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.
Genetic mechanisms that allow GENES to be expressed at a similar level irrespective of their GENE DOSAGE. This term is usually used in discussing genes that lie on the SEX CHROMOSOMES. Because the sex chromosomes are only partially homologous, there is a different copy number, i.e., dosage, of these genes in males vs. females. In DROSOPHILA, dosage compensation is accomplished by hypertranscription of genes located on the X CHROMOSOME. In mammals, dosage compensation of X chromosome genes is accomplished by random X CHROMOSOME INACTIVATION of one of the two X chromosomes in the female.
Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
Processes occurring in various organisms by which new genes are copied. Gene duplication may result in a MULTIGENE FAMILY; supergenes or PSEUDOGENES.
An individual having different alleles at one or more loci regarding a specific character.
A dosage compensation process occurring at an early embryonic stage in mammalian development whereby, at random, one X CHROMOSOME of the pair is repressed in the somatic cells of females.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
The possession of a third chromosome of any one type in an otherwise diploid cell.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
A copy number variation that results in reduced GENE DOSAGE due to any loss-of-function mutation. The loss of heterozygosity is associated with abnormal phenotypes or diseased states because the remaining gene is insufficient.
An individual in which both alleles at a given locus are identical.
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.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
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).
The functional hereditary units of FUNGI.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
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.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Any method used for determining the location of and relative distances between genes on a chromosome.
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
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.
Genes that are located on the X CHROMOSOME.
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.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Congenital absence of or defects in structures of the eye; may also be hereditary.
A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)
Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.
Mice bearing mutant genes which are phenotypically expressed in the animals.
The homologous chromosomes that are dissimilar in the heterogametic sex. There are the X CHROMOSOME, the Y CHROMOSOME, and the W, Z chromosomes (in animals in which the female is the heterogametic sex (the silkworm moth Bombyx mori, for example)). In such cases the W chromosome is the female-determining and the male is ZZ. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.
The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
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.
A group of slowly progressive inherited disorders affecting motor and sensory peripheral nerves. Subtypes include HMSNs I-VII. HMSN I and II both refer to CHARCOT-MARIE-TOOTH DISEASE. HMSN III refers to hypertrophic neuropathy of infancy. HMSN IV refers to REFSUM DISEASE. HMSN V refers to a condition marked by a hereditary motor and sensory neuropathy associated with spastic paraplegia (see SPASTIC PARAPLEGIA, HEREDITARY). HMSN VI refers to HMSN associated with an inherited optic atrophy (OPTIC ATROPHIES, HEREDITARY), and HMSN VII refers to HMSN associated with retinitis pigmentosa. (From Adams et al., Principles of Neurology, 6th ed, p1343)
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
A paired box transcription factor that is essential for ORGANOGENESIS of the CENTRAL NERVOUS SYSTEM and KIDNEY.
The degree of replication of the chromosome set in the karyotype.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
Structures within the nucleus of bacterial cells consisting of or containing DNA, which carry genetic information essential to the cell.
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.
The functional hereditary units of BACTERIA.
A SMN complex protein that is essential for the function of the SMN protein complex. In humans the protein is encoded by a single gene found near the inversion telomere of a large inverted region of CHROMOSOME 5. Mutations in the gene coding for survival of motor neuron 1 protein may result in SPINAL MUSCULAR ATROPHIES OF CHILDHOOD.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
The chromosomal constitution of cells, in which each type of CHROMOSOME is represented once. Symbol: N.
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.
A complex of proteins that assemble the SNRNP CORE PROTEINS into a core structure that surrounds a highly conserved RNA sequence found in SMALL NUCLEAR RNA. They are found localized in the GEMINI OF COILED BODIES and in the CYTOPLASM. The SMN complex is named after the Survival of Motor Neuron Complex Protein 1, which is a critical component of the complex.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
A SMN complex protein that is closely-related to SURVIVAL OF MOTOR NEURON 1 PROTEIN. In humans, the protein is encoded by an often duplicated gene found near the inversion centromere of a large inverted region of CHROMOSOME 5.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
MYELIN-specific proteins that play a structural or regulatory role in the genesis and maintenance of the lamellar MYELIN SHEATH structure.
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)
Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.
Biochemical identification of mutational changes in a nucleotide sequence.
A method of detecting gene mutation by mixing PCR-amplified mutant and wild-type DNA followed by denaturation and reannealing. The resultant products are resolved by gel electrophoresis, with single base substitutions detectable under optimal electrophoretic conditions and gel formulations. Large base pair mismatches may also be analyzed by using electron microscopy to visualize heteroduplex regions.
A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin.
Congenital syndrome characterized by a wide spectrum of characteristics including the absence of the THYMUS and PARATHYROID GLANDS resulting in T-cell immunodeficiency, HYPOCALCEMIA, defects in the outflow tract of the heart, and craniofacial anomalies.
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.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
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.
The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.
Laboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template.
Deletion of sequences of nucleic acids from the genetic material of an individual.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
Proteins found in any species of fungus.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. (Dorland, 28th ed)
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
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)
Actual loss of portion of a chromosome.
A family of transcription factors that control EMBRYONIC DEVELOPMENT within a variety of cell lineages. They are characterized by a highly conserved paired DNA-binding domain that was first identified in DROSOPHILA segmentation genes.
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.
Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.
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).
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.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
In bacteria, a group of metabolically related genes, with a common promoter, whose transcription into a single polycistronic MESSENGER RNA is under the control of an OPERATOR REGION.
A group of disorders marked by progressive degeneration of motor neurons in the spinal cord resulting in weakness and muscular atrophy, usually without evidence of injury to the corticospinal tracts. Diseases in this category include Werdnig-Hoffmann disease and later onset SPINAL MUSCULAR ATROPHIES OF CHILDHOOD, most of which are hereditary. (Adams et al., Principles of Neurology, 6th ed, p1089)
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.
Identification of genetic carriers for a given trait.
Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.
Math calculations done for preparing appropriate doses of medicines, taking into account conversions of WEIGHTS AND MEASURES. Mistakes are one of the sources of MEDICATION ERRORS.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
RNA which does not code for protein but has some enzymatic, structural or regulatory function. Although ribosomal RNA (RNA, RIBOSOMAL) and transfer RNA (RNA, TRANSFER) are also untranslated RNAs they are not included in this scope.
Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Mapping of the KARYOTYPE of a cell.
Complex nucleoprotein structures which contain the genomic DNA and are part of the CELL NUCLEUS of MAMMALS.
A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)
Proteins found in any species of bacterium.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
A specific pair of GROUP C CHROMSOMES of the human chromosome classification.
The genetic unit consisting of three structural genes, an operator and a regulatory gene. The regulatory gene controls the synthesis of the three structural genes: BETA-GALACTOSIDASE and beta-galactoside permease (involved with the metabolism of lactose), and beta-thiogalactoside acetyltransferase.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
Change brought about to an organisms genetic composition by unidirectional transfer (TRANSFECTION; TRANSDUCTION, GENETIC; CONJUGATION, GENETIC, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell's genome.
Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.
Elements of limited time intervals, contributing to particular results or situations.
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.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
The giving of drugs, chemicals, or other substances by mouth.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.
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.
Genotypic differences observed among individuals in a population.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
A characteristic symptom complex.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
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.
Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
A group of enzymes that catalyzes the hydrolysis of terminal, non-reducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause GANGLIOSIDOSIS, GM1.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
Proteins found in ribosomes. They are believed to have a catalytic function in reconstituting biologically active ribosomal subunits.
Proteins prepared by recombinant DNA technology.
Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.
The process by which a DNA molecule is duplicated.

Apontic binds the translational repressor Bruno and is implicated in regulation of oskar mRNA translation. (1/5148)

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

DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model. (2/5148)

Myotonic dystrophy (DM) is the most common form of muscular dystrophy and is caused by expansion of a CTG trinucleotide repeat on human chromosome 19. Patients with DM develop atrioventricular conduction disturbances, the principal cardiac manifestation of this disease. The etiology of the pathophysiological changes observed in DM has yet to be resolved. Haploinsufficiency of myotonic dystrophy protein kinase (DMPK), DM locus-associated homeodomain protein (DMAHP) and/or titration of RNA-binding proteins by expanded CUG sequences have been hypothesized to underlie the multi-system defects observed in DM. Using an in vivo murine electrophysiology study, we show that cardiac conduction is exquisitely sensitive to DMPK gene dosage. DMPK-/- mice develop cardiac conduction defects which include first-, second-, and third-degree atrioventricular (A-V) block. Our results demonstrate that the A-V node and the His-Purkinje regions of the conduction system are specifically compromised by DMPK loss. Importantly, DMPK+/- mice develop first-degree heart block, a conduction defect strikingly similar to that observed in DM patients. These results demonstrate that DMPK dosage is a critical element modulating cardiac conduction integrity and conclusively link haploinsufficiency of DMPK with cardiac disease in myotonic dystrophy.  (+info)

Down-regulation of RpS21, a putative translation initiation factor interacting with P40, produces viable minute imagos and larval lethality with overgrown hematopoietic organs and imaginal discs. (3/5148)

Down-regulation of the Drosophila ribosomal protein S21 gene (rpS21) causes a dominant weak Minute phenotype and recessively produces massive hyperplasia of the hematopoietic organs and moderate overgrowth of the imaginal discs during larval development. Here, we show that the S21 protein (RpS21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein. RpS21 can interact strongly with P40, a ribosomal peripheral protein encoded by the stubarista (sta) gene. Genetic studies reveal that P40 underexpression drastically enhances imaginal disc overgrowth in rpS21-deficient larvae, whereas viable combinations between rpS21 and sta affect the morphology of bristles, antennae, and aristae. These data demonstrate a strong interaction between components of the translation machinery and showed that their underexpression impairs the control of cell proliferation in both hematopoietic organs and imaginal discs.  (+info)

Cloning, molecular analysis and differential cell localisation of the p36 RACK analogue antigen from the parasite protozoon Crithidia fasciculata. (4/5148)

The family of the RACK molecules (receptors for activated C kinases) are present in all the species studied so far. In the genus Leishmania, these molecules also induce a strong immune reaction against the infection. We have cloned and characterised the gene that encodes the RACK analogue from the parasite trypanosomatid Crithidia fasciculata (CACK). The molecule seems to be encoded by two genes. The sequence analysis of the cloned open reading frame indicates the existence of a high degree of conservation not only with other members of the Trypanosomatidae but also with mammalians. The study of the protein kinase C phosphorylation sites shows the presence of three of them, shared with the mammalian species, additional to those present in the other protozoa suggesting a certain phylogenetic distance between the protozoon Crithidia fasciculata and the rest of the Trypanosomatidae. The CACK-encoded polypeptide shows an additional sequence of four amino acids at the carboxy-terminal end, which produces a different folding of the fragment with the presence of an alpha-helix instead of the beta-sheet usual in all the other species studied. A similar result is elicited at the amino-terminal end by the change of three amino acid residues. The immunolocalisation experiments show that the CACK displays a pattern with a distribution mainly at the plasma membrane, different from that of the related Leishmania species used as control, that displays a distribution close to the nucleus. Altogether, the data suggest that the existence of the structural differences found may have functional consequences.  (+info)

The origin and evolution of green algal and plant actins. (5/5148)

The Viridiplantae are subdivided into two groups: the Chlorophyta, which includes the Chlorophyceae, Trebouxiophyceae, Ulvophyceae, and Prasinophyceae; and the Streptophyta, which includes the Charophyceae and all land plants. Within the Streptophyta, the actin genes of the angiosperms diverge nearly simultaneously from each other before the separation of monocots and dicots. Previous evolutionary analyses have provided limited insights into the gene duplications that have produced these complex gene families. We address the origin and diversification of land plant actin genes by studying the phylogeny of actins within the green algae, ferns, and fern allies. Partial genomic sequences or cDNAs encoding actin were characterized from Cosmarium botrytis (Zygnematales), Selaginella apoda (Selaginellales), Anemia phyllitidis (Polypodiales), and Psilotum triquetrum (Psilotales). Selaginella contains at least two actin genes. One sequence (Ac2) diverges within a group of fern sequences that also includes the Psilotum Ac1 actin gene and one gymnosperm sequence (Cycas revoluta Cyc3). This clade is positioned outside of the angiosperm actin gene radiation. The second Selaginella sequence (Ac1) is the sister to all remaining land plant actin sequences, although the internal branches in this portion of the tree are very short. Use of complete actin-coding regions in phylogenetic analyses provides support for the separation of angiosperm actins into two classes. N-terminal "signature" sequence analyses support these groupings. One class (VEG) includes actin genes that are often expressed in vegetative structures. The second class (REP) includes actin genes that trace their ancestry within the vegetative actins and contains members that are largely expressed in reproductive structures. Analysis of intron positions within actin genes shows that sequences from both Selaginella and Cosmarium contain the conserved 20-3, 152-1, and 356-3 introns found in many members of the Streptophyta. In addition, the Cosmarium actin gene contains a novel intron at position 76-1.  (+info)

Thaumatin production in Aspergillus awamori by use of expression cassettes with strong fungal promoters and high gene dosage. (6/5148)

Four expression cassettes containing strong fungal promoters, a signal sequence for protein translocation, a KEX protease cleavage site, and a synthetic gene (tha) encoding the sweet protein thaumatin II were used to overexpress this protein in Aspergillus awamori lpr66, a PepA protease-deficient strain. The best expression results were obtained with the gdhA promoter of A. awamori or with the gpdA promoter of Aspergillus nidulans. There was good correlation of tha gene dosage, transcript levels, and thaumatin secretion. The thaumatin gene was expressed as a transcript of the expected size in each construction (1.9 or 1.4 kb), and the transcript levels and thaumatin production rate decayed at the end of the growth phase, except in the double transformant TB2b1-44-GD5, in which secretion of thaumatin continued until 96 h. The recombinant thaumatin secreted by a high-production transformant was purified to homogeneity, giving one major component and two minor components. In all cases, cleavage of the fused protein occurred at the KEX recognition sequence. This work provides new expression systems in A. awamori that result in very high levels of thaumatin production.  (+info)

Amyloid precursor protein metabolism in fibroblasts from individuals with one, two or three copies of the amyloid precursor protein (APP) gene. (7/5148)

