The relative amount by which the average fitness of a POPULATION is lowered, due to the presence of GENES that decrease survival, compared to the GENOTYPE with maximum or optimal fitness. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
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.
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.
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.
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)
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
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.
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.
An individual having different alleles at one or more loci regarding a specific character.
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.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
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.
Biochemical identification of mutational changes in a nucleotide sequence.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
An individual in which both alleles at a given locus are identical.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Genes that influence the PHENOTYPE only in the homozygous state.
Any method used for determining the location of and relative distances between genes on a chromosome.
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.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
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.
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.
Deletion of sequences of nucleic acids from the genetic material of an individual.
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).
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
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.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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).
Established cell cultures that have the potential to propagate indefinitely.
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.
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).
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.
A characteristic symptom complex.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Proteins produced from GENES that have acquired MUTATIONS.
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.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
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.
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.
The magnitude of INBREEDING in humans.
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.
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.
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.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
Proteins found in any species of bacterium.
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.
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.
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.
Identification of genetic carriers for a given trait.
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.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
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.
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.
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.
The functional hereditary units of BACTERIA.
Genotypic differences observed among individuals in a population.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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).
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.
Mice bearing mutant genes which are phenotypically expressed in the animals.
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.
The systematic study of the complete DNA sequences (GENOME) of organisms.
A method for comparing two sets of chromosomal DNA by analyzing differences in the copy number and location of specific sequences. It is used to look for large sequence changes such as deletions, duplications, amplifications, or translocations.
Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Proteins prepared by recombinant DNA technology.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
The functional hereditary units of FUNGI.
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.
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.
The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.
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.
The rate dynamics in chemical or physical systems.
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).)
Proteins found in any species of fungus.
The relationships of groups of organisms as reflected by their genetic makeup.
A form of GENE LIBRARY containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns).
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.
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.
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.
DNA present in neoplastic tissue.
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.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
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.
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).
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.
That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.
The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.
The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.
Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.
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.
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Proteins 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.
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.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
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.
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.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.
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.
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).
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.
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.
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.
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.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
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.
Distinct units in some bacterial, bacteriophage or plasmid GENOMES that are types of MOBILE GENETIC ELEMENTS. Encoded in them are a variety of fitness conferring genes, such as VIRULENCE FACTORS (in "pathogenicity islands or islets"), ANTIBIOTIC RESISTANCE genes, or genes required for SYMBIOSIS (in "symbiosis islands or islets"). They range in size from 10 - 500 kilobases, and their GC CONTENT and CODON usage differ from the rest of the genome. They typically contain an INTEGRASE gene, although in some cases this gene has been deleted resulting in "anchored genomic islands".
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Mice which carry mutant genes for neurologic defects or abnormalities.
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.
The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
A species of nematode that is widely used in biological, biochemical, and genetic studies.
An essential amino acid that is physiologically active in the L-form.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
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.
The functional hereditary units of INSECTS.
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.
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)
The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992)
The complete genetic complement contained in a DNA or RNA molecule in a virus.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
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)
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.
Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.
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.
A cell line derived from cultured tumor cells.
A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).
The genetic complement of a BACTERIA as represented in its DNA.
Actual loss of portion of a chromosome.
The functional hereditary units of PLANTS.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)
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.
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.
An infant during the first month after birth.
Proteins obtained from ESCHERICHIA COLI.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Elements of limited time intervals, contributing to particular results or situations.
Ribonucleic acid that makes up the genetic material of viruses.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.
Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.
This occurs either by Homologous recombination of the nucleic acid strands or by reassortment of genomic segments. Both these ... Reassortment Mutation Chromosomal crossover Recombination Resulting in Virulence Shift in Avian Influenza Outbreak, Chile. ... The term is also used to refer to naturally occurring recombination between virus genomes in a cell infected by more than one ... A recombinant virus may occur naturally or be produced by recombining pieces of DNA using recombinant DNA technology. This may ...
The acquisition of mutations is random as a result of increased genomic instability with each successive generation. The long- ... The inability to detect mutations in rare subclones. Since these mutations will occur with low frequency in the pooled sample, ... Since the data is pooled, it is not clear which mutations co-occur and which populations they originate from. New tools are ... Evolution of the initial tumour cell may occur by two methods: Sequentially ordered mutations accumulate in driver genes, ...
In addition, novel protein sequences can occur through mutations. these issues can be fixed with the use of proteomic, genomic ... false positives can occur as a result of extremely large protein data bases where miss-matched data leads to incorrect ... Cancer occurs through genetic mutations such as methylation, translocation, and somatic mutations. Research has shown that both ... A specific example of this occurred in a study involving colon cancer that resulted in the discovery of potential targets for ...
Recessive mutations in the other sarcoglycans also result in muscular disorders, further supporting that mutations in the SGCE ... However, genomic imprinting occurs on the mother's allele, so only the father's allele is expressed. Therefore, inheriting a ... Myoclonus dystonia results from mutations in the SGCE gene coding for an integral membrane protein found in both neurons and ... The majority of myoclonus dystonia cases are the result of a mutation in the epsilon sarcoglycan gene (SGCE). This gene is ...
Genomic evolution occurs by processes such as duplication of individual genes, genome segments, or entire genomes. These ... DNA mutations outside of a putative gene can act by positional effect, in which they alter the gene expression. These ... processes can result in loss of function, altered function, or gain of function, and have drastic affects on the phenotype. ... These mutations can be associated with diseases or disorders associated with the gene. Putative genes can be identified by ...
Specifically, the missense mutation would lead to a defective gene and a deficiency in antithrombin which could result in the ... The dissociation occurs easily because the base-pairing between the U's in the RNA and the A's in the template strand are the ... Current genomic analysis seem to suggest the existence of a large excess of perfect inverted repeats in many prokaryotic ... it also creates a frameshift mutation in the nucleotide sequence which alters the reading frame and will result in an incorrect ...
Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains ... The findings that result depend on the cancer's type and location. Few symptoms are specific. Many frequently occur in ... Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter region of a gene and ... p53 mutations).[91] Germ line DNA repair mutations are noted on the figure's left side. However, such germline mutations (which ...
In a study of 158 SDS families, 75% of disease-associated mutations appeared to be the result of gene conversion, while 89% of ... Gene conversion occurs when the intact SBDS gene and its pseudogene copy aberrantly recombine at meiosis, leading to an ... The SBDS gene resides in a block of genomic sequence that is locally duplicated on the chromosome. The second copy contains a ... Two gene conversion mutations predominate; one is a splice site mutation affecting the 5' splice site of intron two, while the ...
Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains ... Finally random mistakes in normal DNA replication may result in cancer causing mutations.[1] A series of several mutations to ... Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter of a gene and affect ... In general, mutations in both types of genes are required for cancer to occur. For example, a mutation limited to one oncogene ...
Examples of genomic recurrent evolution[edit]. Certain mutations occur with measurable and consistent frequencies.[12] ... Most evolution, or changes in allele frequencies from one generation to the next, is the result of drift, or random chance of ... Recurrent genomic evolution can also occur within a lineage. An example of this would include some types of phase variation ... Beyond creating new variation for selection to act upon mutations plays a primary role in evolution when mutations in one ...
Those cancers that may develop as a result of radiation exposure are indistinguishable from those that occur naturally or as a ... Instead, surviving cells appear to have acquired a genomic instability which causes an increased rate of mutations in future ... Major damage normally results in the cell dying or being unable to reproduce. This effect is responsible for acute radiation ... It has been estimated that CT scans performed in the US in 2007 alone will result in 29,000 new cancer cases in future years. ...
Those cancers that may develop as a result of radiation exposure are indistinguishable from those that occur naturally or as a ... Instead, surviving cells appear to have acquired a genomic instability which causes an increased rate of mutations in future ... Skin cancer may occur following ionizing radiation exposure following a latent period averaging 20 to 40 years.[33][34] A ... Major damage normally results in the cell dying or being unable to reproduce. This effect is responsible for acute radiation ...
Mean heterozygosity is calculated as the probability of a mutation occurring at a given generation divided by the probability ... The genomic distribution of heterozygosity[edit]. The human single-nucleotide polymorphism (SNP) map has revealed large ... Studies have been carried out correlating disease occurrence in fraternal and identical twins, and the results of these studies ... Both regular the coalescent and the shattered coalescent (which allows that multiple mutations may have occurred in the ...
Mutations that deactivate p53 in cancer usually occur in the DBD. Most of these mutations destroy the ability of the protein to ... Loss of p53 creates genomic instability that most often results in an aneuploidy phenotype. Increasing the amount of p53 may ... As such, mutations in the DBD are recessive loss-of-function mutations. Molecules of p53 with mutations in the OD dimerise with ... Targeting p53 and Myc proteins with drugs gave positive results on mice with CML. Most p53 mutations are detected by DNA ...
Aneuploidy occurs when nondisjunction at a single chromosome results in an abnormal number of chromosomes. Aneuploidy is often ... Often the resulting genomic variation leads to gene dosage dependent neurological disorders such as Rett-like syndrome and ... Subfunctionalization can occur through neutral processes in which mutations accumulate with no detrimental or beneficial ... Technologies such as genomic microarrays, also called array comparative genomic hybridization (array CGH), are used to detect ...
... resulting from a mitochondrial mutation.[74] In many species where cytoplasmic male sterility occurs, the nuclear genome has ... Genomic imprinting[edit]. Igf2 is an example of genomic imprinting. In mice, the insulin-like growth factor 2 gene, Igf2, which ... When this process occurs during meiosis it is referred to as meiotic drive. Many forms of segregation distortion occur in male ... and its ability to leave a perfectly seamless cut from a genomic site, leaving no sequences or mutations behind.[117] ...
... and as such mutations of the genes encoding these proteins is known to result in various congenital defects. For example, if ... ZIC1 is found in close genomic configuration in another member of this protein family, ZIC4. Correct function of these proteins ... function of both ZIC1 and ZIC4 is lost (which can occur via an interstitial deletion due to their adjacent location) then this ... may result in the Dandy-Walker malformation. ZIC1 has been shown to interact with GLI1 and GLI3. GRCh38: Ensembl release 89: ...
Although silencing of some genes in cancers occurs by mutation, a large proportion of carcinogenic gene silencing is a result ... Bacterial genomic DNA is not recognized by these restriction enzymes. The methylation of native DNA acts as a sort of primitive ... It has been shown that altering Dam activity in bacteria results in increased spontaneous mutation rate. Bacterial viability is ... As a result of DNA replication, the status of GATC sites in the E. coli genome changes from fully methylated to hemimethylated ...
... probably as a result of a combination of tumor genome-specific "progressional" mutations, stochastic genomic phenomena, and ... It is currently thought that most cases of lung cancer probably occur after damage to genomic DNA causes malignant ... EGFR-TKI's have been found to be active against variants exhibiting certain mutations in the EGFR gene. While EGFR mutations ... acquire additional mutations (a process known as tumor progression). The end result is that the tumor acquires specific ...
