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)

*Stepwise mutation model

... rates of mutation than small alleles and including variations that suggest that mutations are split between point mutations ... The original model assumes that if an allele has a mutation that causes it to change in state, mutations that occur in ... The stepwise mutation model (SMM) is a mathematical theory, developed by Motoo Kimura and Tomoko Ohta, that allows for ... For example, it is possible that two individual are identical at a given locus, having the same mutation even from its common ...

*Point mutation

Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of mutation may be increased ... Point mutations in multiple tumor suppressor proteins cause cancer. For instance, point mutations in Adenomatous Polyposis Coli ... mutation in the deoxyribonucleic acid (DNA) that occurs at one point. Point mutations usually take place during DNA replication ... a mutation called a frameshift mutation). Point mutations that occur in non-coding sequences are most often without ...

*Point accepted mutation

... point accepted mutation matrices (PAM matrices) and the PAMn matrix. The term 'point accepted mutation' refers to the mutation ... In particular, silent mutations are not point accepted mutations, nor are mutations which are lethal or which are rejected by ... One of the possible mutations that occurs is the replacement of a single nucleotide, known as a point mutation. If a point ... The term accepted point mutation was initially used to describe the mutation phenomenon. However, the acronym PAM was preferred ...

*Animal model of schizophrenia

ENU introduces missense point mutations; screening for mutations in a particular exon of DISC1 can produce mouse models with ... Sdy mice have homozygous mutations to DTNBP1, and lack the ability to produce dysbindin, heterozygous mutants can be produced ... PPP3CC PPP3CC is a gene in which mutations are risk factors for schizophrenia; knockout animal models have social deficits. ...

*SNP genotyping

"Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)". Nucleic Acids Research 17 (7): ... A SNP is a single base pair mutation at a specific locus, usually consisting of two alleles (where the rare allele frequency is ... cut the genomic sample results in an identifiably larger than expected fragment implying that there is a mutation at the point ... Because DASH genotyping is measuring a quantifiable change in Tm, it is capable of measuring all types of mutations, not just ...

*TUBA1A

The relevant point mutation resulted in S140G; the site of the mutation participates in the N-site of the formed α-tubulin, and ... TUBA1A mutation is common in microlissencephaly Keays et al. describe a mouse with a mutation of the TUBA1A gene induced by N- ... 105 (6 Pt 2): 3065-73. doi:10.1083/jcb.105.6.3065. PMC 2114727 . PMID 3693406. Cowan NJ, Dobner PR, Fuchs EV, Cleveland DW ( ... The S140G mutation resulted in the formation of a "compromised GTP binding pocket". Authors note defects associated with ...

*Ethyl methanesulfonate

This typically produces only point mutations. It can induce mutations at a rate of 5x10−4 to 5x10−2 per gene without ... Mutations induced by EMS can then be studied in genetic screens or other assays. Mutagenesis (molecular biology technique) ... Following subsequent rounds of replication, the original G:C base pair can become an A:T pair (a transition mutation). This ... It produces random mutations in genetic material by nucleotide substitution; particularly by guanine alkylation. ...

*CEBPA

Leroy H, Roumier C, Huyghe P, Biggio V, Fenaux P, Preudhomme C (March 2005). "CEBPA point mutations in hematological ... Characterization of CEBPA mutations in acute myeloid leukemia: most patients with CEBPA mutations have biallelic mutations and ... N-terminal frameshift mutation, and C-terminal mutation. These mutations are most frequently found in acute myeloid leukemia M1 ... Patients with CEBPA mutations have longer remission duration and survival time than those without the mutations. Therefore, the ...

*Short stature homeobox gene

2001). "SHOX point mutations in dyschondrosteosis". J. Med. Genet. 38 (5): 323. doi:10.1136/jmg.38.5.323. PMC 1734877 . PMID ... 1998). "Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis". Nat. Genet. 19 (1): 70-3. ... 1998). "SHOX mutations in dyschondrosteosis (Leri-Weill syndrome)". Nat. Genet. 19 (1): 67-9. doi:10.1038/ng0198-67. PMID ... 2000). "Mutations in short stature homeobox containing gene (SHOX) in dyschondrosteosis but not in hypochondroplasia". Hum. ...

*Kell antigen system

Absence of the XK protein (such as through genetic deletion or through a single point mutation within the coding region of the ... 1998 May 29;273(22):13950-6. "Entrez Gene: KEL". Russo DC, Lee S, Reid ME, Redman CM (Mar 2002). "Point mutations causing the ... a mutation at the splice site of human KEL gene abolishes the expression of Kell blood group antigens". J. Biol. Chem. 276 (13 ... OMIM entry for XK protein Kell at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH KEL protein, human at the US ...

*Demethylase

"KDM6A point mutations cause Kabuki syndrome". Human Mutation. 34 (1): 108-10. doi:10.1002/humu.22229. PMID 23076834. Agger K, ... Deletions and point mutations of KDM6A have been identified as one cause of Kabuki Syndrome, a congenital disorder resulting in ... Mutations to the JmjC domain in Drosophila causes either lethal effects on larval or many developmental defects in those that ... KDM5C mutations (found on the X-chromosome) have also been found in patients with X-linked mental retardation. Depletion of ...

*No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing

1989). "Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)". Nucleic Acids Res. 17: ... In the case of point mutations, oligonucleotides targeted to the lagging strand are designed to alter the either the PAM ... The SCAR-less method is able to induce point mutations, oligonucleotide-mediated deletions, and short sequence insertions with ... Therefore, efficiency can be low (0.1-10% for point mutations; 10−5-10−6 for insertions, deletions, or replacements) and ...

*Blue cone monochromacy

The point mutation is the so-called C203R. The name of the point mutations indicates the position at which mutation has ... Other mutations on genes OPN1LW and OPN1MW that lead to the Blue Cone Monochromacy are constituted by a set of point mutations ... Other point mutations are the P307L and R247X. The last one replaces arginine with the Stop codon, prematurely stopping at ... This type of mutation is named W177R and is a misfolding mutation that, if present on both opsin genes cause cone dystrophy ...

*Indel

... s can be contrasted with a point mutation. An indel inserts and deletes nucleotides from a sequence, while a point ... Tandem-based mutations occur in mouse liver and adipose tissue preferentially as G:C to T:A transversions and accumulate with ... In coding regions of the genome, unless the length of an indel is a multiple of 3, it will produce a frameshift mutation. For ... Indels can also be contrasted with Tandem Base Mutations (TBM), which may result from fundamentally different mechanisms. A TBM ...