Protein kinase C (PKC)-activated modulation of amyloid precursor protein (APP) metabolism has been investigated in natural models of altered APP expression due to the presence of one, two or three copies of the APP gene. We show that levels of APP present in human skin fibroblasts strongly influence the effect of PKC activation of soluble APP (sAPP) release. Thus fibroblasts derived from a patient with a deletion in chromosome 21 including the APP locus (Delta21) had lower levels of both APP mRNA and cell-associated APP, and showed an exaggerated phorbol-ester-induced sAPP release, when compared with fibroblasts from control individuals. In contrast, fibroblasts from chromosome 21 trisomic Down's syndrome patients failed to show a concentration-dependent response to phorbol ester treatment. These results suggest that the levels of APP expression can affect the degree of response to PKC-mediated modulation of the metabolism of this protein.  (+info)

Der(22) syndrome and velo-cardio-facial syndrome/DiGeorge syndrome share a 1.5-Mb region of overlap on chromosome 22q11. (8/5148)

Derivative 22 (der[22]) syndrome is a rare disorder associated with multiple congenital anomalies, including profound mental retardation, preauricular skin tags or pits, and conotruncal heart defects. It can occur in offspring of carriers of the constitutional t(11;22)(q23;q11) translocation, owing to a 3:1 meiotic malsegregation event resulting in partial trisomy of chromosomes 11 and 22. The trisomic region on chromosome 22 overlaps the region hemizygously deleted in another congenital anomaly disorder, velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS). Most patients with VCFS/DGS have a similar 3-Mb deletion, whereas some have a nested distal deletion endpoint resulting in a 1.5-Mb deletion, and a few rare patients have unique deletions. To define the interval on 22q11 containing the t(11;22) breakpoint, haplotype analysis and FISH mapping were performed for five patients with der(22) syndrome. Analysis of all the patients was consistent with 3:1 meiotic malsegregation in the t(11;22) carrier parent. FISH-mapping studies showed that the t(11;22) breakpoint occurred in the same interval as the 1.5-Mb distal deletion breakpoint for VCFS. The deletion breakpoint of one VCFS patient with an unbalanced t(18;22) translocation also occurred in the same region. Hamster-human somatic hybrid cell lines from a patient with der(22) syndrome and a patient with VCFS showed that the breakpoints occurred in an interval containing low-copy repeats, distal to RANBP1 and proximal to ZNF74. The presence of low-copy repetitive sequences may confer susceptibility to chromosome rearrangements. A 1.5-Mb region of overlap on 22q11 in both syndromes suggests the presence of dosage-dependent genes in this interval.  (+info)

