Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.Joint Instability: Lack of stability of a joint or joint prosthesis. Factors involved are intra-articular disease and integrity of extra-articular structures such as joint capsule, ligaments, and muscles.Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).Microsatellite Instability: The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Genome, Bacterial: The genetic complement of a BACTERIA as represented in its DNA.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Genome, Human: 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.Genome, Fungal: The complete gene complement contained in a set of chromosomes in a fungus.DNA Replication: The process by which a DNA molecule is duplicated.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.In Situ Hybridization, Fluorescence: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.Centrosome: The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).RecQ Helicases: A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Chromosome Fragile Sites: Specific loci that show up during KARYOTYPING as a gap (an uncondensed stretch in closer views) on a CHROMATID arm after culturing cells under specific conditions. These sites are associated with an increase in CHROMOSOME FRAGILITY. They are classified as common or rare, and by the specific culture conditions under which they develop. Fragile site loci are named by the letters "FRA" followed by a designation for the specific chromosome, and a letter which refers to which fragile site of that chromosome (e.g. FRAXA refers to fragile site A on the X chromosome. It is a rare, folic acid-sensitive fragile site associated with FRAGILE X SYNDROME.)DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Bloom Syndrome: An autosomal recessive disorder characterized by telangiectatic ERYTHEMA of the face, photosensitivity, DWARFISM and other abnormalities, and a predisposition toward developing cancer. The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Fanconi Anemia: Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)DNA Helicases: Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.Genome, Plant: The genetic complement of a plant (PLANTS) as represented in its DNA.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Chromosomes: In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Chromosome Fragility: Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Karyotyping: Mapping of the KARYOTYPE of a cell.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Sister Chromatid Exchange: An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME.Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.Homologous Recombination: An exchange of DNA between matching or similar sequences.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Telomerase: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Genome, Mitochondrial: The genetic complement of MITOCHONDRIA as represented in their DNA.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Ploidies: The degree of replication of the chromosome set in the karyotype.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Colorectal Neoplasms: Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Radiation, Ionizing: ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.Rad52 DNA Repair and Recombination Protein: A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Nijmegen Breakage Syndrome: A chromosome instability syndrome resulting from a defective response to DNA double-strand breaks. In addition to characteristic FACIES and MICROCEPHALY, patients have a range of findings including RADIOSENSITIVITY, immunodeficiency, increased cancer risk, and growth retardation. Causative mutations occur in the NBS1 gene, located on human chromosome 8q21. NBS1 codes for nibrin, the key regulator protein of the R/M/N (RAD50/MRE11/NBS1) protein complex which senses and mediates cellular response to DNA DAMAGE caused by IONIZING RADIATION.DNA, Neoplasm: DNA present in neoplastic tissue.Chromosomes, Human: Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.Ataxia Telangiectasia Mutated Proteins: A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Aurora Kinase A: An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.Telomere Homeostasis: Maintenance of TELOMERE length. During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING.) Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends.Micronuclei, Chromosome-Defective: Defective nuclei produced during the TELOPHASE of MITOSIS or MEIOSIS by lagging CHROMOSOMES or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes.Cell Line, Tumor: A cell line derived from cultured tumor cells.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Fanconi Anemia Complementation Group D2 Protein: A Fanconi anemia complementation group protein that undergoes mono-ubiquitination by FANCL PROTEIN in response to DNA DAMAGE. Also, in response to IONIZING RADIATION it can undergo PHOSPHORYLATION by ataxia telangiectasia mutated protein. Modified FANCD2 interacts with BRCA2 PROTEIN in a stable complex with CHROMATIN, and it is involved in DNA REPAIR by homologous RECOMBINATION.Genome Size: The amount of DNA (or RNA) in one copy of a genome.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.Exodeoxyribonucleases: A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.Spindle Apparatus: A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Diploidy: The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Werner Syndrome: An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.Cell Aging: The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).Genome, Archaeal: The genetic complement of an archaeal organism (ARCHAEA) as represented in its DNA.Chromosomes, Fungal: Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.Mad2 Proteins: Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.Ataxia Telangiectasia: An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.BRCA2 Protein: A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)Telomere-Binding Proteins: Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization.Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.Gene Dosage: 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.Cytogenetic Analysis: Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Telomere Shortening: The loss of some TELOMERE sequence during DNA REPLICATION of the first several base pairs of a linear DNA molecule; or from DNA DAMAGE. Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS.) Telomere shortening is involved in the progression of CELL AGING.Spectral Karyotyping: The simultaneous identification of all chromosomes from a cell by fluorescence in situ hybridization (IN SITU HYBRIDIZATION, FLUORESCENCE) with chromosome-specific florescent probes that are discerned by their different emission spectra.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Nucleic Acid Hybridization: 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)Comparative Genomic Hybridization: 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.Fanconi Anemia Complementation Group Proteins: A diverse group of proteins whose genetic MUTATIONS have been associated with the chromosomal instability syndrome FANCONI ANEMIA. Many of these proteins play important roles in protecting CELLS against OXIDATIVE STRESS.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Chromosome Disorders: Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)Chromosomal Proteins, Non-Histone: Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.MutS Homolog 2 Protein: MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Micronucleus Tests: Induction and quantitative measurement of chromosomal damage leading to the formation of micronuclei (MICRONUCLEI, CHROMOSOME-DEFECTIVE) in cells which have been exposed to genotoxic agents or IONIZING RADIATION.Fanconi Anemia Complementation Group G Protein: A Fanconi anemia complementation group protein that undergoes PHOSPHORYLATION by CDC2 PROTEIN KINASE during MITOSIS. It forms a complex with other FANCONI ANEMIA PROTEINS and helps protect CELLS from DNA DAMAGE by genotoxic agents.DNA, Fungal: Deoxyribonucleic acid that makes up the genetic material of fungi.Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Genome, Insect: The genetic complement of an insect (INSECTS) as represented in its DNA.Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.Metaphase: The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.Genome, Protozoan: The complete genetic complement contained in a set of CHROMOSOMES in a protozoan.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.DNA Sequence, Unstable: A region of DNA that is highly polymorphic and is prone to strand breaks, rearrangements or other MUTATIONS because of the nature of its sequence. These regions often harbor palindromic, or repetitive sequences (REPETITIVE SEQUENCES, NUCLEIC ACID). Variability in stability of the DNA sequence is seen at CHROMOSOME FRAGILE SITES.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.DNA Topoisomerases, Type I: DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.Gene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.DNA, Satellite: Highly repetitive DNA sequences found in HETEROCHROMATIN, mainly near centromeres. They are composed of simple sequences (very short) (see MINISATELLITE REPEATS) repeated in tandem many times to form large blocks of sequence. Additionally, following the accumulation of mutations, these blocks of repeats have been repeated in tandem themselves. The degree of repetition is on the order of 1000 to 10 million at each locus. Loci are few, usually one or two per chromosome. They were called satellites since in density gradients, they often sediment as distinct, satellite bands separate from the bulk of genomic DNA owing to a distinct BASE COMPOSITION.Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.Microcephaly: A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.Chromosomes, Human, Pair 4: A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Allelic Imbalance: A situation where one member (allele) of a gene pair is lost (LOSS OF HETEROZYGOSITY) or amplified.X-Rays: Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source.Hypoxanthine Phosphoribosyltransferase: An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8.Ligaments, Articular: Fibrous cords of CONNECTIVE TISSUE that attach bones to each other and hold together the many types of joints in the body. Articular ligaments are strong, elastic, and allow movement in only specific directions, depending on the individual joint.Fanconi Anemia Complementation Group C Protein: A Fanconi anemia complementation group protein that regulates the activities of CYTOCHROME P450 REDUCTASE and GLUTATHIONE S-TRANSFERASE. It is found predominately in the CYTOPLASM, but moves to the CELL NUCLEUS in response to FANCE PROTEIN.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesFanconi Anemia Complementation Group A Protein: A Fanconi anemia complementation group protein that is the most commonly mutated protein in FANCONI ANEMIA. It undergoes PHOSPHORYLATION by PROTEIN KINASE B and forms a complex with FANCC PROTEIN in the CELL NUCLEUS.Chromosomes, Human, Pair 17: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Cytokinesis: The process by which the CYTOPLASM of a cell is divided.Genome, Chloroplast: The genetic complement of CHLOROPLASTS as represented in their DNA.Cell Cycle Checkpoints: Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.Ankle Injuries: Harm or hurt to the ankle or ankle joint usually inflicted by an external source.DNA Mismatch Repair: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)Tetraploidy: The presence of four sets of chromosomes. It is associated with ABNORMALITIES, MULTIPLE; and MISCARRAGES.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Chromosome Deletion: Actual loss of portion of a chromosome.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single ZYGOTE, as opposed to CHIMERISM in which the different cell populations are derived from more than one zygote.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.CpG Islands: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.Shoulder Dislocation: Displacement of the HUMERUS from the SCAPULA.Cytidine Deaminase: An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Colonic Neoplasms: Tumors or cancer of the COLON.F-Box Proteins: A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Chromosomes, Human, Pair 7: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Time Factors: Elements of limited time intervals, contributing to particular results or situations.DNA-Directed DNA Polymerase: DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.Genetic Variation: Genotypic differences observed among individuals in a population.Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.Chromosomes, Human, Pair 20: A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Radiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Bystander Effect: The result of a positive or negative response (to drugs, for example) in one cell being passed onto other cells via the GAP JUNCTIONS or the intracellular milieu.Open Reading Frames: 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).Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Genes, cdc: Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Fanconi Anemia Complementation Group F Protein: A Fanconi anemia complementation group protein. It is an essential component of a nuclear core complex that protects the GENOME against CHROMOSOMAL INSTABILITY. It interacts directly with FANCG PROTEIN and helps stabilize a complex with FANCA PROTEIN and FANCC PROTEIN.Genes, Fungal: The functional hereditary units of FUNGI.Hybrid Cells: Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.Precancerous Conditions: Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)Gamma Rays: Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.Colorectal Neoplasms, Hereditary Nonpolyposis: A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.Genome, Plastid: The genetic complement of PLASTIDS as represented in their DNA.Fungal Proteins: Proteins found in any species of fungus.Antigens, Nuclear: Immunologically detectable substances found in the CELL NUCLEUS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Shoulder Joint: The articulation between the head of the HUMERUS and the glenoid cavity of the SCAPULA.
... rapid genome evolution from complex chromosomal rearrangements. Genes & Development, 27(23), 2513-30. doi:10.1101/gad. ... Centrosome dysfunction contributes to chromosome instability, chromoanagenesis, and genome reprograming in cancer. Frontiers in ... Chromoplexy refers to a class of complex DNA rearrangement observed in the genomes of cancer cells. This phenomenon was first ... Chromoplexy has been proposed as a means by which cancer genomes may undergo bursts of evolution by altering multiple cancer ...
Chromosomal rearrangement due to genome instability can cause gene amplification and deletion. Gene amplification is the ... Genomic instability can occur when the replication fork is disturbed or stalled in its migration. This can occur with ... This genomic instability means the cancer cell is actually more sensitive to DNA-damaging chemotherapy drugs. MDR proteins are ... Since cancer is a genetic disease, two genomic events underlie acquired drug resistance: Genome alterations (e.g. gene ...
These mice exhibit chromosomal instability, indicating that NHEJ is important for genome maintenance. In many organisms, Ku has ... Genome Res. 11 (8): 1365-74. doi:10.1101/gr.181001. PMC 311082 . PMID 11483577. Harris R, Esposito D, Sankar A, Maman JD, Hinks ... "DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation". Nature. 404 (6777): 510-4. doi: ...
