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.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.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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.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.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.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.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.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, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.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.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Homozygote: An individual in which both alleles at a given locus are identical.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.Genes, Recessive: Genes that influence the PHENOTYPE only in the homozygous state.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.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.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.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.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).Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.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).Cell Line: Established cell cultures that have the potential to propagate indefinitely.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.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.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Syndrome: A characteristic symptom complex.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.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.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).Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.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.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.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.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.Consanguinity: The magnitude of INBREEDING in humans.Bacterial Proteins: Proteins found in any species of bacterium.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.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.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, 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.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.Heterozygote Detection: Identification of genetic carriers for a given trait.Exome: That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.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.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.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.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.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.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.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.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.DNA, Neoplasm: DNA present in neoplastic tissue.Genetic Variation: Genotypic differences observed among individuals in a population.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.Genes, Bacterial: The functional hereditary units of BACTERIA.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).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.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.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).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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.Jews: An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.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.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.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.Kinetics: The rate dynamics in chemical or physical systems.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).)Eye ProteinsConserved 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.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.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.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.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.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.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.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)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.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.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.Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.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)Ethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.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.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Genes, Fungal: The functional hereditary units of FUNGI.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Abnormalities, MultipleRecombinant 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.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.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.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.BRCA2 Protein: A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)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.Fungal Proteins: Proteins found in any species of fungus.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.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.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.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.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.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.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.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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Eye Abnormalities: Congenital absence of or defects in structures of the eye; may also be hereditary.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.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.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.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.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)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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Drug 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).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.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Genetic Association Studies: The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.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.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.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.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.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Ethyl Methanesulfonate: An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.Arginine: An essential amino acid that is physiologically active in the L-form.Chromosome Deletion: Actual loss of portion of a chromosome.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.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.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.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Osteochondrodysplasias: Abnormal development of cartilage and bone.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.Family: A social group consisting of parents or parent substitutes and children.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.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.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.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.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.Mice, Inbred C57BLHeLa 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.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Genes, APC: Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.BRCA1 Protein: The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)Deafness: A general term for the complete loss of the ability to hear from both ears.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Nerve Tissue ProteinsNucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.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 enzymesSerine: 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.HIV Reverse Transcriptase: A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.Genetic Diseases, Inborn: Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.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.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.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.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.Colorectal Neoplasms: Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.Hearing Loss, Sensorineural: Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.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.Breast Neoplasms: Tumors or cancer of the human BREAST.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell 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.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.

Modified peptidoglycan transpeptidase activity in a carbenicillin-resistant mutant of Pseudomonas aeruginosa 18s. (1/138264)

A carbenicillin-resistant mutant of Pseudomonas aeruginosa 18s was found to possess peptidoglycan transpeptidase activity significantly more resistant to inhibition by benzyl penicillin, ampicillin, carbenicillin, and cephaloridine than that of the parent strain. The mutant was more resistant than the parent strain to all of the beta-lactam antibiotics tested, and 50% inhibition values for these compounds against membrane-bound model transpeptidase activity paralleled this increase. The resistance of the mutant to kanamycin, streptomycin, and chloramphenicol was unchanged.  (+info)

Marker effects on reversion of T4rII mutants. (2/138264)

The frequencies of 2-aminopurine- and 5-bromouracil-induced A:T leads to G:C transitions were compared at nonsense sites throughout the rII region of bacteriophage T4. These frequencies are influenced both by adjacent base pairs within the nonsense codons and by extracodonic factors. Following 2AP treatment, they are high in amber (UAG) and lower in opal (UGA) codons than in allelic ochre (UAA) codons. In general, 5BU-induced transitions are more frequent in both amber and opal codons than in the allelic ochre codons. 2AP- and 5BU-induced transition frequencies in the first and third positions of opal codons are correlated with those in the corresponding positions of the allelic ochre codons. Similarly, the frequencies of 2AP-induced transition in the first and second positions of amber codons and their ochre alleles are correlated. However, there is little correlation between the frequencies of 5BU-induced transitions in the first and second positions of allelic amber and ochre codons.  (+info)

Nonbehavioral selection for pawns, mutants of Paramecium aurelia with decreased excitability. (3/138264)

The reversal response in Paramecium aurelia is mediated by calcium which carries the inward current during excitation. Electrophysiological studies indicate that strontium and barium can also carry the inward current. Exposure to high concentrations of barium rapidly paralyzes and later kills wild-type paramecia. Following mutagenesis with nitrosoguanidine, seven mutants which continued to swim in the ;high-barium' solution were selected. All of the mutants show decreased reversal behavior, with phenotypes ranging from extremely non-reversing (;extreme' pawns) to nearly wild-type reversal behavior (;partial' pawns). The mutations fall into three complementation groups, identical to the pwA, pwB, and pwC genes of Kunget al. (1975). All of the pwA and pwB mutants withstand longer exposure to barium, the pwB mutants surviving longer than the pwA mutants. Among mutants of each gene, survival is correlated with loss of reversal behavior. Double mutants (A-B, A-C, B-C), identified in the exautogamous progeny of crosses between ;partial' mutants, exhibited a more extreme non-reversing phenotype than either of their single-mutant (;partial' pawn) parents.---Inability to reverse could be expected from an alteration in the calcium-activated reversal mechanism or in excitation. A normal calcium-activated structure was demonstrated in all pawns by chlorpromazine treatment. In a separate report (Schein, Bennett and Katz 1976) the results of electrophysiological investigations directly demonstrate decreased excitability in all of the mutants, a decrease due to an altered calcium activation. The studies of the genetics, the survival in barium and the electro-physiology of the pawns demonstrate that the pwA and pwB genes have different effects on calcium activation.  (+info)

Testing for selective neutrality of electrophoretically detectable protein polymorphisms. (4/138264)

The statistical assessment of gene-frequency data on protein polymorphisms in natural populations remains a contentious issue. Here we formulate a test of whether polymorphisms detected by electrophoresis are in accordance with the stepwise, or charge-state, model of mutation in finite populations in the absence of selection. First, estimates of the model parameters are derived by minimizing chi-square deviations of the observed frequencies of genotypes with alleles (0,1,2...) units apart from their theoretical expected values. Then the remaining deviation is tested under the null hypothesis of neutrality. The procedure was found to be conservative for false rejections in simulation data. We applied the test to Ayala and Tracey 's data on 27 allozymic loci in six populations of Drosophila willistoni . About one-quarter of polymorphic loci showed significant departure from the neutral theory predictions in virtually all populations. A further quarter showed significant departure in some populations. The remaining data showed an acceptable fit to the charge state model. A predominating mode of selection was selection against alleles associated with extreme electrophoretic mobilities. The advantageous properties and the difficulties of the procedure are discussed.  (+info)

Apontic binds the translational repressor Bruno and is implicated in regulation of oskar mRNA translation. (5/138264)

The product of the oskar gene directs posterior patterning in the Drosophila oocyte, where it must be deployed specifically at the posterior pole. Proper expression relies on the coordinated localization and translational control of the oskar mRNA. Translational repression prior to localization of the transcript is mediated, in part, by the Bruno protein, which binds to discrete sites in the 3' untranslated region of the oskar mRNA. To begin to understand how Bruno acts in translational repression, we performed a yeast two-hybrid screen to identify Bruno-interacting proteins. One interactor, described here, is the product of the apontic gene. Coimmunoprecipitation experiments lend biochemical support to the idea that Bruno and Apontic proteins physically interact in Drosophila. Genetic experiments using mutants defective in apontic and bruno reveal a functional interaction between these genes. Given this interaction, Apontic is likely to act together with Bruno in translational repression of oskar mRNA. Interestingly, Apontic, like Bruno, is an RNA-binding protein and specifically binds certain regions of the oskar mRNA 3' untranslated region.  (+info)

oko meduzy mutations affect neuronal patterning in the zebrafish retina and reveal cell-cell interactions of the retinal neuroepithelial sheet. (6/138264)

Mutations of the oko meduzy (ome) locus cause drastic neuronal patterning defect in the zebrafish retina. The precise, stratified appearance of the wild-type retina is absent in the mutants. Despite the lack of lamination, at least seven retinal cell types differentiate in oko meduzy. The ome phenotype is already expressed in the retinal neuroepithelium affecting morphology of the neuroepithelial cells. Our experiments indicate that previously unknown cell-cell interactions are involved in development of the retinal neuroepithelial sheet. In genetically mosaic animals, cell-cell interactions are sufficient to rescue the phenotype of oko meduzy retinal neuroepithelial cells. These cell-cell interactions may play a critical role in the patterning events that lead to differentiation of distinct neuronal laminae in the vertebrate retina.  (+info)

Cancer genetics: tumor suppressor meets oncogene. (7/138264)

The adenomatous polyposis coli (APC) tumor suppressor protein is inactivated by mutations in the majority of colorectal cancers. A recent study has revealed that alterations in the APC signaling pathway can result in the transcriptional activation of the c-MYC gene.  (+info)

Alzheimer's disease: clues from flies and worms. (8/138264)

Presenilin mutations give rise to familial Alzheimer's disease and result in elevated production of amyloid beta peptide. Recent evidence that presenilins act in developmental signalling pathways may be the key to understanding how senile plaques, neurofibrillary tangles and apoptosis are all biochemically linked.  (+info)