Association of genetic copy number variations at 11 q14.2 with brain regional volume differences in an alcohol use disorder population Journal Article ...
It has been suggested that a high EGFR gene copy number may be an indicator of good response to EGFR tyrosine kinase inhibitor therapy and a marker of poor prognosis in NSCLC. However, imaging features related to EGFR gene copy number status in adenocarcinoma are still unknown. We therefore retrospectively analyzed CT, FDG-PET, and histopathologic slides of surgical resected lung adenocarcinoma in 132 patients. Tumor characteristics on preoperative chest-CT, such as, GGO proportions, tumor diameters, and cavitation; FDG-PET SUV(max); and histopathologically determined differentiation degrees and tumor subtypes were evaluated. EGFR gene copy number status was categorized as FISH-positive or -negative. FISH-positivity was found in 53 patients (40.2%) and was significantly more frequent in tumors with a SUV(max),7.0 (P=0.007). Furthermore, FISH-negativity was found to be more frequent in tumors with a GGO,50% (P=0.023) and diameter ,15.5mm (P=0.006) on CT, or a well-differentiated histopathology ...
Deregulation of the EGFR signaling pathway is one of the most frequently observed genetic abnormalities that drives cancer development. Although mutations in the downstream components of the EGFR signaling pathway, including KRAS, BRAF and PIK3CA, have been reported in numerous cancers, extensive mutation and copy number analysis of these genes in clinical samples has not been performed for head and neck squamous cell carcinoma (HNSCC). We examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. We used DNA sequencing to detect mutations and the copy number changes were evaluated by qPCR and array comparative genomic hybridization (CGH) analysis. We examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. We identified 3 mutations (2.6%) in K-RAS and 3 mutations (2.6%) in PIK3CA. Copy number amplification was
The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.. ...
Changes in gene and chromosome copy number are widely observed in systems from cancer to drug resistance to genome evolution. Despite the importance of aneuploi...
Rasmussen M, Sundström M, Göransson Kultima H, Botling J, Micke P, Birgisson H, Glimelius B, Isaksson A Genome Biol. 12 (10) R108 [2011-10-24; online 2011-10-24] We describe a bioinformatic tool, Tumor Aberration Prediction Suite (TAPS), for the identification of allele-specific copy numbers in tumor samples using data from Affymetrix SNP arrays. It includes detailed visualization of genomic segment characteristics and iterative pattern recognition for copy number identification, and does not require patient-matched normal samples. TAPS can be used to identify chromosomal aberrations with high sensitivity even when the proportion of tumor cells is as low as 30%. Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors. Affiliated researcher QC bibliography QC xrefs PubMed 22023820. DOI 10.1186/gb-2011-12-10-r108. Crossref 10.1186/gb-2011-12-10-r108. ...
DNA copy number alterations in 146 bladder tumors.A) Whole genome heatmap representing relative copy number profiles of the samples. Segments of gains or deleti
TY - JOUR. T1 - A versatile statistical analysis algorithm to detect genome copy number variation. AU - Daruwala, Raoul Sam. AU - Rudra, Archisman. AU - Ostrer, Harry. AU - Lucito, Robert. AU - Wigler, Michael. AU - Mishra, Bud. PY - 2004/11/16. Y1 - 2004/11/16. N2 - We have developed a versatile statistical analysis algorithm for the detection of genomic aberrations in human cancer cell lines. The algorithm analyzes genomic data obtained from a variety of array technologies, such as oligonucleotide array, bacterial artificial chromosome array, or array-based comparative genomic hybridization, that operate by hybridizing with genomic material obtained from cancer and normal cells and allow detection of regions of the genome with altered copy number. The number of probes (i.e., resolution), the amount of uncharacterized noise per probe, and the severity of chromosomal aberrations per chromosomal region may vary with the underlying technology, biological sample, and sample preparation. Constrained ...
Complement component 4 (C4) gene copy number (GCN) affects the susceptibility to systemic lupus erythematosus (SLE) in different populations, however the possible phenotype significance remains to be determined. This study aimed to associate C4A, C4B and total C4 GCN and SLE, focusing on the clinical phenotype and disease progression. C4, C4A and C4B GCN were determined by real-time PCR in 427 SLE patients and 301 healthy controls, which underwent a detailed clinical evaluation according to a pre-established protocol. The risk of developing SLE was 2.62 times higher in subjects with low total C4 GCN (| 4 copies, OR = 2.62, CI = 1.77 to 3.87, p | 0.001) and 3.59 times higher in subjects with low C4A GCN (| 2 copies; OR = 3.59, CI = 2.15 to 5.99, p | 0.001) compared to those subjects with normal or high GCN of total C4 (≥4) and C4A (≥2), respectively. An increased risk was also observed regarding low C4B GCN, albeit to a lesser degree (OR = 1.46, CI = 1.03 to 2.08, p = 0.03). Furthermore, subjects
Diagnosing constitutional pathogenic copy number variants (CNVs) requires detecting submicroscopic segmental chromosomal imbalances
Sequencing technology is increasingly demonstrating the impact of genomic copy number variation (CNV) on phenotypes. Opposing variation in growth, head size, cognition and behaviour is known to result from deletions and reciprocal duplications of some genomic regions. We propose normative inversion of face shape, opposing difference from a matched norm, as a basis for investigating the effects of gene dosage on craniofacial development. We use dense surface modelling techniques to match any face (or part of a face) to a facial norm of unaffected individuals of matched age, sex and ethnicity and then we reverse the individuals face shape differences from the matched norm to produce the normative inversion. We demonstrate for five genomic regions, 4p16.3, 7q11.23, 11p15, 16p13.3 and 17p11.2, that such inversion for individuals with a duplication or (epi)-mutation produces facial forms remarkably similar to those associated with a deletion or opposite (epi-)mutation of the same region, and vice versa. The
Women more frequently than men have a type of gene mutation linked to schizophrenia and other neuropsychiatric illnesses, but that doesnt translate into increased risk for the condition.
We have developed ascatNgs to aid researchers in carrying out Allele-Specific Copy number Analysis of Tumours (ASCAT). ASCAT is capable of detecting DNA copy number changes affecting a tumor genome when comparing to a matched normal sample. Additionally, the algorithm estimates the amount of tumor DNA in the sample, known as Aberrant Cell Fraction (ACF). ASCAT itself is an R-package which requires the generation of many file types. Here, we present a suite of tools to help handle this for the user. Our code is available on our GitHub site ( This unit describes both one-shot execution and approaches more suitable for large-scale compute farms. © 2016 by John Wiley & Sons, Inc.
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Identifying genetic cues of functional relevance is key to understanding the drivers of evolution and increasingly important for the conservation of biodiversity. This study introduces nuclear ribosomal DNA (nrDNA) to mitochondrial DNA (mtDNA) copy number ratios as a metric with which to screen for this functional genetic variation prior to more extensive omics analyses. To illustrate the metric, quantitative PCR was used to estimate nrDNA (18S) to mtDNA (16S) copy number ratios in muscle tissue from samples of two zooplankton species: Salpa thompsoni caught near Elephant Island (Southern Ocean) and S. fusiformis sampled off Gough Island (South Atlantic). Average 18S:16S ratios in these samples were 9:1 and 3:1, respectively. nrDNA 45S arrays and mitochondrial genomes were then deep sequenced to uncover the sources of intra-individual genetic variation underlying these 18S:16S copy number differences. The deep sequencing profiles obtained were consistent with genetic changes resulting from ...
Importantly, when creating the mimicked data sets we did not generate any simulated ratio values; rather, we formed different selections of values using real experimental data. We believe that this use of real experimental data is of significance for aCGH data. This belief is founded on that, in contrast to expression levels, copy number levels are restricted to a, by comparison, moderate dynamic range. Therefore, when a genomic region is subjected to gain or amplification, the increase of genomic material is relatively substantial. Thus, we reasoned that probes for regions of gain would yield comparably higher average intensities than those for regions of normal copy number and that this, in turn, would result in a correlation between M and A: probes measuring ratios of gain will have higher average intensities. The opposite relationship would apply for probes measuring ratios of loss. Consequently, utilizing normalization strategies based on Lowess would possibly correct for correlations ...
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inproceedings{8564264, author = {{Mus, Liselot and Denecker, Geertrui and Zeltner, Nadja and Ogando, Yudelca and Van Haver, Stéphane and Sanders, Ellen and Jacobs, Eva and Popovic, Mina and Van Neste, Christophe and Vanhauwaert, Suzanne and Durinck, Kaat and Menten, Björn and De Preter, Katleen and Heindryckx, Björn and Studer, Lorenz and Roberts, Stephen and Speleman, Franki}}, booktitle = {{Advances in Neuroblastoma Research, Congress abstracts}}, language = {{eng}}, location = {{San Fransisco, CA, USA}}, title = {{Exploring the contribution of gene dosage effects of 17q gain on ESC and neuroblastoma proliferation}}, year = {{2018 ...
A research team led by Associate Professor Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL) has developed a sensitive and accurate way of identifying gene copy number variations (CNVs). The method, which is ...
Accurate assignment of copy number at known copy number variant (CNV) loci is important for both increasing understanding of the structural evolution of genomes as well as for carrying out association studies of copy number with disease. As with calling SNP genotypes, the task can be framed as a clustering problem but for a number of reasons assigning copy number is much more challenging. CNV assays have lower signal-to-noise ratios than SNP assays, often display heavy tailed and asymmetric intensity distributions, contain outlying observations and may exhibit systematic technical differences among different cohorts. In addition, the number of copy-number classes at a CNV in the population may be unknown a priori. Due to these complications, automatic and robust assignment of copy number from array data remains a challenging problem. We have developed a copy number assignment algorithm, CNVCALL, for a targeted CNV array, such as that used by the Wellcome Trust Case Control Consortiums recent CNV
Large deletions encompassing the NF1 gene and its flanking regions belong to the group of genomic disorders caused by copy number changes that are mediated by the local genomic architecture. Although nonallelic homologous recombination (NAHR) is known to be a major mutational mechanism underlying such genomic copy number changes, the sequence determinants of NAHR location and frequency are still poorly understood since few high-resolution mapping studies of NAHR hotspots have been performed to date. Here, we have characterized two NAHR hotspots, PRS1 and PRS2, separated by 20 kb and located within the low-copy repeats NF1-REPa and NF1-REPc, which flank the human NF1 gene region. High-resolution mapping of the crossover sites identified in 78 type 1 NF1 deletions mediated by NAHR indicated that PRS2 is a much stronger NAHR hotspot than PRS1 since 80% of these deletions exhibited crossovers within PRS2, whereas 20% had crossovers within PRS1. The identification of the most common strand exchange ...
Purpose: As genome-scale technologies begin to unravel the complexity of the equivalent tumors in adults, we can attempt detailed characterization of high-grade gliomas in children, that have until recently been lacking. Toward this end, we sought to validate and extend investigations of the differences between pediatric and adult tumors.. Experimental Design: We carried out copy number profiling by array comparative genomic hybridization using a 32K bacterial artificial chromosome platform on 63 formalin-fixed paraffin-embedded cases of high-grade glioma arising in children and young people (,23 years).. Results: The genomic profiles of these tumors could be subclassified into four categories: those with stable genomes, which were associated with a better prognosis; those with aneuploid and those with highly rearranged genomes; and those with an amplifier genotype, which had a significantly worse clinical outcome. Independent of this was a clear segregation of cases with 1q gain (more common in ...
View article as PDF. In recent years, we have dramatically changed our view of human genome, from a collection of DNA base pairs that was largely quite stable to one whose very structure can change. Weve learned that higher-order structural features, such as specific configurations of repeated base pair sequences, can predispose for DNA rearrangements.1. One of the most intriguing types of DNA rearrangements is copy-number variants (CNVs), deletions or duplications of parts of the genome. While CNVs range in size from a few hundred base pairs to several mega-bases affecting the copy number of one to dozens of juxtaposed genes, they are not identifiable by conventional light microscopy. It was not until a few years ago that improved technology enabled us to perform high-resolution genome-wide surveys of CNVs in individual genomes. These surveys revealed a large amount of copy number variation (at least 12,000 CNVs overlapping more than 1,000 genes), most of which represent benign polymorphic ...
4468 Detecting the genetic changes associated with cancer development and progression is a major focus in current cancer research. We have developed a high-resolution technology to assess DNA copy number changes in cancer and other diseases. The method combines our whole genome sampling analysis (WGSA), which genotypes over 100,000 single nucleotide polymorphisms (SNPs) from nanogram quantities of human genomic DNA, and our chromosomal copy number tool (CCNT). CCNT can detect regions of chromosomal deletion, amplification, and loss of heterozygosity (LOH). Copy number changes are calculated based on SNP hybridization signal intensity data from the experimental sample relative to intensity distributions derived from a reference set containing over 100 individuals. CCNT also provides a statistical significance of this intensity difference. Several advantages of this technique include the simultaneous collection of genotype information and DNA copy number changes, no requirement of a reference ...
MYC copy gain, chromosomal instability and PI3K activation as potential markers of unfavourable outcome in trastuzumab-treated patients with metastatic breast cancer. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Purpose: The expression of HAGE as a novel prognostic and predictive tool was assessed in 1079 TNBCs. Experimental Design: HAGE protein expression was investigated in an early primary TNBC (EP-TNBC; n=520) cohort who received adjuvant chemotherapy (ACT) and in a locally advanced primary TNBC cohort who received anthracycline-combination Neo-ACT (n=110; AC-Neo-ACT). HAGE-mRNA expression was evaluated in the METABRIC-TNBC-cohort (n=311) who received ACT and in a cohort of patients with TNBC who received doxorubicin/cyclophosphamide Neo-ACT, followed by 1:1 randomisation to ixabepilone (n=68) or paclitaxel (n=64) as part of a phase II clinical trial. Furthermore, a cohort of 128 tumours with integrated HAGE gene copy number changes, mRNA and protein levels were analysed. Results: In patients with EP-TNBC, who were chemotherapy-naïve, high HAGE protein expression (HAGE+) was associated with a higher risk of death (HR: 1.3; 95% CI: 1.2-1.5; p=0.000005) when compared HAGE- cases. Patients who ...
By using {\em E. coli} cells in which the unique origin of replication has been moved to a ectopic chromosome location distant from the native one, we probe how perturbation of gene order near the origin of replication impacts genome stability and survival under genomic attack. We find that when challenged with sub-inhibitory doses of ciprofloxacin, an antibiotic that generates replication fork stalling, cells with the ectopic origin show significant fitness loss. We show that genes functionally relevant to the cipro-induced stress response are largely located near the native origin, even in distantly related species. We show that while cipro induces increased copy number of genes proximal to the origin of replication as a direct consequence of replication fork stalling, gene copy number variation was reduced near the ectopic origin. Altered gene dosage in cells with an ectopic origin resulted in impaired replication fork repair and chromosome instability. We propose that gene distribution in ...
These results highlight the benefits of using CNstream, a method for whole-genome CNV discovery and genotyping for Illumina BeadChip arrays. The present method combined a single-locus scoring approach that takes advantage of the joint clustering analysis of all the intensity samples at each probe with the computational speed and analytical accuracy of estimating CNPs from segments of consecutive probes. Compared with PennCNV, CNstream has superior sensitivity in several common CNPs and it can identify different CNPs that are not detected by PennCNV. The CNP detected by CNstream was demonstrated to be the most significantly associated with RA susceptibility using available RT-PCR technology.. With regard to the single-locus scoring method, CNstream reduced the processing time by robustly initializing the GMM before the EM procedure. This allows a whole-genome analysis to be carried out without the need for previously defined CNP maps, which are required for the SCIMM method. In addition, in ...
Bioconductor version: Release (3.6) The CINdex package addresses important area of high-throughput genomic analysis. It allows the automated processing and analysis of the experimental DNA copy number data generated by Affymetrix SNP 6.0 arrays or similar high throughput technologies. It calculates the chromosome instability (CIN) index that allows to quantitatively characterize genome-wide DNA copy number alterations as a measure of chromosomal instability. This package calculates not only overall genomic instability, but also instability in terms of copy number gains and losses separately at the chromosome and cytoband level.. Author: Lei Song, Krithika Bhuvaneshwar, Yue Wang, Yuanjian Feng, Ie-Ming Shih, Subha Madhavan, Yuriy Gusev Maintainer: Yuriy Gusev ,yg63 at, ...
Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with map …
Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME). In addition, genetic variation in factors encoding the major histocompatibility complex have been helpful to predict immune-mediated drug toxicity. This knowledge has been translated into clinical applications through the implementation of pharmacogenomic biomarkers. Over 230 of such markers that can, to a certain extent, predict drug efficacy or the ...
FISH-positive criteria have been used according to the corresponding genes. FGFR1 high-level amplification is defined as copy number ≥ 9 or (1) an FGFR1/CEP8 ratio of ≥ 2.0, (2) the average number of FGFR1 signals per tumor cell nucleus ≥ 6, and (3) the percentage of tumor cells containing ≥ 15 FGFR1 signals or large clusters ≥ 10% [74,87]. According to previously published criteria, the EGFR gene copy number was classified into six FISH strata: disomy (two or fewer copies in more than 90% of cells), low trisomy (two or fewer copies in 40% or more of the cells, three copies in 10%-40% of cells, and four or more copies in less than 10% of cells), high trisomy (two or fewer copies in ≥ 40% of cells, three copies in ≥ 40% of cells, and four or more copies in less than 10% of cells), low polysomy (four or more copies in 10%-40% of cells), high polysomy (four or more copies in 40% of the cells or more), and gene amplification (defined by the presence of tight EGFR clusters and a ratio ...
TY - JOUR. T1 - Chromosome 18 gene dosage map 2.0. AU - Cody, Jannine D.. AU - Heard, Patricia. AU - Rupert, David. AU - Hasi-Zogaj, Minire. AU - Hill, Annice. AU - Sebold, Courtney. AU - Hale, Daniel. PY - 2018/12/1. Y1 - 2018/12/1. N2 - In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps ...
Dr Liesbeth Lenaerts talks to ecancer at ESMO 2018 about a pre-existing pre-natal test which flagged up copy number alterations and cancer in the foetus'
AbstractLow FCGR3 copy numbers (CNs) has been associated with susceptibility to several systemic autoimmune diseases. However, inconsistent associations were reported and errors caused by shaky methods were suggested to be the major causes. In large scale case control association studies, robust copy number determination method is thus warranted, which was the main focus of the current study. In the present study, FCGR3 CNs of 90 HapMap Asians were firstly checked using four assays including paralogue ratio test combined with restriction enzyme digest variant ratio (PRT-REDVR), real-time quantitative (qPCR) using TaqMan assay, real-time qPCR using SYBR Green dye and short tenden repeat (STR). To improve the comparison precision reproductively, the results were compared with those from recently released sequencing data from 1000 genomes project as well as whole-genome tiling BAC array data. The tendencies of inconsistent samples by these methods were also characterized. Refined in-home TaqMan qPCR assay
Canvas is a tool for calling copy number variants (CNVs) from human DNA sequencing data. It can work either with germline data, or paired tumor/normal samples. Its primary input is aligned reads (in .bam format), and its primary output is a report (in a .vcf file) giving the copy number status of the genome. ...
Faster implementation of CRLMM specific to SNP 5.0 and 6.0 arrays, as well as a copy number tool specific to 5.0, 6.0, and Illumina platforms.
Pearson and Spearman correlation coefficients are commonly used to quantify the strength of bivariate associations of genomic variables. For example, correlations of gene-level DNA copy number and gene expression measurements may be used to assess the impact of DNA copy number changes on gene expression in tumor tissue. MVisAGe enables users to quickly compute and visualize the correlations in order to assess the effect of regional genomic events such as changes in DNA copy number or DNA methylation level. Please see Walter V, Du Y, Danilova L, Hayward MC, Hayes DN, 2018. Cancer Research ,doi:10.1158/0008-5472.CAN-17-3464,.. ...
Molecular Cloning, also known as Maniatis, has served as the foundation of technical expertise in labs worldwide for 30 years. No other manual has been so popular, or so influential.
Over the past decade, utilization of microarray technology has flourished in biomedical research. It has evolved rapidly into a revolutionary tool that offers deeper insight into the molecular basis...
Are you proposing a thought experiment in which we subtract all the repeat derived sequences (minus the small proportion of bases that regulate gene expression), and most of the the non regulatory intergenic sequences, reducing intron and intergenic sizes by, say 90%, such that we end up with a small number of short chromosomes (say 50 Mb in size - since we know the current division processes can cope with such a size) but keeping the necessary telomeric and centromeric repeats. This would be done with all members of the human species such that all the current copy number polymorphisms and regulatory snps are maintained and all genes are allowed up to 2000bp of regulatory sequences (although we will allow a proportion of genes to have larger regulatory regions). The ultimate result is a human genome that is say, 90% smaller than the current one. You suggest that the current cellular machinery would be able to cope with this change, such that there would be no viability or evolutionary ...
Genome-wide analysis of copy number changes in breast and colorectal tumors used approaches that can reliably detect homozygous deletions and amplifications. The number of genes altered by major copy number changes-deletion of all copies or amplification of at least twelve copies per cell-averaged thirteen per tumor. These data were integrated with previous mutation analyses of the Reference Sequence genes in these same tumor types to identify genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations include those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that are useful for cancer diagnosis and therapy.
Integrative analysis of multiple layers of molecular profiles, such as somatic mutations, DNA copy-number alterations or mRNA expression, offers an unprecedented opportunity to obtain a comprehensive molecular portrait of an individuals tumor. By looking at the recurrence of the molecular alterations found in an individual and at the location of altered proteins in the human interactome, we can put molecular alterations into clinical and molecular context. This PanorOmic view of personal cancer genomes enables a better understanding and interpretation of the results and increases the diagnostic utility of high throughput methods. The current version of Cancer PanorOmics is 2020_01 ...
Heterokaryons provide a model system in which to examine how tissue-specific phenotypes arise and are maintained. When muscle cells are fused with nonmuscle cells, muscle gene expression is activated in the nonmuscle cell type. Gene expression was studied either at a single cell level with monoclonal antibodies or in mass cultures at a biochemical and molecular level. In all of the nonmuscle cell types tested, including representatives of different embryonic lineages, phenotypes, and developmental stages, muscle gene expression was induced. Differences among cell types in the kinetics, frequency, and gene dosage requirements for gene expression provide clues to the underlying regulatory mechanisms. These results show that the expression of genes in the nuclei of differentiated cells is remarkably plastic and susceptible to modulation by the cytoplasm. The isolation of the genes encoding the tissue-specific trans-acting regulators responsible for muscle gene activation should now be possible. ...
(A) Standard curve for quantitation of DNA copy number. The vertical axis shows copies of target DNA per reaction. The horizontal axis shows the ct values as de
Autor: Kramer, M. et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2010-05-01; Keywords: Paralogs; RAB-like; Gene expression; Paralog ratio test; Pyrosequencing; Titel: Analysis of relative gene dosage and expression differences of the paralogs RABL2A and RABL2B by Pyrosequencing.
Video created by The State University of New York for the course Big Data, Genes, and Medicine. After this module, you will be able to 1. List different types of gene alterations. 2. Compare and contrast methods for detecting gene mutations. 3. ...
Key to successful detoxification is to be on the QS Detox Cube protocol a minimum of 3 months and slowly titrate up doses. The Detox Cube includes all three months dosage requirements and additional suggestions for optimal health and safe detoxification.
Aims The clinical significance of TOP2A as a prognostic marker has not been clarified. The aims of this study were to investigate the frequency of TOP2A copy number change; to correlate TOP2A with HER2 status, hormone ...
Deviation of gene expression from normal levels has been associated with diseases. Both under- and overexpression of genes could lead to deleterious biological consequences. Dosage balance has been proposed to be a key issue of determining gene expression phenotype. Gene deletion or overexpression of any component in a protein complex produces abnormal phenotypes. As a result, interacting partners should be co-expressed to avoid dosage imbalance effects. The strength of transcriptional co-regulation of interacting partners is supposed to reflect gene dosage sensitivity. Although many cases of dosage imbalance effects have been reported, the molecular attributes determining dosage sensitivity remain unknown. This thesis uses a protein structure analysis protocol to explore the molecular basis of gene dosage sensitivity, and studies the post-transcriptional regulation of dosage sensitive genes. Solvent-exposed backbone hydrogen bond (SEBH or called as dehydron) provides a structure marker for ...
Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution. We employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines. Common amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by
The recent genome-wide allele-specific copy number variation data enable us to explore two types of genomic information including chromosomal genotype variations as well as DNA copy number variations. For a cancer study, it is common to collect data for paired normal and tumor samples. Then, two types of paired data can be obtained to study a disease subject. However, there is a lack of methods for a simultaneous analysis of these four sequences of data. In this study, we propose a statistical framework based on the change-point analysis approach. The validity and usefulness of our proposed statistical framework are demonstrated through the simulation studies and applications based on an experimental data set.
Copy number analysis usually refers to the process of analyzing data produced by a test for DNA copy number variation in patients sample. Such analysis helps detect chromosomal copy number variation that may cause or may increase risks of various critical disorders. Copy number variation can be detected with various types of tests such as fluorescent in situ hybridization, comparative genomic hybridization and with high-resolution array-based tests based on array comparative genomic hybridization (or aCGH), SNP array technologies and high resolution microarrays that include copy number probes as well an SNPs. Array-based methods have been accepted as the most efficient in terms of their resolution and high-throughput nature and the highest coverage (choose an array with over 2 million probes) and they are also referred to as Virtual Karyotype. Data analysis for an array-based DNA copy number test can be very challenging though due to very high volume of data that come out of an array platform. ...
In this chapter submicroscopic structural variation is described with a particular focus on copy number variation. There is a growing body of evidence to show that copy number variation is a common and important class of genetic variation. Recent technological advances for mapping the extent of copy number variation including microarray based comparative genomic hybridisation are described, together with the results of large scale surveys of copy number variation among healthy individuals. The consequences of such genetic diversity for gene expression are discussed. The important role of copy number variation in susceptibility to a variety of common multifactorial traits is described including infectious and autoimmune disease. Copy number variation is also discussed in relation to evidence for selection in relation to copy number of the gene encoding salivary amylase and a high starch diet, and in relation to drug metabolism with important consequences for pharmacogenomics.
Recent genome-wide microarray-based research investigations have revealed a high frequency of submicroscopic copy number alterations (CNAs) in the myelodysplastic syndromes (MDS), suggesting microarray-based comparative genomic hybridization (aCGH) has the potential to detect new clinically relevant genomic markers in a diagnostic laboratory. We performed an exploratory study on 30 cases of MDS, myeloproliferative neoplasia (MPN) or evolving acute myeloid leukemia (AML) (% bone marrow blasts ≤ 30%, range 0-30%, median, 8%) by aCGH, using a genome-wide bacterial artificial chromosome (BAC) microarray. The sample data were compared to corresponding cytogenetics, fluorescence in situ hybridization (FISH), and clinical-pathological findings. Previously unidentified imbalances, in particular those considered submicroscopic aberrations (| 10 Mb), were confirmed by FISH analysis. CNAs identified by aCGH were concordant with the cytogenetic/FISH results in 25/30 (83%) of the samples tested. aCGH revealed new
Introduction: Lung cancer, of which 85% is non-small cell (NSCLC), is the leading cause of cancer-related death in the United States. Copy number variations (CNVs) in lung adenocarcinoma do not occur randomly in the genome, but are positionally clustered. However, the functional significance of gene copy number changes remains unclear. We characterized genome-wide copy number profiles in non-small cell lung cancer both positionally and functionally. Methods: A series of 301 tumor samples was collected from NSCLC patients in the Massachusetts General Hospital (MGH), Boston, MA (N=202) and National Institute of Occupational Health in Norway (N=99). Copy numbers were evaluated in genomic DNA extracted from micro-dissected tumor tissue with at least 70% tumor cellularity using dense single nucleotide polymorphism arrays. Inferred copy numbers were obtained with dCHIP, and significance of CNVs for each locus was evaluated with binomial distribution. Gene set enrichment analysis algorithm was used to ...
|i|Background|/i|: C-Myc, a well-known oncogene located on 8q24.12–q24.23, is often amplified and over-expressed in both primary and metastasizing colorectal cancer. In addition, PRL-3 (also known as PTP4A3), a tyrosine phosphatase located on 8q24.3, is amplified in colorectal cancer metastasis. Beside PRL-3 and c-myc, other oncogenes located on the 8q23–24 region might be involved in this process. Therefore, the present study aims to correlate DNA copy number status of a series of genes at 8q23–24 in colorectal cancer at high resolution in correlation to metastatic disease. |i|Materials and Methods|/i|: Thirty-two cases of colorectal cancer, 10 stage B1, 10 B2 and 12 D (Astler–Coller) with their corresponding liver metastasis and one colorectal cell line (colo205, previously analyzed by array-CGH), were included in this study. A chromosome 8 specific MLPA probe mixture was used to analyze the presence of DNA copy number changes. The probe mixture contained 29 probes covering
Background: Congenital malformations are present in approximately 2-3% of liveborn babies and 20% of stillborn fetuses. The mechanisms underlying the majority of sporadic and isolated congenital malformations are poorly understood, although it is hypothesized that the accumulation of rare genetic, genomic and epigenetic variants converge to deregulate developmental networks. Methodology/Principal Findings: We selected samples from 95 fetuses with congenital malformations not ascribed to a specific syndrome (68 with isolated malformations, 27 with multiple malformations). Karyotyping and Multiplex Ligation-dependent Probe Amplification (MLPA) discarded recurrent genomic and cytogenetic rearrangements. DNA extracted from the affected tissue (46%) or from lung or liver (54%) was analyzed by molecular karyotyping. Validations and inheritance were obtained by MLPA. We identified 22 rare copy number variants (CNV) [,100 kb, either absent (n = 7) or very uncommon (n = 15, ,1/2,000) in the control ...
From a number of genome-wide association studies it was shown that de novo and/or rare copy number variants (CNVs) are found at an increased frequency in neuropsychiatric diseases. In this study we examined the prevalence of CNVs in six genomic regions (1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, and 16p11.2) previously implicated in neuropsychiatric diseases. Hereto, a cohort of four neuropsychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and intellectual disability) and control individuals from three different populations was used in combination with Multilpex Amplicon Quantifiaction (MAQ) assays, capable of high resolution (kb range) and custom-tailored CNV detection. Our results confirm the etiological candidacy of the six selected CNV regions for neuropsychiatric diseases. It is possible that CNVs in these regions can result in disturbed brain development and in this way lead to an increased susceptibility for different neuropsychiatric disorders, dependent on ...
Uveal melanomas (UM) are aggressive ocular tumours of adults that are typically characterized by chromosomal aberrations such as loss of 1p, 3, 6q, and gain 6p, and 8q. Of these monosomy 3 (M3) and 8q+ are powerful predictors of prognosis. The relationship of changes affecting chromosome 6 is however more ambivalent, having been linked to both good and poor prognosis, and yet both regions have not been well defined, which suggest the presence of one or more oncogenes in 6p and tumour suppressor gene in 6q. Therefore, different chromosome 6 alterations may have a variable impact on the prognosis of UM, and ultimately contain genes that contribute to the development and metastasis of this disease. It is likely that these changes can act as moderators to the tumour outcome. Although UM disseminates haematogenous with high propensity for the liver, and hepatic involvement reported in over 90% of patients, infrequently some patients will however initially present with metastases in sites other than ...