*Neurofibromatosis type II

In cases with mutations in the splice-acceptor-region, there is no good correlation to determine. Point mutations may have only ... Patients with frameshift mutations or nonsense mutations suffer poor prognosis. Patients with missense mutations have a better ... Mutations of NF II is presumed to result in either a failure to synthesize Merlin or the production of a defective peptide that ... Mutations in the Schwannomin-gene are thought to alter the movement and shape of affected cells with loss of contact inhibition ...

*Germacrene

Point mutation of (+)-germacrene A synthase from Ixeris dentata. Biotechnol Lett. 2005 Mar;27(5):285-8. Rivero-Cruz B, Rivero- ...

*Germacrene-A synthase

Chang YJ, Jin J, Nam HY, Kim SU (2005). "Point mutation of (+)-germacrene A synthase from Ixeris dentata". Biotechnol. Lett. 27 ...

*Factor XI

Pugh RE, McVey JH, Tuddenham EG, Hancock JF (Mar 1995). "Six point mutations that cause factor XI deficiency". Blood. 85 (6): ... deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations". Proceedings of the ... Imanaka Y, Lal K, Nishimura T, Bolton-Maggs PH, Tuddenham EG, McVey JH (Aug 1995). "Identification of two novel mutations in ... Dossenbach-Glaninger A, Hopmeier P (Jun 2005). "Coagulation factor XI: a database of mutations and polymorphisms associated ...

*Forward genetics

Often hundreds of thousands of mutations are generated. Chemicals like ethylmethanesulfonate (EMS) cause random point mutations ... Mutations can also be generated by insertional mutagenesis. For example, transposable elements containing a marker are ... Eventually the hope is that such screens would reach a large enough scale that most or all newly generated mutations would ... This was initially done by using naturally occurring mutations or inducing mutants with radiation, chemicals, or insertional ...

*Antitermination

Point mutations in BOXA induce premature transcription termination. rrn antitermination requires NusB in vivo, as shown by a ... no point mutations in nusG that block N activity have been isolated. A NusG homolog, RfaH, enhances elongation of several ... and these mutations can be suppressed by additional mutations that restore base pairing. Like lambda N and Q, the PUT sequences ... Strains carrying these mutations are unable to support lytic growth of HK022 but are normal in all other respects tested, ...

*Benzimidazole fungicide

Resistant genotypes with certain point mutations were selected. Mutant pathogens resistant to one benzimidazole fungicide are ... The F200Y and E198A,G,K mutations are the most common. Because of resistance problems, use of benzimidazole fungicides has ...

*AMPD3

... screening for the major point mutation and identification of other mutations". Hum. Mol. Genet. 3 (12): 2243-5. doi:10.1093/hmg ... Yamada Y, Goto H, Ogasawara N (1994). "A point mutation responsible for human erythrocyte AMP deaminase deficiency". Hum. Mol. ... Mutations in this gene lead to the clinically asymptomatic, autosomal recessive condition erythrocyte AMP deaminase deficiency ... a branch point in the adenylate catabolic pathway. This gene encodes the erythrocyte (E) isoforms, whereas other family members ...

*Thyroglobulin

"Thyroglobulin gene point mutation associated with non-endemic simple goitre". Lancet. 341 (8843): 462-4. doi:10.1016/0140-6736( ...

*5-Bromouracil

Thus 5-BrU induces a point mutation via base substitution. This base pair will change from an A-T to a G-C or from a G-C to an ... and can induce DNA mutation in the same way as 2-aminopurine. It is used mainly as an experimental mutagen, but its ...

*Melarsoprol

Resistance can occur with point mutations within this transporter. Resistance has been present since the 1970s. Although ...

*Norovirus

The estimated mutation rate (1.21×10−2 to 1.41 ×10−2 substitutions per site per year) in this virus is high even compared with ... 95 (Pt 2): 278-291. doi:10.1099/vir.0.059634-0. ISSN 1465-2099. PMID 24243731. Clarke IN, Lambden PR (2000). "Organization and ... Tan M, Huang P, Meller J, Zhong W, Farkas T, Jiang X (2003). "Mutations within the P2 domain of norovirus capsid affect binding ... Homozygous carriers of any nonsense mutation in the FUT2 gene are called non-secretors, as no ABH antigen is produced. ...