One minor issue is that the two recombination events may not occur simultaneously thus the results need to be interpreted with ... These systems are based on engineered, targeted mutation of defined genetic elements. By generating new, random genomic ... Recurring results showed that the nematode was eutelic(each individual experiences the same differentiation pathways). This ... Zafar, Hamim; Lin, Chieh; Bar-Joseph, Ziv (2020). "Single-cell lineage tracing by integrating CRISPR-Cas9 mutations with ...
Most mutations that occur are single nucleotide polymorphisms which modify single bases of the DNA sequence, resulting in point ... Many genomic features have been ascribed to accumulation of nearly neutral detrimental mutations as a result of small effective ... Mutations are permanent, transmissible changes to the genetic material (DNA or RNA) of a cell or virus. Mutations result from ... Mutations are stochastic and typically occur randomly across genes. Mutation rates for single nucleotide sites for most ...
By contrast, since Cas9 cuts only 3 base pairs upstream of the PAM site, the NHEJ pathway results in indel mutations that ... In theory, repeated rounds of DNA cleavage should cause an increased opportunity for the desired genomic editing to occur. A ... A comparative genomic analysis showed that E. coli and S. enterica evolve much more slowly than S. thermophilus. The latter's ... Cleavage instead occurs by the longer transcript wrapping around the Cas6 to allow cleavage just upstream of the repeat ...
Expansions occur when the fork reverses and restarts, which forms a chicken-foot structure. This structure results in the ... The binding of this genomic repeat to the mRNA results in silencing of the promoter. Beyond this point, the mechanism of ... Some men with alleles in the full mutation range experience partial or no methylation which results in only slightly abnormal ... So far the available therapeutics only have modest results at best with emphasis on the research and studying of genomic ...
This mutation creates a 5' cryptic splice site within exon 11, resulting in a shorter than normal mRNA transcript. When this ... The histone mark H4K20me3 is involved and caused by de novo mutations that occurs in a gene that encodes lamin A. Lamin A is ... Patients also don't have appropriate DNA repair, and they also have increased genomic instability. In normal conditions, the ... These results have been observed only in vitro and are not the results of any clinical trial, although it is believed that the ...
About 1/3 of all intragenic single base pair mutations in human cancers occur in CpG dinucleotides and are the result of C to T ... Mutations in the MBD4 gene (especially expansions/deletions in the polyadenine regions of the MBD4 gene) increase the genomic ... Mutation of MBD4 occurs in about 4% of colorectal cancers. MBD4 mutations also occur in tumor samples of melanoma, ovarian, ... Further, MBD4 gene mutations are detected in tumors with primary microsatellite instability (MSI), a form of genomic ...
The most common mutation, DeltaF508 (ΔF508) results from a deletion (Δ) of three nucleotides which results in a loss of the ... Cystic Fibrosis Mutation Database. "Genomic DNA sequence". Archived from the original on 2016-08-22. Retrieved 2013-04-06. ... Scientists have estimated that the original mutation occurred over 52,000 years ago in Northern Europe. The young allele age ... As a result, the protein does not fold normally and is more quickly degraded. The vast majority of mutations are infrequent. ...
Diabetes occurs because there is a decrease insulin biosynthesis as a result of homozygous mutations. Common phenotype is ... can occur from an isolated genomic imprinting or occur as a defect called, "hypomethylation imprinted loci" (HIL). HIL is ... Mutations that occur in ABCC8 are associated with congential hyperinsulinism and PNDM or TNDM. Patients that have mutations in ... which is a result of 31% and 10% of PNDM cases (results based on Exeter experiment series). Twelve percent of mutations in the ...
A mutation is a change or error in the genomic sequence of a cell. It can occur during meiosis or replication of DNA, as well ... A mutation known as the black mutation causes reduced levels of β-alanine and results in less reactive flies than the wild type ... Mutation accumulation occurs when mutations of small effect accumulate at certain loci, yielding a large phenotypic effect in ... Examples of mutations that increase aggression are mutations in the fruitless or dissatisfaction genes which result in ...
A nonsynonymous mutation that occurs at the genomic or transcriptional levels is one that results in an alteration to the amino ... This can result in lower expression of a particular gene containing that silent mutation if the mutation occurs within an exon ... Codon degeneracy Neutral mutation Genealogical DNA test Missense mutation Nonsense mutation Point mutation Synonymous ... Conversely, silent mutations are mutations in which the amino acid sequence is not altered. Silent mutations lead to a change ...
In theory, repeated rounds of DNA cleavage should cause an increased opportunity for the desired genomic editing to occur.[58] ... By contrast, since Cas9 cuts only 3 base pairs upstream of the PAM site, the NHEJ pathway results in indel mutations which ... A comparative genomic analysis showed that E. coli and S. enterica evolve much more slowly than S. thermophilus. The latter's ... New spacers are added to a CRISPR array in a directional manner,[23] occurring preferentially,[61][95][96][103][104] but not ...
Mutations (nucleotide substitutions) occur in viruses and accumulate with continued viral spread; these mutations result in ... Why is genomic surveillance important for public health?. A comprehensive system for SARS-CoV-2 genetic surveillance is ... Genomic sequencing process for SARS-CoV-2*. *Specimen receipt and initial processing: Specimens are received and entered into ... Ensure that generated genomic data are of the highest quality and provide the most impact for public health and the broader ...
Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results ... A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number ... alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. ... Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as ...
This is our most important result. Even with clonal interference, adaptation is fastest when the genomic mutation rate equals ... mutation in an asexual genome or nonrecombining chromosome region in which both favorable and deleterious mutations occur. ... 6) i.e., when the genomic mutation rate equals the harmonic mean of deleterious effects among new mutations. ... When U , Uopt, there are too many deleterious mutations, mutation-free genomes are too rare, and too many favorable mutations ...
Surprisingly, genomic rearrangements were found to occur predominantly in the heart and to accumulate with age. ... in the brain mainly point mutations were detected. These results suggested that postmitotic tissue is resistant to mutation ... Virtually all other mutations accumulating in the heart appeared to be G·C to A·T transitions at CpG sites. These results ... The results indicate distinct differences between the heart and small intestine in both the type of mutations and their rate of ...
This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of ... This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of ... We know that genomic mutations occur in DIPG, resulting in a number of druggable targets. However, we also know that no single ... 2012) also implicated the Sonic Hedgehog pathway in a trial in which they performed genomic studies on a large number (n = 61) ...
A mutation in HBB results in the production of hemoglobin with an abnormal structure. Figure 5.21 shows how a point mutation in ... The most frequently occurring mutation causes faulty processing of the protein such that the protein is degraded before it ... Genomic medicine predicts the risk of disease in the individual, whether highly probable, as in the case of some of the well- ... A reasonable estimate of the frequency of mutation is on the order of 5 × 10-6 mutations per allele per generation. Because a ...
Albinism results from defective production of melanin from tyrosine through a complex pathway of metabolic reactions. ... If the deletion occurs on the paternal band 15q11-13, then PWS results. However, if the same mutation occurs on the maternally ... but there are 2 separate phenotypes because of genomic imprinting. ... leaky mutations). Null mutations produce OCA 1A, while leaky mutations result in OCA 1B. ...
Our results show the usefulness of this approach for the study of the scarce intra-cultivar genetic diversity in grapevines. We ... also provide evidence on how human actions might have driven the accumulation of different somatic mutations, ultimately ... However, genetic variations accumulate due to the occurrence of somatic mutations. This process is anthropically influenced ... Chimeric mutations are frequent in grapevines, occurring differentially between the L1 and L2 cell layers of the developmental ...
The results of Ingolia et al. [96] suggest that translation may occur from ncRNAs, which could provide new epitopes to develop ... This raises the question, if additional genomic and expression modifications occur, which could explain aberrant gene ... Based on these results and others, one has to reconsider whether tumorigenesis relies solely on mutations in proteins. ... Mutations do not explain all tumors. About 50% of cutaneous melanomas harbour a V600EBRAF mutation [5, 6] followed by 15% that ...
... which eventually results in variable mutation rates throughout the genome. Although detailed molecular mechanisms of DNA damage ... of T-to-G mutations occur in GC-rich DNA. Whilst Signature 17 however contributes more than a quarter of all T-to-G mutations, ... For this, mutations of each mutation type were pooled for each patient group. Mean relative mutation rates over features were ... there is now broad acceptance that mutation rates vary across different genomic regions. Background mutation rates in ...
TP53 mutations, especially codon 249Ser mutations following aflatoxin B1 exposure, result in defective DNA damage responses (38 ... A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature. 2009;460(7259):1149-1153. ... These oncogenic events may occur simultaneously in various populations of hepatic stem/progenitor cells and hepatocytes in CLDs ... Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in ...
... genomic data can be utilized for diagnosis of many diseases such as cancer. Human raw genome data is huge in size for... ... The phenotypes occur as a result of DNA mutations. In our system, we take VCF files, which hold the DNA mutation information, ... This selection of mutation types resulted in 16,383 distinct genes. As a result, our dataset, named as BOUN10CANCER, has 7028 ... The occurrence of complex genetic disorders often results from multiple gene mutations. The effect of each mutation is not ...
These results indicate that multimodal genomic and epigenomic alterations underpin TERT reactivation in GC, converging on ... Abolishment of EBF1 function occurs through 3 distinct (epi)genomic mechanisms. First, EBF1 is epigenetically silenced via DNA ... Second, recurrent, somatic, and heterozygous EBF1 DNA-binding domain mutations result in the production of dominant-negative ... Here, through comprehensive genomic and epigenomic analysis of primary GCs and GC cell lines, we identified the transcription ...
As a result the antitumor barriers will gradually diminish and dysplastic changes as well as further ones may occur. ... When this repair mechanism exceeds its potential, genomic instability will gradually accumulate, leading eventually to mutation ... This is caused by mutations, presence of HPV virus and other molecular alteration occurring in the p53 pathway [35]. The ... It is clear that most of the studies so far have shown indicative results of a precancerous OLP nature. Studies that will ...
Genomic instability is induced when mutation occurs in MMR genes. Loss of MMR results in elevated levels of frameshift mutation ... Mutation of the DNA forms the fundamentals of evolution, but at times mutations pose to be harmful. The DNA sequence provides ... At times even chemotherapy leads to MMR deficiency by selective mutation of its genes. ...
Our results raise questions about manifestations of VDPVs in immunodeficient patients and the role of cellular immunity against ... However, the synonymous mutations, mostly in nonstructural regions, occur at the expected rates. Changes in specific antigenic ... Results. Patients and Manifestations. During 1995-2014, a total of 14 patients (12 boys and 2 girls) infected with iVDPV were ... A high proportion of these changes are nonsynonymous substitutions in the genomic region, which codes for structural proteins. ...
