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.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)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.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.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.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.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.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.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.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.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.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.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.Homozygote: An individual in which both alleles at a given locus are identical.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.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.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.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.Genes, Recessive: Genes that influence the PHENOTYPE only in the homozygous state.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.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.Fructose-1,6-Diphosphatase Deficiency: An autosomal recessive fructose metabolism disorder due to absent or deficient fructose-1,6-diphosphatase activity. Gluconeogenesis is impaired, resulting in accumulation of gluconeogenic precursors (e.g., amino acids, lactate, ketones) and manifested as hypoglycemia, ketosis, and lactic acidosis. Episodes in the newborn infant are often lethal. Later episodes are often brought on by fasting and febrile infections. As patients age through early childhood, tolerance to fasting improves and development becomes normal.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.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.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.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.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.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.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.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.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.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.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Deafness: A general term for the complete loss of the ability to hear from both ears.Syndrome: A characteristic symptom complex.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.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).Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.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.Mice, Inbred C57BLPromoter 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.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.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 Variation: Genotypic differences observed among individuals in a population.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.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.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.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.Factor V: Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.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.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.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.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.Genetic Counseling: An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered.Eye ProteinsCell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.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.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.DNA, Neoplasm: DNA present in neoplastic tissue.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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).Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.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.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.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).Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Nerve Tissue ProteinsBrain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Caenorhabditis elegans: A species of nematode that is widely used in biological, biochemical, and genetic studies.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.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.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.Breast Neoplasms: Tumors or cancer of the human BREAST.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.Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)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.Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Infant, Newborn: An infant during the first month after birth.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.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.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.China: A country spanning from central Asia to the Pacific Ocean.Consanguinity: The magnitude of INBREEDING in humans.Bacterial Proteins: Proteins found in any species of bacterium.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Thyroid Neoplasms: Tumors or cancer of the THYROID GLAND.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.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.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.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.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.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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.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).Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.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.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.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.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).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.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.Jews: An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.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.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.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).)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.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.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.Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.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 Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.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).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.Chloracne: ACNE-like skin eruptions caused by exposure to CHLORINE-containing compounds. Exposure can be by inhalation, ingestion, or through the skin. Chloracne is often seen in people who have occupational contact with chlorinated pesticides, wood preservatives, and sealants.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.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)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.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)HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.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.Abnormalities, MultipleGreen Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.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.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.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 enzymes

*Gene targeting

... "knocking in"), specific mutations of interest to a variety of models. Previously used to engineer rat cell models, advances in ... Cre recombinase Cre-Lox recombination FLP-FRT recombination Gene trapping (random gene knockout technique) Genetic ... For gene targeting these compact genes are just as easily altered. Gene targeting has been widely used to study human genetic ... The method can be used to delete a gene, remove exons, add a gene, and introduce point mutations. Gene targeting can be ...

*Morpholino

Gene knockdown is achieved by preventing cells from making a targeted protein. Knocking down gene expression is a method for ... Common techniques for delivery into cultured cells include the Endo-Porter peptide (which causes the Morpholino to be released ... effects of losing the null gene can be concealed by genetic compensation. Because of their completely unnatural backbones, ... Sarepta Therapeutics received accelerated approval from the US Food and Drug Administration for treatment of some mutations ...

*Knockout rat

... gene knock-outs/knock-ins, and conditional mutations, depend upon the culture and manipulation of embryonic stem (ES) cells. ... Most techniques for genetic manipulation, including random mutagenesis with a gene trap (retroviral-based and non-retroviral- ... A knockout rat is a genetically engineered rat with a single gene turned off through a targeted mutation (gene trapping) used ... Once the random knockout mutations are created, more refined mutations such as conditional mutations can be created by breeding ...

*Smith-Lemli-Opitz syndrome

Genetic models of SLOS are created by knocking out the DHCR7 gene. One study used homologous recombination to disrupt DCHR7 in ... The first is using teratogens, the second is using genetic manipulations to create mutations in the DHCR7 gene. Teratogenic ... Cell to cell interaction, which is very important in development, may be impaired. Exocytosis in synaptic vesicles has been ... Another way of detecting 7DHC is through gas chromatography, a technique used to separate and analyze compounds. Selected ion ...

*Mutagenesis (molecular biology technique)

This method can be used to introduce a mutation or knock out a gene, for example as used in the production of knockout mice. As ... doi:10.1016/j.cell.2014.05.010. PMC 4343198 . PMID 24906146. Muller, H. J. (1927). "Artificial Transmutation of the Gene" (PDF ... Hermann Muller discovered that x-rays can cause genetic mutations in fruit flies (published in 1927), and went on to use the ... artificial synthesis of a complete gene is now a viable method for introducing mutations into gene. This method allows for ...

*Genetic engineering

Some genes do not work well in bacteria, so yeast, insect cells or mammalians cells can also be used. These techniques are used ... engineered nucleases can be used to introduce mutations at endogenous genes that generate a gene knockout. Genetic engineering ... As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can be inserted randomly, or ... The next step is to isolate the candidate gene. The cell containing the gene is opened and the DNA is purified. The gene is ...

*Recombinant AAV mediated genome engineering

These include gene knock-outs for functional genomics, or the 'knock-in' of protein tag insertions to track translocation ... in contrast to mouse ES cells, have low rates of HR. The technique has been widely adopted for use in engineering human cell ... it is able to routinely and accurately model genetic diseases caused by subtle SNPs or point mutations that are increasingly ... September 2007). "Knock-in of mutant K-ras in nontumorigenic human epithelial cells as a new model for studying K-ras mediated ...

*Genetically modified organism

Genetic modification involves the mutation, insertion, or deletion of genes. Inserted genes usually come from a different ... A common technique used to find out where the gene is expressed is to attach it to GUS or a similar reporter gene that allows ... One way to do this is to knock out the gene of interest and see what phenotype develops. Another strategy is to attach the gene ... 2017). "Interspecies Chimerism with Mammalian Pluripotent Stem Cells". Cell. 168 (3): 473-86. doi:10.1016/j.cell.2016.12.036. ...

*Systems biology

The whole-cell model is able to predict viability of M. Genitalium cells in response to genetic mutations. An important ... siRNA-based gene knocking down screenings, computational modeling of the consequences of somatic mutations and genome ... Since the objective is a model of the interactions in a system, the experimental techniques that most suit systems biology are ... tissue or whole cell gene expression measurements by DNA microarrays or serial analysis of gene expression Interferomics ...

*Zinc finger nuclease

Cell Research. 21: 1638-1640. doi:10.1038/cr.2011.153. D. Carroll (2008). "Zinc-finger Nucleases as Gene Therapy Agents". Gene ... The cells in which the mutations are induced ex vivo are filtered out from lymphocytes by apheresis to produce analogous ... "Genetic engineering of T cells for adoptive immunotherapy". Immunologic research. 42 (1-3): 166-181. doi:10.1007/s12026-008- ... Mutagenic lesions at this target site was induced using ZFN technique by a group of researchers in US. They suggested that the ...

*Selfish genetic element

... or both genes are absent. When the maternally expressed gene (Igf2r) is experimentally knocked out the offspring has an ... "Cell. 135 (4): 726-37. doi:10.1016/j.cell.2008.09.037. PMC 2703716. PMID 19013280.. ... This technique has been used in a wide variety of crops, including rice, maize, sunflower, wheat, and cotton.[114] ... Any mitochondrial mutation that can affect the amount of resources the plant invests in the female reproductive functions at ...

*Autophagy

In cancerous cells, autophagy is used as a way to deal with stress on the cell.[84] Once these autophagy related genes were ... There are several genetic mutations implicated in the disease, including loss of function PINK1 [89] and Parkin.[90] Loss of ... A high rate above the survival threshold may kill cancer cells with a high apoptotic threshold.[86][87] This technique can be ... with a knock-in mutation of BCL2 phosphorylation sites to produce progeny that showed normal levels of basal autophagy yet were ...

*Delitto perfetto

... this process must be functional in the cells for the technique to work. In Saccharomyces cerevisiae, the RAD52 gene is ... however this limits the regions of the gene available for mutation. Alternatively, diploid cells can be used. However, using a ... This name is the Italian term for "perfect murder", and it refers to the ability of the technique to create desired genetic ... Oligonucleotides containing the sequence upstream immediately followed by the sequence downstream of the region to be knocked ...

*Epidermolytic hyperkeratosis

This is a dominant genetic condition caused by mutations in the genes encoding the proteins keratin 1 or keratin 10. Keratin 1 ... When cells make a protein from a gene on a chromosome sitting in the nucleus, the gene is first transcribed as a piece of RNA. ... Chen observed that under these conditions, an efficient knock-down of mutant, but not normal, K10 genes could be achieved. The ... UPDATE: OCTOBER 2014 As of late, Paller reports "we are using a new nanotechnology-based technique called 'spherical nucleic ...

*Knockout mouse

The embryonic stem cells that incorporated the knocked-out gene are isolated from the unaltered cells using the marker gene ... Moreover, cells that do not integrate any of the genetic material test negative for both genes and therefore die as a result of ... For example, mutations in the p53 gene are associated with more than half of human cancers and often lead to tumours in a ... Mice are currently the laboratory animal species most closely related to the humans for which the knockout technique can easily ...

*Functional genomics

Gene function can be investigated by systematically "knocking out" genes one by one. This is done by either deletion or ... Functional genomics uses mostly multiplex techniques to measure the abundance of many or all gene products such as mRNAs or ... a yeast cell brings the activation and binding domains of GAL4 close enough together to result in expression of a reporter gene ... Functional genomics may also include studies of natural genetic variation over time (such as an organism's development) or ...

*Transposons as a genetic tool

... inserting the gene of interest and reporter gene. Grow flies and cross to remove genetic variation between the cells of the ... so can be investigated to determine the phenotype due to mutation of existing genes. Possible mutations: Insertion in a ... While genetic sequencing techniques can determine the genotype of a genome, they cannot determine the function or phenotypic ... Several lines of flies are required so comparison can take place and ensure that no additional genes have been knocked out. ( ...

*PTPRT

... these cells do not mediate comparable levels of cell-cell aggregation to wild-type PTPrho, demonstrating that the mutations ... 2012). "A genome-wide screen for genetic variants that modify the recruitment of REST to its target genes". PLoS Genet. 8 (4): ... Knock-down of PTPrho expression decreases the number of synapses in cultured neurons. PTPrho interacts in cis with the ... Using this technique, the authors identified that PTPrho interacts with alpha-actinin, alpha-catenin, beta-catenin, gamma- ...

*Gene knockout

A gene knockout (abbreviation: KO) is a genetic technique in which one of an organism's genes is made inoperative ("knocked out ... Resulting animals with the genetic change in their germline cells can then often pass the gene knockout to future generations. ... Originally, naturally occurring mutations were identified and then gene loss or inactivation had to be established by DNA ... The KO technique is essentially the opposite of a gene knockin. Knocking out two genes simultaneously in an organism is known ...

*Reverse genetics

... with a sensitive DNA-screening technique that identifies point mutations in a target gene. The discovery of gene silencing ... Manis JP (December 2007). "Knock out, knock in, knock down--genetically manipulated mice and the Nobel Prize". The New England ... A molecular genetic approach is the creation of transgenic organisms that overexpress a normal gene of interest. The resulting ... However, the viral genes are still expressed in the host's cell through a single replication cycle, allowing for the ...

*Disease gene identification

... often with only minimal knowledge of the gene sequences they were looking at. Genetic techniques capable of providing this sort ... thus allowing scientists to identify more complex mutations. Disease gene identification techniques often follow the same ... knocked down/out in said samples can then be considered candidate disease genes for the individual in question. Whole exome ... Cell. 137 (5): 835-48. doi:10.1016/j.cell.2009.05.006. PMC 2768667 . PMID 19490893. Fortier S, Bilodeau M, Macrae T, Laverdure ...

*Alcino J. Silva

1992). "Mutations in T-cell antigen receptor genes alpha and ß block thymocyte development at different stages". Nature. 360: ... in Science as a post-doctural fellow in Susumu Tonegawa's laboratory were the first to combine molecular genetic techniques ... reverses behavioral deficits despite its inability to reverse structural deficits discovered in neurons with Disc 1 knock down ... Thomas, K. R.; Capecchi, M. R. (1987). "Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells". Cell. ...

*Gene knockin

The difference between knock-in technology and traditional transgenic techniques is that a knock-in involves a gene inserted ... will grow into a mature chimeric mouse with some cells having the original blastocyst cell genetic information and other cells ... A gene knockin therefore can be seen as a gain of function mutation and a gene knockout a loss of function mutation, but a gene ... In molecular cloning and biology, a knock-in (or gene knock-in) refers to a genetic engineering method that involves the one- ...