*T4 rII system

By various crosses of the many different strains exhibited deletions and point mutations, Benzer located each point mutation ... and ordered the point mutations within that sub-region. Benzer also proposed missense and nonsense mutations from his rII ... Some he classified as deletions, others as point mutations. ... One type of mutation in the T4 bacteriophage identified by ... The principal that three sequential bases of DNA code for each amino acid was demonstrated in 1961 using frameshift mutations ...
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 ...
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 ...
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 $$c.182A|G$$
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 ...
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 ...
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 ...
Point Mutation Cusabio can provide you with point mutation, in the original DNA fragments delete, insert or replacement a sequence of DNA and other services. Order Information Email:[email protected] Tele:+86-27-87582341 Fax:+86-27-87196150 Manual:Point mutation Service Contr
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 ...
Aberrant EGFR signaling is a major contributing force to glioma progression and treatment resistance. The most prevalent mutation, EGFRvIII, is an inframe deletion of the extracellular domain, which occurs in the about 40% of glioblastomas and promotes growth and survival of cancer cells. More recently, new point mutations in the extracellular domain of EGFR have been identified by The Cancer Genome Atlas. We are investigating the signaling of these abnormal receptors to identify the basis of their oncogenicity, and taking a systems-level approach at the mRNA and protein level. We have analyzed the EGFRvIII specific signal using shotgun phosphoproteomics based on recovery of tyrosine-phosphopeptides and mass spectrometry. Glioma cell lines expressing EGFRvIII and wild-type EGFR, and with different PTEN backgrounds were compared by this approach. Spectral intensity and count was used in a label-free quantification, and revealed several EGFRvIII-related phosphorylations, which showed a ...
point mutation when transformed in BL21 - posted in Molecular Biology: Hi everyone, I have a problem regarding the transformation into BL21. I have managed to clone my insert into pET15b in a DH5 alpha host cell. But because i need to express the protein, so i transformed my pET15b:insert into BL21. Here comes the problem, when i transformed my plasmid in to BL21 i always get point mutations and insertion mutation in my plasmid sequence. I am 100% sure that my plasmid sequence in DH5 alph...
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) ...
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 ...
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).. ...
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 ...
How is Mutation at Residue 73 abbreviated? M73 stands for Mutation at Residue 73. M73 is defined as Mutation at Residue 73 very rarely.
Previous studies have suggested that prolonged receptor engagement and altered specificity for growth factors are the only outwardly discernable consequences of the S252W and P253R point mutations [15,16,35,36]. It is thus remarkable to observe such dramatic changes in the properties of the receptor molecules defined by clear differences in glycosylation, phosphorylation, direct interaction with FRS2 and downstream MAPK activity. In addition, bearing in mind the proximity of the point mutations and the structurally subtle nature of the changes which these produce in growth factor recognition, it is also intriguing to observe the profound changes in functional properties between SWFGFR2 and PRFGFR2 themselves.. The receptors appear as more than one band on an immunoblot, which most probably reflects differences in glycosylation. It is not clear mechanistically how this altered glycosylation might impinge on intracellular signalling, and there is no structural basis for glycosylation affecting the ...
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 ...
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 / ...
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 ...
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 ...
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 ...
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
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 ...
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 ...
Looks like an A to me, so its a real mutation. The next question is do we care about this mutation. The answer to that is always yes. Any mutation has the potential to be fatal, and is worthy of noting in your sequencing log and in your notebook. It doesnt necessarily mean that we throw out the plasmid. Very often when we clone genes (from genomic DNA especially), you get mutations. The variation from the expected sequence could be an error in the pubmed file, or it could just be that the particular sample from which you obtained the genomic DNA has drifted a little from the strain the people who sequenced it originally had in their freezer. Most (~90%) of point mutations are neutral. Before we go further, lets describe what types of mutations exist: Large Deletions and Insertions These are what the name sounds like. Either a stretch of sequence is missing or inserted into expecting sequence. This is almost always going to result in a non-functional sequence. If it shows up while cloning, ...
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 ...
Point mutation of Gln136 affects antigen responsiveness. Hybridomas expressing the wt TCR-α chain and wt or mutant β chains were stimulated with DAP.3-DR1-
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
Use a point mutation mouse Knockin to circumvent complex phenotypes arising from complete knockout models (e.g. signaling pathway problems, cross-reactivity).
A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans.: Monogenic deficiency diseases provide unique opportunities to define t
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 ...
Thank you for your comment!. ,Would there not also be a selective pressure to accurately judge the arguments of others?. Yes, that is half our theory.. ,If one persuades many, to their ruin, one profits, but many lose. Does the gain of one outweigh the losses of the many? And if an indiscriminate suspicion of glib arguers were to be selected for, what of the advantages of cooperation? Surely, each argument is meant not only to be told, but to be listened to. Are the listeners not best served by the most accurate judgements?. Yes. For communication to be stable in any species, it has to benefit both senders and receivers, it cant just be manipulation.. ,It has long seemed to me the easiest solution to why our reasoning is flawed is that computation is costly. It costs energy, attention, a huge and delicate brain straining at the limits of anatomical possibility, and time to think. It is designed by a blind and fallible process, out of materials not best suited to the task.. Two problems with ...
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 ...
There are several kinds of gene mutations, and also several kinds of back mutations that can cancel out the effects of a previous mutation. Genetically speaking, spontaneous self-correction of gene mutations is a regular occurrence.
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 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.
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 ...
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 ...
DNA Mutations. Biology - 9 th Grade Chapter 10. How does it happen???. Environmental Influences such as: Chemicals or UV Rays Inherited: mutations can be passed down from parent to offspring During copying of DNA , mistakes can occur. Types of Mutations. Slideshow 1888684 by ikia
Looks like an A to me, so its a real mutation. The next question is do we care about this mutation. The answer to that is always yes. Any mutation has the potential to be fatal, and is worthy of noting in your sequencing log and in your notebook. It doesnt necessarily mean that we throw out the plasmid. Very often when we clone genes (from genomic DNA especially), you get mutations. The variation from the expected sequence could be an error in the pubmed file, or it could just be that the particular sample from which you obtained the genomic DNA has drifted a little from the strain the people who sequenced it originally had in their freezer. Fortunately, most (~90%) of point mutations do not alter the function of the protein product. Before we go further, lets describe what types of mutations exist: Large Deletions and Insertions These are what the name sounds like. Either a stretch of sequence is missing or inserted into the expected sequence. This is almost always going to result in a ...
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 ...
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 ...
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?. ...
This paper presents a mutation analysis tool based on a reflective macro system. Mutation analysis is a powerful and computationally expensive technique th
Characterization of the effect of IVS 5 (c.574+1G|C) and IVS16 (c.2206-2A|G) point mutations on NTRK1 splicing. A. Schematic partial representation of NTR
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.
Chromosomal aberrations, point mutation, deletion and addition of nucleotides, loss of function and gain of function mutations are some of the examples of different type of Genetic mutations. The term mutation…. ...
In order to make a mutation the molecule needs to be an ICM Object. Right click on the amino acid residue you wish to mutate and choose Advanced and then select one of the mutation options. For the extended list of unusual amino acids the codes in the drop down box refer to the codes at the PDB Ligand Expo website here http://ligand-expo.rcsb.org/ ...
However Romesberg and his colleagues believe that the cells not only the passive victims of random mutations, but have ways of initiating mutations in their own
What is the difference between Mutation and Variation? Mutation occurs due to the errors in DNA replication and exposure to UV or chemicals; variation is...
Daily News Thousands of Mutations Accumulate in the Human Brain Over a Lifetime Single-cell genome analyses reveal the amount of mutations a human brain cell will collect from its fetal beginnings until death.. ...
Daily News Thousands of Mutations Accumulate in the Human Brain Over a Lifetime Single-cell genome analyses reveal the amount of mutations a human brain cell will collect from its fetal beginnings until death.. ...
Test Run: Super-Simple Mutation Testing. Mutation testing is known for being difficult and expensive, but were here to show you a real-world system you can build in just a few hours with a
An inactivating mutation has been identified in the KISS1 gene in a consanguineous family, a mutation that results in failure of pubertal progression.
... is a technique that software engineers can use to measure the effectiveness of their overall testing effort. Suppose a team of testers has created many individual tests; lets call the collection of tests the test suite. In mutation testing, the original system/program under test is mutated to create a faulty version called a…
Get tickets to see The Soul Mutation live. Explore the 2017 tour dates schedule for The Soul Mutation. Download the Bandsintown app to never miss a show.
Do NOT use Balance Reward Points to pay for a transaction where you would earn points on an offer that requires a certain dollar amount purchased. You will not get the new points. (You can earn points on a Buy X number of a product offer even if you redeem points ...
CDKN2A encodes for three splice variants, two of which serve as inhibitors of CDK4-kinase. Mutations of CDKN2A are present in a wide variety of tumors.
CDKN2A encodes for three splice variants, two of which serve as inhibitors of CDK4-kinase. Mutations of CDKN2A are present in a wide variety of tumors.
Read about the surprising finding that DNA mutations linked to Parkinsons disease were found most in liver, immune, fat, and developing cells.
gene mutation definition: (genetics) a mutation because of an intramolecular reorganization of a gene; (genetics) a mutation considering an intramolecular reorganization of a gene; (genetics) a mutation…
Where do those mutants come from anyway? Ive recently seen X-Men First Class, and what a trip of a movie. When wondering about who to credit for super-genes and super-powers, we would normally turn to good old Dad. It was long thought that mutations were more likely to be inherited from men. Maybe we would…
Power Lube Industrials MEMOLUB EPC is a single-point or multi-point battery powered lubricator which can be wired to an external switch.