AIM: We assessed the diagnostic accuracy of epidermal growth factor receptor (EGFR) mutant-specific antibodies for detecting two common activating EGFR mutations. METHODS: Immunohistochemical expression of mutation-specific antibodies against EGFR exon 19 deletion E746-A750 ((c.2235_2249del15 or c.2236_2250del15, p. Glu746_Ala750del) and exon 21 L858R point mutation (c.2573T|G, p.Leu858Arg) were assessed in a cohort of 204 resected early stage node negative lung adenocarcinomas, and protein expression was compared with DNA analysis results from mass spectrometry analysis. RESULTS: Of seven cases with L858R point mutation, six were positive by immunohistochemistry (IHC). There were three false positive cases using L858R IHC (sensitivity 85.7%, specificity 98.5%, positive predictive value 66.7%, negative predictive value 99.5%). All seven E746-A750 exon 19 deletions identified by mutation analysis were positive by IHC. Four additional cases were positive for exon 19 IHC but negative by mutation analysis.
Mitochondrial diseases, which altogether represent not so rare diseases, can be due to mutations either in the nuclear or mitochondrial genomes. Several model organisms or cell lines are usually employed to understand the mechanisms underlying diseases, yeast being one of them. However, in the case of mutations within the mitochondrial genome, yeast is a major model because it is a facultative aerobe and its mitochondrial genome can be genetically engineered and reintroduced in vivo. In this short review, I will describe how these properties can be exploited to mimic mitochondrial pathogenic mutations, as well as their limits. In particular; pathological mutations of tRNA, cytb, and ATPase genes have been successfully modeled. It is essential to stress that what has been discovered with yeast (molecular mechanisms underlying the diseases, nuclear correcting genes, import of tRNA into mitochondria or compounds from drug screening) has been successfully transferred to human patient lines, paving the way
Since Fishers (1930) development of the geometric model of the process of adaptation, it has been assumed that a mutation that affects many parts of a complex organism is less likely to be beneficial than a mutation of more restricted effect. Direct evidence supporting the generality of this supposition has been difficult to obtain, in part because of the challenge of studying high-dimensional phenotypes (Houle 2010) and because of the lack of information on the relationship between effects of pleiotropic alleles on phenotypes vs. on fitness (Paaby and Rockman 2013). By using multivariate statistical modeling of the genetic variance generated by new mutations, and of the standing genetic variance in a natural population, we have shown that selection is consistently stronger on pleiotropic mutations, supporting Fishers model of adaptation for populations in the vicinity of an adaptive optimum (Zhang 2012).. In general, we inferred strong selection acting against new mutations affecting the ...
Thesis Defense. Title: Computational Detection of Driver Mutations in Cancer Genomes. Abstract: Cancer is caused largely by the accumulation of somatic mutations during the lifetime of an individual. Recent advances in next generation sequencing (NGS) enable measurement of somatic mutations in a cohort of samples. Large-scale cancer sequencing projects like The Cancer Genome Atlas (TCGA) have generated a huge amount of somatic mutations in thousands of tumors. This thesis addresses two challenges. The first challenge is to distinguish driver mutations that are responsible for cancer development from passenger mutations, random events that do not contribute to the cancer phenotype in a cohort of samples. This is a difficult problem because most somatic mutations measured in tumor samples are passenger mutations, and only a small portion of these mutations are driver mutations. The second challenge is to accurately identify larger genomic variants, also known as structural variants (SV), one type ...
Author Summary Cancer is the consequence of an evolutionary process, which lasts several decades, is impossible to observe during most of its time, and only becomes apparent in late stages. We use mathematical modeling to shed light on the evolutionary dynamics of cancer by studying the accumulation of passenger mutations. We show that the frequencies obtained by passenger mutations depend strongly on the ratio of death and birth rates of cancer cells. We use genetic data of colorectal cancer to estimate this important quantity in vivo. We estimate the size of the cancer cell population that was present when a specific mutation first emerged. Our theory informs the analysis of cancer sequencing data and the phylogenetic reconstruction of cancer evolution.
...A specific gene mutation may be useful in predicting the level of aggr...The mutation called BRAF V600E is a genetic alteration in the BRAF o...Past studies have shown that the mutation frequently occurs in the mos...The findings come at an important time as both the incidence of thyroi...,Presence,of,gene,mutation,helps,guide,thyroid,cancer,treatment,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
To study the cost of chromosomal drug resistance mutations to bacteria, we investigated the fitness cost of mutations that confer resistance to different classes of antibiotics affecting bacterial protein synthesis (aminocyclitols, 2-deoxystreptamines, macrolides). We used a model system based on an in vitro competition assay with defined Mycobacterium smegmatis laboratory mutants; selected mutations were introduced by genetic techniques to address the possibility that compensatory mutations ameliorate the resistance cost. We found that the chromosomal drug resistance mutations studied often had only a small fitness cost; compensatory mutations were not involved in low-cost or no-cost resistance mutations. When drug resistance mutations found in clinical isolates were considered, selection of those mutations that have little or no fitness cost in the in vitro competition assay seems to occur. These results argue against expectations that link decreased levels of antibiotic consumption with the ...
Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data to infer the independent effects of mutation and selection on driver mutation complement. First, we detect associations between a range of mutational processes, including those linked to smoking, ageing, APOBEC and DNA mismatch repair (MMR) and the presence of key driver mutations across cancer types. Second, we quantify differential selection between well-known alternative driver mutations, including differences in selection between distinct mutant residues in the same gene. These results show that while mutational processes play a large role in determining which driver mutations are present in a cancer, the role of selection frequently dominates ...
The genetic factors underpinning the development of cancers are being discovered at an increasing pace. Cancers can have an acquired or an inherited genetic aetiology. Inherited cancer predisposition caused by a single gene mutation is normally inherited in an autosomal dominant fashion. Acquired caner at the cellular level may be caused by the loss of function of both copies of the gene acting in an autosomal recessive fashion. Gene mutations may act in different ways, some drive cell growth-oncogenes, others when the gene mutates fail to stop tumour growth - tumour suppressor genes. Other genetic mutations may cause normal DNA and cellular repair mechanisms to fail. Genetic testing may be used at the level of a tumour to inform treatment decisions or in an inherited cancer susceptibility syndrome to provide information and tailor screening and prevention strategies.
Complex processes such as transcription, replication, repair, and recombination require changes in chromatin structure and the interactions of numerous trans-acting factors with DNA sequences, raising the possibility that these processes may be interrelated. Here the effect of transcription on the rate of spontaneous mutation in the yeast Saccharomyces cerevisiae was examined. With the use of a lys2 frameshift allele under the control of a highly inducible promoter, the rate of spontaneous reversion was shown to increase when the mutant gene was highly transcribed. Thus, transcriptionally active DNA and enhanced spontaneous mutation rates are associated in yeast.. ...
THE number of compensatory mutations that will affect a specific deleterious mutation is a fundamental evolutionary quantity of which little is known. A mutation is compensatory if it has a beneficial effect on fitness that is conditional on the presence of a deleterious mutation at a different site in the genome (Kimura 1985). Hence, a compensatory effect is the outcome of a strong epistatic interaction between two mutations. Each compensatory mutation represents an alternate genetic solution to adaptation; thus, fitness recovery from the accumulation of deleterious mutations becomes less likely to occur by back mutation when compensatory mutations are increasingly common (Whitlock and Otto 1999). Indeed, one must invoke a compensatory mutation to explain the rapid, stepwise recovery of fitness observed in mutationally degraded experimental populations (Burch and Chao 1999; Moore et al. 2000; Estes and Lynch 2003). Compensatory mutations are also implicated in the persistence of alleles that ...
When populations of microorganisms are exposed to nonlethal selections, mutations that relieve the selective pressure arise (7), a phenomenon called adaptive mutation (6). Although it originally seemed that only useful mutations appeared (7), it is now clear that selected mutations are accompanied by nonselected mutations, i.e., the process is not directed to useful genes (12).. Most research on adaptive mutation has focused on a strain of Escherichia coli, called FC40, that cannot utilize lactose (Lac−) but that readily reverts to lactose utilization (Lac+) when lactose is its only carbon source (6). The process that produces adaptive Lac+ mutations is not the same as that which produces Lac+ mutations during normal growth. Unlike growth-dependent mutations, almost all adaptive Lac+ mutations are dependent on recombination functions (6, 10, 24). While several different types of sequence changes revert the Lac− allele during growth, adaptive Lac+ mutations are almost all −1-bp frameshifts ...
Population included 59% of adenocarcinoma, 37% of women and 19% of non-smokers. Overall mutation rate is 46%: 31 EGFR mutations (13%) and 78 KRAS mutations (33%); 40 new mutations compared to previous study were found: 9 EGFR and 31 KRAS. In the ERMETIC 2 cohort, OS and PFS remained significantly (global test p < 0.01) better for EGFR mutated (hazard ration [HR] 0.57 [95%CI: 0.33-1.00] and 0.47 [0.28-0.78] respectively) and worse for KRAS mutated (HR 1.35 [0.97-1.88] and 1.16 respectively [0.85-1.59]) compared to wild-type (WT) NSCLC. No prognostic significant difference was found in the 177 pts common to both cohorts between pts with KRAS mutation in both cohorts (n= 28) and those with new (n = 31) mutations. In the 228 pts with several techniques, KRAS mutations detected by less sensitive technique (n = 42) have a lower OS compared to WT than those detected only by the best sensitive technique (n = 34), but are not significantly different: 1.63 (1.09-2.44) and 1.08 (0.69-1.69); results between ...
Hollander, W F., "Hydrocephalic-polydactyl, a recessive pleiotropic mutant in the mouse and its location in chromosome 6." (1976). Subject Strain Bibliography 1976. 3055 ...
A mutation in a single gene can cause endometrial cancer that is responsive to a specific drug therapy, researchers at UT Southwestern Medical Center have found in an animal study.
3799 Genomic instability involves the accumulation of mutations and is a hallmark of neoplastic development in gastrointestinal malignancies such as colorectal carcinoma. Mutations in specific cancer genes contribute to the malignant phenotype for colorectal carcinoma. For example, mutations in APC, KRAS and TP53 are critical to the development of colorectal cancer. Mutations in genes like EGFR influence the response of molecular-targeted therapies. Undoubtedly, there are other critical gene mutations to be discovered and comprehensive mutation discovery from individual cancer genomes will increase our understanding of the genetics underlying any individual tumors phenotype. This mutation profile may provide prognostic and predictive genetic biomarkers. However, current technologies are severely limited in screening large numbers of genes for mutations. As a solution, we describe the development and application of a novel resequencing strategy for point mutation discovery on a massively ...
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?. ...
Rare mutations in the switch III region of Ras can increase its nanoscale clustering, which enhances effector recruitment and downstream signaling.
|p>p53 is a tumor suppressor protein encoded by the TP53 gene that responds to DNA damage by regulating cell-cycle arrest, apoptosis and senescence. These p53 Hotspot Mutation Cell Panels are composed of select cell lines derived from tumors of various tissue origins. The p53 mutational status of these lines have been sequenced and validated by ATCC.|/p>
|p>p53 is a tumor suppressor protein encoded by the TP53 gene that responds to DNA damage by regulating cell-cycle arrest, apoptosis and senescence. These p53 Hotspot Mutation Cell Panels are composed of select cell lines derived from tumors of various tissue origins. The p53 mutational status of these lines have been sequenced and validated by ATCC.|/p>
Deletion of the I265-F268 and T271-K277 regions in the large lumenally exposed loop of the CP47 protein are known to lead to a loss of photoautotrophic growth. Here, these regions have been investigated by combinatorial mutagenesis and pseudorevertant mapping. No single amino-acid residue in the I265-F268 region was found to be critical for function, but a large hydrophobic residue at position 267 and preferentially an aromatic residue at position 268 appeared to be required for photoautotrophic growth. Starting from an obligate photoheterotrophic mutant lacking the T271-K277 region, photoautotrophic pseudorevertants were generated with short in-frame tandem repeats near the site of the original deletion, partially or fully restoring the length of the original protein. These pseudorevertants were sensitive to oxygen indicating that the T271-K277 region may provide PS II stability and/or protection against oxygen-dependent photoinactivation. Pseudorevertants with much improved photoautotrophic ...
Researchers assigned levels of risk to 25 mutations associated with breast and ovarian cancer in a large, Stanford-led study. The results may be helpful in guiding treatment and screening recommendations.
Using real-time PCR to detect HIV resistance mutations present at low levels, Jeffrey Johnson and colleagues investigate prevalence and clinical implications of minority transmitted mutations.
BioMotiv, a drug development accelerator associated with The Harrington Project, and Rutgers, the State University of New Jersey, are announcing the formation of a new biotechnology startup, Z53 Therapeutics. Z53 Therapeutics aims to develop novel anti-cancer drugs that target tumors with p53 mutations.
Most truncation or deletion mutations underlying HI are thought to lead to severe loss of ABCA12 protein function affecting important nucleotide-binding fold domains and/or transmembrane domains. Thus far, in HI patients, at least one mutation on each allele must be a truncation or deletion mutation within a conserved region to cause serious loss of ABCA12. Complete loss of ABCA12 function due to homozygous or compound heterozygous truncation mutations always results in the HI patient phenotype. ...
Scientists make a DNA breakthrough by using multi-gene test to predict the risk of five diseases.. The key to prevention is identifying people who are at higher risk for diseases early on. Since most common diseases have a genetic component, we could start classifying people based on their genetic risk.. This is where genetic variants come into play. Genetic variants are small changes in DNA that exist between people, which can contribute to disease risk. However, most common diseases of today like heart disease and diabetes, are influenced by more than one gene.. Individually each gene only makes a small contribution towards disease risk. But when found together, they play a significant role in a persons genetic predisposition to disease. Unfortunately predicting disease risk based on multiple genes isnt an easy task.. However, according to ground breaking research published in the journal of Nature Genetics, this is no longer the case. Scientist can now effectively predict the risk of ...
The causes underlying racial disparities in cancer are multifactorial. In addition to socioeconomic issues, biological factors may contribute to these inequities, especially in disease incidence and patient survival. To date, there have been few studies that relate the disparities in these aspects to genetic aberrations. In this work, we studied the impacts of race on the patient survival and tumor mutation burden using the data released by the Cancer Genome Atlas (TCGA). The potential relationship between mutation burden and disease incidence is further inferred by an integrative analysis of TCGA data and the data from the Surveillance, Epidemiology, and End Results (SEER) Program. The results show that disparities are present (p | 0.05) in patient survival of five cancers, such as head and neck squamous cell carcinoma. The numbers of tumor driver mutations are differentiated (p | 0.05) over the racial groups in five cancers, such as lung adenocarcinoma. By treating a specific cancer type and a racial