*Merkel cell polyomavirus

"Once the virus integrates, it could express an oncoprotein, or it could knock out a gene that suppresses tumor growth. Either ... basal cell skin carcinoma, extrapulmonary small cell carcinoma, and EGFR mutation-driven non-small cell lung cancer have been ... Genetic sequences from nearly 400,000 mRNAs were analyzed for the study. Once the virus was found, Feng and coworkers quickly ... A virtual subtraction method was developed by Huichen Feng in the lab as a novel high-throughput sequencing technique of ...

*Recombineering

... (recombination-mediated genetic engineering) is a genetic and molecular biology technique based on homologous ... Gene cloning and gene/protein tagging (His tags etc., see ) is also common. For gene replacements or deletions, usually a ... Wang H.H., Isaacs F. J., Carr P.A., Sun Z.Z., Xu G., Forest C.R., Church G.M. (2009). "Programming cells by multiplex genome ... Recombineering with ssDNA provided a breakthrough both in the efficiency of the reaction and the ease of making point mutations ...

*Epistasis

... within genes[edit]. Just as mutations in two separate genes can be non-additive if those genes interact, mutations in ... This is because, in any given genetic background, very few mutations will be beneficial, even though many mutations may need to ... "Cell. 138 (4): 774-86. doi:10.1016/j.cell.2009.07.038. PMC 3210731. PMID 19703402.. ... mutant phenotype can be suppressed by knocking out one copy of a gene that acts oppositely in the same pathway. In this case, ...
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?
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 ...
... definition, Heritable Disorders Of Connective Tissue mortality and morbidity, Heritable Disorders Of Connective Tissue treatment, manifestations of the Heritable Disorders Of Connective Tissue, Heritable Disorders Of Connective Tissue race, Heritable Disorders Of Connective Tissue function, Heritable Disorders Of Connective Tissue care, Heritable Disorders Of Connective Tissue frequency, what causes Heritable Disorders Of Connective Tissue, Heritable Disorders Of Connective Tissue prevalence, Heritable Disorders Of Connective Tissue role, Heritable Disorders Of Connective Tissue associated with the deficiency, Heritable Disorders Of Connective Tissue recorded mutations , Heritable Disorders Of Connective Tissue hormonal conditions with the deficiency, Heritable Disorders Of Connective Tissue developmental delays, more serious problems caused by the Heritable Disorders Of Connective Tissue, Heritable Disorders Of Connective Tissue inheritance, Heritable Disorders
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 ...
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 ...
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, ...
TY - JOUR. T1 - Clinical characteristics of familial amyotrophic lateral sclerosis with Cu/Zn superoxide dismutase gene mutations. AU - Abe, Koji. AU - Aoki, M.. AU - Ikeda, M.. AU - Watanabe, M.. AU - Hirai, S.. AU - Itoyama, Y.. PY - 1996. Y1 - 1996. N2 - We report clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with 4 different missense point mutations in exons 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene, that result in amino acid substitutions of histidine46 by arginine (H46R), leucine84 by valine (L84V), isoleucine104 by phenylalanine (I104F), and valine148 by isoleucine (V148I), in 5 Japanese families. Although features of progressive neurogenic muscular atrophy were common in patients of these families, patients of each family showed characteristic clinical features. FALS patients with the H46R mutation showed a benign clinical course and stereotype progression of muscular weakness and atrophy ...
Restriction Description: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trials primary publication ...
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 ...
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 ...
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 ...
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 ...
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 ...
We conducted this study to assess whether KRAS codon 12-mutated tumors represent a more aggressive subtype as compared with either KRAS codon 13-mutated tumors or KRAS wild-type tumors, within a group of BRAF wild-type tumors (i.e., controlling for BRAF mutation status). We showed that KRAS codon 12 mutations, but not codon 13 mutations, were associated with significantly higher mortality compared with KRAS wild-type/BRAF wild-type cases. In particular, c.35G,T (p.G12V) mutation was associated with the highest colorectal cancer-specific mortality (multivariate HR, 2.00; 95% CI, 1.38-2.90, P = 0.0003). Our data are consistent with previous laboratory studies (24, 25), suggesting that the presence of a mutation in KRAS codon 12 confers substantially greater oncogenic potential as compared with codon 13 mutation. Our data are also consistent with a recent study that showed that KRAS codon 12 mutations, but not codon 13 mutations, conferred ...
CFP : Confirmation of a clinical diagnosis of cystic fibrosis   Risk refinement via carrier screening for individuals in the general population   Prenatal diagnosis or familial mutation testing when the familial mutations are included in the 106-mutation panel listed above (if familial mutations are not included in the 106-mutation panel, order FMTT / Familial Mutation, Targeted Testing)   Risk refinement via carrier screening for individuals with a family history when familial mutations are not available   Identification of patients who may respond to CFTR potentiator therapy
We wish to construct a mouse model for the human inherited disease cystic fibrosis. We describe here the successful targeting in embryonal stem cells of the murine homologue (Cftr) of the cystic fibrosis transmembrane conductance regulator gene, as the first critical step towards this end. The targeting event precisely disrupts exon 10, the site of the major mutation in patients with cystic fibrosis. The targeted cells are pluripotent and competent to form chimaeras.
Genetic Mutations Worksheet Answers Solving Proportions Worksheet. Genetic Mutations Worksheet Answers Preschool Number Worksheets. Genetic Mutations Worksheet Answers Latitude And Longitude Worksheets. Genetic Mutations Worksheet Answers Prime Factorization Worksheet. Genetic Mutations Worksheet Answers Area Of Composite Figures Worksheet. Genetic Mutations Worksheet Answers Ratio Worksheets. Genetic Mutations Worksheet Answers Christmas Worksheets. Genetic Mutations Worksheet Answers Punnett Square Worksheet. Genetic Mutations Worksheet Answers Math ...
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.
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 ...
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 ...
BACKGROUND Inactivation of the p53 tumor suppressor gene (also known as TP53) through a point mutation and/or loss of heterozygosity is one of the most common genetic changes found in various types of human tumors. PURPOSE Our purpose was to investigate the relationship between the presence of p53 gene mutations and survival of patients with non-small-cell lung cancer (NSCLC) of all stages who underwent surgery with preoperative curative intent as a routine therapeutic intervention. The prognostic significance of factors like sex, age, tumor histology, and the stage of the disease was also evaluated. METHODS We analyzed 120 tumor specimens from patients with histologically confirmed NSCLC for p53 mutations occurring in exons 5 through 8 by polymerase chain reaction-single-strand conformation polymorphism assay of genomic DNA. Univariate and multivariate analyses were performed to assess the association ...
The BRAF V600E mutation, also BRAF V600E, is a common recurrent mutation in the BRAF gene that is seen in many types of tumours and cancer.[1] The BRAF gene, formally known as v-RAF murine sarcoma viral oncogene homolog B1, is a serine threonine kinase.[2] The mutation can be demonstrated with molecular testing (ARMS). Also, a mutation specific immunostain (VE1) is available.[1] ...
...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
Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. Methods: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. Results: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the ...
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 ...
TY - JOUR. T1 - Uncommon frame-shift exon 19 EGFR mutations are sensitive to EGFR tyrosine kinase inhibitors in non-small cell lung carcinoma. AU - Improta, Giuseppina. AU - Zupa, Angela. AU - Natalicchio, Maria Iole. AU - Sisinni, Lorenza. AU - Marinaccio, Anna. AU - Bozza, Giovanni. AU - Vita, Giulia. AU - Aieta, Michele. AU - Landriscina, Matteo. PY - 2018/1/31. Y1 - 2018/1/31. N2 - Exons 19-21 EGFR activating mutations are predictive biomarkers of response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, uncommon exon 19 EGFR mutations, due to their low frequency, have an uncertain biological and clinical significance and very little is known about their TKI sensitivity. This study was designed to describe the TKI sensitivity of a small cohort of lung adenocarcinomas bearing uncommon exon 19 mutations and to evaluate in silico the correlation between frame-shift exon 19 mutations ...
NSCLC-associated EGFR mutations are most frequently heterozygous. However, Paez et al. (18) reported one mutation involving exon 19 that appeared to be homozygous, and we detected two such cases. Interpretation of mutational status solely from DNA sequencing can be problematic. On the one hand, contaminating normal cells with wild-type EGFR could account for apparent heterozygosity; on the other hand, amplification of mutant EGFR, as occurs in lung cancer (23), could account for detection of only mutant sequences. Mouse models expressing mutant EGFR proteins in the lung and analysis of mutant-positive NSCLCs by fluorescence in situ hybridization and/or array-based comparative genomic hybridization may help address these issues. Interestingly, in one of these tumors (G3), we detected a heterozygous intronic polymorphism downstream of exon 19 (data not shown). In this case, it is probable that a gene conversion event occurred, encompassing the area of deletion ...
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 ...
COL4A3/COL4A4 mutations: From familial hematuria to autosomal-dominant or recessive Alport syndrome. BACKGROUND: Mutations of the type IV collagen COL4A5 gene cause X-linked Alport syndrome (ATS). Mutations of COL4A3 and COL4A4 have been reported both in autosomal-recessive and autosomal-dominant ATS, as well as in benign familial hematuria (BFH). In the latter conditions, however, clinical features are less defined, few mutations have been reported, and other genes and non-genetic factors may be involved. METHODS: We analyzed 36 ATS patients for COL4A3 and COL4A4 mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing. Sporadic patients who had tested negative for COL4A5 mutations were included with typical cases of autosomal recessive ATS to secure a better definition of the ...
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.. ...
TY - JOUR. T1 - Black phosphorus nanoelectromechanical resonators vibrating at very high frequencies. AU - Wang, Zenghui. AU - Jia, Hao. AU - Zheng, Xuqian. AU - Yang, Rui. AU - Wang, Zefang. AU - Ye, G. J.. AU - Chen, X. H.. AU - Shan, Jie. AU - Feng, Philip X.L.. PY - 2015/1/21. Y1 - 2015/1/21. N2 - We report on the experimental demonstration of a new type of nanoelectromechanical resonator based on black phosphorus crystals. Facilitated by a highly efficient dry transfer technique, crystalline black phosphorus flakes are harnessed to enable drumhead resonators vibrating at high and very high frequencies (HF and VHF bands, up to ∼100 MHz). We investigate the resonant vibrational responses from the black phosphorus crystals by devising both electrical and optical excitation schemes, in addition to measuring the undriven thermomechanical motions in these suspended nanostructures. Flakes with thicknesses from ∼200 nm down to ∼20 nm clearly exhibit elastic characteristics transitioning from ...
Classic activating mutations in the EGFR tyrosine kinase domain, such as L858R and deletions in exon 19, have been strongly associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with Non-Small Cell Lung Cancer (NSCLC). Other mutations, e.g. T790M, show drug resistance. Detection of EGFR mutations has become an important issue for therapeutic decision-making in NSCLC. The clinical significance of uncommon EGFR mutations, however, remains poorly understood. The present study describes clinical outcomes of 6 patients with uncommon EGFR mutations, receiving TKI.. ...
A set of 1,000 "mutation accumulation" lines of Drosophila melanogaster, which originated from two different wild-type, lethal-bearing second chromosomes (Yamaguchi and Mukai 1974; Mukai and Cockerham 1977), was examined for evidence of a mutator factor by using the occurrence of recessive visible mutations and male recombination to identify its presence. The 1,000 lines were screened at approximately generation 240 for the presence of recessive visible mutations at twelve loci, by outcrossing to a balanced multiply marked second chromosome stock (Mullers "12ple" Bowling Green). Twenty-three lines were found to carry a visible mutation at one of the loci. Seventeen of these lines carried a mutation of either the dp or the vg locus. Mutations found in three lines, two at the dp locus and one at the vg locus, demonstrated instability as revertants to the wild type and were recovered and verified in these three cases. The three revertant lines, ...
TY - JOUR. T1 - Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. AU - Totoki, Yasushi. AU - Tatsuno, Kenji. AU - Covington, Kyle R.. AU - Ueda, Hiroki. AU - Creighton, Chad J.. AU - Kato, Mamoru. AU - Tsuji, Shingo. AU - Donehower, Lawrence A.. AU - Slagle, Betty L.. AU - Nakamura, Hiromi. AU - Yamamoto, Shogo. AU - Shinbrot, Eve. AU - Hama, Natsuko. AU - Lehmkuhl, Megan. AU - Hosoda, Fumie. AU - Arai, Yasuhito. AU - Walker, Kim. AU - Dahdouli, Mahmoud. AU - Gotoh, Kengo. AU - Nagae, Genta. AU - Gingras, Marie Claude. AU - Muzny, Donna M.. AU - Ojima, Hidenori. AU - Shimada, Kazuaki. AU - Midorikawa, Yutaka. AU - Goss, John A.. AU - Cotton, Ronald. AU - Hayashi, Akimasa. AU - Shibahara, Junji. AU - Ishikawa, Shumpei. AU - Guiteau, Jacfranz. AU - Tanaka, Mariko. AU - Urushidate, Tomoko. AU - Ohashi, Shoko. AU - Okada, Naoko. AU - Doddapaneni, Harsha. AU - Wang, Min. AU - Zhu, Yiming. AU - Dinh, Huyen. AU - Okusaka, Takuji. AU - Kokudo, Norihiro. AU - Kosuge, Tomoo. AU - ...
Background: Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS. Methods: We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing. Results: Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding ...
TY - JOUR. T1 - The mutational landscape of adenoid cystic carcinoma. AU - Ho, A.S.. AU - Kannan, K.. AU - Roy, D.M.. AU - Morris, L.G.T.. AU - Ganly, I.. AU - Katabi, N.. AU - Ramaswami, D.. AU - Walsh, L.A.. AU - Eng, S.. AU - Huse, J.T.. AU - Zhang, J.N.. AU - Dolgalev, I.. AU - Huberman, K.. AU - Heguy, A.. AU - Viale, A.. AU - Drobnjak, M.. AU - Leversha, M.A.. AU - Rice, C.E.. AU - Singh, B.. AU - Iyer, N.G.. AU - Leemans, C.R.. AU - Bloemena, E.. AU - Ferris, R.L.. AU - Seethala, R.R.. AU - Gross, B.E.. AU - Liang, Y.P.. AU - Sinha, R.. AU - Peng, L.K.. AU - Raphael, B.J.. AU - Turcan, S.. AU - Gong, Y.X.. AU - Schultz, N.. AU - Kim, S.. AU - Chiosea, S.. AU - Shah, JP. AU - Sander, C. AU - Lee, W.. AU - Chan, T.A.. PY - 2013. Y1 - 2013. U2 - 10.1038/ng.2643. DO - 10.1038/ng.2643. M3 - Article. VL - 45. SP - 791. EP - 798. JO - Nature Genetics. JF - Nature Genetics. SN - 1061-4036. IS - 7. ER - ...
Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C | T and A | G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost ...
Mutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of 10 lines of T. thermophila that had each undergone approximately 1,000 generations of mutation accumulation (MA). We applied an existing mutation-calling pipeline and developed a new probabilistic mutation detection approach that directly models the design of an MA experiment and accommodates the noise introduced by mismapped reads. Our probabilistic mutation-calling method provides a straightforward way of estimating the number of sites at which a mutation could have been called if one was present, providing the denominator for our mutation rate calculations. From these methods, we find that T. ...