... should occur at spatial scales where the dispersal rate among sites is lower than the mutation rate of the genomic marker. As ... These results do not eliminate the possibility that endemism occurs in the AOB. To the contrary, evidence that these bacteria ... we predicted that dispersal limitation would occur primarily across continents, resulting in genetically divergent microbial " ... between faunas as a result of dispersal limitation and the lower turnover rates of bird species within continents as a result ...
Present-day genomes are the result of a large number of more or less randomly occurring mutations, recombinations, matings, and ... Classical work has focused on simple summaries of genomic diversity that could be computed analytically, such as the number of ... and at most one mutation per site can occur. In this model, the mutation term is a source term, with u being the genome-wide ... assuming that mutations occur at previously invariant loci and neglecting back mutations. However, finite genome and back ...
These results further establish that genomic testing for HRR mutations should be a critical step for the diagnosis and ... About Homologous Recombination Repair (HRR) Mutations. HRR mutations occur in approximately 25% of patients with mCRPC. HRR ... HRR gene mutations occur in approximately 20%-30% of patients with mCRPC. ... with LYNPARZA versus abiraterone or enzalutamide in men with mCRPC and BRCA1/2 or ATM gene mutations. Results showed LYNPARZA ...
Associations between genomic alterations and outcomes were analyzed in patients. Results: By 10 months, 8 of 20 IDH1-mutant ... Purpose: Isocitrate dehydrogenase (IDH) gene mutations occur in low-grade and high-grade gliomas. We sought to identify the ... AKT or PTEN mutation or PDGFRA, MET or N-MYC amplification. IDH/CIC mutant tumors were associated with PIK3CA/KRAS mutations ... Targetable signaling pathway mutations are associated with malignant phenotype in IDH-mutant gliomas. Hiroaki Wakimoto, Shota ...
The mutation is an intracisternal A-particle (IAP) retrotransposon insertion into a C3H/HeSnJ genomic region. The IAP is ... Resulting in-frame stop codons from the insertion of IAP sequences resulted in severely reduced protein levels in mutant ... reported that an IAP insertion into Clcc1 had occurred in C3H/HeSnJ, which causes pyknotic granule cells in the cerebellum by 2 ... This strain also does not have the nob5 allele of Gpr179 (Chang, 2015), but does have the Clcc1m1J mutation derived from C3H/ ...
The ,em,Clcc1,sup,m1J,/sup,,/em, spontaneous mutation, which causes increased sensitivity to endoplasmic reticulum stress in ... Mice homozygous for the severe combined immune deficiency spontaneous mutation (,em,Prkdc,sup,scid,/sup,,/em,, commonly ... The mutation is an intracisternal A-particle (IAP) retrotransposon insertion into a C3H/HeSnJ genomic region. The IAP is ... Resulting in-frame stop codons from the insertion of IAP sequences resulted in severely reduced protein levels in mutant ...
These results indicate that, during multiplication in the human gut, Sabin 1 poliovirus carrying one or several mutations ... Genomic modifications in naturally occurring neurovirulent revertants of Sabin 1 polioviruses.. Otelea D1, Guillot S, Furione M ... Analysis was performed by enzymatic restriction and partial sequencing of PCR-amplified genomic segments. All the strains bore ... The fifth strain presented four additional reversions and several new mutations. ...
Now, results of a study of nine women suggest that the genomic roots of many ovarian tumors may indeed arise in the fallopian ... By using results of their genomic studies, the team estimated the fraction of cancer cells in which a mutation was likely to ... occur. Reasoning that there would likely be fewer mutations in the original cancer cells than in their successors, the ... Now, results of a study of nine women suggest that the genomic roots of many ovarian tumors may indeed arise in the fallopian ...
... also occurred in the context of a six-cytosine repeat; this could be due to slippage during DNA replication resulting in gains ... The splice mutation (IVS5-1G,C) caused the skipping of exon 6 (fig 1). This mutation as well as the nonsense mutation (R66X) is ... one nonsense mutation (R66X), one missense mutation (G106S) and one splice mutation (IVS5-1G,C). The patients were homozygotes ... RESULTS. Clinical manifestations. The clinical findings and mutations of the patients studied here are presented in table 1. ...
This mutation results in the replacement of arginine for histidine at position 29 and occurs within a variable stretch of amino ... In addition to providing genomic outbreak data, we include a teaching concepts guide discussing three integral components of ... RESULTS/DISCUSSION: The primary result of the COBD project is an in-depth examination of the question, "What happened and how ... Results: Of 415 sexually active adolescent SMM with a valid HIV test result, 25 (6%) had a positive test. Estimated annual HIV ...
Examples of genomic recurrent evolution[edit]. Certain mutations occur with measurable and consistent frequencies.[12] ... Most evolution, or changes in allele frequencies from one generation to the next, is the result of drift, or random chance of ... Recurrent genomic evolution can also occur within a lineage. An example of this would include some types of phase variation ... Beyond creating new variation for selection to act upon mutations plays a primary role in evolution when mutations in one ...
We are particularly interested in the consequences of whole genome duplications, which recent genomic data suggest occur in ... potentially resulting in cancer-causing mutations. These findings may explain the recently discovered phenomenon of ... We previously found that whole genome duplications resulting from cytokinesis failure can drive tumor development. We recently ...
Although it can result in large scale genomic disruption, there are few studies detailing the insertion-site mutations ... Significance of transformation-induced mutations:. Insertion-site and genome-wide mutations can be hazardous if they occur in a ... Genome-wide mutations:. In this report we also examine what is known about mutations which are introduced as a result of tissue ... very extensive genetic mutation had resulted from the plant transformation procedures. Even though the numbers of mutations ...
... turgidum BAC genomic library using primers within the conserved region of WRKY genes resulted in the isolation of five BAC ... turgidum BAC genomic library using primers within the conserved region of WRKY genes resulted in the isolation of five BAC ... The present results indicate that these genes might play some functional role in the salt tolerance in durum wheat. ... The study showed a very extensive conservation of genomic structure between TdWRKYs and their orthologs from Brachypodium, ...
  • A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. (nature.com)
  • This disease is caused by a heritable mutation in the WRN gene ( 1 ), encoding both a helicase and an exonuclease ( 2 ) and thought to play a role in suppressing genomic instability ( 3 ). (pnas.org)
  • Also, other so-called progeroid syndromes, such as ataxia telangiectasia and Bloom syndrome, show increased genomic instability ( 5 ). (pnas.org)
  • Telomere erosion in telomerase-deficient mice has been shown to result in an early initiation of genetic instability, accelerating the age-related loss of cell viability and increased tumor formation ( 9 , 10 ). (pnas.org)
  • Hence, it appears that genetic defects promoting gross genomic instability are associated with symptoms of accelerated aging. (pnas.org)
  • Indeed, because reporter loci are not expressed in the mouse and are therefore neutral, they can be expected to reflect levels of genomic instability more faithfully than do endogenous expressed genes, which may suffer from a selection bias ( 14 ). (pnas.org)
  • Genomic instability is induced when mutation occurs in MMR genes. (southlaketimes.com)
  • These three genetic disorders are associated with genomic instability, and therefore the RecQ helicases are considered to be guardians of the genome ( 12 - 14 ). (spandidos-publications.com)
  • The acquisition of mutations is random as a result of increased genomic instability with each successive generation. (wikipedia.org)
  • Ionizing radiation induces genomic instability, which is transmitted through many generations after irradiation in the progeny of surviving cells. (aacrjournals.org)
  • These findings provide the possibility that the observed instability results from these DNA breaks, i.e. , the breaks lead to delayed chromosome rearrangements, delayed cell death, and so forth, many generations after irradiation and that activation of p53 function may eliminate cells that have potentially accumulated genomic alterations. (aacrjournals.org)
  • Although genomic instability has been reported commonly in mammalian cells exposed to ionizing radiation, the mechanisms underlying the initiation and manifestation of radiation-induced genomic instability are not fully understood. (aacrjournals.org)
  • Therefore, more than one mechanism may be involved in the initiation of radiation-induced genomic instability. (aacrjournals.org)
  • In contrast, very few studies have examined the mechanism of manifestation of radiation-induced genomic instability. (aacrjournals.org)
  • Because all of these are manifestations of radiation-induced genomic instability, it is highly possible that delayed DNA damage is associated with delayed phenotypes. (aacrjournals.org)
  • Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. (ebi.ac.uk)
  • These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection. (ebi.ac.uk)
  • At the molecular level tumors that develop in these patients display increased genomic mutation rates as indicated by increased instability at microsatellite repeat sequences (termed microsatellite instability, MSI). (yu.edu)
  • Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. (mdpi.com)
  • Genomic instability may result in numerous defects like replication errors, telomere dysfunction, epigenetic changes or defective DNA repair as a few examples. (mdpi.com)
  • Examining cells from a patient with BS shows genomic instability that includes vast amounts of microscopic visible gaps, breakage and rearrangements. (umich.edu)
  • Cancers caused by BS are the result of genomic instability. (umich.edu)
  • These recurrent homozygous deletions occurred either over tumor suppressors or over regions of increased genomic instability called fragile sites. (ashg.org)
  • Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. (mit.edu)
  • Moreover, inverted repetitive regions that are smaller than conventional LCRs, designated self-chains, are also associated with genomic instability furthering the impact of IRs on both structural human differences and phenotypes [ 3 ]. (prolekare.cz)
  • Somatic mutations that contribute to NTN-BBC and NB-TNBC development are possibly not related to this pathway, but may occur randomly due to increased genomic instability in these tumours. (springer.com)
  • This process of somatic evolution begins in the zygote and only comes to rest at death, as cells are constantly exposed to mutagenic stresses, introducing 1-10 mutations per cell division 2 . (nature.com)
  • The types of mutation in cancer genomes are well studied, but little is known about the times when these lesions arise during somatic evolution and where the boundary between normal evolution and cancer progression should be drawn. (nature.com)
  • Somatic mutation accumulation has been implicated as a major cause of cancer and aging. (pnas.org)
  • Evidence that somatic mutations are causally related to the degenerative aspects of the aging process has been derived from human syndromes of accelerated aging, such as Werner syndrome. (pnas.org)
  • Indeed, cultured somatic cells from patients with Werner syndrome display an increased rate of somatic mutations and a variety of cytogenetic abnormalities, such as deletions and translocations ( 4 ). (pnas.org)
  • However, genetic variations accumulate due to the occurrence of somatic mutations. (nature.com)