Vorkas, P.A.; Poumpouridou, N.; Agelaki, S.; Kroupis, C.; Georgoulias, V.; Lianidou, E.S., 2010: PIK3CA hotspot mutation scanning by a novel and highly sensitive high-resolution small amplicon melting analysis method
This report describes mutants of the zebrafish having phenotypes causing a general arrest in early morphogenesis. These mutants identify a group of loci making up about 20% of the loci identified by mutants with visible morphological phenotypes within the first day of development. There are 12 Class I mutants, which fall into 5 complementation groups and have cells that lyse before morphological defects are observed. Mutants at three loci, speed bump, ogre and zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6 complementation groups, arrest development before cell lysis is observed. These mutants seemingly stop development in the late segmentation stages, and maintain a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie, specter, poltergeist and troll were tested for cell lethality by transplanting mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells all survive. The remainder of the mutants tested were autonomously but ...
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 ...
Seven single gene mutations are known to cause hypertension; this article guides clinicians through identification of the relatively uncommon defects, associated laboratory findings, and treatments.
The transcription factor CCAAT-enhancer-binding protein alpha (C/EBPα) is a master regulator of granulopoiesis and regulates the switch between proliferating, uncommitted progenitors and cell-cycle-arrested, differentiated myeloid cells. Usage of two alternative translation initiation sites in the CEBPA mRNA results in expression of a full-length C/EBPα protein p42 (42 kDa) and a shorter p30 isoform (30 kDa). CEBPA mutations are found in 9-15% of Acute Myeloid Leukemia (AML) patients. N-terminal frameshift mutations in the CEBPA gene lead to selective ablation of p42 expression, while C-terminal mutations disrupt the dimerization and DNA-binding ability of C/EBPα. AML patients harbor either mono- or biallelic CEBPA mutations (CEBPAmo or CEBPAbi) and both genotypes are frequently associated with concurrent mutations in other genes. The most commonly co-occurring mutations in both groups are loss-of-function mutations in the methylcytosine dioxygenase TET2 (44.4% in CEBPAmo / 34.8% in CEBPAbi). ...
From Jules: there was quite a bit of discussion at the workshop this year about using sensitive testing to identify low-level or minority genotypic resistance. At last years Resistance Workshop the CDC and Mike Kozal from Yale reported in oral presentations that minority mutations can lead to viral failure. Concerns are how to translate these potential concerns into the clinic. There are some lingering concerns among a few that further confirmation is required before presuming that the presence of low-level mutations is a reliable test for not using a drug, despite several studies reporting that the risk for viral failure significantly increases if these mutations are present; but not everyone fails if minority mutations are present, so are you throwing out a good drug by avoiding it? Still the studies so far presented find there is a significantly increased risk of viral failure. Tests to screen for minority mutations are not clinically available yest, as far as I know. But there were several ...
Ovarian and breast cancer can be either sporadic or hereditary. Sporadic cancers make up the vast majority (85-90%) of ovarian and breast cancers and are not associated with family history of either cancer or inherited cancer-associated mutations. Sporadic cancers arise from genetic mutations acquired in some cells of the body by events part of normal metabolism and environmental factors. This type of cancer can happen to anyone. Most acquired gene mutations are not shared among relatives or passed on to children.. Hereditary (also known as inherited, or familial) cancers are those that occur due to genetic mutations that are inherited from mom or dad. Other blood relatives may also share these same gene mutations. Parents give one copy of each gene to their children. If a parent has a genetic mutation in a gene, each of their children have a 50% chance of inheriting that mutation. Therefore, even in families with hereditary cancer, not all family members inherit the mutation that is causing ...
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 ...
Purpose: : To identify and characterize the gene mutation responsible for photoreceptor degeneration in the rd3 mouse. Methods: : We screened genes in the known rd3 (RBF/DnJ) mapped region by direct sequencing. We additionally screened other rd3 lines (RBJ/Dn, STOCK Rb(11.13)4Bnr/J and STOCK In(5)30Rk) and normal mouse strains to verify the alteration. We carried out a mutation screen of the human RD3 gene in patients with retinopathies and examined 431 patients of Caucasian ethnicity and 103 of Asian-Indian ancestry. Amino acid changes that were identified in patients but not in controls are being examined by immunoblot analysis and immunocytochemisty to determine their effect(s) on protein stability or localization. Results: : The rd3 mutation is a homozygous C to T transition, leading to a stop codon, which is predicted to result in a premature truncation of the rd3 protein. The mutation was present in all rd3 lines tested (RBF/DnJ, RBJ/Dn, 4bnr and IN-30) but not in the control lines ...
We set out to determine the feasibility of using microarray-based resequencing for cancer gene mutation screening by designing GeneChip CustomSeq Resequencing arrays (Affymetrix, Santa Clara, CA, USA) for interrogation of ARAF, BRAF, CDK4, CDK6, CDKN2A, KLF6, HRAS, KRAS, MET, NRAS, PTEN, RAF1, RB1, RET and TP53 (164 exons in total). Arrays also included four intronic bases on either side of the exons to cover splice sites, thus the arrays covered a total of 23,966 bases. Overall performance was very good, with accuracy ,99.99% and coverage ~97.5%. Twenty NSCLC samples were analyzed using the arrays, and several well-characterized somatic mutations and germline variants were found. The most significant novel finding was the detection of a transforming MET mutation (T1010I) in a NSCLC patient. ...
Understanding and predicting molecular cause of disease is one of the major challenges for biology and medicine. One particular area of interest continues to be computational analyses of disease-associated amino acid substitutions. To this end, various studies have been performed to identify molecular functions disrupted by disease-causing mutations. Here, we investigate the influence of disease- associated mutations on post-translational modifications. In particular, we study the loss of modification target sites as a consequence of disease mutation. We find that about 5% of disease-associated mutations may affect known modification sites, either partially (4%) of fully (1%), compared to about 2% of putatively neutral polymorphisms. Most of the fifteen post-translational modification types analyzed were found to be disrupted at levels higher than expected by chance. Molecular functions and physiochemical properties at sites of disease mutation were also compared to those of neutral ...
Stable disease may be annotated as a "clinical response - not further specified" where stable disease is considered by an author as a positive response to therapy and/or where stable disease has been followed by a relapse. Acquired resistance mutations will occur in tumours annotated as a resistant recurrence e.g. Imatinib clinical resistant recurrence. A recurrent tumour or a metastatic site has been screened for mutations following relapse after an initial drug response. Only those secondary mutations reported as proven to be associated with resistance or presumed by authors to be associated with resistance, e.g. based on their gene location, are annotated as acquired resistance mutations and not incidental passenger mutations detected in a recurrent tumour. Intrinsic resistance mutations will occur in tumours annotated as having a primary non response e.g. Imatinib clinical primary non response. Only those mutations reported as associated with resistance are annotated as primary resistance ...
ISI Document Delivery No.: 205FY Times Cited: 0 Cited Reference Count: 25 Cited References: Armstrong SA, 2004, BLOOD, V103, P3544, DOI 10.1182/blood-2003-07-2441 Bardini M, 2010, LEUKEMIA, V24, P169, DOI 10.1038/leu.2009.203 Bardini M, 2011, LEUKEMIA, V25, P175, DOI 10.1038/leu.2010.232 Bueno C, 2010, LEUKEMIA, V25, P400 Chang VY, 2013, BMC CANCER, V13, DOI 10.1186/1471-2407-13-55 Chen WL, 2006, BLOOD, V108, P669, DOI 10.1182/blood-2005-08-3498 Drmanac R, 2010, SCIENCE, V327, P78, DOI 10.1126/science.1181498 Eguchi M, 2005, INT J HEMATOL, V82, P9, DOI 10.1532/IJH97.05042 FORD AM, 1993, NATURE, V363, P358, DOI 10.1038/363358a0 Gale KB, 1997, P NATL ACAD SCI USA, V94, P13950, DOI 10.1073/pnas.94.25.13950 Greaves MF, 2003, BLOOD, V102, P2321, DOI 10.1182/blood-2002-12-3817 Krivtsov AV, 2008, CANCER CELL, V14, P355, DOI 10.1016/j.ccr.2008.10.001 Krzywinski M, 2009, GENOME RES, V19, P1639, DOI 10.1101/gr.092759.109 Liang DC, 2006, CANCER, V106, P950, DOI 10.1002/cncr.21687 Metzler M, 2006, ONCOGENE, ...
In terms of evolution and fitness, the most significant spontaneous mutation rate is likely to be that for the entire genome (or its nonfrivolous fraction). Information is now available to calculate this rate for several DNA-based haploid microbes, including bacteriophages with single- or double-stranded DNA, a bacterium, a yeast, and a filamentous fungus. Their genome sizes vary by approximately 6500-fold. Their average mutation rates per base pair vary by approximately 16,000-fold, whereas their mutation rates per genome vary by only approximately 2.5-fold, apparently randomly, around a mean value of 0.0033 per DNA replication. The average mutation rate per base pair is inversely proportional to genome size. Therefore, a nearly invariant microbial mutation rate appears to have evolved. Because this rate is uniform in such diverse organisms, it is likely to be determined by deep general forces, perhaps by a balance between the usually deleterious effects of mutation and the physiological costs ...
Abstract Background: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next‐generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations. Methods: We sent out a survey to 16 genetic centers performing SCN1A testing. Results: We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation‐negative, both due to technical limitations and human errors. Conclusion: We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A ...
Description of disease Gain-of-function mutation. Treatment Gain-of-function mutation. Symptoms and causes Gain-of-function mutation Prophylaxis Gain-of-function mutation
Mutations affect organisms in two different ways. Genetic mutations are inherited DNA changes that can be passed on to the next generation. Somatic mutations are DNA changes that are acquired after...
Page 1 of 2 - Bacterial Mutations To Resist Antibiotics - posted in Creation vs Evolution: When bacteria mutates to resist antibiotics, is this witnessed evolution?
Drug resistance is an almost inevitable consequence of cancer therapy and ultimately proves fatal for the majority of patients. In many cases this is the consequence of specific gene mutations that have the potential to be targeted and re-sensitize the tumor. The means therefore to saturate the genome with point mutations and that avoids chromosome or nucleotide sequence context bias would open the door to identify all possible drug resistance mutations in cancer models. Here we describe such a method for elucidating drug resistance mechanisms using genome-wide chemical mutagenesis allied to next-generation sequencing. We show that chemically mutagenizing the genome of cancer cells dramatically increases the number of drug-resistant clones and allows the detection of both known and novel drug resistance mutations. We have developed an efficient computational process that allows for the rapid identification of involved pathways and druggable targets. Such a priori knowledge would greatly empower ...
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 ...
Scientists believe theyve discovered a genetic mutation that may turn usually mild-mannered individuals into obnoxious, violent brutes once they get drunk. The mutation is linked to a brain abnormality... Health News Summaries. | Newser
Per bug 769207 we want to remove support for mutation events and that the reason they havent been removed already is that there is existing Web content using them. If we allow apps that use mutation events into the Marketplace, there will be a higher barrier to removing support for mutation events, since presumably we wouldnt want to break Marketplace apps. To address this problem and to make sure that we actually might have a chance of removing support for mutation events in the future, I suggest making mutation events unavailable to applications installed via the Marketplace ...
Bruce E. Johnson, MD, and Mark A. Socinski, MD, outline the evolving treatment paradigm with regard to targeted therapies and mutation testing in non–small cell lung cancer.
The Curl (Cu) and Mouse-ear (Me) mutations of tomato cause two seemingly unrelated developmental syndromes with a wide range of pleiotropic phenotypes. Yet, the distinct morphogenic alterations in shoots, leaves, and inflorescences conferred by the two mutations appear to be caused by unchecked meristematic activity that characterizes dominant mutations in Knotted1 (Kn1)-like genes of monocot plants. We have been unable to separate the two closely linked Cu and Me mutations, and they may lie in the same gene. A homeobox-containing class I Kn1-like gene, TKn2, also maps to the same location. Significantly, the dominant mutations are associated with two aberrant modes of TKn2 transcription. Overexpression of the two in-frame wild-type transcripts of TKn2 is associated with the Cu mutation, whereas misexpression of an abundant and oversized fusion mRNA is associated with the Me mutation. Available molecular evidence strongly suggests that the defective Me-TKn2 transcript is generated via a novel ...
Procaspase-3 is the dimeric precursor of the apoptosis-executioner caspase-3 that displays little activity in vitro. The interface of the procaspase-3 dimer plays a critical role in zymogen maturation, although the active sites are not located at the dimer interface. We show that replacement of valine 266, the residue at the center of the procaspase-3 dimer interface, with arginine or glutamate results in an increase in enzyme activity of about 25-60-fold, representing a pseudo-activation of the procaspase. In contrast, substitution of V266 with histidine abolishes the activity of the procaspase-3 as well as that of the mature caspase. This mutant can be activated by protein exposure at pH 5, followed by dialysis at neutral pH. While the mutations do not affect the dimeric properties of the procaspase, we show that the V266E mutation may affect the formation of a loop bundle that is important for stabilizing the active sites. In contrast, the V266H mutation affects the positioning of loop L3, ...
In a first-of-its-kind study, scientists correct a single gene mutation tied to genetic heart conditions in human embryos using CRISPR.
Health,...Unknown mutations may account for increased odds researchers say ...MONDAY Nov. 17 (HealthDay News) -- The risk of breast cancer for a wo...And in women younger than age 40 without the BRCA mutations but with ...Over a six-year period the researchers followed up nearly 1500 wome...,Family,History,Ups,Breast,Cancer,Risk,Even,Without,BRCA,Gene,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Principal Investigator:OHTA Norio, Project Period (FY):1990 - 1991, Research Category:Grant-in-Aid for General Scientific Research (B), Research Field:Gastroenterology
View Notes - Chapter 9 from BIO SCI 325 at Wisconsin Milwaukee. 1 204-325 2 h h Chromosomal mutations are variations from Chromosomal mutations are variations from wild wild-- type condition in
Mutations . Section 12-4 This section describes and compares gene mutations and chromosomal mutations. Mutations. What are mutations? Mutations are changes in the DNA sequence that affect genetic information. Mutations. Is the following sentence true or false? Slideshow 1277847 by Patman
A. There are plausible disease-causing mutations(i) within, affecting or encompassing an interpretable functional region(ii) of this gene identified in multiple (,3) unrelated cases/families with the phenotype(iii).. OR. B. There are plausible disease-causing mutations(i) within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (,3) unrelated cases/families with the phenotype(iii).. OR. C. As definitions A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g. known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.. AND. D. Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic ...