The aim of this study was to identify the causative mutation in a family with an unusual presentation of autosomal dominant osteopetrosis (OPT), proximal renal tubular acidosis (RTA), renal stones, epilepsy, and blindness, a combination of features not previously reported. We undertook exome sequencing of one affected and one unaffected family member, followed by targeted analysis of known candidate genes to identify the causative mutation. This identified a missense mutation (c.643G|A; p.Gly215Arg) in the gene encoding the chloride/proton antiporter 7 (gene CLCN7, protein CLC-7), which was confirmed by amplification refractory mutation system (ARMS)-PCR, and to be present in the three available patients. CLC-7 mutations are known to cause autosomal dominant OPT type 2, also called Albers-Schonberg disease, which is characterized by osteosclerosis, predominantly of the spine, pelvis and skull base, resulting in bone fragility and fractures. ...
Mutations in SALL1 and GLI3 are responsible for human limb malformation syndromes. The molecular pathophysiology of these mutations is incompletely understood, and many conclusions have been drawn from studies performed in the mouse. We identified truncating mutations in SALL1 and GLI3 in patients with limb malformation and studied the contribution of nonsense-mediated decay (NMD) to the expression of mutant mRNA in patient-derived fibroblasts. Quantification of the relative proportions of mutant and wild-type alleles was performed by pyrosequencing. In SALL1, a mutant allele causing Townes-Brocks syndrome was unexpectedly resistant to NMD, whereas a different mutation causing a much milder phenotype was susceptible to NMD. In GLI3, all three mutant alleles tested were susceptible to NMD. This work provides novel insights into the molecular pathophysiology of SALL1 and GLI3 mutations, extends the phenotypic spectrum of SALL1 ...
t haplotypes are naturally occurring, variant forms of the t complex on mouse chromosome 17, characterized by the presence of four inversions with respect to wild-type. They harbour mutations causing male sterility, male transmission ratio distortion (TRD) and embryonic lethality. Mice carrying t haplotypes have been found throughout the world, and genetic studies of the lethal mutations have identified at least 16 complementation groups. The embryonic lethal phenotypes of many t haplotypes have been characterized in detail, and are thought to be the consequence of homozygosity for single gene mutations. However, the existence of additional mutations in genes that function at later stages of development would be obscured. Here we investigated the possibility of multiple mutations in t haplotypes by screening the t(w73) haplotype for the presence of ...
A research team, headed by Theodore Friedmann, MD, professor of pediatrics at the University of California, San Diego School of Medicine, says a gene mutation that causes a rare but devastating neurological disorder known as Lesch-Nyhan syndrome appears to offer clues to the developmental and neuronal defects found in other, diverse neurological disorders like Alzheimers, Parkinsons and Huntingtons diseases. The findings, published in the October 9, 2013 issue of the journal PLOS ONE, provide the first experimental picture of how gene expression errors impair the ability of stem cells to produce normal neurons, resulting instead in neurological disease. More broadly, they indicate that at least some distinctly different neurodevelopmental and neurodegenerative disorders share basic, causative defects. The scientists say that understanding defects in Lesch-Nyhan could help identify errant processes in other, more common neurological ...
Background:. AZD6244 (ARRY-142886) is an investigational anticancer drug that is designed to block a critical component (MEK (methyl ethyl ketone)) of a pathway (MAP (mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). Approximately 20% of lung cancers have KRAS mutations which can make some cancer treatments including erlotinib, a standard anticancer treatment drug less effective. Researchers are interested in determining whether AZD6244 is effective in treating advanced NSCLC (non small cell lung cancer), including KRAS mutated lung cancer that has not responded to standard therapy.. Objectives:. To determine the effectiveness of AZD6244, either alone or in combination with erlotinib, in preventing tumor growth in individuals ...
TY - JOUR. T1 - Cell cycle regulators in multiple myeloma. T2 - Prognostic implications of p53 nuclear accumulation. AU - Pruneri, Giancarlo. AU - Carboni, Nadia. AU - Baldini, Luca. AU - Intini, Daniela. AU - Colombi, Mariangela. AU - Bertolini, Francesco. AU - Valentini, Stefano. AU - Maisonneuve, Patrick. AU - Viale, Giuseppe. AU - Neri, Antonino. PY - 2003/1/1. Y1 - 2003/1/1. N2 - Multiple myeloma (MM) is characterized by a multistep process of tumorigenesis involving genes that control cell cycle progression. The prevalence and clinical implications of p53, p21, HDM-2, p27, and cyclin E immunoreactivity in MM patients, however, have not been fully elucidated. We evaluated the immunoreactivity (IR) for p53, p21, HDM-2, p27, cyclin E, and Ki-67 in bone marrow biopsies from 48 patients. In 34 (70.8%) cases, TP53 gene mutations and HDM-2 gene amplification were analyzed by polymerase chain reaction-single-strand ...
The morphological features of tumors are closely related to their growth patterns [8]. Polypoid tumors are believed to exhibit a predominantly vertical growth pattern, rather than a horizontal growth pattern, while non-polypoid tumors are believed to exhibit the opposite pattern, resulting in horizontal growth. Although there are some reports that LSTs have distinct biological characteristics compared to polypoid tumors [9, 10], the mechanism by which the LST conformation is generated remains unknown.. LSTs are believed to have distinct characteristics in terms of histological and genetic features [11]. Several molecular characteristics of LSTs have been described, including alteration of the adenomatous polyposis coli (APC) gene or β-catenin [12-14] affecting the WNT/APC/β-catenin signaling pathway, mutation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) [12, 15-20]. However, the molecular background of LSTs ...
Mutation rates at two expanded simple tandem repeat loci were studied in the germ line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and BALB/c mice exposed to either high linear energy transfer fission neutrons or low linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or fission neutrons resulted in increased mutation rates in the germ line of two subsequent generations. Comparable transgenerational effects were observed also in neutron-irradiated C57BL/6 and x-irradiated BALB/c mice. The levels of spontaneous mutation rates and radiation-induced transgenerational instability varied between strains (BALB/c,CBA/H,C57BL/6). Pre- and postmeiotic paternal exposure resulted in similar increases in mutation rate in the germ line of both generations of CBA/H mice, which together with our previous results suggests that radiation-induced expanded simple tandem repeat instability is ...
Cancer genomes contain large numbers of somatic mutations but few of these mutations drive tumor development. Current approaches either identify driver genes on the basis of mutational recurrence or approximate the functional consequences of nonsynonymous mutations by using bioinformatic scores. Passenger mutations are enriched in characteristic nucleotide contexts, whereas driver mutations occur in functional positions, which are not necessarily surrounded by a particular nucleotide context. We observed that mutations in contexts that deviate from the characteristic contexts around passenger mutations provide a signal in favor of driver genes. We therefore developed a method that combines this feature with the signals traditionally used for driver-gene identification. We applied our method to whole-exome sequencing data from 11,873 ...
Several decades have passed since oncogenic RAS was first identified as the transforming factor in the Harvey and Kirsten strains of the Mouse Sarcoma Virus (1, 3-5). Since these discoveries, all three RAS family genes (KRAS, NRAS, and HRAS) have been shown to be somatically mutated in human cancer, most commonly as a result of single point mutations at codons 12, 13, and 61.. Despite overwhelming evidence that oncogenic RAS plays a central role in mediating transformation in human tumors, only recently has limited testing for somatic RAS mutations entered routine clinical practice. Widespread adoption of mutational profiling in the clinic has been delayed for several reasons. First, before recent advances in sequencing technology, RAS mutational testing was expensive and time intensive. Second, until recently, there was no definitive evidence that routine testing for RAS mutations would meaningfully affect clinical practice. This changed ...
TY - JOUR. T1 - Mutation analysis of neurofilament-light gene in Chinese Charcot-Marie-Tooth disease. AU - Luo, Wei. AU - Tang, Bei Sha. AU - Zhao, Guo Hua. AU - Li, Qi. AU - Xiao, Jianfeng. AU - Yang, Qi Dong. AU - Xia, Jia Hui. PY - 2003/4/1. Y1 - 2003/4/1. N2 - Objective: To study the characteristic of the mutation of neurofilament-light (NF-L) gene in Chinese Charcot-Marie-Tooth disease (CMT) patients. Methods: Mutation analysis of NF-L gene was made by use of polymerase chain reaction-single strand conformation polymorphsim combined with DNA direct sequencing in 32 CMT probands from the Hans of five provinces in China who had been diagnosed by clinical feature and electromyography and/or biopsy of sural nerve. Results: In 32 CMT probands, only one sporadic case was found to display variant banding pattern, and this case was confirmed as 1329C to T (Tyr443Tyr) single nucleotide polymorphism by sequencing. Conclusion: Mutation of NF-L ...
New genetic data have allowed a more precise definition of 1.2.3.1 Familial hemiplegic migraine (FHM) than was possible previously. Specific genetic subtypes have been identified: in FHM1 there are mutations in the CACNA1A gene (coding for a calcium channel) on chromosome 19; in FHM2 there are mutations in the ATP1A2 gene (coding for a K/Na-ATPase) on chromosome 1; and in FHM3 there are mutations in the SCN1A gene (coding for a sodium channel) on chromosome 2. There may be other loci not yet identified. If genetic testing is done, the genetic subtype (if discovered) should be specified at the fifth digit.. It has been shown that 1.2.3.1 Familial hemiplegic migraine (FHM) very often presents with brainstem symptoms in addition to the typical aura symptoms, and that headache ...
The temperature-sensitive prp24-1 mutation defines a gene product required for the first step in pre-mRNA splicing. PRP24 is probably a component of the U6 snRNP particle. We have applied genetic reversion analysis to identify proteins that interact with PRP24. Spontaneous revertants of the temperature-sensitive (ts) prp24-1 phenotype were analyzed for those that are due to extragenic suppression. We then extended our analysis to screen for suppressors that confer a distinct conditional phenotype. We have identified a temperature-sensitive extragenic suppressor, which was shown by genetic complementation analysis to be allelic to prp21-1. This suppressor, prp21-2, accumulates pre-mRNA at the non-permissive temperature, a phenotype similar to that of prp21-1. prp21-2 completely suppresses the splicing defect and restores in vivo levels of the U6 snRNA in the prp24-1 strain. Genetic analysis ...
Lebers hereditary optic neuropathy (LHON) or Leber hereditary optic atrophy is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. LHON is only transmitted through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Men cannot pass on the disease to their offspring. Clinically, there is an acute onset of visual loss, first in one eye, and then ...
TY - JOUR. T1 - A cluster of cystic fibrosis mutations in exon 17b of the CFTR gene. T2 - A site for rare mutations. AU - Mercier, B.. AU - Lissens, W.. AU - Novelli, G.. AU - Kalaydjieva, L.. AU - De Arce, M.. AU - Kapranov, N.. AU - Canki Klain, N.. AU - Estivill, Xavier P.. AU - Palacio, Ana. AU - Cashman, S.. AU - Savov, A.. AU - Audrézet, M. P.. AU - Dallapicolla, B.. AU - Liebaers, I.. AU - Quéré, I.. AU - Raguénès, O.. AU - Verlingue, C.. AU - Férec, C.. PY - 1994/9. Y1 - 1994/9. N2 - Intensive screening has improved our understanding of the profile of mutations in the CFTR gene in which more than 400 mutations have been detected to date. In collaboration with several European laboratories we are involved in such analysis. We have identified 14 new mutations in exon 17b of CFTR, having analysed 780 CF chromosomes, and have compared the frequency of mutations in this ...
Somatic genetic mutation in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene has been linked to poor prognosis and resistance to various targeted therapeutics in Non Small Cell Lung Cancer (NSCLC). Therapeutic strategies that target tumors harboring these mutations represent an unmet medical need. In this study, we investigated the relationship between antifolate sensitivity and KRAS mutation/amplification status in NSCLC.. Human NSCLC cell lines (KRAS wild type, KRAS mutant non-amplified and KRAS mutant amplified) were treated with Methotrexate (MTX) or Pemetrexed (PEM) and assayed for proliferation after 72h. In these studies, 5 out of 7 KRASwt (wildtype) cells and all KRASmut (mutant) amplified cells showed resistance to MTX treatment (IC50 ,10μM). In contrast, growth of all KRASmut non-amplified cell lines studied was inhibited with MTX treatment (IC50 ,100nM). ...
BACKGROUND. Microsatellite instability (MI) is a frequent occurrence in endometrioid carcinoma of the endometrium (EC). 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. METHODS. DNA from 24 patients with EC and MI was extracted from blood and from fresh-frozen and paraffin embedded tumor tissue. Seven of these patients were found to have metastatic spread to paraaortic lymph nodes. DNA also was studied from 10 patients with EC without MI. RESULTS. Frameshift mutations at coding mononucleotide repeats were detected by single strand conformation polymorphism analysis and DNA sequencing. Frameshift mutations were detected more frequently in BAX (11 of 24 MI positive (+) tumors; 45.8%) than in TGF-β RII (0 of 24 tumors; 0%), IGFIIR (3 of 24 tumors; 12.5%), hMSH3 (6 of 24 tumors; 25%), or hMSH6 (0 of 24 tumors; 0%). The ...
The results of this study demonstrate the potential prognostic and predictive values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC). It has been proven that KRAS and BRAF mutations are predictive biomarkers for resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared the results with clinicopathological data. KRAS and BRAF mutations were identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of the positive patients, respectively. The KRAS mutation frequency was significantly higher in tumors located in the ascending colon (p=0.043). Thus, we found that approximately 1/3 of the ...
Three recurrent mutations were also identified during sequencing. Two families (nos. 264 and 265) showed a previously reported nonsense mutation predicting truncation of the protein at amino acid 220. [17] One family (no. 69) showed a codon 139 valine right arrow methionine missense mutation, also in the third transmembrane domain. [9] Another family (no. 269) showed recurrence of the codon 156 leucine right arrow arginine missense mutation located in the second extracellular loop. [9] None of the reported families with the same mutation are known to be related. In most cases, families with the same mutation are from different geographic regions. For example, family 69 is from New York, and the other two families with the identical mutation are from South Dakota and Michigan, with no known New York connection.. Nine families analyzed had no mutation within the coding region of Cx32. Seven of these represent sporadic cases, one has affected members in only two generations, ...
This study was prospectively designed to evaluate a phase II study of gefitinib for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Clinical samples were tested for EGFR mutations by peptide nucleic acid-locked nucleic acid PCR clamp, and patients having EGFR mutations were given gefitinib 250 mg daily as the second treatment after chemotherapy. Poor PS patients omitted chemotherapy. Of 107 consecutive patients enrolled, samples from 100 patients were informative, and EGFR mutations were observed in 38 patients. Gefitinib was given to 27 patients with EGFR mutations, and the response rate was 78% (one complete response and 20 partial responses; 95% confidence interval: 58-93%). Median time to progression and median survival time (MST) from gefitinib treatment were 9.4 and 15.4 months, respectively. Grade 3 hepatic toxicity and skin toxicity were observed in one patient ...