  • We also provide evidence on how human actions might have driven the accumulation of different somatic mutations, ultimately shaping the Malbec genetic diversity pattern. (nature.com)
  • Second, recurrent, somatic, and heterozygous EBF1 DNA-binding domain mutations result in the production of dominant-negative EBF1 isoforms. (jci.org)
  • WS somatic cells are characterized by chromosomal aberrations known as 'variegated translocation mosaicism' ( 19 ), representing frequent pseudodiploidy with variable and clonal structural rearrangements associated with a high proportion of genomic deletions ( 20 , 21 ). (spandidos-publications.com)
  • In squamous cell carcinomas, HRAS is the predominant isoform mutated (8%), followed by KRAS (3%) and NRAS (2%) (Catalogue of Somatic Mutations In Cancer [COSMIC] database). (cancer.gov)
  • Somatic and germline mutations in PTEN (phosphatase and tensin homolog deleted on chromosome 10) are found in sporadic cancers and Cowden syndrome patients, respectively. (pubmedcentralcanada.ca)
  • Our data, thus, reveal a novel mechanism of tumorigenesis in patients with germline or somatic mutations affecting PTEN ATP-binding motifs, i.e. qualitative and quantitative impairment of PTEN due to the loss of its phosphatase activity, and nuclear mislocalization, resulting in rapid PTEN protein degradation, suppression of p53-mediated transcriptional activity, loss of protection against oxidative stress as well as accumulation of spontaneous DNA DSBs. (pubmedcentralcanada.ca)
  • In contrast, we identified that both ATP depletion and germline or somatic mutations in PTEN 's ATP-binding motifs (which we will heretofore refer to as PTEN ATP-binding mutations) result in PTEN subcellular mislocalization which we hypothesized results in defects in its nuclear export ( 9 , 10 ). (pubmedcentralcanada.ca)
  • We show that somatic mutations in mitochondrial DNA can reconstruct cell lineage relationships at single cell resolution with high sensitivity and specificity. (elifesciences.org)
  • All dysplasias examined contained somatic mutations absent in the related carcinoma. (biomedcentral.com)
  • Genomic changes occurring in acquired somatic mutations can encode novel amino acid sequences, which if translated and presented by the MHC are termed a neoantigen. (confex.com)
  • With the discovery of microRNAs as important players in melanomagenesis, protein mutations are no longer considered the sole drivers of tumors. (wiley.com)
  • A mutation in this gene alone is not sufficient to induce tumors [ 13 ]. (wiley.com)
  • IDH/CIC mutant tumors were associated with PIK3CA/KRAS mutations while IDH/TP53 tumors correlated with PDGFRA/MET amplification. (aacrjournals.org)
  • Now, results of a study of nine women suggest that the genomic roots of many ovarian tumors may indeed arise in the fallopian tubes, potentially providing insights into the origin of ovarian cancer and suggesting new ways for prevention and intervention of this disease. (hopkinsmedicine.org)
  • This perspective review focused on the Werner syndrome (WS) by addressing the issue of how a single mutation in a WRN gene encoding WRN DNA helicase induces a wide range of premature aging phenotypes accompanied by an abnormal pattern of tumors. (spandidos-publications.com)
  • This perspective review focused on a hypothetical cascade beginning with telomere dysfunction caused by WRN gene mutation leading to multi-phenotypes of premature aging and an abnormal profile of tumors. (spandidos-publications.com)
  • While cancer genome sequencing has been instrumental in identifying the genomic alterations that occur in human tumors, the consequences of these alterations on tumor growth remain largely unexplored. (stanford.edu)
  • In tumors developing from a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. (nih.gov)
  • In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity. (nih.gov)
  • The biology of specific PI3K pathway alterations found in human tumors will be studied by generating cell lines harboring these mutations and assaying gene expression, pathway activation, and the ability to form tumors in animal models. (prostatecancerfoundation.org)
  • To identify the most efficacious strategies for targeting tumors harboring specific mutations in the PI3K pathway, each of the PI3K pathway mutation-bearing cell lines will be treated with various PI3K pathway-inhibitors and examined for effects on cell death. (prostatecancerfoundation.org)
  • If successful, this study will elucidate the biology of PI3K pathway mutations, and develop strategies for therapeutically targeting tumors harboring these mutations. (prostatecancerfoundation.org)
  • Dr. Hsieh and team will delineate the biology of various PI3K pathway mutations that occur in CRPC and develop strategies to effectively target tumors harboring these mutations. (prostatecancerfoundation.org)
  • Genomic characterization of tumors is necessary for making precision medicine treatment decisions. (prostatecancerfoundation.org)
  • Results on a pilot series of 2218 primary tumors across 12 human cancers identified 89 genomic regions recurrently targeted by homozygous deletions. (ashg.org)
  • The detection of Circulating Tumor DNA (ctDNA) is receiving a great deal of attention because studies have shown that it can be detected in many cancers and it can be used to monitoring the therapeutic progress, including the development of drug resistance mutations in tumors that is reflected in the ctDNA. (nist.gov)
  • Genomic analysis is a relatively new way to look for unique genetic mutations in cancer tumors. (breastcancer.org)
  • When they looked only at genomic results from the cancer tumors, they found a number of mutations. (breastcancer.org)
  • But when they compared the genomic results from the cancer tumors to the genomic results from the normal tissue, they found that many of the mutations were also in the normal tissue. (breastcancer.org)
  • Succinate dehydrogenase (SDH) mutations in paraganglial tumors (see below) lead to succinate accumulation resulting in hypoxia-inducible factor 1 (HIF-1) stabilization through inhibition of prolyl hydroxylase-mediated degradation (Hensen and Bayley, 2011, King et al. (atlasgeneticsoncology.org)
  • Colorectal cancers that are mismatch repair deficient have 10 to 100 times more genomic mutations than tumors with this corrective mechanism intact. (genomeweb.com)
  • The FDA estimated that these hypermutated tumors were common in 5 percent of colorectal patients, and also occurred with varying frequency in endometrial, gastrointestinal, breast, prostate, bladder, thyroid, and other cancers. (genomeweb.com)
  • He and a team of researchers tested this observation prospectively in a study involving 41 cancer patients and showed that those with hundreds to thousands of genetic mutations in their tumors were more likely to benefit from Keytruda than those without hypermutated tumors. (genomeweb.com)
  • Diaz and colleagues concluded that the results "show an approach for the treatment of a specific class of tumors that is based solely on genetic status - that is, without regard to the underlying tumor type. (genomeweb.com)
  • Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. (nature.com)
  • With the development of transgenic mouse models harboring bacterial reporter genes that can be retrieved from chromosomal DNA, the possibility has emerged to quantitate and characterize mutation accumulation in postmitotic tissues ( 11 - 13 ). (pnas.org)
  • Like most diseases, these frequently occurring disorders result from the interactions of multiple genes and environmental factors. (encyclopedia.com)
  • This chapter considers some of the disorders believed to be predominantly genetic in origin and some that are the result of genes acted on by environmental factors. (encyclopedia.com)
  • Multifactorial or polygenic disorders result from a complex combination of environmental factors and mutations in multiple genes. (encyclopedia.com)
  • Until recently, the general perception has been that mutations in protein-coding genes are responsible for tumorigenesis. (wiley.com)
  • Our study reveals that oxidative DNA damage accumulation and repair differ strongly across the genome, but culminate in a previously unappreciated mechanism that safeguards the regulatory and coding regions of genes from mutations. (springer.com)
  • Inspired from the field of information retrieval, we propose using the term frequency (tf) and BM25 term weighting measures with the inverse document frequency (idf) and relevance frequency (rf) measures to weight genes based on their mutations. (springer.com)
  • At times even chemotherapy leads to MMR deficiency by selective mutation of its genes. (southlaketimes.com)
  • Moreover, we detected alterations in known cancer driver genes in 13.4% of IDH-mutant glioma patients, including PIK3CA, KRAS, AKT or PTEN mutation or PDGFRA, MET or N-MYC amplification. (aacrjournals.org)
  • A PCR-based screening of a T. turgidum BAC genomic library using primers within the conserved region of WRKY genes resulted in the isolation of five BAC clones. (frontiersin.org)
  • The present results indicate that these genes might play some functional role in the salt tolerance in durum wheat. (frontiersin.org)
  • This doubling seems to protect the genes needed for the tumour's survival in the face of the excessive mutations and chromosomal losses that occur in its genome as it develops 2 . (ucl.ac.uk)
  • The genomic landscape of DIPG has been recently described as an heterogenous collection of mutations and copy number variations in protein-coding genes. (open.ac.uk)
  • Genomic islands (GEIs), specifically pathogenicity islands (PAIs), typically harbor the genes necessary for the pathogenic mechanisms of bacteria and are thought to be important determinants of pathogenicity. (answersingenesis.org)
  • Two groups published the genomic map where the coding genes were cataloged. (hindawi.com)
  • Our large sample size and precision of measurement allowed us to determine that there are significant differences in fitness between mutations in different genes, between different paralogs, and even between different classes of mutations within the same gene. (stanford.edu)
  • Evolution of the initial tumour cell may occur by two methods: Sequentially ordered mutations accumulate in driver genes, tumour suppressor genes, and DNA repair enzymes, resulting in clonal expansion of tumour cells. (wikipedia.org)
  • A) Six missense mutations in six essential genes that are not in annotated functional domains. (g3journal.org)
  • These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. (ebi.ac.uk)
  • Mutations in MMR genes are linked to one of the most prevalent human cancer syndromes, Lynch syndrome and a significant number of sporadic colorectal cancers. (yu.edu)
  • We have generated gene targeted mouse lines with inactivating mutations in all the different MutS and MutL homologs, and also in genes that function in the later MMR steps to study their roles in genome maintenance and tumor suppression. (yu.edu)
  • However, in some cases mutations, like in oncogenes or tumor suppressor genes, may occur that allow the cell to bypass apoptosis and to survive. (mdpi.com)
  • A high rate of SCE in BS cells occurs if you inherit the blm genes identical to your ancestor. (umich.edu)
  • Our past research findings have helped to establish the prevailing view that histone modifications regulate genomic functions, including transcription of genes, DNA replication during cell division, repair of DNA mutations as a result of DNA damage, and other processes. (upenn.edu)
  • Our results add to the emerging evidence of several genes recently proposed in the literature as tumor suppressors (including FAT1 , BIRC2 / BIRC3 , TET1 and MGMT ), and bring forward several novel candidate tumor suppressors (including CASP3 , CASP9 , RAD17 , BAZ1A , CPEB3 and SETD1B ). (ashg.org)
  • Germline mutations are changes in genes inherited from your parents and are in all your DNA (your entire genome). (breastcancer.org)
  • The recent head and neck study of The Cancer Genome Atlas (TCGA) [ 12 ] showed that HNSCC has a particularly mixed set of genomic abnormalities, with few common driver genes. (biomedcentral.com)
  • From the view of heredity, aging is the results of the activation and inhibition of a series of genes as well as the products of their interaction. (scirp.org)