its that over 90% mutations in coding regions are recessive but some mutations are known to be dominant. Recessive mutation is the one that leads to loss of function but you can introduce another allele on plasmid or paralog on the chromosome to substitute phenotype. On the other hand dominant mutation has strong phenotype that is less likely be masked by supplying wildtype allele on plasmid or paralog elsewhere on the chromosome ...
A. There are plausible disease-causing mutations(i) within, affecting or encompassing an interpretable functional region(ii) of this gene identified in multiple (,3) unrelated cases/families with the phenotype(iii).. OR. B. There are plausible disease-causing mutations(i) within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (,3) unrelated cases/families with the phenotype(iii).. OR. C. As definitions A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g. known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.. AND. D. Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic ...
Many mutations in cancer are of unknown functional significance. Standard methods use statistically significant recurrence of mutations in tumor samples as an indicator of functional impact. We extend such analyses into the long tail of rare mutations by considering recurrence of mutations in clusters of spatially close residues in protein structures. Analyzing 10,000 tumor exomes, we identify more than 3000 rarely mutated residues in proteins as potentially functional and experimentally validate several in RAC1 and MAP2K1. These potential driver mutations (web resources: 3dhotspots.org and cBioPortal.org) can extend the scope of genomically informed clinical trials and of personalized choice of therapy.
Because ppGpp influences the expression of many genes including those also controlled by cAMP-CRP (32), it is impossible to elucidate the precise physiological basis for the advantage of the spoT mutation. However, at least two possibilities can be suggested. First, the array data show that the spoT mutation lowers expression of the flagella-encoding flg operons (Table 1). The ancestral strain used in the evolution experiment was nonmotile, the selective environment lacked physical structure, and the production of flagella is known to be costly (34). Hence, reducing the expression of these genes could be beneficial (35). Second, a reduction in the concentration of ppGpp, shown to result from mutations in the regulatory region of spoT (32, 36), might increase the rate of transcription from tRNA and rRNA promoters (37). This increased transcription raises the maximal growth rate (38), presumably via an increased speed of translation during growth in minimal medium (39). Although tRNA and rRNA ...
The much-vaunted medical benefits of sequencing the human genome itself have just received some vindication from the results of clinical trials of the anti-cancer drug PLX4032. The dramatic potential of the drug for shrinking skin-cancer tumours was reported in August, and is confirmed by a recent paper in Nature. But the real excitement stems from the approach: the drug was developed to target a specific carcinogenic mutation of a gene called BRAF, involved in cell growth. The problem is that there are several dangerous mutations of BRAF alone, and thousands of other genetic mutations that also cause cancer. But the new results show that targeting a particular mutation can be highly effective, hitting only those cancer cells that possess it instead of employing the scattershot attack of current cancer chemotherapies. If many mutant-specific drugs come online, rapid gene profiling of patients could enable them to be given precisely the right treatment, without the debilitating side-effects. ...
FREDERICK, Md-Mutations in two genes that produce chemokine receptors-CCR5 and CCR2-account for about 30% of long-term survivors of HIV infection, that is, patients whose disease has not progressed to AIDS within 10 to 20 years of infection, said Stephen J. O Brien, PhD, of the NCIs Laboratory of Genomic Diversity. 1
The much-vaunted medical benefits of sequencing the human genome itself have just received some vindication from the results of clinical trials of the anti-cancer drug PLX4032. The dramatic potential of the drug for shrinking skin-cancer tumours was reported in August, and is confirmed by a recent paper in Nature. But the real excitement stems from the approach: the drug was developed to target a specific carcinogenic mutation of a gene called BRAF, involved in cell growth. The problem is that there are several dangerous mutations of BRAF alone, and thousands of other genetic mutations that also cause cancer. But the new results show that targeting a particular mutation can be highly effective, hitting only those cancer cells that possess it instead of employing the scattershot attack of current cancer chemotherapies. If many mutant-specific drugs come online, rapid gene profiling of patients could enable them to be given precisely the right treatment, without the debilitating side-effects. ...
Maturity-onset diabetes of the young (MODY) is a subtype of diabetes characterized by early age of onset (usually ,25 years), autosomal dominant inheritance, and a progressive defect in β-cell function (1). In U.K. populations, mutations in the hepatocyte nuclear factor-1α (HNF-1α) gene account for ∼65% of cases (2). Over 120 different HNF-1α mutations have been reported (3), of which ∼30% are nonsense or frameshift and lead to the production of premature termination codons (PTCs) (4). The most common HNF-1α mutation results from the insertion of a C nucleotide in a polyC tract in exon 4 (2,5-7). This mutation, P291fsinsC, accounts for ∼20% of families with HNF-1α mutations (4,8,9).. HNF-1α mutations might produce the MODY phenotype by haploinsufficiency or a dominant-negative mutational mechanism. There is considerable support for haploinsufficiency; a mutation in the HNF-1α promoter that disrupts the HNF-4α binding site results in a phenotype indistinguishable from mutations in ...
Chen G, Kong J, Tucker-Burden C, Anand M, Rong Y, Rahman F, Moreno CS, Van Meir EG, Hadjipanayis CG, Brat DJ. (2014) Human Brat ortholog TRIM3 is a tumor suppressor that regulates asymmetric cell division in glioblastoma. Cancer Res. 74:4536-48. Zerrouqi A, Pyrzynska B, Brat DJ, Van Meir EG. (2014) p14ARF suppresses tumor-induced thrombosis by regulating the tissue factor pathway. Cancer Res 74:1371-8.. The Cancer Genome Research Network (2015). Comprehensive and Integrative Genomic Characterization of Diffuse Lower Grade Gliomas. N Eng J Med 372:2481-98. *Corresponding Author. Chen K, Yang D, Li X, Sun B, Song F, Cao W, Brat D, Gao Z, Li H, Liang H,Zhao Y, Zheng H, Li M, Buckner J, Patterson SD, Ye X, Reinhard C, Bhathena A, Joshi D, Mischel PS, Croce C, Wang YM, Kaimal S, Li H, Lu X, Pan Y, Chang H, Ba S, Luo L, Cavenee W, Zhang W, Xishan Hao X. (2015) Mutational landscape of gastric adenocarcinoma in Chinese: implications for prognosis and therapy. Proc Natl Acad Sci. 112:1107-12.. Lin R, Elf ...
As tumors can harbor thousands of mutations, it is technically challenging to sort out the most relevant mutations of potential functional and biologic significance in exceptional responders to chemotherapy. Al-Ahmadie and colleagues (2) provide valuable insights into delineating tumor genome sequencing data. First, they sequenced the recurrent tumor specimen obtained after standard chemotherapy, but before trial enrollment. They then confirmed the mutations in the diagnostic tumor samples collected before chemotherapy. By comparing treated and treatment-naïve tumors, the authors selected mutations that arose early in molecular time, which were more likely to exert biologic driving effects on tumor development. Second, they performed an integrated analysis using the mutation, DNA copy number, and tumor clonality data with pathway analysis relevant to the mechanism of drug action to prioritize genomic aberrations. Third, considering heterogeneity of tumor cells, they confirmed whether the ...
R. Marty, S. Kaabinejadian, D. Rossell, M.J. Slifker, J. van de Haar, H.B. Engin, N. de Prisco, T. Ideker, W.H. Hildebrand, J. Font-Burgada, H. Carter, "MHC-I genotype restricts the oncogenic mutational landscape," Cell, 2017 (In Press).. H. Carter*, R. Marty, M. Hofree, A. Gross, J. Jensen, K. Fisch, X. Wu, C. DeBoever, E. Van Nostrand, Y. Song, E. Wheeler, J. Kreisberg, S. Lippman, G. Yeo, S. Gutkind, T. Ideker, "Widespread interacion of inherited polymorphisms with somatic events in cancer," Cancer Discovery Apr 1;7(4):410-23, 2017. PMID: 28188128 * Corresponding author. B. Engin, J. Kreisberg, H. Carter, "Structure-based Analysis Reveals Cancer Missense Mutations Target Protein Interaction Interfaces," PLoS One Apr 4;11(4):e0152929, 2016. PMID: 27043210. B. Engin, M. Hofree, H. Carter, "Identifying Mutation-Specific Cancer Pathways Using a Structurally Resolved Protein Interaction Network," Pac Symp Biocomput. 84-95, 2015. PMID: 25592571. H. Carter, A. Chen, L. Isik, S. Tyekucheva, V.E. ...
Using molecular genetic techniques, we have generated and characterized six temperature sensitive (ts) alleles of nop2. All failed to support growth at 37 degrees C and one was also formamide sensitive (fs) and failed to grow on media containing 3% formamide. Conditional lethality is not due to rapid turnover of mutant Nop2p proteins at 37 degrees C. Each allele contains between seven and 14 amino acid substitutions and one possesses a nonsense mutation near the C-terminus. Mapping experiments with one allele, nop2-4, revealed that a subset of the amino acid substitutions conferred the ts phenotype and that these mutations have an additive effect. All six mutants exhibited dramatic reductions in levels of 60S ribosome subunits under non-permissive conditions as well as some reduction at permissive temperature. Processing of 27S pre-rRNA to mature 25S rRNA was defective in all six mutants grown under non-permissive conditions. Levels of the 40S ribosomal subunit and 18S rRNA were not ...
Although KRAS is one of the major oncogenes associated with aggressive cancers, drugs designed to block KRAS function have not been able to halt cancer progression in a clinical setting. Until now, KRAS has remained infamously "undruggable.". In a new study, published this month in Cancer Discovery, University of California San Diego School of Medicine researchers report that approximately half of lung and pancreatic cancers that originate with a KRAS mutation become addicted to the gene as they progress. By understanding the mechanism that causes these cancers to remain dependent on KRAS for survival, they were able to identify a drug capable of targeting it.. "Certain tumors use mutant KRAS to boost their survival by helping them take up nutrients and process toxins, causing them to become addicted to KRAS," said David Cheresh, PhD, UC San Diego School of Medicine Distinguished Professor of Pathology and senior author of the paper. "Other tumors that do not use KRAS in this way can do without ...
G3: Genes,Genomes,Genetics is pleased to offer a new format for quickly and easily publishing mutant screen reports.. The Mutant Screen Report provides a useful format for describing the results of mutant screens. The format is succinct, and follows a structured template designed to make it fast and easy for authors to submit, for reviewers to rapidly assess, and for readers to easily understand the screen and its results. The Reports fulfill one of G3s goals: to make data from useful genetic screens available to the community in a timely fashion. Guidelines here.. So find those lab notebooks and submit your Mutant Screen Reports today to G3!. ...
The basic principle behind the data analysis is that we compare the Ct value of a mutation assay in a test sample with the Ct value of the same assay in a wildtype sample. When there is a significant difference (a preset value of 4 Cts) between the Ct values, the test sample is concluded to contain the mutation. The Ct values used for comparison can either be raw Ct (in average Ct method) or normalized Ct (in delta delta Ct case). When the Ct difference falls between 3 and 4, we give a borderline mutation call, which means that the mutation may be present at low percentage. When the Ct difference is smaller than 3, we give a negative mutation call (i.e. the mutation percentage is beyond the detection limit of the array). The wildtype sample can be either a genuine wildtype sample that is tested in the same experiment, or it could be a "virtual" wildtype sample that is computed from all test samples. For detailed description of the data analysis principle, refer to (link to white paper ...
Chromosomal mutations occur inside the chromosome. There are 23 pairs of chromosomes in each human cell. Mutation occurs in the genes DNA base sequence. There are several factors associated with gene mutation. Some mutations are hereditary while others occur due to environmental factors in an individuals lifetime. Learn more facts about chromosomal mutations.
Several different single-gene mutations are known to cause varying degrees of diabetes and obesity in mice. The severity of the diabetes produced depends on both the mutation itself and the interaction of the mutant gene with the inbred background. Establishing the nature of these gene-background interactions should aid us in our understanding of similar interactions that occur in human diabetes. The documentation of several different genes that produce similar, if not identical, diabetes-obesity syndromes suggests that lesions in many pathways can cause diabetes. An understanding of these defects in mice should help us to understand similar defects involved in the human disease. The developmental stages in each mutant are similar. The early symptoms include hyperphagia, hyperinsulinemia, and hypertrophy and hyperplasia of the beta cells of the islets of Langerhans. Hyperglycemia, obesity, and severe diabetes are secondary features that result from insulin resistance and the failure to
There are many disease-related gene mutants and the mutant cDNA clones are critical for disease models in biomedical research. OriGene offers both kinase-dead ORF clones and naturally occurred disease-related mutants. The mutant and variant ORF clones are all provided in a mammalian expression vector.
The phenomenon of mutation, therefore, is a most important component of the evolution model. The evolution model must postulate some mechanism to produce the required upward progress in complexity which characterizes the model in its broadcast dimension. Mutation is supposedly that mechanism.. The basic evolution model would predict, therefore, that mutations must be primarily beneficial, generating a vertical change upward toward higher degrees of order. Each such change must be positively helpful in the environment if it is to be preserved by natural selection and contribute to evolutionary progress.. The creation model, on the other hand, would predict that, if there are any such things as real mutations, causing vertical changes in complexity and order of the kings, they will be harmful, not beneficial.. With these two models in mind, let us now consider some of the actual experimental facts relative to mutations.. 1. Mutations are random, not directed.. ...
4IJT: Structural studies of p53 inactivation by DNA-contact mutations and its rescue by suppressor mutations via alternative protein-DNA interactions.
4IBQ: Structural studies of p53 inactivation by DNA-contact mutations and its rescue by suppressor mutations via alternative protein-DNA interactions.
Using a database of human tumor genomic data, researchers at the University of California San Diego, School of Medicine and Moores Cancer Center discovered that mutation hotspots known as kataegis are a positive marker in breast cancer - patients with kataegis have less invasive tumors and better prognoses. The study, published June 30 in Cell Reports, also suggests kataegis status could help doctors determine treatment options that might work best for patients with the mutation pattern.
Activating mutations in K-Ras are among the most common lesions found in human cancer, and such mutations are generally associated with poor prognosis. Despite numerous efforts in academia and industry, small molecule inhibitors that directly target K-Ras remain elusive. Even more highly desired are molecules that selectively target mutant K-Ras while sparing the wild type protein. We have used a fragment-based screen to discover oncogenic mutant-specific inhibitors of K-Ras. Crystallographic studies with multiple inhibitors in complex with K-Ras reveal that the compounds bind in a novel hydrophobic pocket that is not apparent in any published crystal structure of Ras. These inhibitors disrupt the conformations of Switch I and Switch II, domains that are essential for the association and activation of downstream signaling partners. Our medicinal chemistry effort has greatly improved potency, showing that this pocket is particularly amenable to chemical optimization. In vitro biochemical ...
Thought you all might be interested in this video on whether or not mutations are random. It covers both why we originally thought mutations were random plus