"Aneuploidy and chromosomal instability: a vicious cycle driving cellular evolution and cancer genome chaos". Cancer and ... and genome instability. As aneuploidy and chromosome instability are hallmarks of cancer, her results on how aneuploidy fuels ... moving beyond the parts list that the human genome provides to a mechanistic understanding of the molecular events underlying ...
"A new chromosomal instability disorder: the Nijmegen breakage syndrome". Acta Paediatr Scand. 70 (4): 557-64. doi:10.1111/j. ... Full text Iijima K, Komatsu K, Matsuura S, Tauchi H (2004). "The Nijmegen breakage syndrome gene and its role in genome ... is a rare autosomal recessive congenital disorder causing chromosomal instability, probably as a result of a defect in the ... chromosome instability and fertility defects, but not the developmental defects that are typically found in other NBS patients ...
1999). "Increased ultraviolet sensitivity and chromosomal instability related to P53 function in the xeroderma pigmentosum ... Human AHCYL1 genome location and AHCYL1 gene details page in the UCSC Genome Browser. Pawlak A, Toussaint C, Lévy I, et al. ( ... 2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome ... 1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353-8. doi:10.1101/gr.7.4.353. PMC 139146 . PMID 9110174 ...
2004). "Inactivation of the RRB1-Pescadillo pathway involved in ribosome biogenesis induces chromosomal instability". Oncogene ... 2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biol. 5 (10): R84. doi:10.1186/gb-2004-5-10- ... "Entrez Gene: PES1 pescadillo homolog 1, containing BRCT domain (zebrafish)". "Toward a complete human genome sequence". Genome ... 2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome ...
While other genome instability mechanisms may also induce fold-back inversions and relatively short BFB-like copy number ... Since the role of the BFB cycle in inducing chromosomal instability in tumors has been well established, it is believed to play ... Breakage-fusion-bridge (BFB) cycle (also breakage-rejoining-bridge cycle) is a mechanism of chromosomal instability, discovered ... Gisselsson, David (May 2001). "Chromosomal Instability in Cancer: Causes and Consequences". Atlas of Genetics and Cytogenetics ...
... can lead to genome instability, cancer, and ageing. The events that lead to genome instability occur in the ... Disturbance to this phase can generate negative effects, such as inaccurate chromosomal segregation, for the upcoming mitotic ... Burhans WC1, Weinberger M (2007). "DNA replication stress, genome instability and aging". Nucleic Acids Research. 35 (22): 7545 ... Replication stress is defined as the events that take place when the genome is exposed to various stresses. It typically occurs ...
Mechanisms Genome instability-Repairs & Spatial dynamics of Chromosomal Territories vis-à- vis Genome Repair. Cellular ... Biophysics of genome repair. Computational Biology: Computational Genomics of organellar genomes; Computational analyses of ... His areas of specializations are molecular basis of genome dynamics, computational biology of genomes and protein active sites ... Rao and his collaborators of Genome Dynamics Lab are interested in mapping and understanding the promiscuity scores of protein ...
Therefore, a defective cyclin F may contribute to hypermutator phenotype and chromosomal instability through RRM2, CP110, and ... Whole-genome linkage analysis and genome sequencing identified CCNF to be linked to both familial and sporadic ALS patients. In ... Human CCNF genome location and CCNF gene details page in the UCSC Genome Browser.. ... Cyclin F interacts with RRM2 to control the production of dNTPs in the cell to avoid genomic instability and frequency of ...
These authors noted that repression of ERCC1 (by HGMA2) can reduce DNA repair, leading to increased genome instability. ERCC1 ... This gene encodes a protein that belongs to the non-histone chromosomal high-mobility group (HMG) protein family. HMG proteins ... These properties implicate HMGA2 in the promotion of genome instability and tumorigenesis. Summer et al. found that HGMA2 ... Zha L, Wang Z, Tang W, Zhang N, Liao G, Huang Z (2012). "Genome-wide analysis of HMGA2 transcription factor binding sites by ...
Genome instabilityEdit. Cancer cells generally have severe chromosomal abnormalities which worsen as the disease progresses. ... See genome instability) InflammationEdit. Recent discoveries have highlighted the role of local chronic inflammation in ...
Genome instability and cancer[edit]. SMC1A also takes part in DNA repair. The down-regulation of SMC1A causes genome ... December 2014). "Mutant cohesin drives chromosomal instability in early colorectal adenomas". Human Molecular Genetics. 23 (25 ... "Genome Research. 23 (12): 2066-77. doi:10.1101/gr.161620.113. PMC 3847776. PMID 24002784.. ... Yatskevich S, Rhodes J, Nasmyth K (December 2019). "Organization of Chromosomal DNA by SMC Complexes". Annual Review of ...
... chromosomal abnormalities, and genome instability. These data demonstrated Mdm2-induced genome instability can be mediated ... Cahilly-Snyder L, Yang-Feng T, Francke U, George DL (May 1987). "Molecular analysis and chromosomal mapping of amplified genes ...
Chromosomal instability resulting from dysfunctional caretaker genes is the most common form of genetic instability that leads ... Caretaker genes provide genome stability by preventing the accumulation of these mutations. Factors that contribute to genome ... mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising from improper ... Michor, F; Iwasa, Y; Komarova, N. L.; Nowak, M. A. (2003). "Local regulation of homeostasis favors chromosomal instability". ...
"The human protein kinase gene PKX1 on Xp22.3 displays Xp/Yp homology and is a site of chromosomal instability". Hum Mol Genet. ... 2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome ... 1999). "A selective difference between human Y-chromosomal DNA haplotypes". Curr. Biol. 8 (25): 1391-4. doi:10.1016/S0960-9822( ...