  • Most cancer-causing DNA changes occur in genes, but DNA changes outside of genes can also drive cancer growth. (cancer.gov)
  • 1 2 To date, mutations in 11 human genes have been implicated in the pathogenesis of CMS. (bmj.com)
  • Third, more rarely, genomic deletions and rearrangements proximal to the TERT promoter remobilize or abolish EBF1-binding sites, derepressing TERT and leading to high TERT expression. (jci.org)
  • 2003). Most of the T-DNA insertions resulted in small (1-100 base pair) deletions of plant genomic sequences at the insertion-site. (econexus.info)
  • Notably, in 13 patients in whom only one pathogenic mutation was initially found by Sanger sequencing or NGS, 3 were further identified to carry exon deletions by MLPA. (thefreelibrary.com)
  • From the patterns of the homozygous deletions, the patterns of mutations in COSMIC and the literature, we subsequently identified candidate tumor suppressors. (ashg.org)
  • Analysis of the resulting transformants showed that TALEN-induced double strand breaks led to the introduction of short deletions at the target site. (deepdyve.com)
  • point mutations in PLP1 occur less frequently, and higher copy number gains ( e . g . triplications) and deletions are rare [ 14 - 17 ]. (prolekare.cz)
  • Initially, each point mutation occurs on a single chromosome in a single cell, which gives rise to a lineage of cells bearing the same mutation. (nature.com)
  • I show that the rate of adaptive substitution in an asexual species or nonrecombining chromosome region is a bell-shaped function of the mutation rate: at some point, increasing the mutation rate decreases the rate of substitution. (genetics.org)
  • In the course of this work, I derive an approximation to the probability of fixation of a favorable mutation in an asexual genome or nonrecombining chromosome region in which both favorable and deleterious mutations occur. (genetics.org)
  • The problem of how adaptation rate depends on mutation rate in asexuals (or in chromosome regions that do not recombine) is subtle. (genetics.org)
  • The total rate of mutation per genome (or nonrecombining chromosome region) is U. In the present environment, a fixed proportion p b of all mutations are beneficial. (genetics.org)
  • OCA 1 is a disorder that results from mutations to the tyrosinase gene found on chromosome 11 (band 11q14-21). (medscape.com)
  • It is caused by nonsense, frameshift, and missense mutations of the tyrosinase gene on chromosome 11 (band 11q24). (medscape.com)
  • The results showed that all nine patients lost identical regions of chromosome 17, where the cancer-linked p53 gene is located, in each of the cancer samples, including the early-stage STIC lesions, suggesting that the "misprinted" or flawed p53 gene is an early step in ovarian cancer development. (hopkinsmedicine.org)
  • 9 We have previously ascribed ML III type C to mutations in the UDP -N- acetylglucosamine-1-phosphotransferase gamma subunit gene (GNPTAG) on chromosome 16p. (bmj.com)
  • The DYSF geneis located on chromosome 2p13, which spans a genomic region of more than 230 kbp and comprises 55 exons. (thefreelibrary.com)
  • This report describes CNAs identified on a bacterial artificial chromosome (BAC) array of ∼1.4-Mb resolution [array comparative genomic hybridization (aCGH)], in a set of 50 glioblastoma multiforme (GBM). (aacrjournals.org)
  • The karyotype was stable, with few chromosomal changes, especially gains of chromosomes 5 and 20 and a chromosome 9p21 deletion resulting in p16 INK 4 A loss. (iospress.com)
  • The SBDS gene resides in a block of genomic sequence that is locally duplicated on the chromosome. (wikipedia.org)
  • The rate at which amelioration of horizontally acquired DNA occurs within the chromosome is likely to account for the small differences between chromosomes and stably incorporated GIs compared to the transient or independent replicons such as phages and plasmids. (biomedcentral.com)
  • a) IP‐603 family: the IP patient (II:1) carried a point mutation (mtz, c.1167delC) in the NEMO gene and in Ψ NEMO pseudogene both on the paternal chromosome. (els.net)
  • The cause of CHARGE is usually a new mutation (change) in the CHD7 gene, or rarely, genomic alterations in the region of chromosome 8q12.2 where the CHD7 gene is located. (rarediseases.org)
  • Other errors can occur in mitosis or in meiosis that lead to faulty DNA material in daughter cells, such as non-disjunction of chromosomes or part of a chromosome attaching to another chromosome during separation. (newworldencyclopedia.org)
  • If that chromosomal locus is subsequently duplicated, any point mutation on this allele preceding the gain will subsequently be present on the two resulting allelic copies, unlike mutations succeeding the gain, or mutations on the other allele. (nature.com)
  • However, it should be noted that C3H/HeJ has a point mutation of Tlr4 that renders this subline hyporesponsive to bacterial lipopolysaccharide (Lps). (jax.org)
  • In addition to an exon 11 mutation, shared among all of the analyzed lesions, a novel point mutation in c-Kit exon 14 resulting in T670I substitution was found only in the progressing lesion, which harbored a phosphorylated receptor, as opposed to the finding of an inactive receptor in responding lesions. (nih.gov)
  • T point mutation was found in the second exon of T08B1.1a and the first exon of T08B1.1b . (g3journal.org)
  • This point mutation at a splice site in intron 8 was the first mutation in PSEN1 determined to result in the deletion of exon 9 from mRNA transcripts. (alzforum.org)
  • The father of IP patient (I:2) carried a point mutation (mtz, c.1167delC, chrX:delG_153 868 348-153 868 349) in the Ψ NEMO pseudogene. (els.net)
  • Mutational signatures observed at the latter junction include microhomology, templated insertions, and increased point mutation frequency [ 1 , 20 ]. (prolekare.cz)
  • Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. (nature.com)
  • These results suggested that postmitotic tissue is resistant to mutation accumulation in the nuclear genome and that cytogenetic alterations are limited to cells that are still mitotically capable. (pnas.org)
  • These results indicate that multimodal genomic and epigenomic alterations underpin TERT reactivation in GC, converging on transcriptional repressors such as EBF1. (jci.org)
  • Associations between genomic alterations and outcomes were analyzed in patients. (aacrjournals.org)
  • It has been proven that Bloom syndrome is a rare autosomal recessive disease, which lacks in DNA repair enzymes resulting in genomic alterations. (umich.edu)
  • Second-generation sequencing provides a platform to reveal base alterations occurring in the whole genome due to mutagenesis. (g3journal.org)
  • however, each mutated genome has unique alterations, which are useful to identify causal mutations for their phenotypic changes. (g3journal.org)
  • The functional impact of most genomic alterations found in cancer, alone or in combination, remains largely unknown. (stanford.edu)
  • Some treatments-particularly, some targeted therapies -are effective only for people whose cancer cells have specific genetic alterations that cause the cells to grow out of control (these are sometimes called "driver" mutations). (cancer.gov)
  • Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) 4 , we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. (nature.com)
  • Present-day genomes are the result of a large number of more or less randomly occurring mutations, recombinations, matings, and deaths. (genetics.org)
  • The same or similar changes in the genomes of different lineages indicates recurrent genomic evolution may have taken place. (wikipedia.org)
  • Complex, large and unsequenced genomes, in addition to a lack of genomic resources, hinder the molecular characterization of tolerance mechanisms. (frontiersin.org)
  • The term is also used to refer to naturally occurring recombination between virus genomes in a cell infected by more than one virus strain. (wikipedia.org)
  • GC content has also been associated with genome wide rates of mutation, where organisms of low GC content tend to have more random genomes than GC rich ones [ 10 , 11 ], i.e . the signal-to-noise ratio is lower in AT rich genomes. (biomedcentral.com)
  • These results led us to apply information theoretical methods to examine the extent to which information content differed between the genomes of bacterial chromosomes, plasmids, phages and GIs, and whether such differences could be related to distinct genomic properties of bacterial chromosomes and mobile genomic elements. (biomedcentral.com)
  • I described the results as these genomes looking as though someone threw a miniature grenade into the nucleus of a prostate epithelial cell. (scienceblogs.com)
  • A study strongly suggests that cancer tumor genomes should be compared to genomes from noncancerous tissue from the patient so doctors can be sure any mutations found are unique to the cancer. (breastcancer.org)
  • Fosmid paired-end sequencing of 8 human genomes from diverse populations shows that ~50-100 large genomic inversions not represented in the human genome reference sequence are present in the personal genome of each individual. (prolekare.cz)
  • Such patterns are expected in recently diverged genomes as a result of incomplete lineage sorting. (diva-portal.org)
  • Only a small number of genetic mutations are responsible for reduced neurovirulence in OPV strains ( 5 ). (cdc.gov)
  • As well as explaining a person's immune response against their cancer, the study could guide treatments for targeting the many genetic mutations that accumulate in late-stage cancers that are difficult to treat. (ucl.ac.uk)
  • Stem cell variability is often caused by epigenetic changes, but can also result from clonal evolution of the CSC population where advantageous genetic mutations can accumulate in CSCs and their progeny (see below). (wikipedia.org)
  • These abnormal changes in DNA are called genetic mutations. (breastcancer.org)
  • Not all genetic mutations in a cancer tumor are directly related to the cancer. (breastcancer.org)
  • Other genetic mutations aren't inherited and can happen during your life. (breastcancer.org)
  • Most genetic mutations aren't harmful, but some can cause diseases, such as cancer. (breastcancer.org)
  • Mismatch repair deficiency is a condition that makes cancer cells unable to repair the DNA damage that occurs during replication so that they become inundated by genetic mutations. (genomeweb.com)
  • Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes 3 . (nature.com)
  • Using clock-like mutational processes, we map mutation timing estimates into approximate real time. (nature.com)
  • In this paper, we present the first completely characterized mutational spectra, ranging from point mutations to large genomic rearrangements, in an actively proliferating and a postmitotic organ from young and old mice. (pnas.org)
  • We estimate mutational patterns using sequence datasets from five such clonal pathogens belonging to four diverse bacterial clades that span most of the range of genomic nucleotide content. (nih.gov)
  • These results suggest that bacterial mutational biases are far less variable than previously thought. (nih.gov)
  • We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. (nih.gov)
  • The novel mutations found in this study greatly expanded the mutational spectrum of dysferlinopathy. (thefreelibrary.com)
  • Two factors determine the rate of adaptation of the virus: the rate of mutation and mutational tolerance. (news-medical.net)
  • The mutational mechanisms that can give rise to genomic rearrangements in the IP locus are: NAHR, NHEJ, Alu-Alu mediated recombination and gene conversion. (els.net)
  • Molecular mutational analysis was undertaken on genomic DNA from peripheral blood leukocytes from 6 affected South Africans of different population groups (4 Xhosa, 1 coloured, 1 white). (scielo.org.za)
  • Mutational analysis in the affected patient, who has a history of a serious untoward reaction to treatment with acetylcholinesterase inhibition, revealed two frame-shifting heteroallelic mutations, a maternally inherited 1478delG and a paternally inherited 4804delC . (bmj.com)