A new study provides some of the first links between relatively common mutations in the blood cells of the elderly and atherosclerosis.. Though cardiovascular disease, which is characterized in part by atherosclerosis, or plaque build-up, is a leading cause of death in the elderly, almost 60 percent of elderly patients with atherosclerotic cardiovascular disease (CVD) exhibit no conventional risk factors, or just one. This and other data suggest that age-dependent risk factors that havent yet been identified may contribute to CVD.. Scientists know that accumulation of somatic DNA mutations is a feature of aging, though little data exists on the role of such mutations in age-associated disorders beyond cancer. Meanwhile, recent human studies indicate that aging is associated with an increase in somatic mutations in the hematopoietic system, which gives rise to blood cells; these mutations provide a competitive growth advantage to the mutant hematopoietic cells, allowing for their clonal ...
Ok i was under the impression that exon skipping would work for nonsense mutations, but I was told that it could require multiple skips to get the desired resu…
My research is focused on understanding the molecular pathways that lead to inherited Parkinsons disease linked to mutations in Leucine rich repeat kinase 2 (LRRK2). Mutations in this gene are the single most common genetic cause of Parkinsons disease, affecting 5-10,000 people in the UK alone. LRRK2 itself is a multidomain enzyme, possessing both kinase and GTPase activities, and much of my work over the past 8 years has been directed at dissecting how mutations impact on these activities, and how they regulate one another. To do this, my group uses a combination of cellular and biochemical approaches, including cellular models for LRRK2 function and in vitro enzymatic assays. We have a particular interest in investigating proteins closely related to LRRK2 as a means to achieving a greater understanding of how LRRK2 itself functions. Our research has highlighted a putative role for LRRK2 in the regulation of autophagy ...
In the last two decades, according to the National Institute of Allergy and Infectious Diseases, nearly half of the new pathogens that affect human and animal health have been viruses. As with the influenza A (H1N1) pandemic in 2009, most of these diseases can quickly adapt and morph into nastier strains that resist attacks by vaccines and immune systems.. The Defense Advanced Research Projects Agency (DARPA), through a program called DARPA Prophecy, has tapped Harvard University and APL to develop methods to predict how, and how fast, these viral agents might mutate.. The current approach to dealing with viruses is reactive, explains Andrew Feldman, DARPA Prophecy project manager and principal investigator in the Research and Exploratory Development Department. Existing vaccines and therapies are designed to protect against viruses that are already out there, and new vaccines take years to develop. But we are trying to get out in front of emerging diseases by predicting how viruses ...
While the findings could have implications for other common diseases, in particular neurological disorders such as autism or schizophrenia, several scientists say it is unlikely that rare mutations play an equally large role in common diseases with late onset, where natural selection has had a different effect.
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The following mutations are based on material from earlier editions of Gamma World, adapted for the Alternity edition. The gamemaster can extend the mutation tables or allow the new mutations to be substituted for some existing mutations, if they are being determined randomly. Physical Mutations Burning Hands Good, Activated, WIL The mutant can emit heat from his hands…
Mutations in the promoter region and the three exons of CYP1B1 were analyzed by direct PCR sequencing in a total 109 people, which consisted of 39 affected by PCG and 70 unaffected relatives of the patients. No mutations segregating with the disease were found in the promoter region. We identified a total of 16 distinct DNA mutations in 13 (34.2%) of the 38 unrelated index cases: six transitions (2 G,A and 4 C,T), six transversions (3 C,A, 1 T,A and 2 G,T), three small deletions, and one small duplication (Table 2 and Figure 1). The transitions and transversions predicted nine missense (P52L, G61E, Y81N, A106D, F261L, R390S, P400S, P437L, and R469W) and three nonsense (E262X, W341X, and E173X) amino acid substitutions (Table 2 and Figure 1). On the other hand, the conceptual translation of one nucleotide long and 13 nucleotide long deletions (c.906delG and c.1435_1447delGAGTGCAGGCAGA, respectively) as well as one 10 nucleotide long duplication (c.1571_1580dupTCATGCCACC) resulted in three ...
Contrary to what was thought previously, bacteria seem to be, not merely spectators to their own evolution, but, through a variety of mechanisms, able to increase the rate at which mutations occur and, consequently, to increase their chances of becoming resistant to antibiotics. Laboratory studies and mathematical models suggest that, under stressful conditions, such as antibiotic challenge, selective pressure favors mutator strains of bacteria over nonmutator strains. These hypermutable strains have been found in natural bacterial populations at higher frequencies than expected. The presence of mutator strains in the clinical setting may indicate an enhanced risk of acquiring antibiotic resistance through mutational and recombinational events. In addition, some antibiotics are inducers of mechanisms that transiently increase the mutation rate, and thus probably act, not only as mere selectors of antibiotic resistant clones, but also as resistance-promoters ...
In accordance with the latest scientific findings, we are updating our somatic tumor panel. The total number of genes on this panel is now 710, up from 649. The panel now includes mutational load analysis of the tumor and also supports the examination of leukemia and lymphoma.. The current update was designed to enable personalized therapy decisions, determined by an interdisciplinary tumor board, addressing solid tumors, leukemia and lymphoma. Weve added additional genes that, according to the latest scientific findings, are linked to the development, growth, disease outlook, drug metabolism, and tumor therapy outcome. The examination of selected translocations is now performed in 29 genes.. In addition to the reporting of these treatment-relevant gene changes, we are also expanding our medical reports by reporting the mutation load of the tumor. Data increasingly suggests that tumors with very high mutation load have increased numbers of neo-antigens on the cell surface, and may therefore ...
A mathematical model that combines stochasticity and spatial structure describes the dynamics of the viral population during an infection cycle, and fitting the model to RNA and virus abundances over time shows that poliovirus follows a geometric replication mode.
A gene mutation in the brain can trigger irregular heart beat and sudden death in people with epilepsy, revealed a study released Tuesday.
The enteric pathogen S. typhimurium has a phage-type known as DT104, which is associated with an epidemiology that is extensive and virulent. It was characterised about 30 years ago, and has spread to nearly all areas of the earth since then (2). S. typhimurium DT104 was found to have become resistant to multiple antibiotics in 1972 (2). This strain, now known as MDR-DT104, acquired the relevant mutation through the integration of an additional 43-kilobase genomic island (SGI1) into its genetic profile (3). In 1975, an alternative strain of DT104 also acquired multi-drug resistance in Thailand via different mechanisms (2). SGI1 confers resistance to a specific subset of antibiotics: sulphonamide-types, as well as tetracycline, streptomycin, chloramphenicol and ampicillin (3). However, some MDR-DT104 strains isolated in Britain were found to have added resistance to trimethoprim, (13%) ciprofloxacin (16%) or both (2%) to their anti-drug arsenal (1). In addition, some studies have reported ...
To defeat current commercial antivirus software, the virus developers are employing obfuscation techniques to create mutating viruses. The current antiviru
More recently, another analysis (Ohno, 1984) added further evidence that at least one of the proteins was formed from an essentially random sequence of amino acids. This evidence is a little bit more difficult to understand since its comprehension involves some understanding of how the genetic code works. Ill just have to refer readers who do not have this background to an explanation such as Suzuki, et. al, 1976. It appears that the DNA that formed the gene was somewhat unusual since it could be "read" without finding a "stop" word in any of the three "reading frames." It can be shown that such DNA sequences could easily occur through the well-known process of duplication. The DNA sequence suggests that a simple "frame-shift" mutation could have brought about the chance formation of at least this one enzyme. "Frame-shift" mutations are known for forming totally new and essentially random arrays of amino acids since the code is "read" in a new reading frame. Usually the proteins that are formed ...
Independent mutations in Ad2ts111 cause degradation of cellular DNA and defective viral DNA replication.: An adenovirus mutant, Ad2ts111, has previously been sh
Potential energy (kJ/mol) of native and mutant type SHV β-lactamases.Native is shown in black; S130G mutant form of SHV β-lactamases is shown in red.
TY - JOUR. T1 - Modeling post-translational modifications and cancer-associated mutations that impact the heterochromatin protein 1α-importin α heterodimers. AU - Zimmermann, Michael T.. AU - Williams, Monique M.. AU - Klee, Eric W. AU - Lomberk, Gwen A.. AU - Urrutia, Raul. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Heterochromatin protein 1α (HP1α) is a protein that mediates cancer-associated processes in the cell nucleus. Proteomic experiments, reported here, demonstrate that HP1α complexes with importin α (IMPα), a protein necessary for its nuclear transport. This data is congruent with Simple Linear Motif (SLiM) analyses that identify an IMPα-binding motif within the linker that joins the two globular domains of this protein. Using molecular modeling and dynamics simulations, we develop a model of the IMPα-HP1α complex and investigate the impact of phosphorylation and genomic variants on their interaction. We demonstrate that phosphorylation of the HP1α linker likely regulates its ...
BACKGROUND: In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed. METHODS: We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF ...
The aim of the present study was to investigate the mutation rate of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) patients and to apply logistic regression analysis to investigate the factors associated with EGFR gene mutation to provide data for the treatment of NSCLC. Paraffin tissue, bronchoscopy or pleural effusion specimens were collected from 176 NSCLC patients following pathological diagnosis. The EGFR gene exon 19 delL747-S75linss and delL747-S752ins deletion mutations, and the exon 20 T790M and exon 21 L858R mutations were identified using amplification refractory mutation system analysis. The clinical data and laboratory results of the patients were collected, and the total mutation rate of the EGFR gene in exons 19, 20 and 21 in the 176 NSCLC patients was found to be 48.3% (85/176). In addition, the EGFR gene mutation rate in adenocarcinoma was found to be significantly higher than that in squamous cell and large cell carcinoma (χ²=12.454; ...
We have isolated three independent Chinese hamster ovary cell mutants (B3853, I223, and M311) with temperature-sensitive, pleiotropic defects in receptor-mediated endocytosis. Activities affected at 41 degrees C include uptake via the D-mannose 6-phosphate receptor, accumulation of Fe from diferric transferrin, uptake of alpha 2-macroglobulin, compartmentalization of newly synthesized acid hydrolases, resistance to ricin, and sensitivity to diphtheria and Pseudomonas toxins and modeccin. The three mutants also displayed decreased sialylation of some secreted glycoproteins at 41 degrees C, reminiscent of the nonconditional mutant DTG1-5-4 that showed both endocytic and Golgi-associated defects (Robbins, A.R., C. Oliver, J.L. Bateman, S.S. Krag, C.J. Galloway, and I. Mellman, 1984, J. Cell Biol., 99:1296-1308). Phenotypic changes were detectable within 30 min after transfer of the mutants to 41 degrees C; maximal alteration of most susceptible functions was obtained 4 h after temperature shift. At ...
Looking for online definition of cystic fibrosis transmembrane conductance regulator gene in the Medical Dictionary? cystic fibrosis transmembrane conductance regulator gene explanation free. What is cystic fibrosis transmembrane conductance regulator gene? Meaning of cystic fibrosis transmembrane conductance regulator gene medical term. What does cystic fibrosis transmembrane conductance regulator gene mean?
Objective: Familial hemophagocytic lymphohistiocytosis (FHL) is a fatal disorder of immune dysregulation with defective cytotoxic lymphocyte function. Disease-causing mutations have been identified in the genes encoding perforin (PRF1), syntaxin-11 (STX11), and Munc13-4 (UNC13D). We screened for UNC13D mutations and studied clinical and functional implications of such mutations in a well-defined patient cohort. Methods: Sequencing of UNC13D was performed in 38 FHL patients from 34 families where mutations in the PRF1 and STX11 had been excluded. Results: We identified six different mutations affecting altogether 9/38 individuals (24%) in 6/34 (18%) unrelated PRF1/STX11-negative families. Four novel mutations were revealed; two homozygous nonsense mutations (R83X and W382X), one splice mutation (exon 28), and one missense mutation (R928P). In addition, two known mutations were identified (R214X and a deletion resulting in a frame-shift starting at codon 782). There was considerable variation in ...
TY - JOUR. T1 - Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome. T2 - A prospective, open-label, dose-escalation study. AU - Bulua, Ariel C.. AU - Mogul, Douglas Bradford. AU - Aksentijevich, Ivona. AU - Singh, Harjot. AU - He, David Y.. AU - Muenz, Larry R.. AU - Ward, Michael M.. AU - Yarboro, Cheryl H.. AU - Kastner, Daniel L.. AU - Siegel, Richard M.. AU - Hull, Keith M.. PY - 2012/3. Y1 - 2012/3. N2 - Objective To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Fifteen patients with TRAPS were enrolled in a prospective, open-label, dose-escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary. Blood samples were collected during each period and measured for levels of acute-phase reactants. Between 7 years and 9 years after the conclusion of the initial ...
American Journal of Pathology, Vol. 164, No. 1, January 2004 Copyright © American Society for Investigative Pathology KIT Mutations Are Common in Testicular Seminomas Kathleen Kemmer,* Christopher L. Corless, † Jonathan A. Fletcher, ‡ Laura McGreevey,* Andrea Haley, † Diana Griffith,* Oscar W. Cummings, § Cecily Wait,* Ajia Town,* and Michael C. Heinrich* From the Division of Hematology and Oncology,* Department of Pathology, † Oregon Health and Science University Cancer Institute and Portland Veterans Affairs Medical Center, Portland, Oregon; the Department of Pathology, † Brigham and Womens Hospital, Boston, Massachusetts; and the Department of Pathology, § Indiana University, Indianapolis, Indiana Expression of KIT tyrosine kinase is critical for normal germ cell development and is observed in the majority of seminomas. Activating mutations in KIT are common in gastrointestinal stromal tumors and mastocytosis. In this study we examined the frequency and spectrum of KIT mutations ...
The Online Mendelian Inheritance in Man (OMIM) compendium of human genes and genetic phenotypes includes three types of congenital dyserythropoietic anemia as reported in Table 1. A comprehensive overview of these disorders has been published recently.1. Congenital dyserythropoietic anemia type II is the most common of these inherited disorders. Typical morphological abnormalities of this condition are shown in Figure 1: these abnormalities clearly indicate that incomplete cytokinesis is one of the key features of erythroid cells in this condition.. More than 30 years ago, we investigated the pathophysiology of anemia in patients with congenital dyserythropoietic anemia type II in studies of iron kinetics.2 A wide variation in effectiveness of erythroid activity was observed, and a significant inverse relationship was found between ineffective erythropoiesis and peripheral hemolysis. In 4 patients with prominent peripheral hemolysis, splenectomy was carried out. Marked improvement in their ...
Mutations[edit]. Figure 3. Effects on TBP binding to the TATA box from mutations. Wildtype shows transcription done normally. ... Point mutations[edit]. Point mutations to the TATA box have similar varying phenotypic changes depending on the gene that is ... Mutations to the TATA box can range from a deletion or insertion to a point mutation with varying effects based on the gene ... Based on the sequence and mechanism of TATA box initiation, mutations such as insertions, deletions, and point mutations to ...
Defining mutations. M242. Highest frequencies. Kets 93.8%,[6] Turkmens 73%,[7] Selkups 66.4%.,[6] Altaians 63.6%.,[8] Tuvans ... Technical specification of mutation[edit]. The technical details of M242 are: Nucleotide change: C to T. Position (base pair): ... The subclades of Haplogroup Q-M242 with their defining mutation (s), according to the 2015 ISOGG tree[4] are provided below. ... Human Mutation. 24 (3): 248-60. doi:10.1002/humu.20077. PMID 15300852.. Q-M323 in 3/20=15% of a sample of Yemenite Jews. ...