Power Lube Industrials MEMOLUB EPS is an externally powered single-point or multi-point lubricator with 52 programmable duration settings.
mutation: An alteration in the genetic material (the genome) of a cell of a living organism or of a virus that is more or less permanent and that can be transmitted to the cells or the...
You may have a twinge of doubt when your code passes all its unit tests. They might say that the code is OK, but if the code is definitely incorrect, will the unit tests fail? Mutation Testing is a relatively simple, but ingenious, way of checking that your tests will spot the fact that your code is malfunctioning. It is definitely something that every developer should be aware of.
HI Rich, I saw somewhere that you said you do not recommend low protein for CBS mutation. My doc has recommended that for me and I have not done it...
Docu-fiction, docu-réalité, web-documentaire... Le documentaire, qui existe depuis toujours à la télévision, est aujourdhui en pleine mutation. Rencontre avec Cédric Mal, directeur de publication du Blog documentaire. | Visioni e Linguaggi
Compared to all of our products the Mutation and Abstraction CDs sell the least copies. They were created by a friend, so we sell them for him ...
Kaufen Sie das Actionspiel .hack: Mutation (PS2) bei GamePro.de billiger. Der Preisvergleich zeigt Ihnen das jeweils günstigste Angebot zu .
Inflicts 11100 to 12900 Nature damage and grants a harmful mutation. This is an Uncategorized Spell. Added in World of Warcraft: Mists of Pandaria.
action makes the distinction between actions (something that modifies the state) and reactions (the state needs to trigger a side effect automatically) very clear ...
Finds the word(s) if they exist anywhere in the product information. To restrict the search to a fixed phrase, "put it in quotes ...
Hmm....what relevancy does this have to exercise? None. In the future would you mind posting irrelevant things like this in the lounge. ...
Question: What is the root of mans psychological and physical illnesses? And how can a person not studying Kabbalah influence these processes? Can you
Recorded in 1969 during a rehearsal, "The Intergalactic Thing" introduces about a dozen pieces from the Sun Ra songbook that never got performed ...
The evening will also feature a support band and ZAPPATiKA will take to the stage around 22:30h for a 2 hour show featuring both their own songs and lots of Zappa tunes too ...
Update: Ive still never heard a peep from the company (and Ive tried contacting them a few more times over the past few months), but …
Если Вы не достигли совершеннолетия, или Вам запрещено просматривать подобный материал в вашей стране, пожалуйста, покиньте этот сайт.. Обмен трафиком ...
To analyze the phenotype of cells lacking the vacuolar ATPase, we inactivated the vma-1 gene, which encodes the catalytic subunit of the enzyme. Because preliminary experiments suggested the vma-1 gene was essential, we developed a method of simultaneously inactivating the gene and complementing it with a functional copy. We call this method repeat-induced point mutation (RIP) & Rescue. Two strains, both of which contained an extra copy of the vma-1 gene, were mated. Progeny that had inherited a functional copy of the gene at an ectopic site in the genome were selected. In some of these progeny the endogenous vma-1 gene had been altered by the RIP process. Sequencing showed the endogenous vma-1 gene had been inactivated by multiple point mutations. Progeny from strains with an inactive endogenous vma-1 gene were inviable unless a functional copy of the gene cosegregated, indicating that the vacuolar ATPase is essential in Neurospora crassa.. ...
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 ...
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 ...
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 ...
A distrofina é uma proteína do complexo distrofina-glicoproteínas que liga o citoesqueleto da fibra muscular à matriz extracelular, através da membrana celular. A deficiência nesta proteína é a causa primária de um dos mais graves tipos de distrofia muscular. Foi primeiramente identificada por Louis Kunkel, em 1987, a seguir à descoberta do gene mutante causador da distrofia muscular de Duchenne. A distrofina é produzido pelo maior gene conhecido até à data, medindo 2,5 Mb (0,1% do genoma humano). O locus genético é Xp21 e possui 79 exões, produzindo um mRNA de 14,6 Kb e uma proteína com mais de 3.500 resíduos de aminoácidos. Foi demonstrada a interacção da distrofina com beta-1-sintrofina, alfa-1-sintrofina e alfa-distrobrevina. Roberts RG, Gardner RJ, Bobrow M (1994). «Searching for the 1 in 2,400,000: a review of dystrophin gene point mutations». Hum. Mutat. 4 (1): 1-11. PMID 7951253. doi:10.1002/humu.1380040102 !CS1 manut: Nomes múltiplos: lista de autores (link) ...
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 ...
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 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 ...
Affordable ($69) software for automated DNA sequence assembly, contig assembly, mutation detection, chromatogram editor. Sequence assembly, assemble DNA chromatograms, find heterozygous point mutations, automatic end clip
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 ...
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 ...
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 ...
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% ...
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% ...
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, ...
Page 1 of 2 - Odd point mutations - posted in Molecular Cloning: Lately Ive been doing a lot of cloning into pBluescript and some derivatives made in our lab. The plasmid is then going into XL1-Blue MRF cells by electroporation. This has been a successful and efficient strategy in the past, but lately, sequencing of the plasmid constructs has shown a seemingly inordinate amount of point mutations in the sequence. I originally asked a question regarding this a couple months ago,...
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 ...
The final 3D model used to generate our TE dimer was based on the Mus musculus NEUROD1/E47 complex (see Methods; Table 1). After aligning the four protein sequences using the ClustalW software [40], we mainly observed that NEUROD1 is composed of 357 amino acids with a bHLH domain containing amino acids 101-157, whereas TWIST1 is composed of 202 amino acids with a bHLH domain encompassing amino acids 108-164 (Fig. 1a). The crucial, strong physicochemical R154 residue of TWIST1 is a serine, an asparagine and a glutamine residue in E12, murine NEUROD1 and murine E47, respectively (Fig. 1a). As speculated by Spicer et al. [37], we could clearly observe that the substitution of the arginine residue with a proline residue, the lateral side chains of which contain a cycle known to destabilize the alpha helix, in this crucial position at the dimerization interface of TE altered the conformation of the dimer (Fig. 1b and c). Indeed, while the NH2 groups of arginine are positioned to carry out H-bonds ...
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
Although many organ systems are affected by mitochondrial (mt) DNA point mutations, the nervous system is particularly vulnerable. Maternally inherited mtDNA point mutations may cause chronic progressive encephalopathies and mental retardation. Patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome have the A3243G point mutation and elevated brain lactate levels. Research has shown that lactic acidosis is associated with progressive impairment in patients with MELAS. This study will evaluate the effectiveness of DCA in lowering lactate levels and slowing the progression of MELAS.. Patients with the A3243G mitochondrial mutation and who have had either a stroke or a seizure will be enrolled in this study. Patients will be randomized to receive either DCA or a placebo. At a predetermined time point, patients receiving DCA will be switched to placebo and patients receiving placebo will be switched to DCA. Patients will have study visits ...
We describe a Chinese family with generalized atrophic benign epidermolysis bullosa (GABEB), a non-lethal variant of junctional epidermolysis bullosa. The proband was an offspring of consanguineous parents, had generalized blisters since birth and developed severe alopecia during early childhood, Ultrastructural examination of the proband′s skin revealed fissures in the lamina lucida. Immunofluorescence assays using a monoclonal antibody recognizing the extracellular domain or the 180 kDa buttons pemphigoid antigen (BPAG2) showed loss of fluorescent signal in the basal membrane zone of the skin. DNA sequencing revealed a homozygous C-to-G transversion at nucleotide position 899 in exon 11 of the COL17A1 gene, which encodes BPAG2. This mutation results in serine to cysteine at position 265, which is located in a highly conserved region of the intracellular domain of BPAG2. We showed that the proband′s father was heterozygous for this mutation. In addition, we found a novel polymorphic ...
Genetic abnormalities that involve the PDGFRA gene cause a type of blood cell cancer called PDGFRA-associated chronic eosinophilic leukemia. This condition is characterized by an increased number of eosinophils, a type of white blood cell involved in allergic reactions. These genetic abnormalities are somatic mutations, which are mutations acquired during a persons lifetime that are present only in certain cells. The most common of these genetic abnormalities is a deletion of genetic material from chromosome 4 that brings together parts of two genes, FIP1L1 and PDGFRA, creating the FIP1L1-PDGFRA fusion gene. Occasionally, genes other than FIP1L1 are fused with the PDGFRA gene. Mutations that change single DNA building blocks in the PDGFRA gene (point mutations) can also cause this condition, although these mutations are seen very rarely.. The protein produced from the FIP1L1-PDGFRA fusion gene (as well as other PDGFRA fusion genes) has the function of the PDGFRA protein. However, unlike the ...
Describes how Factor V Leiden mutation and PT 20210 mutation tests are used, when Factor V Leiden mutation and PT 20210 mutation tests are ordered, and what the results of Factor V Leiden mutation and PT 20210 mutation tests might mean
THAP1 mutations have been shown to be the cause of DYT6. A number of different mutation types and locations in the THAP1 gene have been associated with a range of severity and dystonia phenotypes, but, as yet, it has been difficult to identify clear genotype phenotype patterns. Here, we screened the THAP1 gene in a further series of dystonia cases and evaluated the mutation pathogenicity in this series as well as previously reported mutations to investigate possible phenotype-genotype correlations. THAP1 mutations have been identified throughout the coding region of the gene, with the greatest concentration of variants localized to the THAP1 domain. In the additional cases analyzed here, a further two mutations were found. No obvious, indisputable genotype-phenotype correlation emerged from these data. However, we managed to find a correlation between the pathogenicity of mutations, distribution, and age of onset of dystonia. THAP1 mutations are an important cause of dystonia, but, as yet, no ...
Looking for online definition of factor V Leiden mutation in the Medical Dictionary? factor V Leiden mutation explanation free. What is factor V Leiden mutation? Meaning of factor V Leiden mutation medical term. What does factor V Leiden mutation mean?
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a disorder that affects several body systems and usually has its onset in childhood. It is characterized by a progressive encephalopathy and stroke-like episodes leading to disability. MELAS is caused by a genetic mutation and has been associated with at least 6 different point mutations on mitochondrial DNA (mt DNA). The most common mutation for MELAS is an A-to-G switch at nucleotide 3243 in the strand of mitochondrial DNA. Clinical symptoms are determined by various factors including the amount (percentage) of point mutations in each organ (including the brain).. In individuals affected by MELAS, early psychomotor development, involving physical and mental processes, is usually normal, but short stature is common. The first onset of symptoms is frequently between the ages of two and ten years. Common initial symptoms include seizures, recurrent headaches, lack of appetite (anorexia), and recurrent vomiting. ...
Lebers hereditary optic neuropathy (LHON) or Leber hereditary optic atrophy is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. LHON is only transmitted through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Men cannot pass on the disease to their offspring. Clinically, there is an acute onset of visual loss, first in one eye, and then a few weeks to months later in the other. Onset is usually young adulthood, but age ...