Mitochondrial dysfunction, generally characterized as a loss of efficiency in oxidative phosphorylation, is a hallmark of aging and a variety of chronic diseases. Mitochondrial dysfunction results in inefficient cellular energy production and in increased levels of reactive oxygen species (ROS) which may damage lipids, proteins, and nucleic acids. Mitochondrial dysfunction also affects the expression of nuclear genes involved in metabolism, growth, differentiation, and apoptosis. All these changes may explain the contribution of mitochondrial dysfunction to chronic and complex human diseases. A major limitation to the routine evaluation of mitochondrial dysfunction in clinical practice is the lack of reliable measures of mitochondrial dysfunction available for clinical use. Mitochondrial DNA copy number (mtDNA-CN) is a promising biomarker of mitochondrial dysfunction that has the potential to become widely available in clinical practice. Other measures of mitochondrial dysfunction, including ...
Abstract: Resistance to chemotherapeutic agents and radiotherapy has kept surgery the primary treatment of uterine leiomyosarcoma (ULMS). In search of leads for potential therapeutic targets, array CGH (aCGH) was used to obtain a genomewide pattern of ULMS-specific genetic imbalances and to define the affected biological processes. Fine-resolution genomewide aCGH analysis was performed using customised 16K cDNA microarrays on 18 primary ULMS cases. Furthermore, patterns of DNA copy number changes were assessed for associations with clinical parameters, i.e., tumour grade, tumour size and patient status at last follow-up. Our aCGH results demonstrated extensive DNA copy number changes in all chromosomes. Of the 10,590 gene loci included in the analysis, 4,387 were found to be affected by DNA copy number gains and 4,518 by DNA copy number losses in at least one case. Further analyses revealed that 231 of these were commonly gained, and 265 lost in at least 20% of the cases. The gains affected loci ...
We have used a new method of genomic microarray to investigate amplification of oncogenes throughout the genome of glioblastoma multiforme (GBM). Array-based comparative genomic hybridization (array CGH) allows for simultaneous examination of 58 oncogenes/amplicons that are commonly amplified in var …
© 2019, The Author(s). Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in |0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic
DNA copy number variants represent the greatest source of genetic variability in humans [1] and are the underlying cause of many human diseases. Array CGH is recognized as a first-tier test for DNA copy number variants (CNV) [2] and accordingly, many laboratories have already established their pipelines for pre-processing of array CGH data and CNV calling. In many cases these pipelines are based on software packages provided by the companies selling DNA microarrays or scanners such as BlueFuse [3], CytoSure [4] or CytoGenomics [5]. Yet, the scope of these tools is focused on the identification of CNVs and their evaluation in the context of gene content and frequency of a given variant in the healthy population. Comparative analysis, which integrates data obtained from multiple patients, or other experiment types are hardly supported, in particular when they are based on different array platforms or NGS technology.. Such kind of meta-analysis needs the implementation of additional commercial or ...
Oncogenic point mutations in KIT or PDGFRA are recognized as the primary events responsible for the pathogenesis of most gastrointestinal stromal tumors (GIST), but additional genomic alterations are frequent and presumably required for tumor progression. The relative contribution of such alterations for the biology and clinical behavior of GIST, however, remains elusive. In the present study, somatic mutations in KIT and PDGFRA were evaluated by direct sequencing analysis in a consecutive series of 80 GIST patients. For a subset of 29 tumors, comparative genomic hybridization was additionally used to screen for chromosome copy number aberrations. Genotype and genomic findings were cross-tabulated and compared with available clinical and follow-up data. We report an overall mutation frequency of 87.5%, with 76.25% of the tumors showing alterations in KIT and 11.25% in PDGFRA. Secondary KIT mutations were additionally found in two of four samples obtained after imatinib treatment. Chromosomal imbalances
About a decade ago the first large catalogs of copy number variants (CNVs) in the human genome were presented [1, 2]. Numerous studies later, CNVs are known to contribute to the genomic variation to a larger extent than single nucleotide polymorphisms (SNPs) in terms of number of nucleotide differences [3, 4]. CNVs are defined as DNA segments of variable length, up to several megabases (Mb), that varies in copy numbers in comparison to a reference genome [5]. The different types of CNVs include deletions and duplications, while consequences of CNVs include e.g. altered gene dosage and regulation, changed gene structure and unmasking of recessive alleles [5]. The effect of CNVs varies from being benign or neutral, to having subtle effects on disease predisposition or directly causing disease. The contribution and importance of CNVs for phenotypic diversity and disease susceptibility has been repeatedly shown in human and several complex diseases such as psoriasis, Crohns disease, type 2 ...
Arabidopsis thaliana is the model plant and is grown worldwide by plant biologists seeking to dissect the molecular underpinning of plant growth and development. Gene copy number variation (CNV) is a common form of genome natural diversity that is currently poorly studied in plants and may have broad implications for model organism research, evolutionary biology, and crop science. Herein, comparative genomic hybridization (CGH) was used to identify and interrogate regions of gene CNV across the A. thaliana genome. A common temperature condition used for growth of A. thaliana in our laboratory and many around the globe is 22 degrees C. The current study sought to test whether A. thaliana, grown under different temperature (16 and 28 degrees C) and stress regimes (salicylic acid spray) for five generations, selecting for fecundity at each generation, displayed any differences in CNV relative to a plant lineage growing under normal conditions. Three siblings from each alternative temperature or stress
The treatment strategy usually depends on the disease state in the individual patient. However, it is difficult to estimate the disease state before treatment in many patients. The purpose of this study was to develop a BAC (bacterial artificial chromosome) mini-array allowing for the estimation of node metastasis, liver metastasis, peritoneal dissemination and the depth of tumor invasion in gastric cancers. Initially, the DNA copy number aberrations (DCNAs) were analyzed by array-based comparative genomic hybridization (aCGH) in 83 gastric adenocarcinomas as a training-sample set. Next, two independent analytical methods were applied to the aCGH data to identify the BAC clones with DNA copy number aberrations that were linked with the disease states. One of the methods, a decision-tree model classifier, identified 6, 4, 4, 4, and 7 clones for estimating lymph node metastasis, liver metastasis, peritoneal dissemination, depth of tumor invasion, and histological type, respectively. In the other method, a
article{39c3420c-566c-4f24-879b-c3929d10ccd7, abstract = {It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed, significant increased risks of CLL (n=102) with increasing mtDNA ...
Genomic copy number changes are frequently found in cancers and they have been demonstrated to contribute to carcinogenesis; and it is widely accepted that tumors with microsatellite instability (MSI) are genetically stable and mostly diploid. In the present study we compared the copy number alterations and the gene-expression profiles of microsatellite stable (MSS) and MSI colorectal tumors. A total number of 31 fresh-frozen primary tumors (16 MSS and 15 MSI) were used. Twenty-eight samples (15 MSS and 13 MSI) were analyzed with metaphase comparative genomic hybridization (CGH), nine of which plus one additional sample (4 MSS and 6 MSI) were further analyzed by cDNA-based array-CGH. Gene expression analysis was performed with six samples [3 MSS and 3 MSI, four of these used in metaphase CGH (mCGH) analysis] to identify differentially expressed genes possibly located in the lost or amplified regions found by CGH, stressing the biological significance of copy number changes. Metaphase and ...
We conducted a genome-wide scan for large CNVs (≥100 kb) in a case-control dataset of Caribbean Hispanic origin that was previously investigated in a SNP-based GWAS (Lee JH et al. 2010). To generate results with high confidence, we focused on CNVs that were identified by at least two algorithms. We detected 1774 stringent CNVs (Table S4). First, we tested the hypothesis that rare CNVs (≤1%) with a potentially strong impact on AD risk in individual patients might contribute to the overall disease risk, as was previously observed in other common neuropsychiatric disorders (Kirov et al. 2009; Zhang et al. 2009; Glessner et al. 2010). However, the burden analyses of rare CNVs did not find significant differences between cases and controls in CNV rate, total or average CNV size, or the number of genes affected by CNVs.. In addition, we conducted a case-control analysis of large genic CNVs, including common variants, using PLINK regional analysis. The only nominally significant result that ...
|jats:title|Abstract|/jats:title||jats:p|Long regarded as an epicenter of drug-resistant malaria, Southeast Asia continues to provide new challenges to the control of |jats:italic|Plasmodium falciparum|/jats:italic| malaria. Recently, resistance to the artemisinin combination therapy partner drug piperaquine has been observed in multiple locations across Southeast Asia. Genetic studies have identified a single nucleotide polymorphism as well as a copy number variation molecular marker that associate with clinical and |jats:italic|in vitro|/jats:italic| resistance. The copy number polymorphism is a duplication of a region containing members of the plasmepsin multi-gene family of proteases. To accurately and quickly determine the presence of copy number variation in the |jats:italic|plasmepsin 2/3|/jats:italic| duplication in field isolates, we developed a quantitative PCR assay using TaqMan probes. We validated copy number estimates using a separate SYBR green-based quantitative PCR assay as well as a
Figure Novel compound heterozygous mutation in the COLQ gene causes congenital myasthenic syndrome. (A) Pedigree of the proband (II-1). Point mutation (IVS16+3A→G) in the COLQ gene was inherited from the father (I-1), and multiexon deletion from the mother (I-2). (B) Gene list of 21 known congenital myasthenic syndrome (CMS) genes included in the targeted CMS panel. (C) Genome view of PatternCNV analysis shows decreased copy number variation (CNV) log2 ratio for the COLQ gene in chromosome 3. (D) Exon-level CNV summary table shows the start and end position of deletion (984 base pairs) in the COLQ gene, which indicates 1 copy deletion of exons 14 and 15. SNR.db: signal noise ratio expressed in decibels; CNV.ratio: copy number ratio converted from CNV.log2ratio. CNV.ratio of 1 indicates no copy number change. (E) TaqMan Copy Number Assay results confirm exon deletions in the COLQ gene in the proband, which is also found in her mother (data not shown). Longer PCR cycle number (X-axis) denotes 1 ...
TY - JOUR. T1 - Identification of genes involved in squamous cell carcinoma of the lung using synchronized data from DNA copy number and transcript expression profiling analysis. AU - Lo, Ken C.. AU - Stein, Leighton C.. AU - Panzarella, Jenniffer A.. AU - Cowell, John Kenneth. AU - Hawthorn, Lesleyann. PY - 2008/3/1. Y1 - 2008/3/1. N2 - Lung cancer is the leading cause of cancer deaths in the world and squamous cell carcinoma (SqCC) is the second most common in this group. Genomic DNA copy number alterations are fundamental genetic events in the development and progression of SqCC as well as other epithelial-derived cancers. The ability to identify tumor suppressor genes (TSGs) and oncogenes that are affected during tumor initiation and progression could facilitate the identification of novel molecular targets for therapeutic intervention and provide diagnostic biomarkers. Despite the association of many genetic alterations in lung cancer the molecular mechanisms of tumor progression remain ...
BACKGROUND: Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples. RESULTS: We demonstrate an asymmetry in the detection of the two alleles for each SNP, which deleteriously influences both allelic proportions and copy number estimates. The asymmetry is caused by a remaining bias between the two dyes used in the Infinium II assay after using the normalization method in Illuminas proprietary software (BeadStudio). We propose a quantile normalization strategy for correction of this dye bias. We tested the ...
Richard-Carpentier G, Kantarjian HM, Short NJ, Ravandi F, Ferrajoli A, Schroeder HM, et al. Yang J, Bhojwani D, Yang W. Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia. E. Jabbour has research grants with Amgen, AbbVie, Spectrum, BMS, Takeda Oncology, Pfizer, and Adaptive. Seizures 3. The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, et al. Pui CH, Crist WM, Look AT. PubMed Central Google Scholar. Blood. Additional tables. Neumann M, Vosberg S, Schlee C, Heesch S, Schwartz S, Gökbuget N, et al. However, a better understanding of the disease biology has generated important knowledge on the prognostic and predictive value of MRD, which has helped guide our treatment strategies, such as intensification or referral to HSCT, the use of MRD-directed novel agents or even treatment de-escalation. 2016;172(3):392-400. There ...
To select parameters for calling CNVs (that is, the statistical threshold of the ADM2 algorithm, the minimum +/- log2 ratio and the minimum number of consecutive probes in a CNV interval), we calculated the sensitivity and positive predictive value based on the comparison of aCGH-based CNV calls (using our high-resolution Agilent 24M platform) with read-depth sequence data for two samples from Korean individuals (AK1 and AK2). We attempted to obtain `absolute copy number status of the sample from NA10851, which was used as the reference sample for aCGH experiments in this study. For this, we used read-depth data for NA10851 obtained from massively parallel sequencing by the Illumina GA II data. The read-depth data represent the copy number status of NA10851 as compared to the human reference genome (hg18) because the short read sequences were aligned to hg18 ...
Thousands of genomic segments appear to be present in widely varying copy numbers in different human genomes. We developed ways to use increasingly abundant whole-genome sequence data to identify the copy numbers, alleles and haplotypes present at most large multiallelic CNVs (mCNVs). We analyzed 849 genomes sequenced by the 1000 Genomes Project to identify most large (,5-kb) mCNVs, including 3878 duplications, of which 1356 appear to have 3 or more segregating alleles. We find that mCNVs give rise to most human variation in gene dosage-seven times the combined contribution of deletions and biallelic duplications- and that this variation in gene dosage generates abundant variation in gene expression. We describe runaway duplication haplotypes in which genes, including HPR and ORM1, have mutated to high copy number on specific haplotypes. We also describe partially successful initial strategies for analyzing mCNVs via imputation and provide an initial data resource to support such analyses ...
The first estimation of how genomic copy number variation (CNV) can influence anesthetic sensitivity and the magnitude of this influence can be gauged by a new study
A fixed gene copy number is important for the in silico construction of engineered synthetic networks. However, the copy number of integrated genes depends on their genomic location. This gene dosage effect is rarely addressed in synthetic biology. Two studies in Escherichia colipresented conflicting data on the impact of gene dosage. Here, we investigate how genome location and gene orientation influences expression in Bacillus subtilis. An important difference with the E. coli studies is that we used an unbiased genome integration approach mediated by random transposon insertion. We found that there is a strong gene dosage effect in fast growing B. subtilis cells, which can amount to a 5-fold difference in gene expression. In contrast, gene orientation with respect to DNA replication direction does not influence gene expression. Our study shows that gene dosage should be taken into account when designing synthetic circuits in B. subtilis and presumably other bacteria.. ...
Copy number variation can contribute to the variation observed in susceptibility to complex diseases. Here we present the first study to investigate copy number variation of the chemokine gene CCL3L1 with susceptibility to malaria. We present a family-based genetic analysis of a Tanzanian population (n = 922), using parasite load, mean number of clinical infections of malaria and haemoglobin levels as phenotypes. Copy number of CCL3L1 was measured using the paralogue ratio test (PRT) and the dataset exhibited copy numbers ranging between 1 and 10 copies per diploid genome (pdg). Association between copy number and phenotypes was assessed. Furthermore, we were able to identify copy number haplotypes in some families, using microsatellites within the copy variable region, for transmission disequilibrium testing. We identified a high level of copy number haplotype diversity and find some evidence for an association of low CCL3L1 copy number with protection from anaemia.. ...
Copy number variants (CNVs) on the Breakpoint 1 to Breakpoint 2 region Ki8751 at 15q11. of publically obtainable expression data identified a relationship between expression of mRNA and FOXP2 in mind. We suggest that changed medication dosage through aberrant patterning from the lh.SMG may donate to language-related Mouse monoclonal to CD11b.4AM216 reacts with CD11b, a member of the integrin a chain family with 165 kDa MW. which is expressed on NK cells, monocytes, granulocytes and subsets of T and B cells. It associates with CD18 to form CD11b/CD18 complex.The cellular function of CD11b is on neutrophil and monocyte interactions with stimulated endothelium; Phagocytosis of iC3b or IgG coated particles as a receptor; Chemotaxis and apoptosis. Ki8751 issues connected with BP1-2 CNVs. Even more generally this process may be useful in clarifying the contribution Ki8751 of individual genes at CNV risk loci. Introduction Rare multi-gene copy number variants (CNVs) are well established to increase ...
