients, while in a group of 32 normal subjects none of these DGGE patterns could be observed, suggesting that the aberrant patterns represent disease-causing mutations. (tudelft.nl)
  • Analysis of baseline samples from 982 patients revealed that mutations in the BCL2 family are relatively rare events. (bloodjournal.org)
  • Mutational analysis of the PMP22 coding region in two unrelated Dejerine-Sottas patients identified individual missense point mutations present in the heterozygous state. (biomedsearch.com)
  • 26 patients heterozygous for the NGFB-mutation (12 men, mean age 50 (13-90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). (bmj.com)
  • However, only about 40 percent of patients with short telomeres have one of these known mutations. (laboratoryequipment.com)
  • The team discovered ALK mutations in 8% of the tumors, with a higher rate among tumors from older patients and those with high-risk neuroblastoma. (oncologynurseadvisor.com)
  • This will allow easier diagnosis of patients with Parkinson s disease due to mutations in this gene. (michaeljfox.org)
  • It can be a useful tool for other research groups, and could be especially important for recruitment of patients with GBA mutations to clinical trials, because this method, unlike other methods, will be able to identify all forms of GBA mutations. (michaeljfox.org)
  • METHODS 23 patients with FMF and ESRD were analysed for their MEFV mutations and correlated with their corresponding rectal and renal biopsies. (bmj.com)
  • Our findings imply that reduced stability and enhanced dynamics of MBD1 or MBD6 is the origin of ATP7B dysfunction in Wilson disease patients with the G85V or G591D mutation. (diva-portal.org)
  • BCR-ABL Mutations in Chronic Myeloid Leukemia (CML) Patients (pts) with Failure and Warning to First- and Second-Line Tyrosine Kinase Inhibitor (TKI) Therapy: What Is the Advantage of Next-Generation Sequencing (NGS) over Conventional Sequencing? (linkos.cz)
  • CODE PK', vers un registre national des patients déficitaires en pyruvate kinase intraérythrocytaire. (semanticscholar.org)
  • MPL mutations were identified in 8.5% of JAK2 V617F(-) patients and a single V617F(+) patient. (ox.ac.uk)
  • Compared with V617F(-) patients, those with MPL mutations were older with reduced bone marrow cellularity but could not be identified as a discrete clinicopathologic subgroup. (ox.ac.uk)
Potential to induce1
Molecular5
  • In both mouse and man the mutations lie within the dystrophin gene, but the phenotypic differences of the disease in the two species confer much interest on the molecular basis of the mdx mutation. (sciencemag.org)
  • Consequently, our study assembles another part of the molecular puzzle of how loss and gain of function mutations in GDF5 affect bone development in hands and feet resulting in specific types of brachydactyly and SYNS2. (uni-wuerzburg.de)
  • Molecular dynamic simulations demonstrated that the mutations increased backbone fluctuations that extended throughout the domain. (diva-portal.org)
  • Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca. (asm.org)
  • In particular, non-optimal achievement of the key molecular response milestones (10%, 1%, 0.1%) on 1st-line therapy was mostly not associated with BCR-ABL mutations, indicating that other mechanisms of molecular disease persistence have to be investigated in an attempt to optimize therapeutic outcomes. (linkos.cz)
Codons1
  • The influence of p53 status on the efficiency of the principal steps of this repair pathway was investigated after UV-C irradiation in the human ovarian carcinoma cell line IGROV-1 (expressing wild-type p53) and in the derived clone IGROV-1/Pt1 (with p53 mutations at codons 270 and 282). (tudelft.nl)
Inhibitors2
  • Repotrectinib was found to have 10-fold or higher increased potency when compared to proxy investigational and the currently approved TRK inhibitors against wildtype (WT) TRK fusions and solvent-front mutations. (businesswire.com)
  • However, we began to functionally characterize these mutations by taking advantage of an anomaly in the development of inhibitors of human MCL1. (bloodjournal.org)
Mutant3
  • Access to time- and tissue-restricted point mutant models. (genoway.com)
  • 10 As a result of this mutation, about 20% of the mutant pre-mRNAs are processed at the normal splice site, whereas the remaining 80% are spliced at cryptic sites. (bloodjournal.org)
  • point mutation in Pmp22) mutant mice were analyzed at two developmental stages: (i) at postnatal day (P)4, when normal myelination has just started and primary causative defects of the mutations are expected to be apparent, and (ii) at P60, with the goal of obtaining information on secondary disease effects. (uzh.ch)
Strains3
  • E. coli strain PPA305, which has a wild-type PTS system, and PPA316, which utilizes a proton-galactose symport system for glucose uptake, were used as host strains to harbor a phenylalanine overprodn. (epfl.ch)
  • 2. Several recombinants were picked from matings between a single F − p + strain and Hfr strains carrying mutations L8 and L29. (biochemj.org)
  • 5. The same diploid strains were used in experiments to show whether mutations L8 and L29 alleviate the severe catabolite repression caused by growth in glucose plus gluconate. (biochemj.org)
Deletions4
Prediction3
Secretion2
  • Instead, both mutations caused a reduction of phosphatidylcholine secretion compared with the wild-type transfected cell lines. (uniprot.org)
  • Due to the complexity of the biosynthesis, assembly and secretion, collagen II is highly susceptible to mutations leading to disease states which are broadly classified as chondrodysplasias. (uni-koeln.de)
Chromosome 161
Strain6
No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2),...