Chromosomal instability (CIN) which have allelic imbalance at a number of chromosomal loci, including 5q, 8p, 17p, and 18q (Fig ... The arrays themselves can be genome-wide (probes distributed over the entire genome) or targeted (probes for genomic regions ... In addition, virtual karyotypes generate a relative copy number normalized against a diploid genome, so tetraploid genomes will ... "Whole genome SNP arrays as a potential diagnostic tool for the detection of characteristic chromosomal aberrations in renal ...
Genome instability can refer to the accumulation of extra copies of DNA/chromosomes, chromosomal translocations, chromosomal ... expression and chromosomal assignment to 11p15". Biochem. Biophys. Res. Commun. 180 (3): 1241-50. doi:10.1016/S0006-291X(05) ...
Telomeres are necessary at chromosome ends to prevent DNA-damage responses as well as genome instability. To this day, the Q- ... "Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc-/- mice with short telomeres." ... Furthermore, the intra-chromosomal distribution of telomere length in p-arms versus q-arms can be measured. Data from different ... The slide is then placed into a preheated oven where the chromosomal DNA in the cell is denatured at 80°C for several minutes. ...
See genome instability) Recent discoveries have highlighted the role of local chronic inflammation in inducing many types of ... See cancer immunology) Cancer cells generally have severe chromosomal abnormalities which worsen as the disease progresses. ... genome instability, and (4) inflammation. Cancer cells have defects in the control mechanisms that govern how often they divide ...
Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human ... Green, B. M.; Morreale, RJ; Ozaydin, B; Derisi, JL; Li, JJ (2006). "Genome-wide Mapping of DNA Synthesis in Saccharomyces ... Further, these studies indicate that rereplication can result in an increase in aneuploidy, chromosomal fusions, and DNA breaks ... To prevent rereplication, eukaryotic cells have evolved multiple, overlapping mechanisms to inhibit chromosomal DNA from being ...
... that ubiquitously affect the integrity of the genome. Complex chromosomal rearrangements (CCR) are rarely seen in the general ... This instability is usually due to the propensity of these regions to misalign during DNA repair, exacerbated by defects of the ... Structural chromosomal abnormalities are estimated to occur in around 0.5% of newborn infants. Some chromosomal regions are ... In genetics, a chromosomal rearrangement is a type of chromosome abnormality involving a change in the structure of the native ...
... can refer to the accumulation of extra copies of DNA or chromosomes, chromosomal translocations, chromosomal ... Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome ... Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in ... also genetic instability, or even chromosomic instability). The process of genome instability often leads to a situation of ...
Wright, Eric G. (1 January 1999). "Inherited and inducible chromosomal instability: a fragile bridge between genome integrity ... which may result in chromosomal instability. Chromosomal instability can in turn cause cancer. However, chromosomal instability ... the majority of colorectal and other solid cancers have chromosomal instability (CIN). This shows that chromosomal instability ... Chromosomal instability (CIN) is a type of genomic instability in which chromosomes are unstable, such that either whole ...
... (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy. The sources of genome instability have only recently begun to be elucidated. A high frequency of externally caused DNA damage can be one source of genome instability since DNA damages can cause ...
... refers to the structure of sequences for eukaryotic chromosomes. Some fine sequences are included in more than one class, so the classification listed is not intended to be completely separate. Some sequences are required for a properly functioning chromosome: Centromere: Used during cell division as the attachment point for the spindle fibers. Telomere: Used to maintain chromosomal integrity by capping off the ends of the linear chromosomes. This region is a microsatellite, but its function is more specific than a simple tandem repeat. Throughout the eukaryotic kingdom, the overall structure of chromosome ends is conserved and is characterized by the telomeric tract - a series of short G-rich repeats. This is succeeded by an extensive subtelomeric region consisting of various types and lengths of repeats - the telomere associated sequences (TAS). These regions are generally low in gene density, low in transcription, low in recombination, late replicating, ...
Changes in the genome that allow uncontrolled cell proliferation or cell immortality are responsible for cancer. It is believed that the major changes in the genome that lead to cancer arise from mutations in tumor suppressor genes. In 1997, Kinzler and Bert Vogelstein grouped these cancer susceptibility genes into two classes: "caretakers" and "gatekeepers". In 2004, a third classification of tumor suppressor genes was proposed by Franziska Michor, Yoh Iwasa, and Martin Nowak; "landscaper" genes. Caretaker genes encode products that stabilize the genome. Fundamentally, mutations in caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of genomic instability: mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising ...
... (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy. The sources of genome instability have only recently begun to be elucidated. A high frequency of externally caused DNA damage can be one source of genome instability since DNA damages can cause ...
Changes in the genome that allow uncontrolled cell proliferation or cell immortality are responsible for cancer. It is believed that the major changes in the genome that lead to cancer arise from mutations in tumor suppressor genes. In 1997, Kinzler and Bert Vogelstein grouped these cancer susceptibility genes into two classes: "caretakers" and "gatekeepers". In 2004, a third classification of tumor suppressor genes was proposed by Franziska Michor, Yoh Iwasa, and Martin Nowak; "landscaper" genes. Caretaker genes encode products that stabilize the genome. Fundamentally, mutations in caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of genomic instability: mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising ...
... is the process by which a genome changes in structure (sequence) or size over time. The study of genome evolution involves multiple fields such as structural analysis of the genome, the study of genomic parasites, gene and ancient genome duplications, polyploidy, and comparative genomics. Genome evolution is a constantly changing and evolving field due to the steadily growing number of sequenced genomes, both prokaryotic and eukaryotic, available to the scientific community and the public at large. Since the first sequenced genomes became available in the late 1970s, scientists have been using comparative genomics to study the differences and similarities between various genomes. Genome sequencing has progressed over time to include more and more complex genomes including the eventual sequencing of the entire human ...