Welcome to the Cystic Fibrosis Mutation Database (CFTR1), devoted to the collection of mutations in the CFTR gene for the international cystic fibrosis genetics research community. It was initiated by the Cystic Fibrosis Genetic Analysis Consortium in 1989 to increase and facilitate communications among CF researchers, and is maintained by the Cystic Fibrosis Centre at the Hospital for Sick Children in Toronto. The specific aim of the database is to provide up to date information about individual mutations in the CFTR gene. In a major upgrade in 2010, all known CFTR mutations and sequence variants have been converted to the standard nomenclature recommended by the Human Genome Variation Society. In addition, an on-line process for the submission of new mutations has been added. While we will continue to ensure the quality of the data, we ...
Lebers hereditary optic neuropathy (LHON) is a rare, maternally inherited disorder that results in bilateral loss of central vision. Characteristic visual field defects in LHON consist of either central or cecocentral scotomas, with about 70% of the patients being young adult men. More than 90% of these patients carry 1 of 3 mitochondrial DNA (mtDNA) mutations, located at nucleotide positions 3460, 11778, or 14484, respectively, although >20 mtDNA point mutations have been reported in LHON patients worldwide. Retinal ganglion cells decrease by apoptosis, and finally the retinal nerve fiber thins (Read more...) Full Story →. ...
Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis Academic Article ...
Elite controllers (EC) of human immunodeficiency virus type 1 (HIV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8(+) T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear.
Study Rationale: Mutations in the GBA gene are the most common genetic cause of Parkinson s disease. This gene has a nearby pseudogene, which is a genetic material that is very similar to the original gene but does not encode a protein. Because of the presence of the pseudogene, it is often difficult to identify mutations in the gene using traditional mutation detection techniques. Furthermore, specific mutations that occur as a result of a recombination between the gene and the pseudogene are often missed by the traditional genetic methods.. Hypothesis:. By using a novel technology called targeted locus amplification (TLA) we hypothesize that we will be able to better discriminate between the ...
BACKGROUND. Activating KRAS and BRAF mutations predict unresponsiveness to EGFR-targeting therapies in colorectal cancer (CRC), but their prognostic value needs further validation. In this study, we investigated the impact of KRAS codons 12 and 13, and BRAF mutations on survival from CRC, overall and stratified by sex, in a large prospective cohort study.. METHODS. KRAS codons 12 and 13, and BRAF mutations were analysed by pyrosequencing of tumours from 525 and 524 incident CRC cases in The Malmö Diet and Cancer Study. Associations with cancer-specific survival (CSS) were explored by Cox proportional hazards regression, unadjusted and adjusted for age, TNM stage, differentiation grade, vascular invasion and microsatellite instability (MSI) status.. RESULTS. KRAS and BRAF mutations were mutually exclusive. KRAS mutations were found in 191/ 525 (36.4%) cases, 82.2% of these mutations were in codon 12, 17.3% ...
Pyrosequencing Allele Quantification (AQ) is a cost-effective DNA sequencing method that can be used for detecting somatic mutations in formalin-fixed paraffin-embedded (FFPE) samples. The method displays a low turnaround time and a high sensitivity. Pyrosequencing suffers however from two main drawbacks including (i) low specificity and (ii) difficult signal interpretation when multiple mutations are reported in a hotspot genomic region. Using a constraint-based regression method, the new AdvISER-PYRO-SMQ algorithm was developed in the current study and implemented into an R package. As a proof-of-concept, AdvISER-PYRO-SMQ was used to identify a set of 9 distinct point mutations affecting codon 61 of the NRAS oncogene. In parallel, a pyrosequencing assay using the Qiagen software and its AQ module was used to assess selectively the presence of a single point mutation (NRAS ...
Introduction: Mutations in the voltage-gated sodium channel SCN1A gene are the main genetic cause of Dravet syndrome (previously called Severe Myoclonic Epilepsy of Infancy or SMEI).. Objective and methods: Our objectives were to characterize in more detail the mutation spectrum associated with Introduction. Mutations in the voltage-gated sodium channel SCN1A gene are the main genetic cause of Dravet syndrome (previously called Severe Myoclonic Epilepsy of Infancy or SMEI).. Objective and methods: Our objectives were to characterize in more detail the mutation spectrum associated with Dravet syndrome by screening a large series of 333 patients using both direct sequencing and Multiplex Ligation-dependent probe Amplification (MLPA). Additionally, we screened non-coding regions of the gene that are usually not investigated.. Results: SCN1A point ...
Pharmacodynamic and mutant prevention properties of the fluoroquinolone pradofloxacin (PRA) were measured against a set of 17 Escherichia coli strains carrying no, one or two known mutations conferring reduced fluoroquinolone susceptibility. The strains included susceptible wild-types, isogenic constructed mutants, isogenic selected mutants and clinical isolates. The effectiveness of PRA was determined with regard to preventing the selection of resistant mutants, using static and changing concentrations of drug. Ciprofloxacin was used as a reference drug. Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of PRA for the susceptible wild-type strains were in the range 0.012-0.016 mg/L and 0.2-0.3 mg/L, respectively, giving a mean +/- standard deviation mutant prevention index (MPI=MPC/MIC) of 17.7 +/- 1.1. The mean MPI PRA of the 14 mutant strains was 19.2 +/- 12, and the mean MPI across all 17 strains was 18.9 +/- 10.8. In an in vitro kinetic model in which ...
Previous studies suggest that Lebers hereditary optic neuropathy (LHON) may be a systemic disorder with manifestations in organs other than the optic nerves. To evaluate nervous system involvement 38 men and eight women with LHON were re-examined. The patients were divided into three groups according to mtDNA analysis--namely, patients with the 11778 or with the 3460 mutation and patients without these primary mutations. Fifty nine per cent of patients had neurological abnormalities but there was no significant difference between the three groups. Movement disorders were the most common finding; nine patients had constant postural tremor, one chronic motor tic disorder, and one parkinsonism with dystonia. Four patients had peripheral neuropathy with no other evident cause. Two patients had a multiple sclerosis-like syndrome; in both patients MRI showed changes in the periventricular white matter. Thoracic kyphosis occurred in seven patients, five of whom had the 3460 mutation. In one patient ...
BACKGROUND AND OBJECTIVES: Congenital dyserythropoietic anemia type III (CDA-III) is a group of very rare disorders characterized by similar bone marrow morphology. The clinical picture is characterized by hemolytic anemia and dramatic bone marrow changes dominated by active erythropoiesis with big multinucleated erythroblasts. The aim of this review is to describe the clinical manifestations, laboratory findings, and management CDA-III. EVIDENCE AND INFORMATION SOURCES: The present review critically examines relevant articles and abstracts published in journals covered by the Science Citation Index and Medline. The authors have performed several studies on CDA-III. STATE OF ART AND PERSPECTIVES: The clinical and laboratory manifestations of CDA-III indicate that the gene responsible for it, which has been mapped to chromosome 15q22, is expressed not only in erythroblasts during mitosis but also in B-cells, and in cells of the retina. Preliminary results ...
TY - JOUR. T1 - Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita. AU - Bizarro, Jonathan. AU - Meier, U. Thomas. PY - 2017/1/1. Y1 - 2017/1/1. N2 - Background: The inherited bone marrow failure syndrome dyskeratosis congenita (DC) is most frequently caused by mutations in DKC1 (MIM# 300126), the gene encoding NAP57 (aka dyskerin). The typically missense mutations modulate the interaction of NAP57 with its chaperone SHQ1, but no DC mutations have been identified in SHQ1 (MIM# 613663). Here, we report on two compound heterozygous mutations in SHQ1 in a patient with a severe neurological disorder including cerebellar degeneration. Methods: The SHQ1 mutations were identified by patient exome sequencing. The impact of the mutations was assessed in pulldown assays with recombinant NAP57. Results: The SHQ1 ...
Purpose: : Lebers hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of fibers forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the lateral geniculate nucleus (LGN) and the optic radiation (OR) in LHON patients. Methods: : We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at the level of the OR. Furthermore, we studied the optic nerve and the LGN in postmortem specimens obtained from a severe case of LHON compared to an age-matched control. Results: : Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P, 0.05) and healthy subjects (P , 0.01). Increased diffusivity was associated with both disease ...
TY - JOUR. T1 - Proliferative quiescence of normal mast cells resembles that of cold-sensitive mutant mastocytoma cells. Dominant expression of the quiescent state in heterokaryons. AU - Laeng, H.. AU - Harris, David T.. AU - Schindler, R.. PY - 1985. Y1 - 1985. N2 - Normal murine peritoneal mast cells were fused to serum-deprived, non-proliferating cells of a cultured subline (41-SB-4) of the P-815 murine mastocytoma. Upon reincubation in medium containing 10% horse serum for 48 h, mono- and binuclear 41-SB-4 cells reentered S phase of the cell cycle, while mast cell × 41-SB-4 heterokaryons as well as mono- and binuclear mast cells remained in proliferative quiescence, indicating dominant expression of the quiescent state of mast cells. The quiescent state of normal mast cells thus resembles that of cold-sensitive (cs) mutant cells (21-F) of the ...
TY - JOUR. T1 - PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. AU - Glaser, Tom. AU - Jepeal, Lisa. AU - Edwards, Janice G.. AU - Young, S. Robert. AU - Favor, Jack. AU - Maas, Richard L.. PY - 1994/8. Y1 - 1994/8. N2 - The human eye malformation aniridia results from haploinsufficiency of PAX6, a paired box DNA-binding protein. To study this dosage effect, we characterized two PAX6 mutations in a family segregating aniridia and a milder syndrome consisting of congenital cataracts and late onset corneal dystrophy. The nonsense mutations, at codons 103 and 353, truncate PAX6 within the N-terminal paired and C-terminal PST domains, respectively. The wild-type PST domain activates transcription autonomously and the mutant form has partial activity. A compound heterozygote had severe craniofacial and central nervous system defects and no eyes. The pattern of malformations is similar to ...
CEBPA mutations in patients with de novo acute myeloid leukemia: data analysis in a Chinese population Long Su, SuJun Gao, XiaoLiang Liu, YeHui Tan, Lu Wang, Wei Li Cancer Center, The First Hospital, Jilin University, Changchun, Peoples Republic of China Background: This study was aimed to explore the clinical characteristics and prognoses of acute myeloid leukemia (AML) patients with CEBPA mutations. Patients and methods: Three hundred and forty-five patients with de novo AML were retrospectively analyzed with regard to CEBPA mutations, clinical characteristics, therapeutic responses, and long-term outcomes. Results: CEBPA mutations were detected in 59 patients (17.10%), with 47 cases harboring double mutations and 12 cases harboring single mutations. In those with a normal karyotype (NK), 44 cases (25.29%) were detected with CEBPA mutations. The following characteristics were observed ...
Primary microcephaly is defined as reduced occipital-frontal circumference noticeable before 36 weeks of gestation. Large amount of insults might lead to microcephaly including infections, hypoxia and genetic mutations. More than 16 genes are described in autosomal recessive primary microcephaly. However, the cause of microcephaly remains unclear in many cases after extensive investigations and genetic screening. Here, we described the case of a boy with primary microcephaly who presented to a neurology clinic with short stature, global development delay, dyskinetic movement, strabismus and dysmorphic features. We performed microcephaly investigations and genetic panels. Then, we performed whole-exome sequencing to identify any genetic cause. Microcephaly investigations and genetic panels were negative, but ...
Germline mutations in mismatch repair (MMR) genes, predominantly in MLH1 and MSH2, are responsible for hereditary nonpolyposis colorectal cancer (HNPCC), a cancer-susceptibility syndrome with high penetrance. In addition, MSH6 mutations have been reported to account for about 10% of all germline mismatch repair (MMR) gene mutations in HNPCC patients, and have been associated with a later age of onset of the disease compared to MLH1 and MSH2 mutations. Here, we report eight novel germline mutations in MSH6. The patients were selected by having developed tumors with loss of MSH6 protein expression. All tumors showed high-level microsatellite instability (MSI-H). Seven mutations resulted in premature stop codons, comprised of two nonsense mutations (c.426G,A [p.W142X], c.2105C,A [p.S702X]), two insertions (c.2611_2614dupATTA [p.I872fsX10], c.3324dupT ...
The peroxisome biogenesis disorders (PBDs) are a group of neuronal migration/neurodegenerative disorders that arise from defects in PEX genes. A major subgroup of the PBDs includes Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). These three disorders represent a clinical continuum with Zellweger syndrome the most severe. Mutations in the PEX1 gene, which encodes a protein of the AAA ATPase family involved in peroxisome matrix protein import, account for the genetic defect in more than half of the patients in this PBD subgroup. We report here on the results of PEX1 mutation detection in an Australasian cohort of PEX1-deficient PBD patients. This screen has identified five novel mutations, including nonsense mutations in exons 14 and 19 and single nucleotide deletions in exons 5 and 18. Significantly, the ...
TY - JOUR. T1 - Inactivation of the open reading frame slr0399 in Synechocystis sp. PCC 6803 functionally complements mutations near the Q(A) niche of photosystem II. A possible role of Slr0399 as a chaperone for quinone binding. AU - Ermakova-Gerdes, Svetlana. AU - Vermaas, Willem. PY - 1999/10/22. Y1 - 1999/10/22. N2 - The Synechocystis sp. PCC 6803 triple mutant D2R8 with V247M/A249T/M329I mutations in the D2 subunit of the photosystem II is impaired in Q(A) function, has an apparently mobile Q(A), and is unable to grow photoautotrophically. Several photoautotrophic pseudorevertants of this mutant have been isolated, each of which retained the original psbDI mutations of D2R8. Using a newly developed mapping technique, the site of the secondary mutations has been located in the open reading frame slr0399. Two different nucleotide substitutions and a deletion of about 60% of slr0399 were each shown to restore photoautotrophy in different ...
A splice site mutation is a genetic mutation that inserts, deletes or changes a number of nucleotides in the specific site at which splicing takes place during the processing of precursor messenger RNA into mature messenger RNA. Splice site consensus sequences that drive exon recognition are located at the very termini of introns. The deletion of the splicing site results in one or more introns remaining in mature mRNA and may lead to the production of abnormal proteins. When a splice site mutation occurs, the mRNA transcript possesses information from these introns that normally should not be included. Introns are supposed to be removed, while the exons are expressed. The mutation must occur at the specific site at which intron splicing occurs: within non-coding sites in a gene, directly next to the location of the exon. The mutation can be an insertion, deletion, frame shift, etc. The splicing process itself is controlled by the given sequences, known as ...