  • Although the V600E BRAF mutation is the most common mutation in cutaneous melanomas, it is rarely seen in uveal melanomas, those of internal organs [ 9 ] or other types of skin cancers. (wiley.com)
  • Genomic study suggests that most ovarian cancers originate in the fallopian tube. (hopkinsmedicine.org)
  • We are particularly interested in the consequences of whole genome duplications, which recent genomic data suggest occur in nearly 40% of human cancers. (harvard.edu)
  • Historically, despite the more prevalent mutation frequencies of KRAS and NRAS in human cancers, HRAS has been the most intensively studied. (cancer.gov)
  • This contrasts with cutaneous melanoma or acute myelogenous leukemia (AML), where NRAS comprises 94% and 59%, respectively, of RAS mutations in these cancers. (cancer.gov)
  • Why the frequency of RAS gene mutations varies widely in cancers that arise from different tissues remains largely unresolved. (cancer.gov)
  • 2008). Interestingly, although colon and rectal cancers are generally described as a single cancer type, a recent study found that NRAS mutations were associated with rectal versus colon cancer (12.5% versus 0.6%, respectively) (Russo et al. (cancer.gov)
  • Some cancers are initiated when exogenous factors introduce mutations, such as ultraviolet radiation (skin cancers) and tobacco (lung cancer). (wikipedia.org)
  • Our laboratory first reported that germline mutations in PTEN are associated with Cowden syndrome (CS) ( 2 ) and Bannayan-Ruvalcaba-Riley syndrome ( 3 ), which confers a high risk of breast and other cancers. (pubmedcentralcanada.ca)
  • Herceptin is not effective on HER2-negative cancers - cancers that don't have that particular mutation. (breastcancer.org)
  • However, most types of cancers originate from changes to a cell's DNA ( mutations ) due to environmental factors (carcinogens), such as tobacco smoke, UV radiation, chemicals, or infectious agents. (newworldencyclopedia.org)
  • Researchers at Johns Hopkins University in 1993 described how this hobbled DNA repair mechanism resulted in the accumulation of mutations in repetitive DNA regions called microsatellites and caused a hereditary condition called Lynch Syndrome, which increases the risk for colorectal and other cancers. (genomeweb.com)
  • In summary, through copy-number meta-analysis of large-genomic datasets, our study is significantly advancing the landscape of tumor suppressors. (ashg.org)
  • Several different types of mutations to the tyrosinase gene (missense, nonsense, and frameshift) are responsible for producing the 2 types of OCA 1 (OCA 1A and OCA 1B). (medscape.com)
  • Blue bars indicate the missense mutation. (g3journal.org)
  • In addition, we have generated knock-in mouse lines with missense mutations and conditional knockout mouse lines that inactivate specific MMR functions and/or model mutations found in humans. (yu.edu)
  • The base change is a missense mutation that leads to the substitution of arginine with histidine (R206H). (scielo.org.za)
  • We infer timing and patterns of chromosomal evolution and learn typical sequences of mutations across samples of each cancer type. (nature.com)
  • In contrast, in heart about half of the accumulated mutations appeared to be large genome rearrangements, involving up to 34 centimorgans of chromosomal DNA. (pnas.org)
  • Reassortment Mutation Chromosomal crossover Recombination Resulting in Virulence Shift in Avian Influenza Outbreak, Chile. (wikipedia.org)
  • Ionizing radiation causes DNA double strand breaks, which are the initiators for reproductive death, chromosomal aberration, apoptosis, and mutation. (aacrjournals.org)
  • Perturbations in these pathways can lead to increased mutation rates or chromosomal rearrangements that ultimately result in cancer. (yu.edu)
  • It is an autosomal dominant trait and affected persons have mutations in the activin A type 1 receptor gene (ACVR1 ), chromosomal locus 2q23-24. (scielo.org.za)
  • Here, through comprehensive genomic and epigenomic analysis of primary GCs and GC cell lines, we identified the transcription factor early B cell factor 1 (EBF1) as a TERT transcriptional repressor and inactivation of EBF1 function as a major cause of TERT upregulation. (jci.org)
  • On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. (mit.edu)
  • Our global laboratories offer one of the world's most comprehensive genomic screening and testing programs. (perkinelmer.com)
  • These results suggest that distinct mechanisms lead to organ-specific genome deterioration and dysfunction at old age. (pnas.org)
  • Abolishment of EBF1 function occurs through 3 distinct (epi)genomic mechanisms. (jci.org)
  • I propose that bacterial pathogenicity is the result of multiple events in any given bacterium (vs. singular events) that occurred after the Fall and that no intentional pathogenic mechanisms exist. (answersingenesis.org)
  • It was also envisioned that processing mechanisms could be discerned by comparing the genomic structure with the RNA sequence determined using cDNA methods. (hindawi.com)
  • However, very little is known about the underlying mechanisms of PTEN ATP-binding mutations in tumorigenesis. (pubmedcentralcanada.ca)
  • Using phosphospecific antibodies for six phosphorylation sites, we investigated the mechanisms involved in estradiol (E2)-induced SRC-3 phosphorylation and found that this occurs only when either activated estrogen receptor α (ERα) or activated ERβ is present. (asm.org)
  • Moreover, a high frequency of micro‐/macro‐homologies, tandem repeats and repeat/repetitive sequences characterise the local architecture of the locus increasing its vulnerability to the production of de novo genomic rearrangements through different mechanisms. (els.net)
  • The complex architecture of the locus enhances its vulnerability to the production of de novo genomic rearrangements through different mechanisms. (els.net)
  • The mechanisms for such complex genomic rearrangements (CGRs) have only begun to be elucidated. (prolekare.cz)
  • Animal models of human diseases have significantly facilitated our understanding of the mechanisms driving pathologies and resulted in the development of more efficient therapies. (biologists.org)
  • Recurrent genomic evolution can also occur within a lineage. (wikipedia.org)
  • In organisms with longer generation times, any potential recurrent genomic evolution within a lineage would be difficult to detect. (wikipedia.org)
  • Recurrent evolution has been studied most extensively at the organismic level but with cheaper and faster sequencing technologies more attention is being paid to recurrent genomic evolution. (wikipedia.org)
  • Confirmation of the presence of this recurrent mutation facilitates diagnostic accuracy in affected persons in South Africa, and allows researchers to narrow the search for molecular targets for rational intervention to the ACVR1/ALK2 domain. (scielo.org.za)
  • A recurrent mutation also causes FOP in indigenous South Africans. (scielo.org.za)
  • This Clcc1 m1J mutation is homozygous in this congenic strain. (jax.org)
  • Mice homozygous for the severe combined immune deficiency spontaneous mutation ( Prkdc scid , commonly referred to as scid ), are characterized by an absence of functional T cells and B cells, lymphopenia, hypogammaglobulinemia, and a normal hematopoietic microenvironment. (jax.org)
  • Results: Among the 89 index patients, 79 patients were demonstrated to carry two disease-causing (73 cases) or possibly disease-causing mutations (6 cases), including 26 patients with homozygous mutations. (thefreelibrary.com)
  • These people are not homozygous for the mutation at blm gene, but instead are compound heterozygous. (umich.edu)
  • Mice homozygous for the null mutation lack detectable mRNA, but the mice are viable and anatomically normal. (jneurosci.org)
  • Relative rates of the six nucleotide pair mutations. (nih.gov)
  • DNA mutations occur when a nucleotide is deleted, changed or added to the DNA sequence. (hopkinsmedicine.org)
  • The x-axis indicates the mutation site (the nucleotide position in mitochondrial genome). (elifesciences.org)
  • Single-nucleotide polymorphisms were found in every 208 kb (AS) and 202 kb (AM) with a bias mutation of G/C-to-A/T changes at low percentage. (g3journal.org)
  • A single nucleotide polymorphism (SNP) may lead to codon changes that result in no change in the amino acid (a synonymous or silent mutation). (perkinelmer.com)
  • Whereas in the liver a substantial fraction of the spontaneous mutations were large genome rearrangements, in the brain mainly point mutations were detected. (pnas.org)
  • Surprisingly, genomic rearrangements were found to occur predominantly in the heart and to accumulate with age. (pnas.org)
  • It is known, however, that rearrangements of genomic DNA at T-DNA insertion sites can be very substantial. (econexus.info)
  • Exonic rearrangements were found in 23% of patients with only one pathogenic mutation identified by Sanger sequencing or NGS. (thefreelibrary.com)
  • Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. (ebi.ac.uk)
  • Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. (ebi.ac.uk)
  • Changes in this physical map as a result of genomic rearrangements are therefore identified by 4C technology. (europa.eu)
  • Excitingly, 4C technology therefore offers the first high-resolution genomic approach that can identify both balanced and unbalanced genomic rearrangements. (europa.eu)
  • These events, occurring during both meiosis and mitosis, reveal that the region is prone to generate complex human genomic rearrangements. (els.net)
  • Genomic rearrangements in the NEMO gene can be generated during meiosis or mitosis. (els.net)
  • An IP locus comprehensive map of the genomic rearrangements. (els.net)
  • SV can consist of deletion, duplication, or inversion of a genomic segment, or combinations thereof, the latter referred to as complex genomic rearrangements (CGR). (prolekare.cz)
  • The importance of IRs to human genomic rearrangements and resultant genomic disorders and the expanded scope by which IRs can facilitate genomic change are now apparent [ 2 , 3 , 5 - 7 ]. (prolekare.cz)
  • Linear expansion is less likely to reflect the endpoint of a malignant tumour because the accumulation of mutations is stochastic in heterogeneic tumours. (wikipedia.org)
  • Examining the numbers of shared mutations and the rate of accumulation of mutations showed evidence that all samples contain a population of sub-clones, with little evidence of selective advantage of a subset of these. (biomedcentral.com)
  • The data obtained demonstrate that whole genomic sequencing is applicable as a high-throughput tool to investigate genomic changes due to mutagenesis. (g3journal.org)
  • Spatial mapping of genomic data to tissue context in a high-throughput and high-resolution manner has been challenging due to technical limitations. (biomedcentral.com)
  • Here, we describe PHLI-seq, a novel approach that enables high-throughput isolation and genome-wide sequence analysis of single cells or small numbers of cells to construct genomic maps within cancer tissue in relation to the images or phenotypes of the cells. (biomedcentral.com)
  • CDC regularly collects genomic sequence data from multiple sources to support national surveillance . (cdc.gov)
  • Commercial laboratories transfer genomic sequence data to CDC at step 3 where it is processed and submitted for publishing. (cdc.gov)
  • Single-gene disorders (also called Mendelian or monogenic) are caused by mutations in the deoxyribonucleic acid (DNA) sequence of one gene. (encyclopedia.com)
  • Leveraging cancer genomic data, we also find locally reduced SNV rates in promoters, coding sequence, and other functional elements. (springer.com)
  • Point mutations in DNA, arising from single changes in the genome sequence, were also prevalent. (ucl.ac.uk)
  • Most of these mutations are private and there are no hotspots,[sup][18] which makes screening of the entire coding sequence of the DYSF gene necessary. (thefreelibrary.com)
  • An organism's DNA sequence that has been subjected to numerous random mutations is assumed to possess less information than the DNA of an organism under strong selective pressure. (biomedcentral.com)