Scientists reported the development of a robust procedure for whole-genome copy number profiling of circulating tumor cells (CTCs) from a blood test. In contrast to existing methods that are complex and costly, the single-tube, single-step protocol detect absolute copy number alterations (CNA) in single cells and maintain accuracy at a lower cost than conventional genomic analysis procedure, opening up to the possibility for genome-driven targeted therapy selection and monitoring of disease progression in liquid biopsy.
The authors profiled either unselected [3-5], triple-negative [1], or estrogen-receptor positive breast cancer [2] utilizing various technical approaches, including whole-genome sequencing, whole-exome sequencing, copy number profiling, and transcriptome analysis. Curtis and colleagues [5] integrate expression and copy number to identify ten subtypes of breast cancers and reveal aberration hotspots responsible for these groups. These hotspots contain known (ERBB2, MYC) and candidate driver loci that can impact patient prognosis. Stephens and colleagues [4] combined copy-number and sequencing to identify a number of novel driver genes (MAP3K1, MAP2K4, MAP3K13, and AKT2), albeit each at relatively low frequency. Together, however, these mutations all impact JUN signaling activation and encompass approximately 50% of all breast tumors, thus identifying a major recurrent pathway alteration in breast cancer. Banerji and colleagues [3] similarly utilize sequencing to identify driver mutations and copy ...
Complex focal chromosomal rearrangements in cancer genomes, also called firestorms, can be scored from DNA copy number data. The complex arm-wise aberration index (CAAI) is a score that captures DNA copy number alterations that appear as focal complex events in tumors, and has potential prognostic value in breast cancer. This study aimed to validate this DNA-based prognostic index in breast cancer and test for the first time its potential prognostic value in ovarian cancer. Copy number alteration (CNA) data from 1950 breast carcinomas (METABRIC cohort) and 508 high-grade serous ovarian carcinomas (TCGA dataset) were analyzed. Cases were classified as CAAI positive if at least one complex focal event was scored. Complex alterations were frequently localized on chromosome 8p (n = 159), 17q (n = 176) and 11q (n = 251). CAAI events on 11q were most frequent in estrogen receptor positive (ER+) cases and on 17q in estrogen receptor negative (ER-) cases. We found only a modest correlation between ...
Author Summary Mutations in noncoding sequence can cause disease but are very difficult to recognize. Here, we present two approaches intended to help identify noncoding regions of the genome that may carry mutations influencing disease. The first approach is based on comparing observed and predicted levels of standing human variation in the noncoding exome sequence of a gene. The second approach is based on the phylogenetic conservation of a genes noncoding exome sequence using GERP++. We find that both approaches can predict genes known to cause disease through changes in expression level, genes depleted of loss-of-function alleles in the general population, and genes permissive of copy number variants in the general population. We find that both scores aid in interpreting loss-of-function mutations and in defining regions of noncoding sequence that are more likely to harbor mutations that influence risk of disease.
BACKGROUND: Tandem repeat variation in protein-coding regions will alter protein length and may introduce frameshifts. Tandem repeat variants are associated with variation in pathogenicity in bacteria and with human disease. We characterized tandem repeat polymorphism in human proteins, using the UniGene database, and tested whether these were associated with host defense roles.. RESULTS: Protein-coding tandem repeat copy-number polymorphisms were detected in 249 tandem repeats found in 218 UniGene clusters; observed length differences ranged from 2 to 144 nucleotides, with unit copy lengths ranging from 2 to 57. This corresponded to 1.59% (218/13,749) of proteins investigated carrying detectable polymorphisms in the copy-number of protein-coding tandem repeats. We found no evidence that tandem repeat copy-number polymorphism was significantly elevated in defense-response proteins (p = 0.882). An association with the Gene Ontology term protein-binding remained significant after covariate ...
Environmental risk factors have been shown to alter DNA copy number variations (CNVs). Recently, CNVs have been described to arise after low-dose ionizing radiation in vitro and in vivo. Development of cost- and size-effective laser-driven electron accelerators (LDEAs), capable to deliver high energy beams in pico- or femtosecond durations requires examination of their biological effects. Here we studied in vitro impact of LDEAs radiation on known CNV hotspots in human peripheral blood lymphocytes on single cell level. Here CNVs in chromosomal regions 1p31.1, 7q11.22, 9q21.3, 10q21.1 and 16q23.1 earlier reported to be sensitive to ionizing radiation were analyzed using molecular cytogenetics. Irradiation of cells with 0.5, 1.5 and 3.0 Gy significantly increased signal intensities in all analyzed chromosomal regions compared to controls. The latter is suggested to be due to radiation-induced duplication or amplification of CNV stretches. As significantly lower gains in mean fluorescence intensities were
Most behavioral, physiological and cellular effects of theneurotransmitter dopamine require concomitant activation of both D1 and D2 receptors, a phenomenon referred to as D1/D2 synergism. Since D1 and D2 receptors are located mostly on separate neurons, and since D1/D2 synergism occurs in the absence of action potentials, we have suggested that electrotonic coupling via gap junctions plays an important role in this phenomenon. A major constituent of gap junctions is connexin36 (Cx36), a protein that is abundant in neurons. The role Cx36 in D1/D2 synergism, as manifested behaviorally, was studied here in mice genetically engineered to express normal, reduced, or undetectable amounts of this protein. The results show that D1/D2 synergism and its breakdown were not affected by the presence or absence of Cx36. Unexpectedly, it was observed that the absence of Cx36 leads to resistance to the cataleptic effects of reserpine in a gene dosage-dependent manner.
Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion , control, duplication). In contrast, gene dosage varied negatively with mean cortical thickness (deletion , control , duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric ...
... is the number of copies of a particular gene present in a genome. Gene dosage is related to the amount of gene ... Changes in gene dosage can be a result of copy number variation (gene insertions or gene deletions), or aneuploidy (chromosome ... Thus gene dosage is increased by 50% for the genes on that chromosome. Though not fully understood, it is thought that the ... These slight gene dosage differences are responsible for variation in gene expression depending on the position on the ...
... and a few genes had equal expression in both male and female Z chromosomes. In chickens, most of the dosage compensated genes ... Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological ... If the S. latifolia did not practice dosage compensation, the expected level of X-linked gene expression in males would be 50% ... 2009). "Dosage analysis of Z chromosome genes using microarray in silkworm, Bombyx mori". Insect Biochemistry and Molecular ...
Unusual gene dosage effect in heterozygotes". Hum. Genet. 77 (2): 168-71. doi:10.1007/BF00272386. PMID 3308682. S2CID 19941299 ... v t e (Genes on human chromosome 11, All stub articles, Human chromosome 11 gene stubs). ... "Entrez Gene: PTS 6-pyruvoyltetrahydropterin synthase". Werner ER, Werner-Felmayer G, Fuchs D, et al. (1991). "Biochemistry and ... Thöny B, Blau N (1997). "Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes". Hum. Mutat. 10 ...
Gabriel JM, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Steck AJ (December 1997). "Gene dosage effects in hereditary ... A 2017 Cochrane systematic review found that daily dosages between (1800 - 3600) mg of gabapentin could provide good pain ... even at high dosages (200 - 400) mg. A 2013 Cochrane systematic review of topimirate found that the included data had a strong ...
September 2007). "Adipose is a conserved dosage-sensitive antiobesity gene". Cell Metabolism. 6 (3): 195-207. doi:10.1016/j. ... WDTC1 ("Adipose") is a gene associated with obesity. WDTC1 is a gene that codes for a protein acting as a suppressor in lipid ... Born lucky: Scientists discover "skinny gene" - MSNBC v t e (Protein pages needing a picture, Genes on human chromosome 1, ... "ScienceDaily: 'Skinny Gene' Exists". Retrieved 2007-09-05. Lai CQ, Parnell LD, Arnett DK, García-Bailo B, Tsai MY, Kabagambe EK ...
... discovery of the master control gene involved in sex determination; and studies of gene regulation, particularly dosage ... Meyer's work has revealed mechanisms of sex determination and dosage compensation-that balance X-chromosome gene expression ... Further analysis of the mechanism underlying dosage compensation produced many key insights into gene regulation. In 1990, ... But it wasn't clear whether the worms accomplished this by upregulating genes on the X chromosome in males or by downregulating ...
The dosage-sensitive genes vary from species to species. Birchler JA, Pal-Bhadra M, Bhadra U (March 2003). "Dosage dependent ... Natural selection occurs efficiently in Drosophila so the genes that are dosage-sensitive are increased. ... X hyperactivation is regulated by the alternative splicing of a gene called sex-lethal. The gene was named sex-lethal due to ... The X chromosome, compared to an autosomal gene, contains more silent genes which influences measuring the amount of influence ...
It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area it leads to microcephaly. ... HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2. GJA5 has been identified as the gene ... New genes are expected in the gaps. Because the gaps are still a topic of research, it is hard to find the exact start and end ... In this way the number of chromosomes will be halved in each cell, while all the parts on the chromosome (genes) remain, after ...
Aneuploidy often alters gene dosage in ways that are detrimental to the organism; therefore, it is unlikely to spread through ... Comparative genomics DbDNV (2010) De novo gene birth Exon shuffling Gene fusion Horizontal gene transfer Human genome ... In addition, gene dosage effects play a significant role. Thus, most duplicates are lost within a short period, however, a ... Experiments on human gene function can often be carried out on other species if a homolog to a human gene can be found in the ...
It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area, it leads to microcephaly. ... HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2. Research on the genes CHD1L and ... New genes are expected in the gaps. Because the gaps are still a topic of research, it is hard to find the exact start and end ... In this way the number of chromosomes will be halved in each cell, while all the parts on the chromosome (genes) remain, after ...
Gout, Jean-Francois; Lynch, Michael (2015). "Maintenance and Loss of Duplicated Genes by Dosage Subfunctionalization". ... of the original gene. First, a gene undergoes a gene duplication event. This event produces a new copy of the same gene known ... In this case, the two genes now only carry out the individual subfunctions of the original gene, and the organism is dependent ... The concept of subfunctionalization is that one original (ancestral) gene gives rise to two paralogous copies of that gene, ...
This results in deletions and duplications of dosage sensitive genes. It has been speculated that CNVs underlie a significant ... Variations near the gene FXYD6 have also been associated with schizophrenia in the UK but not in Japan. In 2008, rs7341475 ... A 2009 study was able to create mice matching symptoms of schizophrenia by the deletion of only one gene set, those of the ... Together, these candidate genes pointed to an importance of neurotransmission and immunology as important factors in the ...
Acampora, D; Avantaggiato, V; Tuorto, F; Simeone, A (1997). "Genetic control of brain morphogenesis through Otx gene dosage ... In zebrafish, it was shown that the expression of two SHH genes, SHH-a and SHH-b (formerly described as twhh) mark the MDO ... Hirata, T.; Nakazawa, M; Muraoka, O; Nakayama, R; Suda, Y; Hibi, M (2006). "Zinc-finger genes Fez and Fez-like function in the ... SHH signaling from the MDO induces a posterior-to-anterior wave of expression the proneural gene Neurogenin1 in the major ( ...
Papp, Balázs; Pál, Csaba; Hurst, Laurence D. (2003). "Dosage sensitivity and the evolution of gene families in yeast". Nature. ... Lercher, M.J.; Urrutia, A.O.; Hurst, L.D. (2002). "Clustering of housekeeping genes provides a unified model of gene order in ... This has resulted in work on housekeeping genes, gene orders, and the evolution of drug resistance in Staphylococcus aureus, ... Similarly, in showing that genomes are arranged into gene expression domains, Hurst revealed that genes can affect the ...
Chen, Jianping (2009). Molecular Basis of Gene Dosage Sensitivity (Ph.D.). Rice University. ISBN 9781109217346. ProQuest ... Proline-rich 12 (PRR12) is a protein of unknown function encoded by the gene PRR12. The Homo sapiens PRR12 gene is 34,785 base ... "PRR12 proline rich 12 [Homo sapiens (human)] - Gene - NCBI". Retrieved 2014-01-26. "PRR12 Gene - GeneCards , ... Within its gene neighborhood, PRR12 is flanked by PRRG2 and SCAF1 on the sense strand and RRAS and NOSIP on the antisense ...
Papp, Balázs; Pál, Csaba; Hurst, Laurence D. (July 2003). "Dosage sensitivity and the evolution of gene families in yeast". ... Birchler, J. A.; Veitia, R. A. (20 August 2012). "Gene balance hypothesis: Connecting issues of dosage sensitivity across ... They demonstrated that gene loss initiates adaptive genomic changes that rapidly restores fitness, but this process has ... They specifically tested what is now known as the dosage balance hypothesis. The hypothesis offers a synthesis on seemingly ...
"Temperature Sex Reversal Implies Sex Gene Dosage in a Reptile". Science. 316 (5823): 411. Bibcode:2007Sci...316..411Q. doi: ... Threshold changes in gene expression for either male- or female-determining factors is enough to change modes of sex ... Sex-determining mechanisms include genetic sex determination, where sex is determined by genes on sex chromosomes, and ... or hitchhiking genes. Sex-reversed female bearded dragons can lay twice as many eggs per year as genetic ZW females, suggesting ...
"Imprinted gene dosage is critical for the transition to independent life". Cell Metabolism. 15 (2): 209-221. doi:10.1016/j.cmet ... Ferguson-Smith, Anne Carla (1989). A genomic analysis of the human homeobox gene loci HOX 1 and HOX 2 (PhD thesis). hdl:10079/ ... She moved to the Biology Department at Yale University to undertake a PhD identifying human Hox genes and characterising ... The team identified one of the first endogenous imprinted genes, and showed that the process was epigenetically regulated by ...
"HLA DQ gene dosage and risk and severity of celiac disease". Clinical Gastroenterology and Hepatology. 5 (12): 1406-12. doi: ... is a human gene and also denotes the genetic locus that contains this gene. The protein encoded by this gene is one of two ... "Entrez Gene: HLA-DQB1 major histocompatibility complex, class II, DQ beta 1". Lau M, Terasaki PI, Park MS (1994). " ... v t e (Genes on human chromosome 6, MHC class II, All stub articles, Protein stubs). ...
"Dosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplification". Br. J. Cancer. 91 (6): ... then the dosage quotient DQ = (a/b) / (A/B). Although dosage quotients may be calculated for any pair of amplicons, it is ... detection of gene copy number, detection of duplications and deletions in human cancer predisposition genes such as BRCA1, ... Dosage quotient analysis is the usual method of interpreting MLPA data. If a and b are the signals from two amplicons in the ...
Tissenbaum, H.A.; L. Guarente (2001). "Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans". Nature. ... For the first nine years, his lab studied gene regulation in yeast. In 1991 his lab started to study genes involved in aging. ... In 1993, Cynthia Kenyon's lab at UCSF discovered that a single-gene mutation in (Daf-2) could double the lifespan of C. elegans ... In 1995 the Guarente lab identified the gene SIR4 (Silent information regulator 4) as a longevity regulator. When SIRT4 was ...
Trieu M, Ma A, Eng SR, Fedtsova N, Turner EE (Jan 2003). "Direct autoregulation and gene dosage compensation by POU-domain ... Trieu M, Ma A, Eng SR, Fedtsova N, Turner EE (Jan 2003). "Direct autoregulation and gene dosage compensation by POU-domain ... This can be explained by gene dosage compensation due to autoregulation, in which expression of the remaining copy of the ... "Entrez Gene: POU4F1 POU domain, class 4, transcription factor 1". Gerrero MR, McEvilly RJ, Turner E, Lin CR, O'Connell S, Jenne ...
For example, increasing the gene dosage of the gene SIR-2, which regulates DNA packaging in the nematode worm Caenorhabditis ... Tissenbaum HA, Guarente L (March 2001). "Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans". Nature. ... The gene designations shown in red, gray or cyan indicate genes frequently epigenetically altered in various types of cancers. ... In particular, the gene-rich, early-replicating regions of the human genome exhibit lower mutation frequencies than the gene- ...
Changes in gene dosage, the number of times a given gene is present in the cell nucleus, can create a genetic imbalance. This ... Diminishing the dosage of most genes produces no obvious change in phenotype. For some genes the phenotypic consequences of a ... For some rare genes, the normal diploid level of gene expression is essential to individual survival; fewer than two copies of ... Genetic imbalance is to describe situation when the genome of a cell or organism has more copies of some genes than other genes ...
The alteration in the gene dosage, which is caused by the loss of a functional allele, is also called allelic insufficiency. An ... The haploinsufficiency is caused by the copy-number variation (CNV) of 28 genes led by the deletion of ~1.6 Mb. These dosage- ... This leads to too many or too few of the dosage sensitive genes. The genomic rearrangements, that is, deletions or duplications ... There are two wild-type alleles of this gene-a high-expressivity allele and a low-expressivity allele. When the mutant gene is ...
Dallapiccola B, Novelli G, Giannotti A (1988). "Deletion 2q31.3----2q33.3: gene dosage effect of ribulose 5-phosphate 3- ... v t e (Articles to be expanded from May 2016, Genes on human chromosome 2, All stub articles, Protein stubs). ... "Entrez Gene: RPE ribulose-5-phosphate-3-epimerase". Boss GR, Pilz RB (1985). "Phosphoribosylpyrophosphate synthesis from ... Ribulose-phosphate 3-epimerase is an enzyme that in humans is encoded by the RPE gene. GRCh38: Ensembl release 89: ...