75 to 80 percent of Leigh syndrome is caused by mutations in nuclear DNA; mutations affecting the function or assembly of the ... The most common MT-ATP6 mutation found with Leigh syndrome is a point mutation at nucleotide 8993 that changes a thymine to a ... Mutations in mitochondrial DNA (mtDNA) and over 30 genes in nuclear DNA (gene SURF1[8] and some COX assembly factors) have been ... Mitochondrial DNA mutations[edit]. Mitochondria are essential organelles in eukaryotic cells. Their function is to convert the ...
Consonant mutation[edit]. Another feature of the language is initial consonant mutation between singular and plural forms of ... nouns and of verbs (except in Pular, there is no consonant mutation in verbs, only in nouns). ...
Initial mutations[edit]. Main article: Irish initial mutations. In Irish, there are two classes of initial consonant mutations ... Due to initial mutation, prefixes, clitics, suffixes, root inflection, ending morphology, elision, sandhi, epinthesis, and ... Mutations are often the only way to distinguish grammatical forms. For example, the only non-contextual way to distinguish ... possessive pronouns "her," "his" and "their", is through initial mutations since all meanings are represented by the same word ...
Rare mutations[edit]. Women with CAIS, who are completely insensitive to the AR-mediated actions of androgens, have, as a group ...
MDR1 gene mutation[edit]. Recent research at Washington State University indicates that, in addition to many other herding ... breeds, approximately 15% of the English Shepherd population is subject to the MDR1 gene mutation. Dogs that are tested ...
EGFR mutations[edit]. Roughly 10-35% of people who have NSCLC will have drug sensitizing mutations of the EGFR.[43] The ... likely cause the high level of mutation in lung cancer cells of more than 100,000 mutations per genome (see Whole genome ... Several studies have also shown that ALK mutations and EGFR activating mutations are typically mutually exclusive. Thus, it is ... People with these mutations are more likely to have adenocarcinoma histology and be non-smokers or light smokers. These people ...
Mutation[edit]. Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency ... Cause of mutations[edit]. The likely major underlying cause of mutations in carcinomas is DNA damage.[13] For example, in the ... The high mutation frequencies in carcinomas reflect the genome instability characteristic of cancers.[citation needed] ... While a mutation or epimutation in a DNA repair gene, itself, would not confer a selective advantage, such a repair defect may ...
Mutations[edit]. Panem uses genetic engineering to create animals which figure into the Hunger Games or otherwise serve its ... part-human mutations during the second rebellion, so that he could save Katniss's life. This results in Annie being the only ...
Mutation breeding[edit]. Conventional hybridization is difficult to carry out in roselle due to its cleistogamous nature of ... Because of this, a mutation breeding programme was initiated to generate new genetic variability.[21] The use of induced ... Roselle improvement through conventional and mutation breeding. Proc. Intern. Nuclear Conf. 2002, 15-18 Oct 2002, Kuala Lumpur ... These new varieties were developed using Arab as the parent variety in a mutation breeding programme which started in 2006. ...
Sports (mutations)[edit]. Many sports of Gala have been selected, mostly for increased red color, including the popular Royal ...
Mitochondrial mutations in disease[edit]. See also: Mitochondrial diseases. Mutations in mitochondrial DNA are usually single ... This refers to hundreds of independent mutations in one organism, with each mutation found in about 1-2% of all mitochondrial ... In most cases, a muscle mutation level of approximately 18% or less confers a 95% risk reduction.[12] ... Additionally, there is a dose-dependent decrease in reproduction ability for females that have mutations in mitochondrial DNA. ...
Mutation mechanisms and mutation rates[edit]. DNA strand slippage during replication of an STR locus. Boxes symbolize ... Unlike point mutations, which affect only a single nucleotide, microsatellite mutations lead to the gain or loss of an entire ... Microsatellite mutation rates[edit]. Microsatellite mutation rates vary with base position relative to the microsatellite, ... Thus, the mutation rate at microsatellite loci is expected to differ from other mutation rates, such as base substitution rates ...
Deleterious mutation clearance[edit]. Mutations can have many different effects upon an organism. It is generally believed that ... Once a mutation occurs in the DNA or other genetic carrying sequence, there is no way for the mutation to be removed from the ... The next mutation that occurs turns the ratchet once more. Additional mutations in a population continually turn the ratchet ... Muller described this occurrence by comparing the mutations that accumulate as a ratchet. Each mutation that arises in ...
Mutations[edit]. Approximately four hundred type X Charcot-Marie-Tooth causing mutations have been identified within the GJB1 ... Some of these mutations also cause hearing loss in patients with CMTX.[14] Currently it is unknown how the mutations of the ... Most of the mutations of the GJB1 gene switch or change a single amino acid in the gap junction (connexin-32) protein, although ... With the creation of genetic testing, 90% of CMTX cases are now diagnosed using the mutations of the GJB1 (Cx32) gene.[11] The ...
COD has been linked to several genetic mutations including mutations in the guanylate cyclase activator 1A (GUCA1A) and ... Mutations[edit]. Cone dystrophy (COD) is a retinal degradation of photoreceptor function wherein cone function is lost at the ... 2011). "Mutation analysis at codon 838 of the guanylate cycllase 2D gene in spanish families with autosomal dominant cone, cone ... Therefore, mutations in the RETGC-1 can cause COD by increasing intracellular calcium levels and stimulating cone photoreceptor ...
Genetic mutations occur when nucleotide sequences in an organism are altered. These mutations lead to not only observable ... The sources for these mutations can be errors during replication, spontaneous mutations, and chemical and physical mutagens (UV ... Mutations in polycomb-group response elements (PREs)[edit]. The Polycomb-group (PcG) regulatory complexes are known for their ... A mutation in either the NRSF or NRSE can lead to an undesirable development of ventricular myocytes, due to lack of repression ...
Gene mutations[edit]. Genetic mutations and chromosomal abnormalities are two sources of HPG axis alteration.[15] Single ... For example, the male mutation of the GnRH coding gene could result in hypogonadotrophic hypogonadism. A mutation that cause a ... These mutations can occur in the genes coding for GnRH, LH, and FSH or their receptors. Depending on which hormone and receptor ... In females mutations would have analogous effects. Hormone replacement can be used to initiate puberty and continue if the gene ...
In this mutation, the adult male is melanistic with black wings.[8][12] Young birds with the nigripennis mutation are creamy ... Mutations and hybrids[edit]. A white peafowl that is maintained by selective breeding in many parks such as this one at the ... The black-shouldered or Japanned mutation was initially considered as a subspecies P. c. nigripennis (or even a species),[11] ... There are several colour mutations of Indian peafowl. These very rarely occur in the wild, but selective breeding has made them ...
Most mutations have little effect on an organism's phenotype, health, or reproductive fitness.[76] Mutations that do have an ... Mutations occasionally occur within cells in the body as they divide. Although these mutations will not be inherited by any ... Figure (2) shows a missense, single point, non silent mutation. Figures (3 and 4) both show frameshift mutations, which is why ... somatic mutations). The most frequent mutations are a loss of function of p53 protein, a tumor suppressor, or in the p53 ...
a b Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R. Viral mutation rates. Journal of Virology. 2010;84(19):9733-48. doi: ... Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, Chang Y. T antigen mutations are a human tumor-specific signature for ... However, viruses are not classified on the basis of phylum or class, as their small genome size and high rate of mutation makes ... Most of these point mutations are "silent" - they do not change the protein that the gene encodes - but others can confer ...
High mutation rate[edit]. Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The ... Three mutations were introduced into the H5N1 virus genome, and the virus was then passed from the noses of infected ferrets to ... Mutations occurring within this genotype are increasing their pathogenicity.[66] Birds are also able to shed the virus for ... Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of ...
High mutation rate[edit]. The human Y chromosome is particularly exposed to high mutation rates due to the environment in which ... These two conditions combined put the Y chromosome at a greater risk of mutation than the rest of the genome.[16] The increased ... Thus, although a male may have a well adapted Y chromosome free of excessive mutation, it may never make it in to the next gene ... Even if a well adapted Y chromosome manages to maintain genetic activity by avoiding mutation accumulation, there is no ...
Gene mutations[edit]. Several gene mutations have been identified in patients with camptocormia. These include the RYR1 gene in ...
Consonant mutation[edit]. Celtic languages[edit]. See also: Irish initial mutations § Changes to vowel-initial words ...
These mutations can be passed down genetically and either be lost or become fixed. Since mutation usually affects a single ... To connect the idea of mutations back to our discussion of DNA and proteins, here are some examples of how a mutation in the ... Finally, a common mutation in humans causes red blood cells to be shaped in a sickle pattern as shown above on the upper left. ... A mutation in these garden moss roses (shown in the left) has caused some of the flowers to grow orange rather than yellow. ...
Most of these mutations are in two genes, one of which codes for myosin, a protein crucial to muscle contraction. These myosin ... "She walked up to me and said, We need to work together to understand how different mutations affect the myosin motif." ... "Wed very much like to work with Raúl to solve these structures using human specimens, with and without HCM mutations," Seidman ... as she discovered many of the mutations we were mapping in the myosin model in our poster," he said. " ...
A suppressor mutation is a second mutation that alleviates or reverts the phenotypic effects of an already existing mutation in ... suppression relieves the effects of a mutation in one gene by a mutation somewhere else within the genome. The second mutation ... Intragenic suppression results from suppressor mutations that occur in the same gene as the original mutation. In a classic ... Genetic suppression therefore restores the phenotype seen prior to the original background mutation.[1] Suppressor mutations ...
A germline mutation can also occur due to exogenous factors. Similar to somatic mutations, germline mutations can be caused by ... Germline mutation is distinct from somatic mutation. Germline mutations can be caused by a variety of endogenous (internal) and ... Patients with this mutation are also at a risk for Li-Fraumeni syndrome.[16] Other examples include mutations in the BRCA1 and ... These mutations can occur in germ cells, allowing them to be heritable.[15] Individuals who inherit germline mutations in TP53 ...
"mutation" in le Trésor de la langue française informatisé (The Digitized Treasury of the French Language). ... Names for a group: A flute or mutation of thrushes.. *2013, Jason Sacher, A Compendium of Collective Nouns: From an Armory of ... From Middle French mutation, from Old French mutacion, borrowed from Latin mutatio, mutationem. ... A Mutation of Thrushes. The authors of the books of venery were not predicting Darwin with this term, but taking a cue from a ...
... mutation refers to any sudden change in DNA-deoxyribonucleic acid, the genetic blueprint for an organism-that creates a change ... MUTATION CONCEPT A word familiar to all fans of science fiction [1], ... Mutation Biology COPYRIGHT 2002 The Gale Group Inc.. Mutation. Mutations are physical changes in genes and chromosomes . They ... Mutation UXL Encyclopedia of Science COPYRIGHT 2002 The Gale Group, Inc.. Mutation. A mutation is a permanent change in a gene ...
... everything you need for studying or teaching Mutation. ... Immediately download the Mutation summary, chapter-by-chapter ... Same-Sense Mutation A same-sense mutation is form of silent mutation where a change in the base sequence of a gene does not ... Gene Mutation Gene mutation is a sudden change in the DNA making up an individual gene. Gene mutation is a fairly infrequent ... Mutation A mutation is any heritable change in the genome of an organism. For a population, heritable mutations provide the ...
Change in the genetic structure (DNA); it may occur spontaneously or be induced (e.g., by radiation, drugs, or certain mutagenic chemicals ...
5. Mutations affect and are affected by many genes.. The mutation concept is no longer as simple as it once was. Instead of a ... 1. Mutations are random, not directed.. It remains true to say that we know of no way other than random mutation by which new ... 2. Mutations are rare, not common.. It is probably fair to estimate the frequency of a majority of mutations in higher ... 4. The Net Effect of All Mutations is Harmful. Even if the mutations are not harmful enough to cause their carriers to be ...
The production by further mutation [1] of a premutation gene [2] from a mutant gene. This reverse mutation restores the ability ... Strictly, reversion is the correction of a mutation, i.e. ... reverse mutation (reversion) The production by further mutation ... reverse mutation (reversion) The production by further mutation of a premutation gene from a mutant gene. This reverse mutation ... the term is applied also to a mutation at another site that masks or suppresses the effect of the first mutation (in fact such ...
The Mechanisms of Mutation group studies the detailed mechanisms by which mutations occur using the bacterium E. coli as a ... Many E. coli mutator mutants, which have a higher mutation rate than the wild-type strain, have been identified, and their ... Mutations may arise from a multitude of sources, which include errors of DNA replication, multiple DNA damage pathways that ... Conversely, antimutator mutants, displaying a lower mutation rate than the wild-type, have also been isolated. Such ...
... the pivotal points is called mutation. It enabled the singer to apply the solmization syllables to any series of notes he ... the pivotal points is called mutation. It enabled the singer to apply the solmization syllables to any series of notes he ... Other articles where Mutation is discussed: hexachord: … ... Mutation. music. THIS IS A DIRECTORY PAGE. Britannica does not ...
... (also known as i-umlaut) is the raising and fronting of a root vowel in anticipation of i or y s ... I-Mutation. I-MUTATION (also known as i-umlaut) is the raising and fronting of a root vowel in anticipation of i or y ... 6. I-mutation turns up in an adjective formed from a noun by adding -ish in at least one important case: English (Old English ... I-mutation is caused by the very human habit of laziness: taking the shortest distance between two points. The plural of man in ...
... gene mutations are associated with bone marrow disorders called myeloproliferative neoplasms (MPNs) caused by the production of ... The JAK2 mutation test may be used, along with other tests such as CALR mutation and MPL mutation testing, to help diagnose ... have a JAK2 mutation, most for the JAK2 V617F mutation. Additionally, the mutation is also rarely found in people with chronic ... The primary JAK2 test is JAK2 V617F, named for a mutation at a specific location in the JAK2 gene. JAK2 V617F mutation is ...
Other family members could still inherit the mutation and should still be tested for the mutation that runs in your family. ... Other family members could still inherit the mutation and should be tested for the mutation that runs in your family. ... You cannot pass the mutation on to your child. If you have LDL cholesterol levels higher than 100 mg/dL, you may be at risk for ... What the test results mean for you and your family if the FH-causing mutation in your family has been found through genetic ...
CHAMP Mutations, United States Excel fileexcel icon. CHBMP F9 Mutation List. The CHBMP F9 Mutation List is an Excel database ... CHAMP F8 Mutation List. The CHAMP F8 mutations that have been reported worldwide. It was compiled from mutations listed ... CHBMP Mutation List Database Excel fileexcel icon. CHBMP F9 Mutations in the United States. As part of the Hemophilia Inhibitor ... CHAMP Mutation List Database Excel fileexcel icon. CHAMP F8 Mutations in the United States. As part of the Hemophilia Inhibitor ...
Mutation. Definition. A mutation is any detectable and heritable change in nucleotide sequence that causes a change in genotype ... Elucidation of the unique mutation spectrum of severe hearing loss in a Vietnamese pediatric population *Jae Joon Han ... microphthalmia plus posterior capsule defect in monozygotic twins caused by a novel GJA8 mutation *Hongfang Zhang ...