  • B ) ATAC-seq enriches for mtDNA reads compared to whole exome sequencing (WES), low coverage whole genome sequence (WGS_L), or PCR-free, high-coverage whole genome sequence (WGS_H). ( C ) Bimodal distribution of variant allele frequency (VAF) of mtDNA mutations discovered using ATAC-seq. (elifesciences.org)
  • NIST genomic DNA sequence reference materials will be used as the source of wild type DNA. (nist.gov)
  • there is little to no recombination, and the sequence only changes when mutations occur. (wired.com)
  • Normally, following gene editing, precise DNA repair - cut and paste of a mutation-free gene sequence - only occurs in dividing cells. (medizin-aspekte.de)
  • Sometimes, mutations occur in the genetic material, whereby there is a change in the base pair sequence of the DNA. (newworldencyclopedia.org)
  • They may also examine the DNA sequence of your healthy cells to determine if you have any inherited, or germline, mutations that increase your risk of cancer and can also influence treatment decisions. (cancer.gov)
  • Broad DNA sequencing tests analyze the sequence of large regions of DNA rather than specific mutations. (cancer.gov)
  • Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. (nature.com)
  • Functional analyses showed that KIT/T670I is insensitive to imatinib and that T670I mutation, introduced in a receptor responding to imatinib, subverted its sensitivity to the drug. (nih.gov)
  • However, despite disti nct 3 p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. (nih.gov)
  • Mutagenesis provides a powerful technique to improve plant breeding and assist functional and genomic analyses of crop plants. (g3journal.org)
  • To bridge the gap between our understanding of DNA repair and mutation distributions, we developed a novel method, AP-seq, capable of mapping apurinic sites and 8-oxo-7,8-dihydroguanine bases at approximately 250-bp resolution on a genome-wide scale. (springer.com)
  • These transformation-induced mutations can be separated into two types: those introduced at the site of transgene insertion, which we refer to as insertion-site mutations and those introduced at other random locations, which we refer to as genome-wide mutations. (econexus.info)
  • Recently, genome-wide datasets have revealed clusters of differentiated loci ('genomic islands of divergence') that are thought to play a role in reproductive isolation and therefore have reduced gene flow. (royalsocietypublishing.org)
  • Earlier work provided experimental evidence for genome-wide inversions and suggested these can occur somatically and with aging [ 9 ]. (prolekare.cz)
  • In 2015, researchers at The Jackson Laboratory discovered C3H/HeSnJ inbred mice harbor a spontaneous, intracisternal A-particle (IAP) retrotransposon-mediated insertion in exon 2 of Clcc1 locus ( Clcc1 m1J ) resulting in a loss of function mutation. (jax.org)
  • Here we report the assembly of several TALENs for a specific genomic locus in barley. (deepdyve.com)
  • Conclusions: A subset of IDH-mutant gliomas with mutations in driver oncogenes has a more malignant phenotype in patients. (aacrjournals.org)
  • Conclusions: DYSF mutations in Chinese patients clustered in the N-terminal region of the gene. (thefreelibrary.com)
  • This has caused some doubt about the accuracy of CSC results and the conclusions about which cells have tumourigenic potential. (wikipedia.org)
  • Loss of MMR results in elevated levels of frameshift mutation and base substitution. (southlaketimes.com)
  • No theropod fossils indicate a frameshift occurring. (grisda.org)
  • At background levels, a human cell is estimated to undergo 100 to 500 such modifications per day, most commonly resulting in 8-oxo-7,8-dihydroguanine (8-oxoG) and related products [ 1 ], which are then processed into repair intermediates. (springer.com)
  • Clinically, OLP appears more commonly with the classic reticular form, which results from coalition of papules and may be asymptomatic or may cause mild discomfort. (hindawi.com)
  • [1] While most commonly used to describe recurring patterns of selection, it can also be used to describe recurring patterns of mutation , for example transitions are more common than transversions . (wikipedia.org)
  • Recently, we argued that many adaptive mutations might also be commonly overdominant in fitness. (stanford.edu)
  • The changes are often unnoticed as they don't result in physical changes, but sometimes these mutations, more commonly referred to as variants, can have significant effects on physical characteristics. (hopkinsmedicine.org)
  • Mutation screening was performed on 204 MDS patients using our established gene panel targeting mutations commonly occurring in MDS (Mohemdali, Leukaemia 2015). (confex.com)
  • These patients are commonly tested for the genetic mutation the therapy targets. (cancer.gov)
  • Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. (nih.gov)
  • We perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. (nih.gov)
  • Recent identification of naturally occurring cancer and germline mutations within the ATP-binding motifs of PTEN (heretofore referred to as PTEN ATP-binding mutations) has revealed that these mutations disrupted the subcellular localization and tumor-suppressor activity of PTEN. (pubmedcentralcanada.ca)
  • Some mutations are what researchers call germline changes. (breastcancer.org)
  • 1995. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. (jax.org)
  • This occurs either by Homologous recombination of the nucleic acid strands or by reassortment of genomic segments. (wikipedia.org)
  • The maintenance of genomic integrity in all organisms requires multiple DNA repair pathways that are involved in the processes of DNA replication, repair and recombination. (yu.edu)
  • Furthermore, aspects of genomic architecture such as proximity to centromeres can contribute to reduced recombination rates, resulting in slower breakdown of linkage disequilibrium between loci within islands and higher susceptibility to selective sweeps and/or background selection [ 5 , 10 - 12 ]. (royalsocietypublishing.org)
  • In species with genomic islands of divergence, introgression and subsequent recombination will test these differentiated loci in new genomic and environmental contexts. (royalsocietypublishing.org)
  • Mutations can occur during viral replication, from spontaneous nucleic acid damage, or from recombination events. (perkinelmer.com)
  • The Clcc1 m1J spontaneous mutation, which causes increased sensitivity to endoplasmic reticulum stress in the cerebellum, was identified in C3H/HeSnJ (Jia et al. (jax.org)
  • First, most spontaneous mutations in the germ line seem to be due to errors in DNA replication. (blogspot.com)
  • The amount of genomic information about leukemia cells currently far exceeds our overall understanding of the precise genetic events that ultimately drive disease development and progression. (aacrjournals.org)
  • The over-all amount of genomic admixture from Neandertals is similar to that in present-day non-Africans and there is no evidence for admixture from Denisovans. (blogspot.com)
  • Multiplex ligation-dependent probe amplification (MLPA) was performed to detect exon duplication/deletion in patients with only one pathogenic mutation. (thefreelibrary.com)
  • one is a splice site mutation affecting the 5' splice site of intron two, while the second is an exon two nonsense mutation . (wikipedia.org)
  • Now, several unique mutations have been identified that result in the exclusion of exon 9 and are variously known as ΔE9, Δ9, delE9, or deltaE9. (alzforum.org)
  • However, it was not clear from the report which exon 9 deletion mutation these individuals carried. (alzforum.org)
  • The skipping of exon 9 occurs in-frame and also results in an amino acid change at the splice junction of exon 8 and 10 (S290C). (alzforum.org)
  • The following summary refers to studies of PSEN1 mutants that result in the exclusion of exon 9 (denoted here as PSEN1ΔE9). (alzforum.org)
  • We previously found that whole genome duplications resulting from cytokinesis failure can drive tumor development. (harvard.edu)
  • Another finding is that whole-genome doubling often occurs early on in those with lung cancer who have a history of smoking 1 . (ucl.ac.uk)
  • Resulting in-frame stop codons from the insertion of IAP sequences resulted in severely reduced protein levels in mutant tissues. (jax.org)
  • Based on the ever-increasing number of RNA sequences, it was determined that most coding RNAs mature as a result of alternative splicing. (hindawi.com)
  • As a result, the virus is hardly exposed to antibodies before it is transmitted, explaining why viral genomic sequences show little evidence of positive selection. (news-medical.net)
  • Analysis of available sequences shows that 23 of 32 naturally occurring mutations in circulating SARS-CoV-2 strains are associated with in vitro resistance, and are therefore able to escape mutations. (news-medical.net)
  • Gene conversion occurs when the intact SBDS gene and its pseudogene copy aberrantly recombine at meiosis , leading to an incorporation of pseudogene-like sequences into the 'good copy' of the SBDS gene, thereby inactivating it. (wikipedia.org)
  • In other words, due to more accumulated mutations, it appears as if less information is carried by the DNA sequences of AT rich microbes compared to GC rich microbes. (biomedcentral.com)
  • Thus, to test the assertion that accumulated mutations lower the information capacity we explored the use of information theory as a means of measuring information capacity in DNA sequences. (biomedcentral.com)
  • This results in a library of sequences amplified from the virus which are then purified and must be accurately quantified prior to sequencing. (perkinelmer.com)
  • Genomic modifications in naturally occurring neurovirulent revertants of Sabin 1 polioviruses. (nih.gov)
  • A recombinant virus may occur naturally or be produced by recombining pieces of DNA using recombinant DNA technology. (wikipedia.org)
  • Neoantigen-MHC affinity was predicted using NetMHCpan3.0 with neoantigen affinities ranked against 400,000 naturally occurring peptides. (confex.com)
  • Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection. (nature.com)
  • He attributed the high turnover rate across continents to evolutionary diversification (i.e., speciation) between faunas as a result of dispersal limitation and the lower turnover rates of bird species within continents as a result of environmental variation. (pnas.org)
  • The overall rate of evolutionary change is consistent with the mutation rate of DNA replication + repair, suggesting that it is the dominant form of mutation. (blogspot.com)
  • Strikingly, mutations induced by smoking tend to dominate the 'trunk' of the tumour's evolutionary tree. (ucl.ac.uk)
  • During this evolutionary process, cancer cells diverge and form distinct lineages, resulting in intratumor heterogeneity. (sciencemag.org)
  • We use simulations to further examine the evolutionary forces that shape and maintain genomic islands of divergence between two subspecies of the migratory songbird, Swainson's thrush ( Catharus ustulatus ), which have come into secondary contact since the last glacial maximum. (royalsocietypublishing.org)
  • These findings confirm the notion that a second mutation/alteration or even a third is necessary for the transformation of cells, which reflects Knudson's original two-hit theory [ 14, 15 ]. (wiley.com)
  • These findings suggest that most of the genomic changes driving oral cancer occur in the pre-cancerous state by way of gradual random accumulation rather than a dramatic single event. (biomedcentral.com)
  • Analysis of tumours from the first 100 people enrolled in the study has revealed many genomic changes. (ucl.ac.uk)
  • This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity). (wikipedia.org)
  • In this model, tumours arise from a single mutated cell, accumulating additional mutations as it progresses. (wikipedia.org)
  • We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. (ebi.ac.uk)
  • Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. (mit.edu)
  • We recently identified a mechanism by which errors in the segregation of intact chromosomes can cause DNA breaks, potentially resulting in cancer-causing mutations. (harvard.edu)