Coordinate inter-genomic gene expression Duplicated genes often result in increased dosage of gene products. Doubled dosages ... The mechanism of retaining duplicated genes is poorly understood. It has been hypothesized that dosage balance may play a key ... First, the eliminated copy restores the normal gene dosage in the diploid organism. Second, the changes in chromosomal genetic ... The main goals of diploidization are: (1) To ensure proper gene dosage; and (2) to maintain stable cellular division processes ...
Huang GY, Wessels A, Smith BR, Linask KK, Ewart JL, Lo CW (1998). "Alteration in connexin 43 gap junction gene dosage impairs ... Thus, B-catenin is stabilized in the presence of Wnt and regulates gene transcription through interaction with TCF/LEF ... Cardiac neural crest cells express Hox genes that supports the development of arteries 3, 4 and 6 and the simultaneous ... regression of arteries 1 and 2. The ablation of Hox genes on cardiac neural crest cells causes defective outflow septation. One ...
This gene is localized in the DSS (dosage-sensitive sex reversal) critical region. It is expressed in testis and placenta, and ... This gene is a member of the MAGEB gene family. The members of this family have their entire coding sequences located in the ... The promoters and first exons of the MAGEB genes show considerable variability, suggesting that the existence of this gene ... "Entrez Gene: MAGEB2 melanoma antigen family B, 2". Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the ...
... the master switch gene controlling sex-determination system and dosage compensation. This protein is normally expressed in ... 2009). "xol-1, the master sex-switch gene in C. elegans, is a transcriptional target of the terminal sex-determining factor TRA ... Genes Dev. 17 (8): 977-90. doi:10.1101/gad.1082303. PMC 196039. PMID 12672694. This article incorporates text from the public ... males, where it promotes male development and prevents dosage compensation. The function of the Xol-1 protein is to act as a ...
The pills are created from sulfate salts and are sold in dosages of 100, 200, 333, and 400 mg of indinavir. It is normally used ... As a result, structural proteins, resulting from polypeptide products of gag and gag-pol genes, that are necessary for the HIV ... "Crixivan (Indinavir Sulfate): Side Effects, Interactions, Warning, Dosage & Uses". RxList. Retrieved 2018-11-08. Cohen J (June ...
Some "Withdrawal Symptoms" can emerge despite a constant dosage with the body needing extra dosage in order to feel normal. ... Gene; Roth, Thomas (August 2007). "Nightly Treatment of Primary Insomnia With Eszopiclone for Six Months: Effect on Sleep, ... This is sometimes associated with dosage escalation. Lormetazepam has a short to intermediate half-life of approximately 10-12 ... reason it is generally recommended to cross from lormetazepam to an equivalent dose of diazepam to gradually taper the dosage. ...
The SRY gene plays an important role in developing the testes of a male individual. Following the development of the testes, ... Utilizing sex steroids as hormonal therapy is deemed controversial with concerns of its duration of initiation, dosage and ... Differentiation of the gonads begins after the 6th week, which is determined by the sex-determining region Y (SRY) gene in the ... genes associated with sexual development, prenatal androgen exposure, interactions with family, and cultural and societal ...
While seed dormancy is linked to many genes, abscisic acid (ABA), a plant hormone, has been linked as a major influencer to ... effective dosages of which would seem to be a function of sublethal stress, which results in stimulation of ethylene production ... In a study on rice and tobacco plants, plants defective in zeaxanthin epoxidase gene, which are linked to ABA-synthesis pathway ...
Cowpox strains tend to have the most intact genes. Predicting the phylogeny by sequence or by gene content produces somewhat ... The recommended dosage of the currently available VIG is 0.6 ml/kg of body weight. VIG must be administered intramuscularly and ... Late genes are expressed from 140 min to 48 hours postinfection, producing all viral structural proteins. Assembly of progeny ... The Modified vaccinia Ankara strain in this regard has much gene loss related to in vitro passage, and horsepox being a ...
Standardization of purity and dosage is not mandated in the United States, but even products made to the same specification may ... Phytochemical researcher Varro Eugene Tyler described paraherbalism as "faulty or inferior herbalism based on pseudoscience", ... which generally does not provide standards for purity or dosage. The scope of herbal medicine commonly includes fungal and bee ...
doi:10.1016/S0040-4039(98)01584-6. Eaton, Andrew D.; Greenberg, Arnold E.; Rice, Eugene W.; Clesceri, Lenore S.; Franson, Mary ... ISBN 978-0-8342-1657-0. Wilhelm N, Kaufmann A, Blanton E, Lantagne D (February 2018). "Sodium hypochlorite dosage for household ... Lantagne DS (2018). "Sodium hypochlorite dosage for household and emergency water treatment". IWA Publishing. 16 (1). "What is ...
The researchers suggested that in order to achieve equivalent exposure, based on an average dose of 100%, the dosage of doxepin ... Since doxepin is mainly metabolized by CYP2D6, CYP2C9, and CYP2C19, genetic variations within the genes coding for these ...
Rarely, mutations in SNCA, the gene for alpha-synuclein, or LRRK2, a gene for a kinase enzyme, can cause any of DLB, ... Decreasing the dosage of dopaminergic or atypical antipsychotic drugs may be needed with orthostatic hypotension, and high ... The APOE gene has three common variants. One, APOE ε4, is a risk factor for DLB and Alzheimer's disease, whereas APOE ε2 may be ... Decline may be more rapid when the APOE gene is present, or when AD-or its biomarkers-is also present. The severity of ...
Carmona-Mora, P; Walz, K (December 2010). "Retinoic Acid Induced 1, RAI1: A Dosage Sensitive Gene Related to Neurobehavioral ... For example, in one study, it was shown that mice with 2 copies of the RAI1 gene and 3 copies of each of the other 18 genes in ... Other candidate genes have been identified within the duplicated section, including SREBF1, DRG2, LLGL1, SHMT1 and ZFP179. In ... In other words, RAI1 is dosage-sensitive. This provides evidence that it is the number of RAI1 copies present that affects the ...
Barbiturates showed some hydrolytic problems in regard to formulation of liquid dosage forms. The difficulty is -OH catalyzed ... "Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A ... Several efficient benzodiazepines offer choices about dosage form, length of action, metabolic interaction and safety. ...
... of substance by consuming a lethal dosage of it. This allows him to not only increase or decrease the lethal dosage needed to ... He was originally Eugene Currier, a boy who was befriended by the Soul Society scientist Ran'tao before being forced to leave ...
... extends the dark pigment so much that it actually masks the effect of the bay pattern gene, A. He called this the gene for ... This type of dosage-dependent behavior was not observed with Agouti. Rieder, Stefan; Sead Taourit; Denis Mariat; Bertrand ... where the blank indicates that the paired gene has no effect. There is no direct evidence that the gene ED exists in the horse ... Both bay and chestnut may be darkened by the sooty gene. Buckskin, tan or gold body coat with the black areas of a bay (above ...
Johnson, Gene (June 26, 2018). "17 states sue to force Trump administration to reunite migrant families separated at border". ... The report noted that staff "described some concerns that dosages or types of medication may not have been right". In December ...
Although compelling evidence on the effect of low dosage of radiation was hard to come by, by the late 1940s, the idea of LNT ... 1 (1). Muller HJ (July 1927). "Artificial Transmutation of the Gene" (PDF). Science. 66 (1699): 84-7. Bibcode:1927Sci....66... ... Several expert scientific panels have been convened on the accuracy of the LNT model at low dosage, and various organizations ... of research on the mutation rate of 1 million lab mice showed that six major hypotheses about ionizing radiation and gene ...
... explained to the President that submariners in the new type craft get an average radiation dosage of about 200 milliroentgens a ... the first nuclear-powered submarine and served under commanding officer Commander Eugene Parks Wilkinson. Ebersole was a member ...
Wormser, Gary P.; Dattwyler, Raymond J.; Shapiro, Eugene D.; Halperin, John J.; Steere, Allen C.; Klempner, Mark S.; Krause, ... and determine dosage are insufficient because they focus on TSH levels as an indicator of thyroid function and miss a large ...
December 2019). "Dosage analysis of the 7q11. 23 Williams region identifies BAZ1B as a major human gene patterning the modern ... This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23. ... is an enzyme that in humans is encoded by the BAZ1B gene. This gene encodes a member of the bromodomain protein family. The ... "Entrez Gene: BAZ1B bromodomain adjacent to zinc finger domain, 1B". Zanella M, Vitriolo A, Andirko A, Martins PT, Sturm S, ...
... functional copy of the gene at the molecular level to affected muscle cells. Dosage, as well as a viable means for systemic ... Biostrophin is a drug which may serve as a vehicle for gene therapy, in the treatment of Duchenne and Becker muscular dystrophy ... As mutations in the gene which codes for the protein dystrophin is the underlying defect responsible for both disorders, ...
Birchler is known for his contributions to the study of gene dosage, dosage compensation, and gene balance using both maize ( ... Between 1978 and 1985 he worked as a postdoc studying gene dosage mechanisms in fruit flies, first at Oak Ridge National ... Professor at University of Missouri where he studies gene dosage, polyploidy, and cytogenetics in both maize and drosophila. In ... he moved to Indiana University where he studied maize dosage effects using B chromosomes with Drew Schwartz, graduating in 1977 ...
... gene were identified. Inactivation of TET2 gene caused by loss-of-function mutations in mice leads to abnormal haematopoiesis, ... High dosage of chemotherapy may damage the bone marrow, in which autologous stem cell therapy is a recommended follow-up ... Some subtypes of mature T-cell lymphoma may be associated with viral exposure as well as gene mutations. Diagnosis is done by ... Mature T-cell lymphoma can be associated with viral exposure and gene mutations. Mature T-cell lymphoma can be associated with ...
... human gene location in the UCSC Genome Browser. CITED2 human gene details in the UCSC Genome Browser. v t e (Genes on ... "Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage". Development. 134 (12): 2349-58. doi: ... Sun HB, Zhu YX, Yin T, Sledge G, Yang YC (Nov 1998). "MRG1, the product of a melanocyte-specific gene related gene, is a ... "Entrez Gene: CITED2 Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2". Bhattacharya S, Michels ...
The oral dosage administrative form is considered less effective than nasal or parental forms and has been discontinued in ... They are calcitonin gene-related peptide (CGRP) receptor antagonists. Gepants have been suggested to have less pain relief at 2 ... and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies". Pharmaceutics. 12 (12): 1180. doi:10.3390/ ...
High dosages of testosterone but not low dosages of testosterone enhance the effects of low dosages of estrogens on sexual ... the good genes hypothesis). Following natural or surgically induced menopause, many women experience declines in sexual ... Further higher dosages of testosterone may result in greater effects on sexual desire in women. High dosages of testosterone ( ... Low dosages of testosterone that result in physiological levels of testosterone (< 50 ng/dL) do not increase sexual desire in ...
In these tumors, the INI1 gene (SMARCB1)on chromosome 22q functions as a classic tumor suppressor gene. Inactivation of INI1 ... "Allelic dosage analysis with genotyping microarrays". Biochem Biophys Res Commun. 333 (4): 1309-14. doi:10.1016/j.bbrc.2005.06. ... Copy neutral LOH (acquired uniparental disomy) has been reported at key loci in ALL, such as CDKN2A gene at 9p, which have ... It contains 1.8 million polymorphic and non-polymorphic markers for a practical resolution of 10-20kb-about the size of a gene ...
Genomic variants affecting homoeologous gene expression dosage contribute to agronomic trait variation in allopolyploid wheat ... The frequency and expression of homoeologous gene alleles showing strong expression dosage bias are predictive of variation in ... Though trans-acting effects play major role in expression regulation, the expression dosage of homoeologs is largely influenced ... Our study highlights the importance of genomic variants affecting homoeolog expression dosage in shaping agronomic phenotypes ...
Zygotically transcribed genes Sex Determination and Dosage Compensation Genes. A simplified model for sex determination in the ... 30 genes or 1.2% of X chromosome genes tested). Second, the ratio of average gene expression between X chromsome genes and ... Chromosome topology guides the Drosophila Dosage Compensation Complex for target gene activation. X chromosome dosage ... Dosage compensation of neo-X genes is advantageous because ~40% of homologous neo-Y genes are pseudogenized; however, because ...
The maize Hm2 gene provides protection against the leaf spot and ear mold disease caused by Cochliobolus carbonum race 1 (CCR1 ... In this regard, it is similar to Hm1, the better-known disease resistance gene of the maize--CCR1 pathosystem. However, in ... The maize Hm2 gene provides protection against the leaf spot and ear mold disease caused by Cochliobolus carbonum race 1 (CCR1 ... In contrast, however, the Hm2 transcript is much more abundant in plants homozygous for this gene compared with plants that ...
The contribution of APP gene dosage to the molecular phenotypes of Alzheimers disease in human trisomy 21 neurons ... Having three copies of the APP gene, which resides on Chr 21 is attributed to the incidence of Alzheimers disease in trisomy ... To study the contribution of increased APP dosage to AD-related phenotypes, CRISPR Cas9 was used to introduce out of frame ... I found that the extra copy of the APP gene contributed to enlarged early endosomes and impaired autophagic degradation, which ...
Influence of CYP4F2, ApoE, and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility ... Influence of CYP4F2, ApoE, and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility ... Influence of CYP4F2, ApoE, and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility ... Influence of CYP4F2, ApoE, and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility ...
Correcting Dyrk1a gene dosage The Dyrk1a gene dosage was genetically normalized in TS mice via repeatedly backcrossing TS ... diploid gene dosage (CO +/+). Correction of the Dyrk1a dosage in TS +/+/- mice was validated by karyotyping and immuoblot. ... Titration of gene trisomy in Down syndrome. Down syndrome (DS) is a condition in which trisomy of chromosome 21 leads to ... Despite changes in the biology of hippocampal neurons in TS +/+/- mice, correction of Dyrk1a dosage in these mice does not ...
Dosage effect of some genes in the concerned genomic region is known, but several genes have no evidence to have dosage ... On the other hand increased dosage of the KLF13 gene seems to have no direct causal relationship with heart morphology. The ... We assume dosage dependence in the case of CHRNA7 and OTUD7A, which might be involved in growth regulation. ... genomic environment of the affected genes may be responsible for the observed phenotype. ...
Tissenbaum, H. A. & Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227- ... Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans *Heidi A. Tissenbaum ... Bamps, S., Wirtz, J., Savory, F. R., Lake, D. & Hope, I. A. The Caenorhabditis elegans sirtuin gene, sir-2. 1, is widely ... Viswanathan, M., Kim, S. K., Berdichevsky, A. & Guarente, L. A role for SIR-2.1 regulation of ER stress response genes in ...
This study aims to clone male-specific lethal 1 gene Hamsl1 from H. armigera and to investigate whether it regulates dosage ... Identification and functional analysis of the dosage compensation related gene Hamsl1 in Helicoverpa armigera (Lepidoptera: ... Identification and functional analysis of the dosage compensation related gene Hamsl1 in Helicoverpa armigera (Lepidoptera: ... armigera and may regulate the dosage compensation by inhibiting the expression of Z-linked genes in male H. armigera. This ...
Complexity of Gene Expression Evolution after Duplication: Protein Dosage Rebalancing. Igor B. Rogozin ... Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes. Dorra Hmida-Ben Brahim ... Generalized Portrait of Cancer Metabolic Pathways Inferred from a List of Genes Overexpressed in Cancer. Eugenia Poliakov , ... Using new understanding of genes and pathways to develop powerful new therapeutic approaches to disease ...
We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic ... Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in monozygotic twins ... gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in ...
cáncer ; oncogenes ; dosis génica ; PCR en tiempo real ; sondas TaqMan ; cancer ; oncogenes ; gene dosage ; real time PCR ; ... Gene dosage tests are very important for the molecular diagnosis of diseases caused by either deletion or amplification of a ... Development and validation of a taqman multiplex pcr assay for the gene dosage quantification in cancer. ... In the present study, we have developed an assay using TaqManTM multiplex Real-time PCR for gene dosage analysis of oncogenes ...
Sex-chromosome dosage effects on gene expression in humans. Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):7398-7403. doi: ... It can include several genes, but only duplication of the GPR101 gene is necessary to cause X-LAG. The GPR101 gene provides ... The translocation affects the gene responsible for development of a fetus into a male (the SRY gene). The SRY gene, which is ... Some genes on the X chromosome escape X-inactivation. Many of these genes are located at the ends of each arm of the X ...
Gene and genome duplications: The impact of dosage-sensitivity on the fate of nuclear genes. Read our blog about seriously cool ...
... gene exons by comparing the intensity of the amplification signals from some exon of this gene with that of the β-globin gene ( ... Deletions and duplications of single exons or exon groups account for a large proportion of the gene mutations. Direct ... the internal control). We analyzed rearrangements in exons 1-12 of the PARK2 gene in 64 patients from Russia with early-onset ... and reproducible method applicable to the rapid detection of exon rearrangements in the PARK2 gene. It is suitable for the ...