The Chimpanzee Genome Project is an effort to determine the DNA sequence of the Chimpanzee genome. It is expected that by comparing the genomes of humans and other apes, it will be possible to better understand what makes humans distinct from other species from a genetic perspective. It will also aid in the study of diseases that affect (or, conversely, do not affect) various primate species. Human and chimpanzee chromosomes are very similar. The primary difference is that humans have one fewer pair of chromosomes than do other great apes. Humans have 23 pairs of chromosomes and other great apes have 24 pairs of chromosomes. In the human evolutionary lineage, two ancestral ape chromosomes fused at their telomeres, producing human chromosome 2. There are nine other major chromosomal differences between chimpanzees and humans: chromosome segment inversions on human chromosomes 1, 4, 5, 9, 12, 15, 16, 17, and 18. After the completion of the ...
The genome of a female Hereford cow has been sequenced by the Bovine Genome Sequencing and Analysis Consortium, a team of researchers led by the National Institutes of Health and the U.S. Department of Agriculture.[1] It is one of the largest genomes ever sequenced. The results, published in the journal Science on April 24, 2009,[2] are likely to have a major impact on livestock breeding.[3] They were obtained by more than 300 scientists in 25 countries after six years of effort.. The size of the bovine genome is 3 Gb (3 billion base pairs). It contains approximately 22,000 genes of which 14,000 are common to all mammalian species. Bovines share 80 percent of their genes with humans; cows are less similar to humans than rodents (humans and rodents belong to the clade of Supraprimates). They also have about 1,000 genes shared with dogs and rodents but not identified in humans.[4]. The charting of key DNA differences, also known as haplotypes, ...
Genom (Ing. genome), dalam genetika dan biologi molekular modern, adalah keseluruhan informasi genetik yang dimiliki suatu sel atau organisme, atau khususnya keseluruhan asam nukleat yang memuat informasi tersebut.[2] Secara fisik, genom dapat terbagi menjadi molekul-molekul asam nukleat yang berbeda (sebagai kromosom atau plasmid), sementara secara fungsi, genom dapat terbagi menjadi gen-gen.[3] Istilah genom diperkenalkan oleh Hans Winkler dari Universitas Hamburg, Jerman, pada tahun 1920, mungkin sebagai gabungan dari kata gen dan kromosom atau dimaksudkan untuk menyatakan kumpulan gen.[4]. Setiap organisme memiliki genom yang mengandung informasi biologis yang diperlukan untuk membangun tubuhnya dan mempertahankan hidupnya serta diwariskan ke generasi berikutnya.[5] Dengan sejumlah interaksi kompleks, urutan nukleotida komponen penyusun asam nukleat digunakan untuk membuat semua protein pada suatu organisme pada waktu dan tempat yang sesuai. Protein ini menjadi komponen pembentuk tubuh ...
Different virus families have different levels of ability to alter their genomes and trick the immune system into not recognizing. Some viruses have relatively unchanging genomes like paramyxoviruses while others like influenza have rapidly changing genomes that inhibit our ability to create long lasting vaccines against the disease. Viruses in general have much faster rate of mutation of their genomes than human or bacterial cells. In general viruses with shorter genomes have faster rates of mutation than longer genomes since they have a faster rate of replication.[15] It was classically thought that viruses with an RNA genome always had a faster rate of antigenic variation than those with a DNA genome because RNA polymerase lacks a mechanism for checking for mistakes in translation but recent work by Duffy et al. shows that some DNA viruses have the same high rates of ...
Mae'r genom dynol yn cynnwys tri biliwn pâr o fasau, sy'n codio am tua 20,000-25,000 genyn. Ond does dim llawer i'w ganfod o wybod dilyniant y genom ar ben ei hun heb wybod hefyd am leoliadau genynau a'r cysylltiadau rhyngddynt. Mae modd anodi'r lleoliadau yma â llaw, gan ddefnyddio data o arbrofion wedi eu cyhoeddi mewn cyfnodolion gwyddonol. Fodd bynnag, mae hyn yn waith araf a dyfal. Opsiwn arall yw anodiad awtomatig - defnyddio pŵer cyfrifiadurol i gymharu dilyniannau protein a DNA. Yn y prosiect Ensembl, mae data dilyniant genom yn cael ei fwydo i mewn i system anodi gyfrifiadurol (cyfres o sgriptiau yn yr iaith gyfrifiadurol Perl), gan greu casgliad o leoliadau genynau rhagweledig a'u harbed mewn cronfa ddata ar gyfer eu hymdrin ymhellach. Mae Ensembl yn rhyddhau'r holl wybodaeth i'w defnyddio gan y gymuned ymchwil fyd-eang. Gall unrhyw un lawrlwytho data a chôd y prosiect,[3] ac mae gweinydd cronfa ddata agored ar gael er mwyn cysylltu o bell. Mae gwefan Ensembl hefyd yn cynnwys ...
Balstoties uz DNS pētījumiem, zinātnieki uzskata, ka Āfrikas cilvēkpērtiķu apakšdzimta sāka dalīties ciltīs ne ātrāk kā pirms 8 miljoniem gadiem. Mūsdienās šimpanzes un gorillas mājo tropu mežos ar skābu augsni, kurā ļoti reti saglabājas fosilijas. Lai arī nav atklāta neviena gorillu fosilija, Austrumāfrikā Kenijā ir atklāti 4 šimpanžu zobi, kas ir 500 000 gadus veci. Lielā Rifta ielejā, kur atrada šos zobus, ir atrastas daudzas hominīnu fosilijas.[5]. Ģenētiski šimpanzes ir tuvāk radniecīgas cilvēkiem, nekā gorillām. Gorillu genoms sakrīt ar cilvēka genomu par 95%, bet šimpanžu genoms sakrīt par 98%.[6][7] Pirmā no kopējā priekšteča nodalījās gorillu cilts, pēc tam šimpanzes.[1] Uzskata, ka cilvēks no šimpanzēm pilnībā bija atdalījies pirms 2,5 miljoniem gadu.[8]. ...