The xeroderma pigmentosum group D (XPD) protein has a dual function, both in nucleotide excision repair of DNA damage and in basal transcription. Mutations in the XPD gene can result in three distinct clinical phenotypes, XP, trichothiodystrophy (TTD), and XP with Cockayne syndrome. To determine if the clinical phenotypes of XP and TTD can be attributed to the sites of the mutations, we have identified the mutations in a large group of TTD and XP-D patients. Most sites of mutations differed between XP and TTD, but there are three sites at which the same mutation is found in XP and TTD patients. Since the corresponding patients were all compound heterozygotes with different mutations in the two alleles, the alleles were tested separately in a yeast complementation assay. The mutations which are found in both XP and TTD patients behaved as null alleles, suggesting that the disease phenotype ...
TY - JOUR. T1 - Targeting protein translation in human non-small cell lung cancer via combined MEK and mammalian target of rapamycin suppression. AU - Legrier, Marie Emmanuelle. AU - Yang, Chia Ping Huang. AU - Yan, Han Guang. AU - Lopez-Barcons, Lluis. AU - Keller, Steven M.. AU - Pérez-Soler, Roman. AU - Horwitz, Susan Band. AU - McDaid, Hayley M.. PY - 2007/12/1. Y1 - 2007/12/1. N2 - Lung cancer is a genetically heterogeneous disease characterized by the acquisition of somatic mutations in numerous protein kinases, including components of the rat sarcoma viral oncogene homolog (RAS) and AKT signaling cascades. These pathways intersect at various points, rendering this network highly redundant and suggesting that combined mitogen-activated protein/extracellular signal-regulated kinase (MEK) and mammalian target of rapamycin (mTOR) inhibition may be a promising drug combination that can overcome its intrinsic plasticity. ...
Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous disorder characterized by hyperkeratosis in addition to dry, scaly skin. There are six genes currently known to be associated with the disease. Exome sequencing data for two affected individuals with ichthyosis from two apparently unrelated consanguineous Pakistani families was analysed. Potential candidate mutations were analysed in additional family members to determine if the putative mutation segregated with disease status. A novel mutation (c.G4676T, p.Gly1559Val) in |i|ABCA12|/i| occurred at a highly conserved residue, segregated with disease status in both families, and was not detected in 143 control chromosomes. Genotyping with microsatellite markers demonstrated a partial common haplotype in the two families, and a common founder mutation could not be excluded. Comparison to previously reported cases was consistent with the ...
Purpose : Retinitis pigmentosa, the most common hereditary retinal disease causing blindness worldwide, refers to a heterogeneous group of progressive retinal degenerations. Mutations in the rhodopsin gene (RHO) are suggested to be the most common cause of autosomal dominant retinitis pigmentosa. This study is aimed at identification of the mutations in RHO gene in Retinitis pigmentosa patients in a Chinese population. Methods : A cohort of 225 Chinese families with Retinitis pigmentosa was collected from 15 cities of China. In this study, Sanger sequencing was used to analyze all five coding exons and adjacent intronic regions of RHO in 225 Chinese probands with different forms of retinitis pigmentosa. Results : A cohort of 225 Chinese families with Retinitis pigmentosa was collected from 15 cities of China. In this study, Sanger sequencing was used to analyze all five coding exons and adjacent intronic ...
Looking for online definition of Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene homolog in the Medical Dictionary? Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene homolog explanation free. What is Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene homolog? Meaning of Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene homolog medical term. What does Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene homolog mean?
PURPOSE: To characterize the molecular defect in the TGFBI gene in a Chinese family affected with an atypical lattice corneal dystrophy.. DESIGN: Case report and experimental study.. METHODS: Molecular genetic analysis was performed on the DNA extracted from peripheral leucocytes from a Chinese family with atypical lattice corneal dystrophy. Fifty normal unrelated subjects of Chinese origin were used as controls. All exons of the TGFBI gene were amplified by polymerase chain reaction and directly sequenced.. RESULTS: Bilateral, symmetrical, ridgy round pattern of opacities with uneven surfaces and thin lattice lines were noted in the proband. Analysis of exon 14 revealed a heterozygous T to A transition on codon 625. The mutation was not detected in the unaffected family member and 50 unaffected individuals.. CONCLUSIONS: The novel TGFBI gene mutation (V625D) is associated with an early,onset variant of lattice corneal ...
TY - JOUR. T1 - Presenilin 1 mutations increase amyloid precursor protein production and proteolysis in Xenopus laevis oocytes. AU - Heyn, Sietske N.. AU - Vulliet, Philip R. PY - 2001/6/22. Y1 - 2001/6/22. N2 - Recent findings suggest that Presenilin 1 (PS1) mutations play a major role in the development of Alzheimers disease (AD) by increasing the production of the beta amyloid peptide (Aβ). The exact mechanism whereby mutations in PS1 lead to this effect is not clear. To examine the question of how PS1 might be involved in amyloid precursor protein (APP) processing, we constructed a chimera of human APP695 fused at the C-terminal to enhanced green fluorescent protein (EGFP). This construct was injected into Xenopus laevis oocytes in the presence of wild type PS1 or one of three PS1 mutations associated with AD. The cellular location of the APP695-EGFP construct was examined by fluorescent confocal microscopy. In addition, membrane ...
Mendels Accountant User Manual: Maximal beneficial mutation effects A realistic upper limit must be placed upon beneficial mutations. This is because a single nucleotide change can expand total biological functionality of an organism only to a limited degree. The larger the genome and the greater the total genomic information, the less a single nucleotide is likely to increase the total. Researchers must make a judgment for themselves of what is a reasonable maximal value for a single base change. The MENDEL default value for this limit is 0.001. This limit implies that a single point mutation can increase total biological functionality by as much as 0.1%. In a genome such as man s, assuming only 10% of the genome is functional, such a maximal impact point mutation might be viewed as equivalent to adding 300,000 new information-bearing base pairs each of which had the genome-wide average fitness contribution. Researchers need to honestly define the upper limit they feel is realistic for ...
TY - JOUR. T1 - The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6. AU - Matsumoto, N.. AU - Tamura, S.. AU - Moser, Ann B.. AU - Moser, H. W.. AU - Braverman, N.. AU - Suzuki, Y.. AU - Shimozawa, N.. AU - Kondo, N.. AU - Fujiki, Y.. PY - 2001. Y1 - 2001. N2 - Human genetic peroxisomal biogenesis disorders (PBDs), such as Zellweger syndrome, comprise 13 different complementation groups (CGs). Eleven peroxin genes, termed PEXs, responsible for PBDs have been identified, whereas pathogenic genes for PBDs of 2CGs, CG-A (the same CG as CG8 in the United States and Europe) and CG6, remained unidentified. We herein provide several lines of novel evidence indicating that PEX6, the pathogenic gene for CG4, is impaired in PBD of CG6. Expression of PEX6 restored peroxisome assembly in fibroblasts from a CG6 PBD patient. This patient was a ...
Press Release issued Sep 24, 2014: Whole exome sequencing (WES) refers to a technique for sequencing the coding region of the genome (exon). Whole exome sequencing helps to detect rare variants in the exome for identifying genomic cause of various diseases such as cancer, genetic disorders, monogenic disorders and others. Whole exome sequencing is used by research centers, pharmaceutical companies, hospitals, clinics, biotechnology companies and government institutions for sequencing of genome. Some of the application areas for whole exome sequencing are drug discovery and development, agriculture, cancer, personalized medicine, monogenic disorders, diagnostics and others.
a-Galactosidase AgaB from Bacillus stearothermophilus displays a major a(1~6) and a minor a(1~3) regioselectivity in hydrolysis and transglycosylation. Its corresponding gene, agaB, was subjected to saturation mutagenesis at codon 442 in order to change its regioselectivity. The mutant genes were cloned and expressed in Escherichia coli using pBTac2 as vector. The regioselective activity of the mutants was determined using thin layer chromatography and nuclear magnetic resonance spectroscopy. A single point mutation, G442R, resulted in a mutant displaying an a(1~2) regioselectivity. Other amino acid substitutions at this site also gave mutants with altered regioselectivity and transglycosylation profiles. This is the first demonstration that single point mutations can lead to a strong modification of the regioselectivity of a glycosyl hydrolase. The kinetic parameters of the enzyme variants were determined and a preliminary investigation of ...
The radial basis function-based high-dimensional model representation (RBF-HDMR) is very promising as a metamodel for high dimensional costly simulation-based functions. But in the modeling procedure, it requires well-structured regular points sampled on cut lines and planes. In practice, we usually have some existing random points that do not lie on cut lines or planes. For this case, RBF-HDMR cannot utilize the information of these random points because of its inner regular sampling process. To utilize the existing random points, this article presents two strategies to build a generalized RBF-HDMR (GRBF-HDMR) model. The GRBF-HDMR model using the error model (EM) strategy, called GRBF-HDMREM, constructs an error RBF model based on the prediction errors at all the sampled points to improve the RBF-HDMR predictions. While the GRBF-HDMR model using the error allocation (EA) strategy, called GRBF-HDMREA, employs the virtual regular points projected from the random points and the estimated ...
TY - JOUR. T1 - Dorfin prevents cell death by reducing mitochondrial localizing mutant superoxide dismutase 1 in a neuronal cell model of familial amyotrophic lateral sclerosis. AU - Takeuchi, Hideyuki. AU - Niwa, Jun Ichi. AU - Hishikawa, Nozomi. AU - Ishigaki, Shinsuke. AU - Tanaka, Fumiaki. AU - Doyu, Manabu. AU - Sobue, Gen. PY - 2004/4. Y1 - 2004/4. N2 - Dorfin is a RING-finger type ubiquitin ligase for mutant superoxide dismutase 1 (SOD1) that enhances its degradation. Mutant SOD1s cause familial amyotrophic lateral sclerosis (FALS) through the gain of unelucidated toxic properties. We previously showed that the accumulation of mutant SOD1 in the mitochondria triggered the release of cytochrome c, followed by the activation of the caspase cascade and induction of neuronal cell death. In the present study, therefore, we investigated whether Dorfin can modulate the level of mutant SOD1 in the mitochondria and subsequent caspase activation. We showed that Dorfin significantly reduced the ...
Research Summary Mutations in mitochondrial DNA (mtDNA) lead to a spectrum of neurodegenerative diseases for which no effective treatment exists. The most common of these is Leber hereditary optic neuropathy (LHON) caused by mutations in NADH dehydrogenase subunit genes (ND1, ND4 or ND6), which is complex I of the respiratory chain. Therapies for LHON in common with all disorders caused by mutated mtDNA are inadequate, in large part because of the barrier in delivering DNA into the organelle. We have successfully broken through this barrier by developing a pioneering adeno-associated virus (AAV) vector to which a mitochondrial targeting sequence (MTS) was appended to the viral capsid. The modified vector delivered the ND4 gene directly to the mitochondria for reversal of visual loss in mice with mutated G11778A ND4 responsible for more than half of all LHON cases, the rest caused by mutated ND1 and ND6. We will now design, ...
Muscular dystrophy in the Cavalier King Charles Spaniel. A Duchenne Muscular Dystrophy Gene Hot Spot Mutation in Dystrophin-Deficient Cavalier King Charles Spaniels. Research News. A Duchenne Muscular Dystrophy Gene Hot Spot Mutation in Dystrophin-Deficient Cavalier King Charles Spaniels is amenable to Exon 51 Skipping. In new research published in PLoS ONE on 13th January 2010, veterinary scientists, including Dr Richard Piercy and Gemma Walmsley at the Comparative Neuromuscular
Objective: To investigate the mechanisms underlying myoclonus in Leber hereditary optic neuropathy (LHON).. Methods: Five patients and one unaffected carrier from two Italian families bearing the homoplasmic 11778/ND4 and 3460/ND1 mutations underwent a uniform investigation including neurophysiologic studies, muscle biopsy, serum lactic acid after exercise, and muscle (31P) and cerebral (1H) magnetic resonance spectroscopy (MRS). Biochemical investigations on fibroblasts and complete mitochondrial DNA (mtDNA) sequences of both families were also performed.. Results: All six individuals had myoclonus. In spite of a normal EEG background and the absence of giant SEPs and C reflex, EEG-EMG back-averaging showed a preceding jerk-locked EEG potential, consistent with a cortical generator of the myoclonus. Specific comorbidities in the 11778/ND4 family included muscular cramps and psychiatric disorders, whereas features common to both families were migraine and cardiologic ...
The purpose of this study was to identify the genetic basis of hereditary hearing loss using next-generation sequencing technology in small families who could not be analyzed using the current genetic approaches. Eight small families with autosomal dominant, non-syndromic, sensorineural hearing loss were selected, and 80 target genes associated with hearing loss were screened using target capture and massively parallel sequencing methods. In current study, 5 non-synonymous mutations were confirmed in 5 of the 8 families. The causative genes underlying the hearing loss in the 3 other families are still awaiting discovery. There are 2 possible explanations for the hearing loss in these families: (1) pathogenic mutations exist in 1 of the 80 candidate genes studied but in an exon that was not covered by our sequencing (approximately 6-10%) or ...
The horizontal axis represents time, and the vertical axis represents a percentage of the population. When a mutation enters the population, it occurs in only one individual and is plotted as a point somewhere on the x axis. If the mutation is passed on, for example to four new offspring, then it will be in a higher percentage of the population at the next time step. Most mutations will soon drop out of the population. Either the individual where the mutation originates will not survive, or if it does survive and mate, by chance it may not pass the mutation to its children. Even then the children may not pass the mutation any further. Mutations that eventually die out show up as inverted ``V shapes in the figure: they are introduced, they are passed on to some proportion of the population in the next few generations, and eventually the percentage drops to 0 as the mutation disappears. Some small percentage of new mutations are passed on ...
sage -t --long devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py ********************************************************************** File "devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py", line 1259, in sage.combinat.cluster_algebra_quiver.mutation_type._mutation_type_test Failed example: _mutation_type_test(2) # long time Expected: True (A, 2) True (A, (1, 1), 1) True (B, 2) True (BC, 1, 1) True (G, 2) Got: True (A, (1, 1), 1) True (A, 2) True (B, 2) True (BC, 1, 1) True (G, 2) ********************************************************************** File "devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py", line 1266, in sage.combinat.cluster_algebra_quiver.mutation_type._mutation_type_test Failed example: _mutation_type_test(3) # long time Expected: True (A, 3) True (A, (2, 1), 1) True (B, 3) True (BB, 2, 1) True (BC, 2, 1) True (C, 3) True (CC, 2, 1) True (G, 2, -1) True (G, 2, 1) Got: True (A, (2, 1), 1) ...