Pages in category "Manx mutation templates". The following 2 pages are in this category, out of 2 total. ... Retrieved from "https://en.wiktionary.org/w/index.php?title=Category:Manx_mutation_templates&oldid=28295291" ...
Mutations in which one base is changed are called point mutations-for example, substitution of the nucleotide pair AT by GC, CG ... Mutations arise from changes to the DNA of a gene. These changes can be quite small, affecting only one nucleotide pair, or ... Any mutation that results in a lack of function for a particular gene is called a "null" mutation. Less-severe mutations are ... Mechanisms of mutation. Mutations arise from changes to the DNA of a gene. These changes can be quite small, affecting only one ...
hack Part 2: Mutation Movie 1. Take a look the intro movie to .hack Part 2: Mutation in this clip. ... hack Part 2: Mutation Review. Even if you really liked the first .hack game, you probably wont like the second installment as ... hack Part 2: Mutation Movie 4. Take a look at some new footage of the second installment of the .hack series. ... hack Part 2: Mutation Movie 2. Kite and a friend explore the depths of a dungeon in The World. ...
A clinician advocates genetic testing to identify asymptomatic mutation carriers who are at risk for several cancers associated ... has written extensively on genetic testing for mutations related to multiple endocrine neoplasia type 1 - a rare, autosomal- ...
A version of this archives appears in print on August 30, 1909, on Page 6 of the New York edition with the headline: MUTATION ...
14 Spirant Mutation. 14.1 The spirant mutation happens after the conjunction/preposition a (and, with -- really the same ...
CpG Mutations.. CpG dinucleotides are known to be mutation hotspots in some cancer types (1, 3-5). Thirty-two percent of the ... We also excluded mutations in intronic splice sites. Analysis of mutation data from ref. 1 for Fig. 3 used version 1 of the ... Mutation frequencies for data from refs. 1 and 3-5 were calculated by dividing the observed number of nonsynonymous mutations ... Transition mutations occur at a significantly higher rate than transversion mutations (6-8). Substitution rates depend on ...
... mutation (Montreal Permutation, Käferfrühstück and more). 30 tracks (132:35). Discover more music, concerts, videos, and ...
  • Several genes known to contain mononucleotide short tracts in their coding sequences (TGF-β RII, IGFIIR, BAX, hMSH6, and hMSH3) are likely targets for mutations in these tumors. (uniroma1.it)
  • 0%). The mutations frequently were distributed heterogeneously throughout the tumors. (uniroma1.it)
  • Overall, frameshift mutations at i or more of these mononucleotide repeat microsatellites were found in 17 of 24 MI+ tumors (70.8%) but in none of the 10 MI negative neoplasms. (uniroma1.it)
  • In the seven EC patients with lymph node metastases, mutations in IGFRH were found more commonly in those with metastatic (three of seven patients) rather than primary (one of seven) tumors. (uniroma1.it)
  • The frequent detection of IGFRII frameshift mutations in lymph node metastases suggest that IGFRII may play a role in tumor progression in these patients. (uniroma1.it)
  • Frameshift mutations at coding mononucleotide repeats were detected by single strand conformation polymorphism analysis and DNA sequencing. (uniroma1.it)
  • Earlier studies of asbestos have already shown that the thin fibers, which penetrate the body by inhalation or through consumption of food contaminated with the material, not only cause certain cancers but also genetic mutations in DNA structures. (medicalnewstoday.com)
  • Data from the Israeli Ministry of Health indicate a rise in the number of cancer patients from exposure to asbestos in the Western Galilee region of northern Israel, and therefore the scientists set out to examine whether genetic mutations are found in the mouse population living in its northern town of Nahariya. (medicalnewstoday.com)
  • In the first part of the study, mice with particular genetic mutations (including a mutation in a gene called LKB1) were given a virus that causes lung tumours. (www.nhs.uk)
  • The researchers then investigated the effects of the mutations and the interactions between the different genetic mutations and the characteristics of the lung tumours that developed in the mice. (www.nhs.uk)
  • A new research effort carried out by the drug titan Pfizer was able to successfully locate 15 genetic mutations linked to depression, thanks to the 450,000 individuals who gave 23andMe permission to use their genetic data for such research. (extremetech.com)
  • The treatment goes after one major genetic mutations that causes the disease, called G551. (discovermagazine.com)
  • Researchers unveiled a comprehensive look at the genetic mutations responsible for two cancers Wednesday as part of a broad government-sponsored initiative to enlist the power of genomic information to transform cancer treatment. (foxnews.com)
  • None of these patients had any family with a history of the condition, suggesting that their condition may have been caused by genetic mutations. (redorbit.com)
  • A pioneering stem-cell trial has been halted after genetic mutations were discovered in the cells of the second trial participant. (newscientist.com)
  • Researchers showed that mutations caused by either a single base insertion (+) or a single base deletion (-) could be "suppressed" or restored by a second mutation of the opposite sign, as long as the two mutations occurred in the same vicinity of the gene. (wikipedia.org)
  • Therefore, researchers concluded that the second mutation of opposite sign suppresses the original mutation by restoring the reading frame, as long as the portion between the two mutations is not critical for protein function. (wikipedia.org)
  • Researchers examined a mutation called the missense rs4238001 variant, which alters the type of protein made by the gene SCARB1, and thereby the body's cholesterol regulation. (medicalnewstoday.com)
  • But now that the UConn study made the connection between the mutation in SCARB1 and heart disease, the researchers want to figure out a way to fix it. (medicalnewstoday.com)
  • Two other mutations causing congenital analgesia are being actively explored by researchers alongside pharmaceutical firms, but have yet to yield any breakthrough drugs. (ucl.ac.uk)
  • Heart disease is one of the world's leading killers, but now that researchers have identified this common mutation, carried by one in 25 people of Indian origin, we have hope of reducing the burden that the disease causes. (redorbit.com)
  • Researchers have discovered the first definitive proof that a mutation in a single gene can cause Parkinson's disease, the second most common brain degenerative disorder after Alzheimer's disease. (wsj.com)
  • By investigating 7,329,860 somatic mutations from the cancer genomes, the researchers were able to effectively look back in time, calculating which mutations each cell had had before it became a cancer cell. (lanl.gov)
  • NEW YORK, Jan. 31 (UPI) -- A gene mutation could increase the potential of aggressive tumor development in men suffering from prostate cancer, U.S. researchers say. (upi.com)
  • After HIV researchers made CCR5 -Δ32 famous, scientists in other fields got interested in the mutation, too. (theatlantic.com)
  • The second part of this study found that only 34% of human lung tumours had the mutations in the gene that the researchers were investigating. (www.nhs.uk)
  • In the second part of the study, the researchers looked at DNA from 144 frozen samples of human lung cancer tumours and looked for the presence of four mutations, including the mutation at LKB1. (www.nhs.uk)
  • In the second part of the study, the researchers found an LKB1 mutation in 34% of the human lung adenocarcinomas and in 19% of the human squamous cell carcinomas. (www.nhs.uk)
  • Knowing that there is an association between the LKB1 mutation and some lung cancers does not mean that researchers would know how to prevent cancer in people with this mutation. (www.nhs.uk)
  • This led the researchers to identify the gene Gabrb1 which changes alcohol preference so strongly that mice carrying either of two single base-pair point mutations in this gene preferred drinking alcohol (10% ethanol v/v - about the strength of wine), over water. (ucl.ac.uk)
  • The researchers found that the gene mutation caused the receptor to activate spontaneously even when the usual GABA trigger was not present. (ucl.ac.uk)
  • Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion - a mutation that confers the highest known genetic risk for schizophrenia - is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled. (psychcentral.com)
  • Researchers had access to samples from both early and later stages of the disease, enabling them to see the order in which key mutations appeared in affected blood cells. (newscientist.com)
  • Researchers discovered a genetic mutation, which makes breastfeeding physically harder to achieve. (dailymail.co.uk)
  • Reuters) - A specific mutation in the new coronavirus can significantly increase its ability to infect cells, according to a study by U.S. researchers. (reuters.com)
  • The researchers say that it is still unknown whether this small mutation affects the severity of symptoms of infected people, or increases mortality. (reuters.com)
  • Image 2 (below): Researchers identify the single genetic mutation responsible for rare condition in UK Paracycling Champion, Tom Staniford. (redorbit.com)
  • In a study of Bayer AG (BAYN) 's drug Stivarga, researchers analyzed tissue and blood samples from patients with gastrointestinal stromal tumors, or GIST, to find cancer-driving mutations. (bloomberg.com)
  • As cancer treatments increasingly home in on known genetic causes of the disease, researchers need better tools to determine just what mutations each patient has, said George Demetri, director of the Ludwig Center at Dana-Farber Cancer Institute and Harvard Medical School, who led the trial. (bloomberg.com)
  • Bayer jointly promotes Stivarga with Onyx Pharmaceuticals Inc. In the study, researchers took blood samples from patients once their cancer had progressed and analyzed them for mutations, including so- called secondary mutations that cause resistance to those drugs. (bloomberg.com)
  • Newer versions of the technology are being worked on now that would enable researchers to seek out unidentified cancer-causing mutations, which could be helpful for drug development. (bloomberg.com)
  • Using data from 25,000 people, researchers from the Faculty of Medicine and University College London's Institute of Neurology discovered that a rare genetic mutation in the TREM2 gene - which helps trigger immune system responses - is also associated with increased risk of Alzheimer's. (utoronto.ca)
  • DALLAS - Feb. 10, 2010 - A mutation in a single gene can cause endometrial cancer that is responsive to a specific drug therapy, researchers at UT Southwestern Medical Center have found in an animal study. (eurekalert.org)
  • The finding suggests that eventually it might be possible to screen women with endometrial cancer to see if they have that mutation and use the drug as targeted therapy, the researchers said. (eurekalert.org)
  • CAMBRIDGE, England, March 18-Researchers have identified a mutation in the tyrosine kinase JAK2 gene that could lead to better diagnostic tests and novel treatments for certain myeloproliferative blood disorders, according to a study in Saturday's issue of The Lancet . (medpagetoday.com)
  • To distinguish myeloproliferative disorders from reactive conditions, particularly secondary thrombocytosis and erythrocytosis, can be difficult and so detection of the Val617Phe mutation could become a widely used diagnostic test," the researchers said. (medpagetoday.com)
  • A word familiar to all fans of science fiction , mutation refers to any sudden change in DNA - deoxyribonucleic acid, the genetic blueprint for an organism - that creates a change in an organism's appearance, behavior, or health. (encyclopedia.com)
  • Mutations that allow an organism to survive and reproduce better than other members of its species are always beneficial, though a mutation that may be beneficial in some circumstances can be harmful in others. (encyclopedia.com)
  • Mutation A mutation is any heritable change in the genome of an organism. (bookrags.com)
  • Spontaneous Mutations and Reversions Mutations and reversions are events that change the expression of traits of an organism. (bookrags.com)
  • A proportion of favorable mutations of one in a thousand does not sound much, but is probably generous, since so many mutations are lethal, preventing the organism living at all, and the great majority of the rest throw the machinery slightly out of gear. (angelfire.com)
  • In most cases, the somatic cell with the mutation will die, an event that is generally of little consequence in a multicellular organism . (britannica.com)
  • a mutation occurring in a somatic cell, resulting in a change in the morphology or some other aspect of one part of an organism (usually a plant). (dictionary.com)
  • It was clear to me then that cancer is an evolutionary process that the organism does not want," he said: After malignant cells arise through mutation, competition among those cells selects for the ones best able to run rampant through the body. (wired.com)
  • In biology , mutation is a sudden change in the base pair sequence of the genetic material of a living organism , whether the genetic material be deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). (newworldencyclopedia.org)
  • In biology , a mutation is the permanent alteration of the nucleotide sequence of the genome of an organism , virus , or extrachromosomal DNA or other genetic elements. (wikipedia.org)
  • Mutations may or may not produce discernible changes in the observable characteristics (phenotype) of an organism. (wikipedia.org)
  • We then show that the increased CpG mutation frequency observed in some cancers primarily occurs outside of CpG islands and CpG island shores, thus rejecting the hypothesis that the increase is a byproduct of island or shore methylation followed by deamination. (pnas.org)
  • We observe an A→G vs. T→C mutational asymmetry in some cancers similar to one that has been observed in germline mutations in transcribed regions, suggesting that the mutation process may be influenced by gene expression. (pnas.org)
  • In contrast, TpC dinucleotides are a mutation hotspot in breast cancers ( 16 ), but not in the germline ( 17 ). (pnas.org)
  • We first examine the overall impact of selection on the mutation spectra by comparing synonymous and nonsynonymous substitution frequencies (mutations per site sequenced) in pancreatic cancer and glioblastoma multiforme ( 4 , 5 ) and by examining the nature of amino acid changes in breast and colorectal cancers ( 1 ). (pnas.org)
  • To evaluate the risks of other cancers in BRCA1 mutation carriers, we conducted a cohort study of 11 847 individuals from 699 families segregating a BRCA1 mutation that were ascertained in 30 centers across Europe and North America. (nih.gov)
  • BRCA1 mutations may confer increased risks of other abdominal cancers in women and increased risks of pancreatic cancer in men and women. (nih.gov)
  • If the effects of mutation order were established for all common cancers, it could have a dramatic impact on treatment, says Kent. (newscientist.com)
  • We hope that our study will stimulate the search in other cancers for whether or not the order of mutation acquisition matters," he says. (newscientist.com)
  • Still a woman's lifetime risk of developing the aforementioned cancers increases exponentially if she inherits a detrimental mutation in BRCA1 or BRCA2 . (inquisitr.com)
  • The risk of BRCA-related breast cancers for men with the mutation is higher than for non-mutation carriers, but breast cancer occurrences in men are still low - accounting for only one percent of all breast cancers and typically to males over the age of 60. (inquisitr.com)
  • But BRCA mutations can escalate the risk of other cancers in men, such as colon cancer, pancreatic cancer, and prostate cancer. (inquisitr.com)
  • In 2018, a Chinese scientist named He Jiankui made the mutation infamous when he attempted to use CRISPR to edit CCR5 -Δ32 (pronounced "CCR5-delta-32") into human embryos. (theatlantic.com)
  • A basic principle of genetics is that the likelihood that a particular mutation occurs is independent of its phenotypic consequences. (nih.gov)
  • Few investigators of the genetics of RNA viruses have focused specifically on mutation rates , although mutant frequencies are often noted to be high compared with those observed in microbes with DNA chromosomes. (genetics.org)
  • Working at the MRC Mammalian Genetics Unit, a team led by Professor Howard Thomas from Imperial College London introduced subtle mutations into the genetic code at random throughout the genome and tested mice for alcohol preference. (ucl.ac.uk)
  • An international team of scientists writing in the journal Nature Genetics has helped to identify a single genetic mutation in National Paracycling Champion Tom Staniford that has led to his extremely rare condition. (redorbit.com)
  • Human Mutation is a peer-reviewed medical journal of human genetics published by Wiley-Liss on behalf of the Human Genome Variation Society. (wikipedia.org)
  • It is quite remarkable that a single mutation in a relatively rare GABA receptor gene can lead to such a profound change in alcohol consumption. (ucl.ac.uk)