Prokineticinski receptor 2 (PKR2), je G-protein spregnuti receptor kodiran PROKR2 genom kod ljudi.[1] Prokineticini su sekretivni proteini koji mogu da promovišu angiogenezu i da indukuju jake kontrakcije gastrointestinalnih glatkih mišića. Protein kodiran ovim genom je integralni membranski protein i G protein-spregnuti receptor za prokineticine. Ovaj protein je sličan po aminokiselinskoj sekvenci sa GPR73, koji je takođe G protein-spregnuti receptor za prokineticine.[1] ...
Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution. Sally M. ... Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution ... Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution ... Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution ...
Chromosomal Instability and Rearrangement Were Not Randomly Distributed Across the Genome.. Chromosome instability began as ... Chromosomal Instability Was Not Equal Across the Genome.. Thirty-eight S10:11 lines could be karyotyped, and only two lines ( ... Chromosomal Dosage Requirements Compensated for Chromosomal Instability.. In mammals and plants, changes in gene dosage ... Using a C genome-specific BAC clone as a probe, the frequency of chromosome translocations from the C genome to the A genome ...
Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible ... Clearly, genetic instability and clonal evolution are driving forces for leukemic transformation. Understanding the mechanisms ... Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to ... and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and ...
... this is the first study illustrating the prognostic value of chromosomal instability derived from cfDNA in MBC. ... Low-coverage whole-genome sequencing of cfDNA was performed to generate the chromosomal instability represented by chromosomal ... Genome-wide chromosomal instability by cell-free DNA sequencing predicts survival in patients with metastatic breast cancer ... Genome-wide chromosomal instability by cell-free DNA sequencing predicts survival in patients with metastatic breast cancer ...
Consistent molecular mechanisms responsible for the CIN+ phenotype and hence means to target this pattern of genome instability ... Chromosomal Instability Confers Intrinsic Multidrug Resistance. Alvin J.X. Lee, David Endesfelder, Andrew J. Rowan, Axel ... Chromosomal Instability Confers Intrinsic Multidrug Resistance. Alvin J.X. Lee, David Endesfelder, Andrew J. Rowan, Axel ... Chromosomal Instability Confers Intrinsic Multidrug Resistance. Alvin J.X. Lee, David Endesfelder, Andrew J. Rowan, Axel ...
This further emphasizes the importance of chromosomal instability in colorectal adenoma-to-carcinoma progression. Chromosomal ... P values , 1e-5 were considered significant at the genome-wide level. This procedure yielded key genes for five out of six ... From the "chromosomal instability" gene set, AURKA and TPX2 (targeting protein for XKLP2) have been reported to interact with ... For two such key genes for which good antibodies were available, AURKA (chromosomal instability gene set) and PDGFRB (invasion ...
Interpreting Genome Sequence Information from Telomere to Telomere, Chromosomal Instability; Somatic Cell Recombination and ... LabRoots Produces 7th Annual Genetics & Genomics Virtual Conference Showcasing the Newest Advances in Genome Editing and ... The event includes the following tracks, Progress in Genome Editing Including Single Base Editing and Application; ... will be presenting on Interpreting the Zero Dollar Genome via Base Editing, Organoids & in Situ Omics. Church is a pioneer in ...
Global hypomethylation of genome. Chromosomal instability and reactivation of repetitive genomic sequences. [20]. ... Apart from the global hypomethylation of genome, aberrations in methylation of oncogenes/proto-oncogenes as well as tumor ... instability of the compounds in the acidic conditions of the tumor environment [77,80]. The drugs gained clinical approval ... deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol. ...
... for homologous recombination and gross chromosomal rearrangements (GCR) in... ... Inverted repeats Secondary structures Genome instability DSB detection Gross chromosomal rearrangements This is a preview of ... Here, we provide protocols for studying chromosomal instability triggered by hairpin- and cruciform-forming palindromic ... any DNA sequence motif can be assessed for its breakage potential and ability to drive genome instability. ...
Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet 2008;9:204-17. ... The chromosomal instability phenotype initiated by partial Bre1b knockdown (shBre1b1 cells grown without doxycycline) for 3 ... A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol Cell 2009;35:228- ... Deficiency in Mammalian Histone H2B Ubiquitin Ligase Bre1 (Rnf20/Rnf40) Leads to Replication Stress and Chromosomal Instability ...
Background: Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is ... CENPA Overexpression Promotes Genome Instability in pRb-depleted Human Cells Mol Cancer. 2009 Dec 10;8:119. doi: 10.1186/1476- ... Functional inactivation of the Retinoblastoma protein (pRb) has been indicated as a cause promoting chromosomal instability as ...
C-terminal PTEN mutants disrupt the association of PTEN with centromeres and cause centromeric instability. Furthermore, Pten ... Mouse Genome Informatics (MGI). Miscellaneous. *NCI CPTC Antibody Characterization Program. *NCI CPTC Antibody Characterization ... Essential role for nuclear PTEN in maintaining chromosomal integrity.. Shen WH1, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, ... We report a nuclear function for PTEN in controlling chromosomal integrity. Disruption of Pten leads to extensive centromere ...
Blooms and Werners syndrome cell lines both exhibit chromosomal instability. sgslΔ strains show mitotic hyperrecombination, ... Although there was an increase in subtelomeric Y instability in sgs1Δ strains due to hyperrecombination, no evidence was found ... SGS1, a Homologue of the Blooms and Werners Syndrome Genes, Is Required for Maintenance of Genome Stability in Saccharomyces ... We conclude that the SGS1 gene product is involved in the maintenance of genome stability in S. cermisiae. ...