mutation: Point Mutations | FactMonstermutation: Point Mutations | FactMonster

In a frameshift mutation, a nucleotide is added or ... mutation: Point Mutations mutation: Point Mutations. Enter your ... Occasionally a mutation can be offset by either another mutation on the same gene or on another gene that suppresses the effect ... For example, the inherited sickle cell disease is the result of a mutation that results in the substitution of the amino acid ... A single gene mutation may have many effects if the enzyme it controls is involved in several metabolic processes. ...
more infohttps://www.factmonster.com/encyclopedia/science/biology/genetics/mutation/point-mutations

Tissue P Systems with Point Mutation Rules | SpringerLinkTissue P Systems with Point Mutation Rules | SpringerLink

Alhazov A., Freund R., Ivanov S., Verlan S. (2019) Tissue P Systems with Point Mutation Rules. In: Hinze T., Rozenberg G., ...
more infohttps://link.springer.com/chapter/10.1007%2F978-3-030-12797-8_4

Point mutation - WikipediaPoint mutation - Wikipedia

Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of mutation may be increased ... Point mutations in multiple tumor suppressor proteins cause cancer. For instance, point mutations in Adenomatous Polyposis Coli ... mutation in the deoxyribonucleic acid (DNA) that occurs at one point. Point mutations usually take place during DNA replication ... a mutation called a frameshift mutation). Point mutations that occur in non-coding sequences are most often without ...
more infohttps://en.wikipedia.org/wiki/Point_mutation