Common Clawed Frogs articles
-
Encyclopedia of LifeCommon Clawed Frogs articles - Encyclopedia of Life

7 Genetic studies. * 8 Gene expression knockdown techniques *8.1 Morpholino oligonucleotides. *9 References ... Xenopus cell-free extracts for biochemical studies of proteins encoded by human disease genes: A unique advantage of the ... MOs can knock down gene expression by inhibiting mRNA translation, blocking RNA splicing, or inhibiting miRNA activity and ... In a recent study, mutations in the SMAD7 locus were revealed to associate with human colorectal cancer. The mutations lay in ...
more infohttps://eol.org/pages/15797/articles

Knockout mice & gene targetingKnockout mice & gene targeting

... for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells. ... They replaced a specific gene with a similar genetic sequence, which was modified to contain a mutation. The plasmid was ... The mutant gene could not function, and so was knocked out. This showed how a mouse with a non-functioning copy of the gene ... that a technique used to mutate bacteria through exposing them to x-rays could also introduce mutations into mammalian genes. ...
more infohttp://www.animalresearch.info/en/medical-advances/nobel-prizes/knockout-mice-gene-targeting/

BIOCHEM 3235 - Cancer, Stem Cells & Development III (Biomed Sc) | Course OutlinesBIOCHEM 3235 - Cancer, Stem Cells & Development III (Biomed Sc) | Course Outlines

... genetic mutations, oncogenes and tumour suppressor genes, clonal selection, the hallmarks of cancer and metastasis, ... generation of transgenic/knock-out mice using CRISPR/Cas9 and other techniques, with medical and other applications. Finally, ... topics include the molecular mechanisms of cell-cell communication, signal transduction pathways, genetic mutations, oncogenes ... 2. Stem Cells and Development: topics include the embryonic and adult stem cells, cellular reprogramming and induced ...
more infohttps://www.adelaide.edu.au/course-outlines/106134/1/sem-2/

In hands-on lab, undergrads learn basics of CRISPR gene-editing technique - University at BuffaloIn hands-on lab, undergrads learn basics of CRISPR gene-editing technique - University at Buffalo

The same series of steps can be used not only to knock out targeted genes, but also to repair unwanted genetic mutations and ... a revolutionary gene-editing technique.. CRISPR allows scientists to disable or alter specific sections of DNA in cells of ... The cells and colonies have turned a bubblegum pink after students used CRISPR successfully to break a gene called ADE2. Credit ... dishes after carefully mixing the cells with a DNA plasmid and DNA fragment used to perform the CRISPR gene-editing technique. ...
more infohttps://www.buffalo.edu/news/releases/2018/11/033.html

Johns Hopkins Greenberg Bladder Cancer Institute awards grants for 10 bladder cancer research projectsJohns Hopkins Greenberg Bladder Cancer Institute awards grants for 10 bladder cancer research projects

... and a plan to use stem cells to grow novel urinary tubes are among 10 research projects awarded funding by the Johns Hopkins ... bladder cancer cells will be pretreated with genetic material called small interfering RNA to knock down individual gene ... Cells that respond very well or very poorly to treatment may predict genetic mutations associated with exceptional response or ... Johnson and colleagues will use a novel technique to expand immune cells that are designed to recognize cancer. They will ...
more infohttps://www.news-medical.net/news/20160307/Johns-Hopkins-Greenberg-Bladder-Cancer-Institute-awards-grants-for-10-bladder-cancer-research-projects.aspx

Genetic engineering - Stock Image - C028/7911 - Science Photo LibraryGenetic engineering - Stock Image - C028/7911 - Science Photo Library

GE, also called genetic modification, a direct manipulation of an organisms genome using biotechnology. ... Conceptual image of genetic engineering showing a DNA double helix made up from a metal construction kit. ... Genes may be removed, or knocked out, using a nuclease. Gene targeting is a different technique that uses homologous ... It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across ...
more infohttps://www.sciencephoto.com/media/717292/view

2009 News Feature: Making a Mightier Knockout Mouse - National Human Genome Research Institute (NHGRI)2009 News Feature: Making a Mightier Knockout Mouse - National Human Genome Research Institute (NHGRI)

... using genetic engineering techniques to completely disrupt, or "knock out", one or more genes in the laboratory animals. ... They use ES cells because these cells can differentiate into any type of adult cell. That means if a gene is knocked out in an ... Black 6 mice carry a genetic mutation that makes their coats black. The normal version of this gene produces a reddish-brown ... After a targeted gene is knocked out, researchers inject the altered ES cells into early-stage mouse embryos. The embryos are ...
more infohttps://www.genome.gov/27532436/making-a-mightier-knockout-mouse/

Genetic editing: Promise and peril | Inquirer TechnologyGenetic editing: Promise and peril | Inquirer Technology

BACKSTORY: Britain approves controversial gene-editing technique , Is the happiness gene in your DNA?. ADVERTISEMENT ... a very rare condition which destroys nerve cells, for example), or repair a naturally-occurring mutation. ... This allows researchers to "knock out" genes that cause disease (certain forms of cancer or Tay-Sachs, ... TAGS: DNA, embryonic engineering, embryos, genes, genetic editing, genetic engineering, genome, In vitro fertilization, IVF, ...
more infohttps://technology.inquirer.net/46471/genetic-editing-promise-and-peril

DiMeN Doctoral Training Partnership: Characterizing the functions of a microcephaly-related gene in a knock-out mouse model...DiMeN Doctoral Training Partnership: Characterizing the functions of a microcephaly-related gene in a knock-out mouse model...