  • In pancreatic ductal adenocarcinoma (PDAC) there is a near 100% frequency of KRAS mutations (Figure 1. (cancer.gov)
  • However, the preferential mutation of KRAS versus NRAS in colorectal carcinoma (CRC) cannot be explained simply on this basis. (cancer.gov)
  • 2008) are both expressed in mouse colonic cells, yet KRAS mutations are six times more common than NRAS , and HRAS mutations are not found in CRC. (cancer.gov)
  • When applied to HRAS -null mice, KRAS mutation (G12, G13 or Q61) and skin papilloma formation occurred, albeit at a sixfold lower frequency (Ise et al. (cancer.gov)
  • Another study addressed this question by using a urethane carcinogenesis model in which treatment of mice with this carcinogen causes KRAS mutation and lung tumor formation. (cancer.gov)
  • We are currently developing the expertise in the measurement of low frequency alleles using quantitative PCR and droplet digital PCR of model mutations (KRAS and BRAF) that occur frequently in cancer. (nist.gov)
  • Dysferlinopathy is a group of autosomal recessive muscular dystrophies caused by mutations in dysferlin( DYSF ) gene showing marked clinical heterogeneity. (thefreelibrary.com)
  • A minimal level of intra-tumour heterogeneity is a simple consequence of the imperfection of DNA replication: whenever a cell (normal or cancerous) divides, a few mutations are acquired-leading to a diverse population of cancer cells. (wikipedia.org)
  • The CSC model posits that the heterogeneity observed between tumour cells is the result of differences in the stem cells from which they originated. (wikipedia.org)
  • By applying PHLI-seq, we reveal the heterogeneity of breast cancer tissues at a high resolution and map the genomic landscape of the cells to their corresponding spatial locations and phenotypes in the 3D tumor mass. (biomedcentral.com)
  • However, the mutagenesis and genetic evolution in the tumor mass [ 2 ], resulting in intra-tumor heterogeneity, impede precise deciphering of a causation underlying carcinogenesis. (biomedcentral.com)
  • We analyzed the differences in information capacity between prokaryotic chromosomes, genomic islands (GI), phages, and plasmids. (biomedcentral.com)
  • However, for a significant number (24/112) there was evidence for large-scale rearrangement of plant genomic DNA at the insertion-site. (econexus.info)
  • In addition, most of the reported mutations are point mutations, small deletion/insertions, and intronic mutations. (thefreelibrary.com)
  • NRAS joined the family only after its detection in an NIH 3T3 focus formation assay to detect activated oncogenes in genomic DNA isolated from a human neuroblastoma cell line. (cancer.gov)
  • In small intestine, only point mutations were found to accumulate, including G·C to T·A, G·C to C·G, and A·T to C·G transversions and G·C to A·T transitions. (pnas.org)
  • This deletion occurs in-frame, so presenilin protein is produced, but it lacks amino acids 290-319. (alzforum.org)
  • A null mutation for the α7 subunit was prepared by deleting the last three exons of the gene. (jneurosci.org)
  • The distribution of NEMO mutations in different exons of the gene. (els.net)
  • In familial melanoma, which accounts for about 10% of melanomas, 40% of the patients have a mutation in CDKN2 [ 7 ]. (wiley.com)
  • The underlying assumption is that the more mutations a gene has in patients with a certain disease and the less mutations it has in other patients, the more discriminative that gene is. (springer.com)
  • Our results raise questions about manifestations of VDPVs in immunodeficient patients and the role of cellular immunity against enterovirus infections. (cdc.gov)
  • HRR gene mutations occur in approximately 20%-30% of patients with mCRPC. (astrazeneca-us.com)
  • Fatal adverse reactions occurred in 4% of patients treated with LYNPARZA. (astrazeneca-us.com)
  • Serious adverse reactions occurred in 36% of patients receiving LYNPARZA. (astrazeneca-us.com)
  • If studies in larger groups of women confirm our finding that the fallopian tubes are the site of origin of most ovarian cancer, then this could result in a major change in the way we manage this disease for patients at risk. (hopkinsmedicine.org)
  • 10 Here, we report the genomic structure of this gene and its mutations in 14 additional patients belonging to eight families of various ethnic backgrounds. (bmj.com)
  • Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy. (thefreelibrary.com)
  • In a study of 158 SDS families, 75% of disease-associated mutations appeared to be the result of gene conversion , while 89% of patients harbored at least one such mutation. (wikipedia.org)
  • We examined genomic copy number changes in 256 pre-invasive and invasive samples from 69 oral cancer patients. (biomedcentral.com)
  • Colobomas occur most frequently in the retina and are present in at least 70-90% of patients with CHARGE syndrome. (rarediseases.org)
  • Examination of 38 eyes in 19 patients with CHARGE syndrome and confirmed CHD7 mutations revealed colobomata affected the posterior segment of 35 eyes in 18 patients. (rarediseases.org)
  • Several years ago, with the increasing availability of genomic testing and advances in immunotherapy, Diaz, while at JHU, began noticing that patients with mismatch repair deficiencies appeared to be responding better to immunotherapies like Keytruda than patients with normal mismatch repair functions. (genomeweb.com)
  • In 2015, they published in the New England Journal of Medicine that 40 percent of colorectal cancer patients with mismatch repair deficiency responded to Keytruda, but there was no response among colorectal cancer patients without this genomic characteristic. (genomeweb.com)
  • Expansion into multiple subclonal populations occurs through a splitting mechanism. (wikipedia.org)
  • During this time, we discovered the existence of normal copy number variants (CNVs) in the human population ( 2 ), and I became enthralled with the question of whether genomic diversity existed within tumor cell populations. (sciencemag.org)
  • Here, selection on a few beneficial alleles occurs in one or both populations and ultimately leads to genomic regions of differentiation between groups, accelerating the evolution of genomic islands [ 6 , 9 , 10 ]. (royalsocietypublishing.org)
  • This simple result is independent of the shape of the distribution of effects among favorable and deleterious mutations, population size, and the action of clonal interference. (genetics.org)
  • Thus all else being equal, that clonal lineage having the highest mutation rate might seem best poised for long-term evolution. (genetics.org)
  • However, there is currently a large gap in knowledge regarding our understanding of clonal diversity and its role in important biological processes that occur in cancer, such as invasion, clonal evolution, metastasis, and evolving resistance to therapy. (sciencemag.org)
  • At old age, however, distinct patterns of mutations had developed. (pnas.org)
  • The key event caused by WRN gene mutation is the dysfunction of telomeres. (spandidos-publications.com)
  • Thus, the majority of wide and complex pathological phenotypes of WS may be explained in a unified manner by the cascade beginning with telomere dysfunction initiated by WRN gene mutation. (spandidos-publications.com)
  • This possibility was tested in several mouse models of carcinogen-induced RAS gene mutation and cancer induction. (cancer.gov)
  • Analysis was performed by enzymatic restriction and partial sequencing of PCR-amplified genomic segments. (nih.gov)
  • However, the size of the genomic segments of Neandertal ancestry in the Ust-Ishim individual is substantially larger than in present-day individuals. (blogspot.com)
  • From the size distribution of these segments we estimated that this individual lived about 200-400 generations after the admixture with Neandertals occurred. (blogspot.com)
  • Our results show that retained segments of Neanderthal ancestry can be used to detect ancient epidemics. (stanford.edu)
  • All xenograft-producing gliomas harbored "lineage-defining" mutations in CIC (oligodendroglioma) or TP53 (astrocytoma), and 6 of 8 additionally had activating mutations in PIK3CA or amplification of PDGFRA, MET or N-MYC. (aacrjournals.org)
  • Only IDH1 and CIC/TP53 mutations were detected in non-xenograft-forming gliomas (P=.0007). (aacrjournals.org)
  • TP53 was wild-type and the cell cycle was arrested in response to genomic stress. (iospress.com)
  • Previously observed copy number changes and TP53 mutations were very frequently observed, and almost always shared between dysplasia and carcinoma. (biomedcentral.com)
  • In particular, they showed that the rate of substitution does not increase without bound as the mutation rate increases. (genetics.org)
  • In particular, I derive the rate of adaptive substitution when favorable mutations encounter traffic problems due to both other favorable mutations and to deleterious mutations. (genetics.org)
  • the resulting amino acidic substitution, T670I, affecting the ATP/imatinib pocket of KIT, makes it insensitive to the drug. (nih.gov)
  • Interestingly, this substitution is a homologue to the T315I mutation already reported in CML, where it is responsible for acquired resistance to imatinib. (nih.gov)
  • Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark of cancer, occurring in 90% of human malignancies. (jci.org)
  • A C228T TERT promoter mutation was present, but no other mutation typical of urothelial carcinoma. (iospress.com)
  • The results obtained by aCGH confirmed other characterizations of the GBM genome. (aacrjournals.org)
  • Adaptive evolution plays a large role in generating the phenotypic diversity observed in nature, yet current methods are impractical for characterizing the molecular basis and fitness effects of large numbers of individual adaptive mutations. (stanford.edu)
  • We found only two major classes of adaptive mutations: self-diploidization and mutations in the nutrient-responsive Ras/PKA and TOR/Sch9 pathways. (stanford.edu)
  • Few studies have "quantitatively" probed how adaptive mutations result in increased fitness. (stanford.edu)
  • One of the adaptive explanations for this excess DNA is that it protects the functional DNA from mutations. (blogspot.com)
  • What this means is that the rate of mutation in functional DNA is independent of how much other DNA is being replicated. (blogspot.com)
  • The second copy contains a non-functional version of the SBDS gene that is 97% identical to the original gene, but has accumulated inactivating mutations over time. (wikipedia.org)
  • Our understanding of these networks is expanded by the use of functional genomic and proteomic approaches in addition to computational modeling. (springer.com)
  • With the advent of large-scale functional genomic and proteomic ("omic") methodologies, additional mechanistic insights into neoplasia have been uncovered. (springer.com)
  • A functional wild type blm that corrects the high SCE phenotype of BS cell resulted from this procedure. (umich.edu)
  • New genomic sequencing technologies have enabled the detection of tumor aberrations from circulating tumor DNA (ctDNA), which is DNA shed from tumor cells into the circulation. (prostatecancerfoundation.org)
  • In the current EDRN NIST Interagency agreement we have recently started a program to ensure high-quality measurements of low frequency mutations in circulating tumor DNA (ctDNA). (nist.gov)
  • Clinical tumor DNA sequencing can reveal whether a patient's lung tumor has an EGFR mutation. (cancer.gov)
  • A new study released on the medRxiv * preprint server indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - the agent responsible for the current coronavirus disease 2019 (COVID-19) pandemic - is developing multiple mutations that affect neutralization by antibodies. (news-medical.net)
  • In addition, the host may have suffered changes (genetic or otherwise) that altered the relationship between itself and the bacteria resulting in pathogenicity. (answersingenesis.org)
  • Displacement and genetic alteration (through mutation and HGT) in the post-Fall world are likely necessary for the adaptation and survival of bacteria but in some cases also have the "side effect" of pathogenicity in living things. (answersingenesis.org)