The point mutation which made humanityThe point mutation which made humanity

There was no point where mutation made humanity. But there was one where long mixed hybridization between Neaderthals and near ... The point mutation which made humanity. By Razib Khan , August 16, 2011 1:30 am ... Steve Hsu points me to a piece in The New Yorker on the science and personality of Svante Pääbo. The personality part includes ... Razib, fantastic points. and I agree with you about the bisexuality line. It seemed gratuitous, especially since the article ...
more infohttp://blogs.discovermagazine.com/gnxp/2011/08/the-point-mutation-which-made-humanity/

Familial Parkinsons point mutation abolishes multiple system atrophy prion replication | PNASFamilial Parkinson's point mutation abolishes multiple system atrophy prion replication | PNAS

Familial Parkinsons point mutation abolishes multiple system atrophy prion replication. Amanda L. Woerman, Sabeen A. Kazmi, ... Familial Parkinsons point mutation abolishes multiple system atrophy prion replication Message Subject (Your Name) has sent ... To investigate this hypothesis, we infected cell lines expressing PD-causing point mutations in α-synuclein with MSA patient ... This alteration is consistent with the inability of the A53T mutation to rescue the effects of the E46K mutation in vitro. ...
more infohttp://www.pnas.org/content/115/2/409.full

Multiple point mutations - Molecular BiologyMultiple point mutations - Molecular Biology

Multiple point mutations - (Sep/19/2006 ). Hi All,. Was wondering whether anyone has a protocol for doing multiple point ... I tried doing two at once, and I only got one mutation to take. ... mutations in a single PCR reaction doing an inverse PCR ...
more infohttp://www.protocol-online.org/biology-forums/posts/20309.html

MAESTRO--multi agent stability prediction upon point mutations.  - PubMed - NCBIMAESTRO--multi agent stability prediction upon point mutations. - PubMed - NCBI

Data are given for the three main single point mutation sets (SP1, SP3, SP4) as well as the multi-point mutation set (MP). The ... iii) It provides high throughput scanning for multi-point mutations where sites and types of mutation can be comprehensively ... MAESTRO--multi agent stability prediction upon point mutations.. Laimer J1,2, Hofer H3, Fritz M4, Wegenkittl S5, Lackner P6. ... Point mutations can have a strong impact on protein stability. A change in stability may subsequently lead to dysfunction and ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/25885774

Multipyrene Tandem Probes for Point Mutations Detection in DNAMultipyrene Tandem Probes for Point Mutations Detection in DNA

... Svetlana A. Kholodar, Darya S. Novopashina, Mariya I. ... N. N. Dioubankova, A. D. Malakhov, D. A. Stetsenko, and V. A. Korshun, "Detection of point mutations using pyrene-labeled DNA ...
more infohttps://www.hindawi.com/journals/jna/2013/860457/ref/

TNO Repository search for: subject:point mutationTNO Repository search for: subject:'point mutation'

Missense mutation · Mutational analysis · Netherlands · Nonsense mutation · Onset age · Point mutation · Polymerase chain ... and six missense mutations. Six of the mutations have been previously reported, while ten are novel mutations. These results ... A large number of genetic aberrations (n = 978), including point mutations (n = 833), deletions (n = 126) and insertions (n = ... Point Mutation · Receptors, LDL · Triglycerides To investigate the relative roles of the LDL receptor- and non-LDL receptor- ...
more infohttps://repository.tudelft.nl/search/tno/?q=subject%3A%22point%20mutation%22

Structural Consequences of Point Mutations in Nine Human HPRT Variants | SpringerLinkStructural Consequences of Point Mutations in Nine Human HPRT Variants | SpringerLink

Davidson B.L., Palella T.D., Fujimori S., Kelley W.N. (1989) Structural Consequences of Point Mutations in Nine Human HPRT ... Genetic evidence for identical mutations in two partially deficient subjects. J. Clin. Invest. In Press (1988).Google Scholar ...
more infohttps://link.springer.com/chapter/10.1007/978-1-4684-5673-8_22

SNV vs point mutation? - Biology Forum | Biology-Online Dictionary, Blog & ForumSNV vs point mutation? - Biology Forum | Biology-Online Dictionary, Blog & Forum

My professor seems to distinguish an SNP from an SNV from a point mutation.. I seemed to think that an SNV and a point mutation ... SNV vs point mutation?. Discussion of all aspects of biological molecules, biochemical processes and laboratory procedures in ... So, what is the difference between a single nucleotide variant (SNV) and a point mutation?. I cant seem to get it. ...
more infohttps://www.biology-online.org/biology-forum/viewtopic.php?t=36117

Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples.  - PubMed - NCBISensitive detection of somatic point mutations in impure and heterogeneous cancer samples. - PubMed - NCBI

Overview of somatic point mutation detection using MuTect.. MuTect takes as input tumor (T) and normal (N) next generation ... Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples.. Cibulskis K1, Lawrence MS, Carter ... Benchmarking mutation detection methods. (a) Comparison of sensitivity as a function of tumor sequencing depth and mutation ... Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/23396013?dopt=Abstract

PCNT point mutations and familial intracranial aneurysms | NeurologyPCNT point mutations and familial intracranial aneurysms | Neurology

PCNT point mutations and familial intracranial aneurysms. Oswaldo Lorenzo-Betancor, Patrick R. Blackburn, Emily Edwards, Rocío ... PCNT point mutations and familial intracranial aneurysms. Oswaldo Lorenzo-Betancor, View ORCID ProfilePatrick R. Blackburn, ...
more infohttps://n.neurology.org/content/91/23/e2170/tab-article-info

Mutational spectrometry: a general approach for hot-spot point mutations in selectable genes. | PNASMutational spectrometry: a general approach for hot-spot point mutations in selectable genes. | PNAS

Mutational spectrometry: a general approach for hot-spot point mutations in selectable genes.. P Keohavong and W G Thilly ... Mutational spectrometry: a general approach for hot-spot point mutations in selectable genes. ... Mutational spectrometry: a general approach for hot-spot point mutations in selectable genes. ... Mutational spectrometry: a general approach for hot-spot point mutations in selectable genes. ...
more infohttps://www.pnas.org/content/89/10/4623?ijkey=a87e29da64421ccd8b9527ecb2b8dee27ab57e12&keytype2=tf_ipsecsha

FLEx Inducible Point Mutation | Genetically Modified Models | genOwayFLEx Inducible Point Mutation | Genetically Modified Models | genOway