Characterizing the functions of a microcephaly-related gene in a knock-out mouse model using in vivo MRI, histology and ... Rare human genetic diseases can highlight previously unrecognised, but important gene functions. Mutations in the human TRAPPC9 ... primary cultures of neural progenitor cells (NPCs) and neurons, as well as molecular genetic analyses of gene regulation. ... Histological techniques will be used to validate findings. Since the developmental onset of microcephaly is currently unclear, ...
more infohttps://www.findaphd.com/search/projectdetails.aspx?PJID=93035

Scientists Create First Targeted Knockout Rats Using Zinc Finger Nuclease Technology - RedorbitScientists Create First Targeted Knockout Rats Using Zinc Finger Nuclease Technology - Redorbit

Previously, ZFNs were used to knock out specific genes in fruit flies, worms, cultured human cells and zebrafish embryos and ... Generating rats with knockout mutations has been a major challenge, but the new technique will increase the rats usefulness in ... Extensive genetic characterization has revealed that approximately 90 percent of the rats 25,000-30,000 estimated genes are ... "Until now, rat geneticists lacked a viable technique for "knocking out," or mutating, specific genes to understand their ...
more infohttp://www.redorbit.com/news/technology/1725891/scientists_create_first_targeted_knockout_rats_using_zinc_finger_nuclease/

Molecular Mechanisms Section | National Eye InstituteMolecular Mechanisms Section | National Eye Institute

The Molecular Mechanisms Section of the NEI Laboratory of Retinal Cell and Molecular Biology studies vitamin A and lipid ... Mutations in the human RPE65 gene result in Lebers congenital amaurosis (LCA) and autosomal recessive childhood-onset severe ... We are currently studying knock-in mouse models for less severe forms of human LCA. Human RPE65 mutations cause a spectrum of ... Without these cells the retinal photoreceptor cells, and vision itself, could not function. RPE dysfunction has serious ...
more infohttps://www.nei.nih.gov/research/research-labs-and-branches/laboratory-retinal-cell-and-molecular-biology/molecular-mechanisms-section

Knocking Out HIV Infection? | Science Translational MedicineKnocking Out HIV Infection? | Science Translational Medicine

A genetic mutation in the gene for CCR5, a molecule used by HIV to enter human immune cells, renders these cells resistant to ... This technique resulted in CCR5 modification in 11 to 28% of cells. The cells were then reinfused into each patients ... Zinc-finger nucleases-proteins used to cut the cells DNA at specific sites in the CCR5 gene-made the gene permanently ... Infusion of HIV-infected patients own immune cells after genetic alteration was safe and made the cells more resistant to HIV ...
more infohttp://stm.sciencemag.org/content/6/228/228ec50

Information Processing: The dawn of genetic engineering?Information Processing: The dawn of genetic engineering?

... to human cells. In short order, the technique has taken off like wildfire. And now, two papers appearing in Cell Stem Cell ... Cas9 can cut the double strand, nick it, or even knock down gene expression. After Cas9 injures the DNA, repair systems fix the ... In one of the new papers, a team from China used CRISPR/Cas9 to replace a single base pair mutation that causes cataracts in ... "I think CRISPR/Cas9 system may be the easiest strategy to cure genetic disease than any other available gene-editing techniques ...
more infohttps://infoproc.blogspot.com/2013/12/the-dawn-of-genetic-engineering.html

Information Processing: The dawn of genetic engineering?Information Processing: The dawn of genetic engineering?

... to human cells. In short order, the technique has taken off like wildfire. And now, two papers appearing in Cell Stem Cell ... Cas9 can cut the double strand, nick it, or even knock down gene expression. After Cas9 injures the DNA, repair systems fix the ... In one of the new papers, a team from China used CRISPR/Cas9 to replace a single base pair mutation that causes cataracts in ... "I think CRISPR/Cas9 system may be the easiest strategy to cure genetic disease than any other available gene-editing techniques ...
more infohttps://infoproc.blogspot.com/2013/12/the-dawn-of-genetic-engineering.html?showComment=1387650719388

New NIMH Project: ASD heterogeneity to synaptic function | The Department of Molecular and Cellular Physiology | Stanford...New NIMH Project: ASD heterogeneity to synaptic function | The Department of Molecular and Cellular Physiology | Stanford...

Instead, heterogeneous genetic changes, including many single gene mutations and copy-number variations (CNVs) are found in ... The approach will be to overexpress (to mimic gene duplications) or knock down (to mimic gene inactivations) mRNAs ... Cell viability, neuronal development, synapse density and synapse function will be assessed in cultured mouse neurons using ... function and plasticity will then be examined in acute slices from these mice using standard electrophysiological techniques ...
more infohttps://med.stanford.edu/sudhoflab/news/Autism_Project.html

Efficient CRISPR-mediated gene targeting and transgene replacement in the beetle Tribolium castaneum | DevelopmentEfficient CRISPR-mediated gene targeting and transgene replacement in the beetle Tribolium castaneum | Development

... labor-intensive techniques. Gene targeting in mammals required first modifying an allele in embryonic stem cells, then ... CRISPR-mediated gene knock-ins. (A) Illustration of a CRISPR-induced knock-in at the Pig-19 locus. The double-strand break ... 1989). Genetic analysis of the homeotic gene complex (HOM-C) in the beetle Tribolium castaneum. Dev. Biol. 133, 196-209. doi: ... carry such mutations in their germ line and transmit them to the next generation. We show that CRISPR-mediated gene knockout of ...
more infohttp://dev.biologists.org/content/142/16/2832.full

Eron, Kuhlman named Smithies Investigators - News Room - UNC Health CareEron, Kuhlman named Smithies Investigators - News Room - UNC Health Care

He co-discovered a technique he called "gene-targeting," which allows scientists to study genetic mutations by knocking out ... Bispecific antibodies can be used to induce immune cells to kill cancer cells. This work has generated several new bispecific ... In the last four years, authors of more than 30 papers in the journals Nature, Science, and Cell made critical use of Rosetta ... The genes for this switch are now available through Addgene. Within the last year, over 460 samples were distributed to ...
more infohttps://news.unchealthcare.org/news/2018/december/eron-kuhlman-named-smithies-investigators

Controlling the body clock | EurekAlert! Science NewsControlling the body clock | EurekAlert! Science News

Published in Molecular Cell, the study shows how this technique was used to quickly create numerous mouse lines, each with ... Studying each mutation and the effects on behavior showed that specific changes to the protein affected the duration of the ... different mutations in a circadian regulator called CRY1. ... timekeeping with a novel approach to creating genetic knock-out ... The most effective versions of the Cry1 genes to be knocked-in had a mutation near the p-loop, which codes for a pocket-like ...
more infohttps://www.eurekalert.org/pub_releases/2016-12/r-ctb122116.php

Fabry Disease: Ion channels and neuropathic pain | eLifeFabry Disease: Ion channels and neuropathic pain | eLife

When comparing young and old animals with or without the mutation, the team showed that older mice with the genetic change ... knocked out). It was already known that as these mice get older, Gb3 accumulates within and around the cell bodies of their ... electrophysiological and behavioral techniques to study a mouse model of Fabry disease in which the gene for α-GAL has been ... This caused Gb3 to accumulate in these cells, and their sodium currents to falter. When the cells were then exposed to an ...
more infohttps://elifesciences.org/articles/42849

Genetic Modifications | eMICE: electronic Models Information, Communication, and EducationGenetic Modifications | eMICE: electronic Models Information, Communication, and Education

The complexities of the experimental designs are beyond the scope of this site, but the general aspects of genetic ... A variety of strategies are used to manipulate the genomes of mice so that certain genes can be turned on, turned off, altered ... Similar techniques are employed to create all types of transgenic mice: knock-out mice, in which a gene or segment has been ... Embryonic Stem Cells. Another way to accomplish genetic modification of mice is to employ embryonic stem (ES) cells to deliver ...
more infohttps://emice.nci.nih.gov/generating-models/mouse-cancer-models-1/genetic-modifications

genetic techniques - Everything2.comgenetic techniques - Everything2.com

... and various molecular biology/cell biology related issues. These can be g... ... transgenic mice that have had their Myosin 5 encoding gene knocked out, appear almost completely without pigment, because this ... more specifically it is a result of genetic mutation of the Y chromosome (females, which are XX, do not have the Y chromosome ... generally involves gene knockout or gene replacement (the addition, change, or removal of a part of the genetic material the ...
more infohttps://everything2.com/title/genetic+techniques

Criticism of industrial plantationsCriticism of industrial plantations

Genes may be removed, or "knocked out", using a nuclease. Gene targeting is a different technique that uses homologous ... add a gene, or introduce point mutations. An organism that is generated through genetic engineering is considered to be a ... Enzymes used in laundry detergent and medicines such as insulin and human growth hormone are now manufactured in GM cells, ... Genetic engineering techniques have been applied in numerous fields including research, agriculture, industrial biotechnology, ...
more infohttp://artolook.com/Criticism_of_industrial_plantations.html

Cardiovascular Disease Vol 1 Genetics - Methods and Protocols (Methods in Molecular Medicine) | Qing Wang | downloadCardiovascular Disease Vol 1 Genetics - Methods and Protocols (Methods in Molecular Medicine) | Qing Wang | download

... smooth muscle cells, angiogenesis, cell proliferation, adhesion, migration, and apoptosis assays). • Gene transfer and gene ... Chromosome staining techniques, fluorescence in situ hybridization (FISH), and PCR for the presence of certain genetic markers ... Generation of knockout, knock-in, and conditional mutant mice and transgenic overexpression mice for cardiovascular genes. • ... 13 Mutation Detection in Congenital Long QT Syndrome: Cardiac Channel Gene Screen Using PCR, dHPLC, and Direct DNA Sequencing ...
more infohttps://ru.b-ok.org/book/916158/838fad

Frontiers | Gene Targeting Using Homologous Recombination in Embryonic Stem Cells: The Future for Behavior Genetics? | GeneticsFrontiers | Gene Targeting Using Homologous Recombination in Embryonic Stem Cells: The Future for Behavior Genetics? | Genetics

This review will discuss the pros and cons of the technique along with these advancements from the perspective of the ... For example, two decades ago, issues about compensatory changes and about genetic linkage were raised. Since then, the ... Thus, gene targeting became highly popular. However, with this popularity came the realization that like other methods, gene ... Thus, gene targeting became highly popular. However, with this popularity came the realization that like other methods, gene ...
more infohttps://www.frontiersin.org/articles/10.3389/fgene.2016.00043/full

Protocols and Video Articles Authored by Hugh P. J. Bennett (Translated to Turkish)Protocols and Video Articles Authored by Hugh P. J. Bennett (Translated to Turkish)