Others within the genome-instability camp think that much bigger changes are needed, such as gains or losses of whole ... Research into how chromosomal derangements might arise is also lending support for the idea of an early role for genomic ... "If you want to understand cancer, you need to know the answers" to the many questions about the role genome instability plays ... DNA-repair machinery can also malfunction and lead to genome instability. Genes linked to such defects are indicated in red. ...
HL patients and survivors present persistent chromosomal instability, including nonclonal chromosomal aberrations. The ... Both regimens have long-term effects in somatic cells, presenting nonclonal chromosomal aberrations and genomic chaos in a ... frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example ... is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal ...
Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution. Cancer Discov, 4 ... Indeed, consortia such as TCGA (the Cancer Genome Atlas) and ICGC (the International Cancer Genome Consortium) have made ... Cancer Genome Evolution Research Group. Group Leader: Dr Nicholas McGranahan Research. Our lab focuses on using computational ... The cancer genome contains within it an archaeological record about its past, with each genomic event representing a scar from ...
By sequencing the nearly identical genomes from monozygotic twins and considering shared SNVs as true variants and discordant ... Distinguishing single-nucleotide variants (SNVs) from errors in whole-genome sequences remains challenging. Here we describe a ... use the genome sequences of monozygotic twins to evaluate the performance of filters individually and in combination, leading ... to reliably identify somatic mutations in a highly rearranged tumor and to identify variants in the NA19240 HapMap genome ...
Genome instability can refer to the accumulation of extra copies of DNA or chromosomes, chromosomal translocations, chromosomal ... Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome ... Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in ... also genetic instability, or even chromosomic instability). The process of genome instability often leads to a situation of ...
Genome-wide analyses show that cluster genes changing in expression are enriched for cohesin-SMC1B binding. ... In addition, SMC1B safeguards genome stability following irradiation whereas its ablation has no effect on chromosome ... regulates gene expression and preserves genome stability. In mammalian cells, the mitotic cohesin complex consists of two ... Mutant cohesin drives chromosomal instability in early colorectal adenomas. Hum Mol Genet 23, 6773-8 (2014). ...
Fast and accurate mutation detection in whole genome sequences of multiple isogenic samples with IsoMut. Publication: Research ... basal-like phenotype and displayed the highest chromosomal structural complexity and chromosomal numerical instability. We ... Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer. Publication: Research - peer-review › ... Chromosomal instability (CIN) is associated with poor prognosis in human cancer. However, in certain animal tumor models ...
2003) Chromosomal Instability and Aging: Basic Science and Clinical Implications (CRC, Boca Raton, FL).. ... where a genome is paired to the most similar phenotypic profile, for m. N. , each genome was paired to one and only one ... and a mapping of genomes, ϕ. P. :. G. →. E. P. , into a common D. -dimensional embedding-space E. P. ∈. R. D. . As mappings, we ... genome data may be linked to metadata through online social networks and services, thus complicating the protection of genome ...
In a study last year, researchers from Pellmans lab used genome-wide approaches to discover how this clustering occurs. In the ... According to Pellman, chromosomal instability, it turns out, "is actually a side effect of the cells ability to cluster their ... Link Unraveled Between Chromosomal Instability, Centrosome Defects In Cancer Cells. by Sam Savage ... but the correction process creates other problems that result in chromosomal instability." ...
Chromosomal instability correlates with genome-wide dna demethylation in human primary colorectal cancers. Cancer Res 2006, 66 ... Mbd-isolated genome sequencing provides a high-throughput and comprehensive survey of DNA methylation in the human genome. ... Genome-wide approaches can be broadly grouped into three strategies according to how DNA is modified before it is interrogated ... Wang, Y.; Leung, F.C. An evaluation of new criteria for CPG islands in the human genome as gene markers. Bioinformatics 2004, ...
The Contribution of Radiation-Induced Large Deletion of the Genome to Chromosomal Instability ... The Contribution of Radiation-Induced Large Deletion of the Genome to Chromosomal Instability. Radiat. Res. 171, 198-203 (2009 ... Because no induction of X-chromosomal instability was observed in clones that lacked such large deletions, the present findings ... GM638 cells were irradiated with 3 Gy of X rays, and chromosomal aberrations were analyzed in clones derived after irradiation ...
2013 Aneuploidy and chromosomal instability: a vicious cycle driving cellular evolution and cancer genome chaos. Cancer ... The most frequently identified mutation is a chromosomal duplication. Analysis of genome-wide sequencing coverage indicated ... PCR-mediated chromosomal deletion. Similar to Sugiyama et al. (2008), PCR-mediated chromosomal deletion (PCD) was implemented ... integrated these differences into the BY genome, and then remapped reads for that progenitor to the modified genome sequence. ...