FLEx: Inducible Point Mutation. TET On/Off Systems. IRES: Co-Expression Models. Quick Knockin: Rosa26 / Hprt. RMCE. ... FLEx: Inducible Point Mutation. FLEx technology allows scientists to induce the expression of a mutated gene or a reporter gene ... Access to time- and tissue-restricted point mutant models.. This technique has become the gold standard for the generation of ... With FLEx mice scientists can reproduce a particular pathology that is triggered by a mutation and that normally manifests in ...
more infohttps://www.genoway.com/technologies/flex-inducible-point-mutation.htm

Myeloma Patient-Derived MCL1 Point Mutations Can Influence MCL1-Inhibitor Function | Blood JournalMyeloma Patient-Derived MCL1 Point Mutations Can Influence MCL1-Inhibitor Function | Blood Journal

... mutations were also rare with no mutations in BCL2, BCL2L1 (BCLX) and BCL2L10 (BCLB). A single sample had a mutation in BCL2A1 ... Myeloma Patient-Derived MCL1 Point Mutations Can Influence MCL1-Inhibitor Function. Brandon Chen, Wong Pamela, Daniel Auclair, ... Myeloma Patient-Derived MCL1 Point Mutations Can Influence MCL1-Inhibitor Function. Brandon Chen, Wong Pamela, Daniel Auclair, ... Myeloma Patient-Derived MCL1 Point Mutations Can Influence MCL1-Inhibitor Function. Brandon Chen, Wong Pamela, Daniel Auclair, ...
more infohttp://www.bloodjournal.org/content/132/Suppl_1/951?sso-checked=true

Point Mutation in Essential Genes with Loss or Mutation of the Second Allele | JEMPoint Mutation in Essential Genes with Loss or Mutation of the Second Allele | JEM

Point Mutation in Essential Genes with Loss or Mutation of the Second Allele. Gabriele B. Beck-Engeser, Paul A. Monach, Dominik ... Point Mutation in Essential Genes with Loss or Mutation of the Second Allele ... Interestingly, a somatic tumor-specific point mutation in EF-2 was found to be the target of a CD8+ T cell response to a human ... In the case of 6139B, the two alleles of L26 have different point mutations (position 22P→S and position 96H→Y), with no wt ...
more infohttp://jem.rupress.org/content/194/3/285?ijkey=571003195646860517b9b791bc0b310755dd1bcc&keytype2=tf_ipsecsha

Reversed Enantiopreference of an omega-Transaminase by a Single-Point MutationReversed Enantiopreference of an omega-Transaminase by a Single-Point Mutation

A single-point mutation, V328A, turn the (S)-selective omega-transaminase into an (R)-selective enzyme. This switch in ... Reversed Enantiopreference of an omega-Transaminase by a Single-Point Mutation. Svedendahl, Maria KTH, School of Biotechnology ... By combining these mutations, five enzyme variants are created. The performance of these variants is explored using a model ...
more infohttp://kth.diva-portal.org/smash/record.jsf?pid=diva2:374790

Point mutation - WikipediaPoint mutation - Wikipedia

Repeat-induced point mutation. In molecular biology, repeat-induced point mutation or RIP is a process by which DNA accumulates ... Wikimedia Commons has media related to Point mutation.. *Point+Mutation at the US National Library of Medicine Medical Subject ... Specific diseases caused by point mutations. Cancer. Point mutations in multiple tumor suppressor proteins cause cancer. For ... Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of mutation may be increased ...
more infohttp://www.bioscience.ws/encyclopedia/index.php?title=Point_mutation

Aphid Thermal Tolerance Is Governed by a Point Mutation in Bacterial SymbiontsAphid Thermal Tolerance Is Governed by a Point Mutation in Bacterial Symbionts

... Helen E Dunbar, Alex C. C Wilson,¤ Nicole R ... The first such mutation occurred in January 2001, and the same mutation recurred in October 2005 in a different line (Figure 3 ... and is about 1,000-fold higher than per-site estimates of mutation [22]. Furthermore a genome-wide screen of Buchnera mutations ... Under this scenario of mutation-selection balance, a frequency of 10% or more would imply an implausibly high mutation rate for ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC1847839/?lang=en-ca

The molecular basis of muscular dystrophy in the mdx mouse: a point mutation | ScienceThe molecular basis of muscular dystrophy in the mdx mouse: a point mutation | Science

The molecular basis of muscular dystrophy in the mdx mouse: a point mutation ... The molecular basis of muscular dystrophy in the mdx mouse: a point mutation ... The molecular basis of muscular dystrophy in the mdx mouse: a point mutation ... The molecular basis of muscular dystrophy in the mdx mouse: a point mutation ...
more infohttps://science.sciencemag.org/content/244/4912/1578

Dejerine-Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene.Dejerine-Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene.

These findings suggest that Dejerine-Sottas syndrome can result from dominant point mutation alleles of PMP22.. ... or from PMP22 point mutation. Mutational analysis of the PMP22 coding region in two unrelated Dejerine-Sottas patients ... identified individual missense point mutations present in the heterozygous state. ...
more infohttp://www.biomedsearch.com/nih/Dejerine-Sottas-syndrome-associated-with/8275092.html

A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration. | Sigma-AldrichA point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration. | Sigma-Aldrich

A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration.. [Satoshi Nojima ... In humans, mutations in Sema4A are thought to contribute to retinal degenerative diseases. Here we generate a series of knock- ... The F350C mutation results in abnormal localization of the Sema4A protein, leading to impaired endosomal sorting of molecules ... in mouse lines with corresponding mutations (D345H, F350C or R713Q) in the Sema4A gene and find that Sema4A(F350C) causes ...
more infohttps://www.sigmaaldrich.com/catalog/papers/23360997

A novel NGFB point mutation, a phenotype study of heterozygous patients | Journal of Neurology, Neurosurgery & PsychiatryA novel NGFB point mutation, a phenotype study of heterozygous patients | Journal of Neurology, Neurosurgery & Psychiatry

... type V having a point mutation in the Nerve growth factor beta (NGFB) gene. The homozygous genotype gives disabling symptoms. ... Conclusions: The NGFB mutation in its heterozygous form results in a milder disease than in homozygots with a variable clinical ... Methods: 26 patients heterozygous for the NGFB-mutation (12 men, mean age 50 (13-90) years) were examined clinically and ... without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined ...
more infohttp://jnnp.bmj.com/content/early/2008/04/17/jnnp.2007.136051

A Single Point Mutation Controls the Cholesterol Dependence of Semliki Forest Virus Entry and Exit | JCBA Single Point Mutation Controls the Cholesterol Dependence of Semliki Forest Virus Entry and Exit | JCB