No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2),... (journals.plos.org)
Improved Adsorption of an Enterococcus faecalis Bacteriophage ΦEF24C with a Spontaneous Point Mutation
Improved Adsorption of an Enterococcus faecalis Bacteriophage ΦEF24C with a Spontaneous Point Mutation (journals.plos.org)
A Point Mutation in cycA Partially Contributes to the D-cycloserine Resistance Trait of Mycobacterium bovis BCG Vaccine Strains
A Point Mutation in cycA Partially Contributes to the D-cycloserine Resistance Trait of Mycobacterium bovis BCG Vaccine Strains (journals.plos.org)
Adenine base editing in an adult mouse model of tyrosinaemia | Nature Biomedical Engineering
Adenine base editing in an adult mouse model of tyrosinaemia | Nature Biomedical Engineering (nature.com)
Α subunits in GABA A receptors are dispensable for GABA and diazepam action | Scientific Reports
Α subunits in GABA A receptors are dispensable for GABA and diazepam action | Scientific Reports (nature.com)
A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes | Nature Genetics
A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes | Nature Genetics (nature.com)
In This Issue | The Journal of Immunology
In This Issue | The Journal of Immunology (jimmunol.org)
Tissue P Systems with Point Mutation Rules | SpringerLink
Tissue P Systems with Point Mutation Rules | SpringerLink (link.springer.com)
How do Cells Read Genes?
How do Cells Read Genes? (learn.genetics.utah.edu)
Familial Parkinson's point mutation abolishes multiple system atrophy prion replication | PNAS
Familial Parkinson's point mutation abolishes multiple system atrophy prion replication | PNAS (pnas.org)
JCI - Volume 91, Issue 4
JCI - Volume 91, Issue 4 (jci.org)
A mutation operator guided by preferred regions for set-based many-objective evolutionary optimization | SpringerLink
A mutation operator guided by preferred regions for set-based many-objective evolutionary optimization | SpringerLink (link.springer.com)
The point mutation which made humanity
The point mutation which made humanity (blogs.discovermagazine.com)
Frontiers | Commentary: Programmable base editing of A·T to G·C in genomic DNA without DNA cleavage | Genetics
Frontiers | Commentary: Programmable base editing of A·T to G·C in genomic DNA without DNA cleavage | Genetics (frontiersin.org)
Multicore OCaml GC - Speaker Deck
Multicore OCaml GC - Speaker Deck (speakerdeck.com)
Is Sustained Macroevolutinary Progres Possible? by Brig Klyce
Is Sustained Macroevolutinary Progres Possible? by Brig Klyce (panspermia.org)
Topic List | News Center | Stanford Medicine
Topic List | News Center | Stanford Medicine (med.stanford.edu)
Tyk2 - Model 13762 | Mouse Models | GEM Collection | Taconic Biosciences
Tyk2 - Model 13762 | Mouse Models | GEM Collection | Taconic Biosciences (taconic.com)
Frontiers | CodY Regulates Thiol Peroxidase Expression as Part of the Pneumococcal Defense Mechanism against H2O2 Stress |...
Frontiers | CodY Regulates Thiol Peroxidase Expression as Part of the Pneumococcal Defense Mechanism against H2O2 Stress |... (frontiersin.org)
ARNT PAS-B has a fragile native state structure with an alternative β-sheet register nearby in sequence space | PNAS
ARNT PAS-B has a fragile native state structure with an alternative β-sheet register nearby in sequence space | PNAS (pnas.org)
Replication Errors Made During Oogenesis Lead to Detectable De Novo mtDNA Mutations in Zebrafish Oocytes with a Low mtDNA Copy...
Replication Errors Made During Oogenesis Lead to Detectable De Novo mtDNA Mutations in Zebrafish Oocytes with a Low mtDNA Copy... (genetics.org)
Multiplexed RNA structure characterization with selective 2′-hydroxyl acylation analyzed by primer extension sequencing (SHAPE...
Multiplexed RNA structure characterization with selective 2′-hydroxyl acylation analyzed by primer extension sequencing (SHAPE... (pnas.org)