  • Consistent molecular mechanisms responsible for the CIN + phenotype and hence means to target this pattern of genome instability in colorectal and other solid tumors remain poorly defined. (aacrjournals.org)
  • Microarray mRNA expression studies allow to compare gene expression at a genome-wide level and to explore the transcriptional programs that are turned on or off in tumors during progression from normal through premalignant stages to cancer. (springer.com)
  • To better understand this seemingly contradictory relationship between CIN and cancer cell biological fitness and its relationship with clinical outcome, we applied the CIN70 expression signature, which correlates with DNA-based measures of structural chromosomal complexity and numerical CIN in vivo, to gene expression profiles of 2,125 breast tumors from 13 published cohorts. (dtu.dk)
  • Tumors with extreme CIN, defined as the highest quartile CIN70 score, were predominantly of the estrogen receptor negative (ER-), basal-like phenotype and displayed the highest chromosomal structural complexity and chromosomal numerical instability. (dtu.dk)
  • Analyses of single tumor entities revealed that colorectal, gastric and endometrial cancers have similar highly methylated subgroups that are associated with tumors with microsatellite instability and hypermethylation of the MLH1 promoter. (biomedcentral.com)
  • Spontaneous chromosome missegregation events in aneuploid cells promote chromosomal instability (CIN) that may contribute to the acquisition of multidrug resistance in vitro and heighten risk for tumor relapse in animal models. (aacrjournals.org)
  • Given that Bre1 affects multiple functions involved in genome maintenance, it is plausible that Bre1 homologs have a major tumor-suppressing role in higher organisms. (aacrjournals.org)
  • To prove that our filtering strategy was highly efficient, we subsequently applied it using different sequencing technologies to various whole genomes, including those of monozygotic twins, a tumor-normal pair and a HapMap subject. (nature.com)
  • When study lead author Neil Ganem, PhD, of Dana-Farber used newly developed microscope equipment to watch living cancer cells for a week or more, he found that not only were such abnormal divisions quite rare, but the resulting daughter cells were so discombobulated by their chromosomal quirks, they generally survived for only a few days "" far too briefly to deliver abnormal chromosome content to a tumor. (redorbit.com)
  • In order to persist in proliferating tumor cells, the viral genome replicates once per cell cycle and then segregates to daughter cell nuclei. (frontiersin.org)
  • To identify candidate drivers involved in oncogenesis and tumor evolution, we conduct an extensive genome sequencing analysis of metastatic progression in a diffuse gastric cancer. (biomedcentral.com)
  • Remarkable progress in precision medicine and immune-oncology, driven by extraordinary recent advances in genome-wide sequencing, big-data analytics, blood-based technologies, and deep understanding of the tumor immune microenvironment (TME), has provided unprecedented possibilities to study the biology of premalignancy. (aacrjournals.org)
  • With array-based comparative genomic hybridization (aCGH) a genome wide profile of the copy number alterations in the tumor can be obtained. (biomedcentral.com)
  • We are particularly interested in understanding how DNA damage is identified and resolved during DNA replication, when the genome is particularly vulnerable due to stalling of the replication fork at naturally arising and induced DNA lesions, structures or protein-DNA complexes. (stanford.edu)
  • In 2017, co-founder Tom Maniatis was appointed Scientific Director and Chief Executive Officer of the New York Genome Center. (wikipedia.org)
  • During latent infection, the viral genome exists as a multi copy, extrachromosomal, circular episome (plasmid). (frontiersin.org)
  • Different assays are now available that can detect small amounts of HPV DNA, quantify the amount of viral DNA in clinical specimens, identify a broad spectrum of genital and cutaneous HPV types, test for selected HPV types and localize the viral genome and viral transcripts to individual cells. (inchem.org)
  • The advent of next-generation sequencing, coupled with its exponential cost decrease, has led to the sequencing of exomes and entire cancer genomes at a large-scale. (ucl.ac.uk)
  • Full sequencing of breast cancer genomes could potentially refine classification and give a more complete picture of the mutational profile of cancer and thus aid therapy decisions. (biomedcentral.com)
  • We are now in the exciting era of full sequencing of cancer genomes. (biomedcentral.com)
  • One of the world's leading geneticists and keynote speaker, George Church, Ph.D., Professor of Genetics, Director of the Center for Computational Genetics, Harvard Medical School, will be presenting on Interpreting the Zero Dollar Genome via Base Editing, Organoids & in Situ Omics. (prweb.com)
  • Our data demonstrate that defects in double-strand break repair lead to an increase in genome instability, while drug resistance arises more rapidly in C. albicans strains lacking mismatch repair proteins or proteins central to double-strand break repair. (asm.org)
  • For example, in mice, if there is a deficiency for SIRT6 (family member of Sir2), the mice experience genomic instability, metabolic defects, and degenerative pathologies in terms of aging, everything opposite of the roles of Sir2. (wikibooks.org)
  • Then, we detail an approach to monitor chromosomal DSBs by Southern blot hybridization. (springer.com)
  • DNA double-strand breaks (DSBs) are the most problematic result of radiation exposure and are known to greatly stimulate genome rearrangement. (cityofhope.org)
  • By sequencing the nearly identical genomes from monozygotic twins and considering shared SNVs as 'true variants' and discordant SNVs as 'errors', we optimized thresholds for 12 individual filters and assessed which of the 1,048 filter combinations were effective in terms of sensitivity and specificity. (nature.com)
  • We recently used genome sequencing to study the evolutionary history of the Darwin's finches. (diva-portal.org)
  • He developed the first methods for the first genome sequence & dramatic cost reductions since then (down from $3 billion to $600), contributing to nearly all "next generation sequencing" methods and companies. (labroots.com)
  • We used formaldehyde assisted isolation of regulatory elements (FAIRE) to map genome-wide chromatin conformations. (wiley.com)
  • In contrast to growing cells, whose genomes are rich with features of both open and closed chromatin, FAIRE profiles of senescent cells are significantly smoothened. (wiley.com)
  • However, only for topics under supervision of Dr. V. Guryev, who works on bioinformatic aspects of ageing, having taken one or more of the following courses is strongly recommended: Programmeren Lw or Wiskunde Lw or Humane genetica en genomics or Bioinformatica or Computational molecular biology research. (rug.nl)
  • Using large-scale genome variation cohorts to decipher the molecular mechanism of cancer. (embl.de)
  • Zhang Y, Shishkin AA, Nishida Y, Marcinkowski-Desmond D, Saini N, Volkov KV, Mirkin SM, Lobachev KS (2012) Genome-wide screen identifies pathways that govern GAA/TTC repeat fragility and expansions in dividing and nondividing yeast cells. (springer.com)
  • In an update published in 2011 ("Hallmarks of cancer: the next generation"), Weinberg and Hanahan proposed two new hallmarks: (1) abnormal metabolic pathways, (2) evading the immune system and two enabling characteristics: (1) genome instability, and (2) inflammation. (wikipedia.org)