A Single Point Mutation Controls the Cholesterol Dependence of Semliki Forest Virus Entry and Exit. Malini Vashishtha, Thomas ... The most surprising finding of this study is that a single point mutation in E1 substitutes for the specific cholesterol ... A Single Point Mutation Controls the Cholesterol Dependence of Semliki Forest Virus Entry and Exit ... Mutation Responsible for Cholesterol Independence. To define the mutation that confers srf cholesterol independence, we ...
more infohttp://jcb.rupress.org/content/140/1/91
  • Here we present MuTect, a method that applies a Bayesian classifier to detect somatic mutations with very low allele fractions, requiring only a few supporting reads, followed by carefully tuned filters that ensure high specificity. (nih.gov)
  • To observe point mutational spectra with a high degree of precision, independent large cultures of human lymphoblastoid cells were treated with a mutagen, benzo[a]pyrene diol epoxide, and mutants at the HPRT gene were selected en masse by 6-thioguanine resistance. (pnas.org)
  • The variation among independent experiments is consistent with the numerical expectation that all 16 mutations fulfill reasonable statistical criteria for mutational hot spots. (pnas.org)
  • The agreement with data from various systems using clone-by-clone analysis shows that the protocol reported herein can be a useful tool to study hot-spot point mutational spectra for DNA sequences for which phenotypic selection systems exist. (pnas.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)
  • 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)
  • a ) Sensitivity and specificity of MuTect for mutations with an allele fraction of 0.2, tumor depth of 30x and normal depth of 30x using various values of the LOD threshold ( θ T ) (0.1 ≤ θ T ≤ 100). (nih.gov)
  • These results provide evidence that a point mutation of a cytokine receptor has the potential to induce autoimmune disease. (rupress.org)
  • An average of 1.6 x 10(4) 6-thioguanine-resistant mutants were created per experiment and the kinds, positions, and numbers of the most frequent mutations were examined in exon 3 of the HPRT gene by using a high-fidelity polymerase chain reaction and denaturing gradient gel electrophoresis. (pnas.org)
  • A single gene mutation may have many effects if the enzyme it controls is involved in several metabolic processes. (factmonster.com)
  • Hi All, Was wondering whether anyone has a protocol for doing multiple point mutations in a single PCR reaction doing an inverse PCR technique such as Quikchange. (protocol-online.org)
  • The predictive power of MAESTRO for single point mutations and stabilizing disulfide bonds is comparable to similar methods. (nih.gov)
  • Regression results for MAESTRO on the single mutation data sets SP1 (left) and SP3 (right). (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)
  • A single sample had a mutation in BCL2A1 (A1) while 2 samples had mutations in BCL2L2 (BCLW). (bloodjournal.org)
  • A single-point mutation, V328A, turn the (S)-selective omega-transaminase into an (R)-selective enzyme. (diva-portal.org)
  • Studying Buchnera gene expression in pea aphids, we identified a recurring mutation (a single-base deletion) in the transcriptional promoter of the small heat-shock protein, ibpA . (pubmedcentralcanada.ca)
  • This mutation arose and was fixed twice in sublines derived from a single female aphid in the lab and kept at constant 20 °C. Experiments using aphid lines that differed only in the presence of this Buchnera mutation revealed that it eliminates the ibpA transcriptional response to heat shock and affects ibpA expression at low temperatures. (pubmedcentralcanada.ca)
  • Compared with other methods, MuTect has higher sensitivity with similar specificity, especially for mutations with allelic fractions as low as 0.1 and below, making MuTect particularly useful for studying cancer subclones and their evolution in standard exome and genome sequencing data. (nih.gov)
  • The calculated sensitivity using a model of independent sequencing errors and accurate read placement with uniform Q35 base quality scores (solid lines) are shown as well as results from the virtual tumor approach (circles) and the downsampling of validated colorectal mutations (diamonds). (nih.gov)
  • The V249L, N223S and R214Q mutations mimicked the sensitivity of the WT MCL1 suggesting they did not alter MCL1 function in the cells. (bloodjournal.org)
  • A mutation thus revealed the presence of an unknown cis -acting determinant that influences the NMD sensitivity of a putative NMD substrate. (bloodjournal.org)
  • We report a mutation in Buchnera of the aphid Acyrthosiphon pisum that recurs in laboratory lines and occurs in field populations. (pubmedcentralcanada.ca)
  • 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)
  • In the first tumor, 6132A-PRO, the antigen is encoded by a point-mutated L9 ribosomal protein gene. (rupress.org)
  • As an example of the latter, in a murine tumor designated 6132A, a somatic point mutation in the ribosomal protein L9 gives rise to an immunodominant CD4 + T cell-recognized tumor-specific antigen ( 3 ). (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)
  • Point mutations can have a strong impact on protein stability. (nih.gov)
  • Of the 10 mutations detected, 1 was in the N-terminal region (G32R) and 4 were in the PEST domain in the N-terminal half of MCL1 that is associated with regulating protein stability (V140I, P142S, E149Q and E173K). (bloodjournal.org)
  • Interestingly MCL1 was mutated in 10 baseline samples (1.02%) and the frequency of the mutations in these samples was high (median 0.391, range 0.066-0.531). (bloodjournal.org)
  • Other cases in which symbiont microevolution has a major effect on host ecological tolerance are likely to be widespread because of the high mutation rates of symbiotic bacteria and their crucial roles in host metabolism and development. (pubmedcentralcanada.ca)
  • 11 Constructs based on this mutation should therefore express high levels of incorrectly spliced mRNAs with PTCs in phase-shifted ORFs. (bloodjournal.org)
  • 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)
  • MSA prions robustly infected wild-type, A30P, and A53T α-synuclein-YFP cells, but they were unable to replicate in cells expressing the E46K mutation. (pnas.org)
  • In order to support basic research and protein design tasks, several computational tools for predicting the change in stability upon mutations have been developed. (nih.gov)
  • MAESTRO is a versatile tool in the field of stability change prediction upon point mutations. (nih.gov)
  • Conversely, the change may allow the cell to continue functioning albeit differently, and the mutation can be passed on to the organism's offspring. (wikipedia.org)
  • Most proteins can withstand one or two point mutations before their function changes. (wikipedia.org)
  • In contrast the L267V mutation resulted in a dose curve that was more similar to the empty vector control suggesting this mutation either resulted in loss of function or in an MCL1 molecule that could not be inhibited by the drug. (bloodjournal.org)
  • To investigate this hypothesis, we infected cell lines expressing PD-causing point mutations in α-synuclein with MSA patient samples. (pnas.org)
  • An additional mutation was found in an uncharacterized region between the PEST and BH1 domains (L186F). (bloodjournal.org)
  • 28 relatives (15 men, mean age 44 (15-86) years) without the mutation served as controls in the clinical examination part. (bmj.com)