An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, ... Furthermore, using striatal cells from huntingtin knock-in mice we observed that small interfering ribonucleic acid (siRNA) ... In C. elegans, we observe that genetic loss-of-function mutations for nematode orthologs of TDP-43 or FUS reduced behavioral ... The microinjection technique is simple and results are reproducible. We defined the expression pattern of the proprotein ...
more infohttps://www.jove.com/author/Hugh+P.+J._Bennett?language=Turkish
  • GE, also called genetic modification, a direct manipulation of an organism's genome using biotechnology. (sciencephoto.com)
  • New DNA may be inserted in the host genome by first isolating and copying the genetic material of interest using molecular cloning methods to generate a DNA sequence, or by synthesizing the DNA, and then inserting this construct into the host organism. (sciencephoto.com)
  • Launched in 2006, the five-year project plans to build a comprehensive and publicly available resource of knockout mutations for each of the approximately 21,000 genes in the mouse genome. (genome.gov)
  • Gene editing is the direct, surgical modification at the molecular level of a genome, which is the genetic blueprint for every individual animal or plant. (inquirer.net)
  • We believe that this technology will become the method of choice for genome engineering in cells, plants and transgenic animals. (redorbit.com)
  • It was less than a year ago that scientists first applied CRISPR, a genome-editing technique, to human cells. (blogspot.com)
  • Some large environmental organizations are critical of these high-yield plantations and are running an anti-plantation campaign, notably the Rainforest Action Network and Greenpeace.Genetic engineering, also called genetic modification, is the direct manipulation of an organism's genome using biotechnology. (artolook.com)
  • The review provides a brief discussion of some of the principle and technical challenges that the technology faced in the past, the solutions that have been offered to address them, and the future of the technology in the light of new developments in the field of gene manipulation and genome engineering. (frontiersin.org)
  • Such genome-scale engineering - in contrast to traditional strategies that only target a single gene or a limited number of genes - allows researchers to study the role of each gene individually, as well as in combination with other genes. (illinois.edu)
  • Their technique, named CRISPR/Cas9 and homology-directed-repair assisted genome-scale engineering or CHAnGE, has the advantages of being quick, efficient and low-cost, in addition to its precision. (illinois.edu)
  • Zhao's group developed a library of knockout yeast, one for each gene in the S. cerevisiae genome, and are making it available to other researchers for a $50 handling fee. (illinois.edu)
  • Her group already has identified mutations in the tumor suppressor gene KDM6A in more than one-half of low-grade stage Ta bladder tumors, and data suggest that bladder cancer in females has distinct epigenetic features. (news-medical.net)
  • The spatial and temporal control of gene function permitted in these new mouse models can answer questions about tumor cell of origin, the number of mutations required to initiate a tumor, and what secondary changes are required by a cancer for its progression. (aacrjournals.org)
  • By controlling the time and place at which tumor initiation occurs, one can bypass nonspecific birth defects associated with the broad expression of oncogenes (or due to the absence of tumor suppressors), thereby controlling the precise moment and cell type in which tumor initiation events occur. (aacrjournals.org)
  • Apoptosis is a programmed form of cell death that plays an important role in malignancy by shifting the balance from tumor proliferation to its regression. (dtic.mil)
  • Anticancer drugs act by activating apoptosis in tumor cells. (dtic.mil)
  • Mutations in apoptotic pathways can lead to anticancer drug resistance and therefore can promote tumor progression. (dtic.mil)
  • We expect that further insight into mechanisms of programmed cell death in oncogenically-transformed MEFs will provide a fuller understanding of the role of apoptosis in real tumor progression such as breast cancer and will lead to the developing new strategies for anti-cancer therapy. (dtic.mil)
  • Xenopus has long been an important tool for in vivo studies in molecular, cell, and developmental biology of vertebrate animals. (eol.org)
  • Characterizing the functions of a microcephaly-related gene in a knock-out mouse model using in vivo MRI, histology and cellular/molecular biology approaches. (findaphd.com)
  • It provides an opportunity to learn a variety of techniques and methods through application of neuroimaging (magnetic resonance imaging, MRI), histological analyses of brain abnormalities, primary cultures of neural progenitor cells (NPCs) and neurons, as well as molecular genetic analyses of gene regulation. (findaphd.com)
  • Gene editing makes it possible to remove or insert snippets of DNA at precise locations using molecular "scissors", like altering a film sequence or using the "find & replace" function in a word-processing software. (inquirer.net)
  • Published in Molecular Cell , the study shows how this technique was used to quickly create numerous mouse lines, each with different mutations in a circadian regulator called CRY1. (eurekalert.org)
  • Methods for studying various things like disease, cellular protein expression, and various molecular biology / cell biology related issues. (everything2.com)
  • A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. (wikipedia.org)
  • The two best-known species of this genus are Xenopus laevis and Xenopus tropicalis , which are commonly studied as model organisms for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects. (eol.org)
  • Additionally, there are practical reasons: the mouse mammary glands are amenable to in vivo and in vitro manipulations and techniques used in developmental biology and cancer research and the animal has a short life-cycle. (leica-microsystems.com)
  • The adenovirus E1A oncoprotein sensitizes primary cells to undergo apoptosis following treatment with anticancer agents. (dtic.mil)
  • To target genes in moss, this construct is incubated together with freshly isolated protoplasts and with Polyethylene glycol. (wikipedia.org)
  • Many scientists welcomed the decision to create a regulatory framework for the technique, but others expressed concern that gene editing may one day be used to make "designer babies" with selected physical or intellectual traits. (inquirer.net)
  • scientists used ZFNs to knock out an inserted reporter gene and two native rat genes without causing measurable effects on other genes. (redorbit.com)
  • These RNA sequences serve an immune function in archaea and bacteria, but in the last year or so, scientists have seized upon them to rewrite genes. (blogspot.com)
  • We are currently studying knock-in mouse models for less severe forms of human LCA. (nih.gov)
  • Studying each mutation and the effects on behavior showed that specific changes to the protein affected the duration of the circadian period. (eurekalert.org)
  • They replaced a specific gene with a similar genetic sequence, which was modified to contain a mutation. (animalresearch.info)
  • The cell's machinery automatically recognizes the identical stretches of DNA sequence and swaps out the existing mouse gene with the artificial piece of DNA. (genome.gov)
  • The RNA sequence serves as a guide to target a DNA sequence in, say, a zygote or a stem cell. (blogspot.com)
  • Transformed microorganisms having reduced activity of at least one protein, e.g. galactomannanase, can be provided by disrupting a gene encoding the protein or introducing antisense nucleic acid sequence, providing xanthan gum essentially free of galactomannanase, amylase, cellulase or protease activity. (justia.com)
  • it is the process by which the information in a gene, encoded as a sequence of bases in DNA, is converted into the structure of a protein. (wikipedia.org)
  • Importantly, offspring of the ZFN-mutated rats also carried the modifications, demonstrating the genetic changes were permanent and heritable. (redorbit.com)
  • Although ASDs are highly heritable, ASDs are heterogeneous, and no single genetic cause contributes to ASDs in a large proportion of patients. (stanford.edu)
  • Thus, a key question is whether different genetic changes contribute to ASDs via multiple, independent, pathogenic pathways, or whether the various genetic changes in ASDs converge onto a single pathogenic pathway. (stanford.edu)
  • The approach will be to overexpress (to mimic gene duplications) or knock down (to mimic gene inactivations) mRNAs corresponding to nearly 100 ASD candidate genes, and to test the effect of these manipulations on synapses using standardized assays. (stanford.edu)
  • Genes that were found to affect neuronal development, synapse formation, or synapse function in cultured neurons will be studied by the same manipulations in vivo after stereotaxic injection of lentiviruses into the mouse hippocampus. (stanford.edu)
  • of the ease of gene manipulations (retroviral mediated gene transfer technique) in MEFs. (dtic.mil)
  • New discoveries of unknown genes and mutations relevant to cancer may arise from this method. (nih.gov)
  • Here recent discoveries on the mechanism of how progesterone and its downstream signaling protein Wnt4, which promotes mammary gland development, control mammary stem cell function is reported. (leica-microsystems.com)
  • In the first commercial application of this technique, OMT, a private biotechnology company developing a new rat-based human antibody platform, used Sangamo's ZFNs to knock out the gene encoding rat immunoglobulin M (IgM), an important gene for rat antibody production. (redorbit.com)
  • This will be an interdisciplinary PhD project, which investigates a knock-out (KO) mouse model for a human neurodevelopmental disorder. (findaphd.com)
  • Mutations in the human TRAPPC9 gene cause microcephaly, intellectual disability, speech impairment and developmental delays. (findaphd.com)
  • A third aspect is concerned with the epigenetic regulation of murine Trappc9 in comparison to the human gene regulation. (findaphd.com)
  • A genetic mutation in the gene for CCR5, a molecule used by HIV to enter human immune cells, renders these cells resistant to HIV. (sciencemag.org)
  • Inactivation of rat IgM expression is the first step in generating rats that exclusively express human antibodies encoded by transgenic human immunoglobulin genes. (redorbit.com)
  • GeCKO knockout in human cells. (blogspot.com)
  • Application to Cystic Fibrosis in human stem cells , Cataracts in mouse . (blogspot.com)
  • Mutations in the human RPE65 gene result in Leber's congenital amaurosis (LCA) and autosomal recessive childhood-onset severe retinal dystrophy (arCSRD), with about 100 separate mutations identified since 1997. (nih.gov)
  • Following much preclinical research, human RPE65 gene therapy clinical trials were launched in 2008. (nih.gov)
  • Human RPE65 mutations cause a spectrum of disease from severe early-onset disease to milder forms. (nih.gov)
  • Previously used to engineer rat cell models, advances in gene targeting technologies are enabling the creation of a new wave of isogenic human disease models. (wikipedia.org)
  • The hallmark of human alveolar rhabdomyosarcoma is the presence of the chromosomal translocation fusion gene, Pax3:Fkhr . (aacrjournals.org)
  • Generating rats with knockout mutations has been a major challenge, but the new technique will increase the rat's usefulness in research pertaining to physiology, endocrinology, neurology, metabolism, parasitology, growth and development and cancer. (redorbit.com)
  • He developed a way to alter the stem-cells, and then inject them into a fertilized mouse egg cell. (animalresearch.info)
  • The offspring of the host mouse carried the mutant gene, and the offspring of two mutants expressed the mutant gene. (animalresearch.info)
  • The short-life span of the mouse was crucial to the development of this technique. (animalresearch.info)
  • In the meantime, a team supported with partial funding from the National Institutes of Health (NIH), has figured out how to build a better "knockout" mouse, a key research tool for exploring the genetic factors involved in health and disease. (genome.gov)
  • That means if a gene is knocked out in an ES cell, the effects can be observed in any tissue in an adult mouse. (genome.gov)
  • Because the artificial DNA is inactive, the swap knocks out the function of the mouse gene. (genome.gov)
  • Furthermore, we found that the Trappc9 gene is regulated by epigenetic mechanisms (genomic imprinting) in the mouse brain. (findaphd.com)
  • In this project we intend to further characterize the disease symptoms/brain phenotypes of the knock-out mouse model, determine the cellular functions of the Trappc9 protein in neurons and progenitor cells and shed light on the epigenetic regulation of the gene. (findaphd.com)
  • Cell viability, neuronal development, synapse density and synapse function will be assessed in cultured mouse neurons using optical and electrophysiological assays that are well established in the PI's laboratories. (stanford.edu)
  • This finding was previously exploited when an HIV-infected patient was treated for leukemia with a stem cell transplant from a donor whose cells had this mutation. (sciencemag.org)
  • Bone Marrow and Stem Cell Transplantation, edited by Meral Beksac, 2007 133. (b-ok.org)
  • While mutant strains have been bred for many years, gene targeting allows specific physiological features to be studied. (animalresearch.info)
  • The group used this new KO-rescue technique to better understand cryptochromes--proteins associated with physiological functions that are controlled by environmental light. (eurekalert.org)
  • Replacement of anionic phosphates with the uncharged phosphorodiamidate groups eliminates ionization in the usual physiological pH range, so Morpholinos in organisms or cells are uncharged molecules. (wikipedia.org)
  • The technology allowed unprecedented precision with which one could manipulate genes and study the effect of this manipulation on the central nervous system. (frontiersin.org)
  • In 2001, a Briard dog LCA model harboring a RPE65 mutation was treated with adeno-associated virus (AAV)-mediated RPE65 gene therapy and functional vision was successfully restored. (nih.gov)
  • It typically contains part of the gene to be targeted, a reporter gene, and a (dominant) selectable marker. (wikipedia.org)
  • The RPE is a single layer of cells lining the back of the retina and plays a pivotal role in the development and function of the outer retina. (nih.gov)
  • Without these cells the retinal photoreceptor cells, and vision itself, could not function. (nih.gov)
  • However, most of the other genetic changes observed in ASDs have no known effect on synapses in fact, have no known effect on any brain function. (stanford.edu)
  • The results of this project will provide a standardized reference point for the function of ASD candidate genes, and provide an initial test of the hypothesis that despite their clinical and genetic heterogenity, ASDs involve a common, if diverse, pathway acting on synaptic communication in the brain. (stanford.edu)
  • That makes a minimal disturbance in the function of the neighboring genes, so we can study how important the gene is in its cellular context. (illinois.edu)
  • in a similar manner, causing a specific exon to be spliced out of the RNA transcript encoding a protein can help to determine the function of the protein moiety encoded by that exon or can sometimes knock down the protein activity altogether. (wikipedia.org)
  • The second Cre driver, Pax7:Cre , generated the fusion gene during midgestation and importantly in muscle satellite cells. (aacrjournals.org)
  • The modified cells persisted in the blood and rectal tissue of patients, with an average half-life in the blood of 48 weeks. (sciencemag.org)
  • This study demonstrates that zinc-finger nucleases can be used to genetically modify CD4 immune cells outside of the body and that these cells can be safely infused into HIV-infected patients. (sciencemag.org)
  • Infusion of HIV-infected patients' own immune cells after genetic alteration was safe and made the cells more resistant to HIV infection. (sciencemag.org)
  • Understand and apply advanced experimental techniques required to solve specific biochemical problems, and understand of the ethical implications of this research. (edu.au)
  • For certain experimental designs this may be a faster route to explore the roles of genes or treatment situations. (nih.gov)
  • Time course quantitative RT-PCR analyses were performed following retinoic acid (RA)-induced neuroectodermal differentiation of P19 cells. (jove.com)
  • The DNA construct is designed to have the desired characteristics, and then introduced to ES cells. (nih.gov)
  • Should the gene be expressed in a given tissue or not? (nih.gov)
  • After cells with the correct insertion have been selected, they can be used to contribute to a mouse's tissue via embryo injection. (wikipedia.org)
  • Pubmed ID: 16277664 Progranulin is an epithelial tissue growth factor (also known as proepithelin, acrogranin and PC-cell-derived growth factor) that has been implicated in development, wound healing and in the progression of many cancers. (jove.com)