  • We had to look at thirty million base pairs in Tom's DNA, and similar numbers in his family members and the other patients, to identify the single mutation. (redorbit.com)
  • It is probably fair to estimate the frequency of a majority of mutations in higher organisms between one in ten thousand and one in a million per gene per generation. (angelfire.com)
  • However, the majority of mutations actually identified are presumed to be "passenger" mutations that are not advantageous to the cancer cell ( 2 ). (pnas.org)
  • A mutation is any detectable and heritable change in nucleotide sequence that causes a change in genotype and is transmitted to daughter cells and succeeding generations. (nature.com)
  • Changes in chromosome number may involve even larger mutations, where segments of the DNA within chromosomes break and then rearrange. (wikipedia.org)
  • On the right, a fairly common mutation in mice causes bands in the coat around the body. (mit.edu)
  • Finally, a common mutation in humans causes red blood cells to be shaped in a sickle pattern as shown above on the upper left. (mit.edu)
  • A common mutation in a gene that regulates cholesterol levels may raise the risk of heart disease in carriers, according to a new UConn Health study. (medicalnewstoday.com)
  • In a diploid cell, a dominant mutation will be expressed over the wild type allele, but a recessive mutation will remain masked by the wild type. (britannica.com)
  • The D614G mutation in particular has been flagged as an urgent concern because it appeared to be emerging as a dominant mutation. (reuters.com)
  • In the course of running those assays, we came across a particular mutation in a patient and his mother," senior author Deborah L. Levy, PhD, director, Psychology Research Laboratory, McLean Hospital, Boston, told Medscape Medical News . (medscape.com)
  • One particular mutation involved a structural rearrangement that included a triplication of the glycine decarboxylase gene. (medscape.com)
  • People who had one particular mutation, in a gene called the VIPR2, which regulates brain neuron development and activity, were 14 times more likely to have schizophrenia than people without the mutation, the study said. (livescience.com)
  • It was found that the reason the second amber mutation could suppress the first one is that the two numerically reduced structural proteins would now be in balance. (wikipedia.org)
  • They determined that the Stellar mutation, which occurs in one of the proteins that make up the SPT complex, causes an increase in the number of "long" 20-carbon sphingolipids. (cnbc.com)
  • If we can identify women who will have trouble with breast-feeding while they're still pregnant - by identifying mutations in their ZnT2 proteins - then maybe we can help them better prepare before the baby comes. (dailymail.co.uk)
  • From one point of view, passenger mutations are an annoying "haystack" complicating the search for causal mutations. (pnas.org)
  • ETDEWEB / Search Results / Mutation breeding newsletter. (osti.gov)
  • This test looks for mutations in JAK2 that are associated with bone marrow disorders caused by the production of too many blood cells. (labtestsonline.org)
  • The bone marrow disorders caused by JAK2 mutations are known as myeloproliferative neoplasms (MPNs) in which the bone marrow produces too many white blood cells, red blood cells, and/or platelets. (labtestsonline.org)
  • The primary JAK2 test is JAK2 V617F, named for a mutation at a specific location in the JAK2 gene. (labtestsonline.org)
  • JAK2 V617F mutation is acquired as opposed to inherited and results in the change of a single DNA nucleotide base pair. (labtestsonline.org)
  • Other mutations in the JAK2 gene are also associated with MPNs. (labtestsonline.org)
  • There are tests available to detect mutations in JAK2 exon 12 and to identify other non-V617F mutations. (labtestsonline.org)
  • Of these, the team identified 12 samples in which TET2 had unequivocally mutated first, and another 12 in which the JAK2 mutation came first. (newscientist.com)
  • They found that disease was noticeable 10 years earlier in people with JAK2 -first mutations, because they were overproducing blood cells at high levels from the outset. (newscientist.com)
  • In cell culture, these mutants were easier to kill with targeted JAK2 inhibitor drugs than cells from those with TET2 -first mutations, but Kent's team has yet to test that this is also true inside the human body. (newscientist.com)
  • By contrast, the disease was more hidden in those who developed TET2 mutations first and was more likely to develop into full-blown leukaemia, but people in this group were less likely to suffer or die from blood clots than those who developed JAK2 mutations first. (newscientist.com)
  • In a study comparing 140 patients with myeloproliferative disorders against 90 controls with type 1 diabetes, scientists at Cambridge University here found that a remarkable 71 of 73 patients (97 percent) with polycythemia vera had the acquired, single-point mutation of the JAK2 gene, known as Val617Phe. (medpagetoday.com)
  • Identification of the Val617Phe mutation will also stimulate clinical development of small-molecule inhibitors of JAK2, which could provide novel approaches to treatment," the scientists added. (medpagetoday.com)
  • Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. (medpagetoday.com)
  • Mice inhabiting a northern town of Israel known for its high concentration of asbestos-contaminated dust, have a higher level of genetic somatic mutations, compared with other regions where asbestos pollution levels are lower. (medicalnewstoday.com)
  • They chose to probe mutations in mice because their generations are renewed every three months, so it could be assumed for the study that dozens of generations of this sample population in Nahariya had already been exposed to the fibers. (medicalnewstoday.com)
  • The results indicated differences between the groups' DNA and that the Nahariya-based mice had higher levels of genetic somatic mutations. (medicalnewstoday.com)
  • They then bred a new line of mice that had the relevant mutation, and those mice were notably insensitive to high temperatures. (ucl.ac.uk)
  • Mice with the LKB1 mutation also developed a greater range of tumours than those with the other mutations. (www.nhs.uk)
  • However, mice with a genetic mutation to the gene Gabrb1 overwhelmingly preferred drinking alcohol over water, choosing to consume almost 85% of their daily fluid as drinks containing alcohol. (ucl.ac.uk)
  • The group showed that mice carrying this mutation were willing to work to obtain the alcohol-containing drink by pushing a lever and, unlike normal mice, continued to do so even over long periods. (ucl.ac.uk)
  • Their experiments on mice suggest that ZnT2 mutations cause deficiencies in breast milk and may create difficulty for breastfeeding in general. (dailymail.co.uk)
  • Much work remains to be done before scientists understand precisely how the newly discovered gene mutation leads to Alzheimer's, but already there are some indications from studies in mice. (nytimes.com)
  • Recombination and its enabling partner, sex, probably persist primarily because of the deleterious consequences of mutation ( 1 ). (pnas.org)
  • a mutation that is deleterious or advantageous in a large population may be neutral in a small population, where random drift outweighs selection coefficients. (genetics.org)
  • Natural selection is proposed to increase beneficial mutations and select against and eliminate deleterious mutations. (newworldencyclopedia.org)
  • We also demonstrate that the relative frequency of mutations at dinucleotide "hotspots" can be used as a tool to detect likely technical artifacts in large-scale studies. (pnas.org)
  • Attempts to detect order in these mutation rates have revealed certain underlying patterns. (genetics.org)
  • The screen, called BEAMing technology, is sensitive enough to detect even rare mutations circulating in the blood stream in the form of free DNA, genetic material shed from tumors. (bloomberg.com)
  • reverse mutation ( reversion ) The production by further mutation of a premutation gene from a mutant gene. (encyclopedia.com)
  • Ignoring rare precise back mutations and in the absence of selection, this mutant subpopulation will persist at the frequency f 1 . (pnas.org)
  • A germline mutation , or germinal mutation , is any detectable variation within germ cells (cells that, when fully developed, become sperm and ovum ). (wikipedia.org)
  • The mutations were not detectable in the original skin cells from the patient, suggesting that they probably occurred as a result of the iPS-cell procedure. (newscientist.com)
  • on the other hand, if a germinal mutation is involved, what was once an abnormality may become so common in certain populations that it emerges as the norm. (encyclopedia.com)
  • They found several mutations that seemed to be associated with schizophrenia. (livescience.com)
  • The results showed several mutations in the TREM2 gene occurred more frequently in people who had the disease than in those without the disease. (utoronto.ca)
  • Over the eons, advantageous mutations, examples of which we look at later, have allowed life to develop and diversify from primitive cells into the multitude of species - including Homo sapiens - that exist on Earth today. (encyclopedia.com)
  • Those structures stymie evolution by denying advantageous mutations any chance to take over a population. (wired.com)
  • The frequency of these mutations can be increased by using special age. (bookrags.com)
  • The man probably more responsible than any other for the modern view of evolution known as neo-Darwinism, which says evolution proceeds by the accumulation of small mutations preserved by natural selection, is even less confident in the frequency of beneficial mutations. (angelfire.com)
  • This study clearly indicates that there is a link between the higher levels of asbestos in the environment and the frequency of genetic somatic mutations in the mammals," the scientists said. (medicalnewstoday.com)
  • Here, we describe a robust relationship among the mutation frequency f , the easily determined growth parameter c , and the mutation rate μ. (pnas.org)
  • Their familial descent was chosen since the Ashkenazi Jewish population is much more likely to have a BRCA1 and BRCA2 gene mutation. (upi.com)
  • Cancer Incidence in BRCA1 mutation carriers. (nih.gov)
  • Germline BRCA1 mutations confer a substantial lifetime risk of breast and ovarian cancer, but whether cancer at other sites is increased is less clear. (nih.gov)
  • Relative risks (RRs) of each cancer type in BRCA1 carriers relative to risks for the general population were estimated by weighting individuals according to their estimated probability of being a mutation carrier. (nih.gov)
  • In carriers of BRCA1 mutations, the overall increased risk of cancer at sites other than breast and ovary is small and is observed in women but generally not in men. (nih.gov)
  • Mutations in BRCA1 and BRCA2 are uncommon. (inquisitr.com)
  • It's been suggested BRCA1 mutations may increase a woman's risk of developing cervical, uterine, pancreatic, and colon cancer, and BRCA2 the risk of pancreatic cancer, stomach cancer, gallbladder and bile duct cancer, and melanoma. (inquisitr.com)
  • Genetic testing can assess if the mutations are present in the BRCA1 and BRCA2 through a DNA blood analysis. (inquisitr.com)
  • A good example is mutations that disrupt seed dispersal, leaving the seeds on the heads long after they are ripe. (wiktionary.org)
  • Mutations in Lkb1 disrupt its "braking" action on cancer and contribute to the disease in lungs, skin and other tissues. (eurekalert.org)
  • The mutation affects a gene that regulates learning and behavior, which makes sense considering these cognitive abilities are often impaired in people with schizophrenia, said study researcher Jonathan Sebat, an assistant professor of psychiatry and cellular and molecular medicine at the University of California, San Diego. (livescience.com)
  • A mutation on a gene that regulates brain development is associated with a 14-fold increased risk of schizophrenia. (livescience.com)
  • We first show that selection (negative or positive) has affected only a small fraction of mutations, allowing us to attribute observed trends to underlying mutational processes rather than selection. (pnas.org)
  • Some of the mutational processes generating these mutations do so in bursts and these will often be through external exposures such as sunbathing or tobacco smoking. (lanl.gov)
  • Other mutational processes, however, may be internal to the cell and generate mutations continuously, at a constant rate over decades. (lanl.gov)
  • They might be the result of a mutation in cells, or the result of a chemical or nuclear reaction. (dezeen.com)
  • Blood samples from people in the study showed that the people with the mutation had greater expression and greater activity of the gene than people without the mutations, the study said. (livescience.com)
  • Earlier and much smaller studies have shown more vulnerability to the flu and West Nile in people with the mutation, but there is no evidence of increased mortality in the 500,000 people of the U.K. Biobank database. (theatlantic.com)
  • In two double-blind, placebo-controlled trials, investigators studied a mother and a son, each of whom had a different psychotic disorder but carried the same rare genetic mutation - a copy number variant (CNV) involving four, instead of the usual two, copies of the gene that encodes glycine decarboxylase ( GLDC ). (medscape.com)
  • The basic evolution model would predict, therefore, that mutations must be primarily beneficial, generating a 'vertical' change upward toward higher degrees of order. (angelfire.com)
  • As a matter of fact, the phenomenon of a truly beneficial mutation, one which is known to be a mutation and not merely a latent characteristic already present in the genetic material but lacking previous opportunity for expression, and one which is permanently beneficial in the natural environment, has yet to be documented. (angelfire.com)
  • A central premise of the theory of evolution through natural selection is that when beneficial mutations appear, they should spread throughout a population. (wired.com)
  • It will be updated annually with newly published or submitted mutations and corrections. (cdc.gov)
  • Mutation is a newly formed 4 piece heavy metal band from the Twin Cities. (first-avenue.com)
  • Because the mutations in the newly discovered gene are rare, occurring in no more than 2 percent of Alzheimer's patients, it makes no sense to start screening people for them, Dr. Thies said. (nytimes.com)
  • A simple blood sample turned up cancer-causing mutations more frequently than a tumor biopsy in a study that suggests the approach could help deliver a clearer picture of the disease and better tailor patients' treatments. (bloomberg.com)
  • Evolving responsively: adaptive mutation. (nih.gov)
  • The concept of adaptive mutation seemed to challenge this principle with the discoveries of mutations stimulated by stress, some of which allow adaptation to the stress. (nih.gov)
  • In this report we investigate several hypotheses to account for the role of selection in the production of these "directed" or "adaptive" mutations. (genetics.org)
  • Both parents were heterozygous carriers of the mutation. (medscape.com)
  • The bad news is that many of these mutation carriers have no warning that they are in danger," said Perundurai S. Dhandapany from Madurai Kamaraj University, Madurai, India, "but the good news is that we now know the impact of this mutation. (redorbit.com)
  • 001). There was some evidence of an elevated risk of prostate cancer in mutation carriers younger than 65 years old (RR = 1.82, 95% CI = 1.01 to 3.29, P =.05) but not in those 65 years old or older (RR = 0.84, 95% CI = 0.53 to 1.33, P =.45). (nih.gov)
  • Mutation is a phenomenon significant to many aspects of life on Earth and is one of the principal means by which evolutionary change takes place. (encyclopedia.com)
  • Mutations become especially important when an organism's environment is changing - something that has happened often over the course of evolutionary history. (encyclopedia.com)
  • It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates. (genetics.org)
  • The existence of strong taxonomic patterns of mutability implies that genomic mutation rates are close to an evolutionary equilibrium whose driving forces we consider here. (genetics.org)
  • In evolutionary theory , specifically the theory of evolution by natural selection , mutation is considered the main source of new variation in a population. (newworldencyclopedia.org)
  • A suppressor mutation is a second mutation that alleviates or reverts the phenotypic effects of an already existing mutation in a process defined synthetic rescue . (wikipedia.org)
  • The second mutation is not on the same gene as the original mutation. (wikipedia.org)
  • Since mutation usually affects a single individual in a population, the initial fraction is small and the probability of fixation is thus also small (high probability of loss). (mit.edu)
  • The authors concluded that mutation in the LKB1 gene affects the ability of a cell to suppress the development of a tumour. (www.nhs.uk)
  • The mutation makes a patient three times more likely to develop the disease, although it affects just 0.3 per cent of the population. (utoronto.ca)