Gene Duplication. Genome. Macaca mulatta. Nucleic Acid Hybridization. Gene Dosage. Biological Evolution. Genome, Human. Pan ...
SMN1 -targeted mutation analysis is used diagnostically to detect deletion of exons 7 and 8. SMN gene dosage analysis, ... Is $3.5 Million a Fair Price for a Lifesaving Gene Therapy? * EMA Seeks to Issue Guidance on Liver Damage From Novartis Gene ... Mutations in several genes, including the C9orf72, SOD1, TARDBP, FUS, ANG, ALS2, DAO, OPTN, VCP, UBQLN2, and VAPB genes, are ... Type I-III spinal muscular atrophy (SMA) is caused by alterations in the survival motor neuron gene (SMN). This gene becomes ...
Is There a Role for MDR1, EPHX1 and Protein Z Gene Variants in Modulation of Warfarin Dosage? A Study on a Cohort of the ... The gene vitamin K epoxide reductase complex subunit 1 (VKORC1), which encodes a small transmembrane protein of the endoplasmic ... Warfarin dose/week was not influenced by each of the MDR1 C3435T, EPHX1 H139R, and PZ A-13G gene polymorphisms when examined ... Frequency of VKORC1 Gene Polymorphisms and Its Association with Warfarin Dose Requirement in Patients from Mazandaran Province ...
The combination of CRISPR Cas9-based gene editing and bioluminescent detection using the HiBiT system enables the study of a ... Monitor physiological expression levels: no gene dosage effect. *Study genes under control of a native promoter and epigenetic ... Using CRISPR/Cas9 gene editing, endogenous downstream target genes can be tagged and the expression of their corresponding ... Downstream Target Gene Regulation. Changes in the abundance or activity of proteins upstream in a signaling pathway often ...
There appears to be a direct relationship of gene dosage at the PMP22 locus with the phenotype palsies (20). ... Mutations in the peripheral myelin genes and associated genes in inherited peripheral neuropathies. Human Mutat. 1999;13:11-28 ... The deletion at 17p11.2 includes the gene for peripheral myelin protein-22 (PMP22) (23, 27). The gene for PMP22 spans ... In FAP2 patients, there is more frequent carpal tunnel manifestation (39). In the United States, the gene frequency for FAP1 ...
Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. 26 July 2012. 26 July 2012. - by ... Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus Read More ...
... we utilize a human DEFA1A3 gene knock-in mouse with a 4 copy gene per haploid genome to study gene-dosage interactions. This ... α-Defensins 1-3 Gene-Dosage Drives Protection of the Urinary Tract From Uropathogenic Bacterial Challenge. November 05, 2022 , ... α-Defensins 1-3 Gene-Dosage Drives Protection of the Urinary Tract From Uropathogenic Bacterial Challenge. Session Information ... The human DEFA1A3 gene knock-in mouse represents a critical tool to evaluate novel α-defensins 1-3 gene-immune interactions. ...
ClinGen curation activities (Dosage Sensitivity and Gene-Disease Validity). ClinGen CNVs. hide. dense. squish. pack. full. ... HUGO Gene Nomenclature. IKMC Genes Mapped. hide. dense. squish. pack. full. International Knockout Mouse Consortium Genes ... Gene Prediction Archive. SIB Genes. hide. dense. squish. pack. full. Swiss Institute of Bioinformatics Gene Predictions from ... Genscan Genes. hide. dense. squish. pack. full. Genscan Gene Predictions. Geneid Genes. hide. dense. squish. pack. full. Geneid ...
... well-established rodent models of glaucoma including optic nerve injury models and transcriptomic gene expression profiling, ... overview of pathological features in a variety of animal models of glaucoma and top differentially expressed genes (DEGs) ... overview of pathological features in a variety of animal models of glaucoma and top differentially expressed genes (DEGs) ... well-established rodent models of glaucoma including optic nerve injury models and transcriptomic gene expression profiling, ...
Gene dosage alterations were not detected in the TTBK2-gene. Clinically, our SCA11 patients had phenotypic characteristics as ... For both cohorts, the gene-dosage alterations were assessed using a customized multiplex ligation probe amplification (MLPA) ... Methods: In the German ADCA cohort the complete coding sequence of the TTBK2-gene was PCR-amplified and screened for mutations ... and six genes with classical mutations (SCA5, 13, 14, 15/16, 27, adn 28). Recently, a large British pedigree linked to SCA11 ...
The long non-coding RNA Paupar regulates the expression of both local and distal genes. Vance, K. W., Sansom, S. N., Lee, S., ... of transcriptional dynamics allows robust estimation of transcription rates in populations of single cells with variable gene ...
Muller, C.R.; Migl, B.; Traupe, H.; Ropers, H.H. X-linked steroid sulfatase: Evidence for different gene-dosage in males and ... Filaggrin Gene Nutation. Th2 Regulation by DHEA. Th2 Regulation by Sex Hormones. Th2 Regulation by DHEA. Skin Barrier ... Filaggrin Gene Nutation. Exposure to Ni. Stimulation of Th1 Response to Ni by DHEA. Exposure to Ni. Regulation of Th2 Response ... AD patients mostly show reduction of filaggrin expression partly due to mutation of this gene [1,2,3] and reveal decreases in ...
Triticum aestivum; Puccinia recondita; rust diseases; disease resistance; genetic resistance; alleles; gene dosage; dose ... The Lr34 gene is known to confer durable resistance. We evaluated the effect of Lr34 on grain yield and other traits in the ... A RAPD marker and a RFLP marker were located on opposite flanks of the resistance gene and were sho .... DOI:. 10.1139/g97-025 ... Genes for resistance to BYDV do not exist in wheat (Triticum aestivum). Using the tissue-blot immunoassay, the partial ...
  • We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. (
  • Due to the lack of this gene in mice, we utilize a human DEFA1A3 gene knock-in mouse with a 4 copy gene per haploid genome to study gene-dosage interactions. (
  • One of the goals of genome sequencing is to identify all the genes in an organism. (
  • Yeast genome sequence analysts probably would not have guessed that careful computational analyses had missed the presence of two large gene families and almost 100 new genes. (
  • Although entire genome sequences are available for numerous species, lack of reverse genetic tools has hindered cross-species comparisons of gene function. (
  • These RNA molecules are coded in the genome, but different organisms have different 'copy numbers': some genomes contain just a few copies of each of these genes, while others have thousands. (
  • We consider issues of study design, and we discuss common variant approaches including candidate gene studies and genome-wide association studies (GWAS). (
  • In participating UK research institutions, investigators can publish open access in Genome Research, Genes & Development, RNA, and Learning & Memory without article publication charges and all staff can read the entire renowned Cold Spring Harbor journal collection. (
  • After RNAi of Hamsl 1 via microinjection of Hamsl 1 siRNA into the 3rd instar larvae of H. armigera , the expression levels of 15 Z-linked genes were detected by qPCR to verify whether Hamsl 1 regulates the dose of genes on Z chromosome. (
  • The qPCR analysis demonstrated that Hamsl 1 gene was located on the Z chromosome of H. armigera . (
  • Conclusion】 This study preliminarily proves that Hams l1 gene is located on the Z chromosome of H. armigera and may regulate the dosage compensation by inhibiting the expression of Z-linked genes in male H. armigera . (
  • Some genes on the X chromosome escape X-inactivation. (
  • Many of these genes are located at the ends of each arm of the X chromosome in areas known as the pseudoautosomal regions. (
  • Although many genes are unique to the X chromosome, genes in the pseudoautosomal regions are present on both sex chromosomes. (
  • Identifying genes on each chromosome is an active area of genetic research. (
  • Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. (
  • The X chromosome likely contains 900 to 1,400 genes that provide instructions for making proteins. (
  • The SRY gene, which is normally found on the Y chromosome, is misplaced in this condition, almost always onto an X chromosome. (
  • A fetus with an X chromosome that carries the SRY gene will develop as a male despite not having a Y chromosome. (
  • Having extra copies of multiple genes on the X chromosome affects many aspects of development, including sex development before birth and at puberty. (
  • The sex of human and other mammal babies is decided by a male-determining gene on the Y chromosome. (
  • But the human Y chromosome is degenerating and may disappear in a few million years, leading to our extinction unless we evolve a new sex gene. (
  • But the Y chromosome packs a punch because it contains an all-important gene that kick-starts male development in the embryo. (
  • In turn, this must mean the Y chromosome has lost 900-55 active genes over the 166 million years that humans and platypus have been evolving separately. (
  • What they discovered was a tiny difference near the key sex gene SOX9, on chromosome 3 of the spiny rat. (
  • Karyotype, as a proxy for X chromosome (Xchr) gene dosage, has been associated with DM risk in TS - however, no specific Xchr genes or loci have been implicated in the TS hyperglycemia phenotype. (
  • The locus at chromosome 1q21 was identified by linkage mapping in 1998, but the gene has only recently been discovered due to difficulty with sequencing this highly repetitive region and was previously missed using next-generation sequencing. (
  • The presence of extra chromosome 21 (or critical regions of it) associated with this syndrome, and the resultant change in gene dosage, is responsible for many structural and functional abnormalities in the nervous system of these children, which can be evidenced by psychomotor developmental delay commonly observed. (
  • Our study highlights the importance of genomic variants affecting homoeolog expression dosage in shaping agronomic phenotypes and points at their potential utility for improving yield in polyploid crops. (
  • To study the contribution of increased APP dosage to AD-related phenotypes, CRISPR Cas9 was used to introduce out of frame mutations to disrupt the reading frame of mRNA in one copy of the APP gene, and I discovered that three functional copies of the APP gene are required to cause AD phenotypes in trisomy 21 neurons. (
  • In trisomy 21 neurons, APP dosage contributed to the molecular phenotypes of Alzheimer's disease and the dysregulation of lysosomal degradation pathways, which provides a cellular mechanism for tau accumulation. (
  • examined the contribution of trisomic gene Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a) to the cognitive and morphological phenotypes of the Ts65Dn (B6EiCSN.BLiA-TS(17 16 )65Dn/J ( 005252 )) DS mouse model. (
  • These experiments demonstrate that decreased Dyrk1a dosage in TS +/+/- mice reduces a number of the cognitive and behavioral phenotypes associated with this DS model, including deficits in working memory, fear conditioning, and hyperactivity/anxiety. (
  • Included are methods for assessing phenotypes caused by loss-of-function mutations in the worm CCM genes kri-1 and ccm-3 , CRISPR-based gene editing techniques, and protocols for conducting high-throughput forward genetic and small molecule screens. (
  • How many of the systematic gene knockouts being generated in yeast will also knock out an unsuspected RNA gene (especially intronic ones), and thus superpose two genetic phenotypes on the resulting disruption? (
  • Doxorubicin (Dox), as a first-line drug for breast cancer therapy, upregulates several EMT-related genes, including HIF1α, Twist1, Snail, and ZEB1 that can promote cancer cells to acquire more aggressive phenotypes. (
  • Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. (
  • Following gene expression antimicrobial response array and qRT-PCR in DEFA1A3 +/+ and DEFA1A3 0/0 kidneys, the most significantly differentially expressed genes were Rac1 and Lyz2 (Figure 2). (
  • In this review, we present a comprehensive overview of pathological features in a variety of animal models of glaucoma and top differentially expressed genes (DEGs) depending on disease progression, RGC subtypes, retinal regions or animal species. (
  • Several transcriptomic studies with RNA sequencing (RNA-seq) or microarray have uncovered differentially expressed genes (DEGs) in RGCs or whole retina depending on disease progression, retinal regions, animal species or RGC subtypes. (
  • Gene dosage in the dysbindin schizophrenia susceptibility network differentially affect synaptic function and plasticity. (
  • We evaluated real-time (kinetic) reverse transcription-polymerase chain response (RT-PCR) to validate differentially expressed genes identified by DNA arrays. (
  • 9, 10 In this study, we explored the applicability of kinetic RT-PCR as a rapid procedure for the validation of a number of differentially expressed genes identified by HDFA. (
  • The number of copies of a given gene present in the cell of an organism. (
  • Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by inactivating mutations of the MEN1 tumor suppressor gene at the 11q13 locus. (
  • Aim】 The dosage compensation mechanism of Helicoverpa armigera is still unclear. (
  • This study aims to clone male-specific lethal 1 gene Hamsl 1 from H. armigera and to investigate whether it regulates dosage compensation of H. armigera by RNA interference technology. (
  • Sex-dimorphic gene expression and ineffective dosage compensation of Z-linked genes in gastrulating chicken embryos. (
  • GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage. (
  • As reproductive isolation restricts gene flow, it also can facilitate genomic divergence between populations [6-9]. (
  • To identify the deletion, we conducted gene dosage analysis and array-based comparative genomic hybridization (aCGH) analysis. (
  • Variants in only one gene showed genomic signatures of positive, evolutionary selection within Caucasian populations melanophilin (MLPH). (
  • Genetic screening of a yeast genomic library in a high-copy-number vector identified the normally single-copy tRNA CCU Arg gene as one of the genes that reduces Ty1 transposition frequency when overexpressed. (
  • Having three copies of the APP gene, which resides on Chr 21 is attributed to the incidence of Alzheimer's disease in trisomy 21, supported by APP locus duplication which is fully penetrant for early onset familial Alzheimer's disease. (
  • Genetically, HSPs are classified by the mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and are subdivided by chromosomal locus or causative gene. (
  • In this study, we employed the PCR-RFLP method to investigate such an effect of the common Ava II (exon 13) and Nco I (exon 18) polymorphisms at the low density lipoprotein (LDL) receptor gene locus in 54 normolipidemic Thai subjects. (
  • Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes. (
  • Is There a Role for MDR1, EPHX1 and Protein Z Gene Variants in Modulation of Warfarin Dosage? (
  • Computational methods for protein coding gene identification are reasonably well developed, especially for compact genomes with few or no introns. (
  • Protein coding genes have open reading frames, codon bias, and other telltale statistical signals that can be recognized. (
  • The protein encoded by this gene is a RING-H2 zinc finger protein. (
  • Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder, usually caused by mutations in the methyl-CpG-binding protein 2 ( MECP2 , OMIM#300005) gene. (
  • Immunoblot analyses of Ty1-encoded proteins indicate an inverse correlation between the copy number of the tRNA gene and the production of the TYB protein. (
  • Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. (
  • Instead of replacing a defective gene, the treatment inserts a gene directing eye cells to produce a protein that inhibits the abnormal growth of blood vessels - the reason for her vision loss. (
  • Xu, H & Boeke, JD 1990, ' Host genes that influence transposition in yeast: The abundance of a rare tRNA regulates Ty1 transposition frequency ', Proceedings of the National Academy of Sciences of the United States of America , vol. 87, no. 21, pp. 8360-8364. (
  • The rate and accuracy of translation hinges upon multiple components - including transfer RNA (tRNA) pools, tRNA modifying enzymes, and rRNA molecules - many of which are redundant in terms of gene copy number or function. (
  • We manipulated redundancy in multiple translation components of Escherichia coli by deleting 28 tRNA genes, 3 tRNA modifying systems, and 4 rRNA operons in various combinations. (
  • This nutrient-dependent cost of redundant tRNA genes stems from upper limits to translation capacity and growth rate, and therefore varies as a function of the maximum growth rate attainable in a given nutrient niche. (
  • The loss of redundancy in rRNA genes and tRNA modifying enzymes had similar nutrient-dependent fitness consequences. (
  • Importantly, these effects are also contingent upon interactions across translation components, indicating a layered hierarchy from copy number of tRNA and rRNA genes to their expression and downstream processing. (
  • The developmentally specified phenotype of Hm2 is not dictated transcriptionally, because the expression level of the gene, whether occurring constitutively or undergoing substantial and transient induction in response to infection, does not change with plant age. (
  • Changes in gene copy number may lead to under- or over expression of genes responsible for the disease phenotype. (
  • A Tbx6 -/mh (mild-hypomorphic) mouse model supported that a gene dosage effect underlies the TACS phenotype. (
  • Therapeutic interventions targeting these identified genes and molecular pathways could be promising therapies. (
  • Because it often uses repurposed viruses to deliver therapeutic genes, gene therapy has been caught in a vicious cycle for nearly two decades owing to immune response, insertional mutagenesis, viral tropism, off-target activity, unwanted clinical outcomes (ranging from illness to death of participants in clinical trials), and patchy regulations (23, 28-31). (
  • She recently had a virus, modified to carry a therapeutic gene, injected into one of her eyes. (
  • DMSO, when given to a patient undergoing chemotherapy may help the doctor reduce the dosage of the chemo-therapeutic agent. (
  • Variation at the GABAA receptor gene, Rho 1 (GABRR1) associated with susceptibility to bipolar schizoaffective disorder. (
  • the temephos discriminating dosage for susceptibility monitoring of An. (
  • L'ACPA identifie des anomalies de dosage génique pathogènes à type de délétion ou duplication chez 12 à 18 % des patients avec déficience intellectuelle syndromique. (
  • An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. (
  • Dyrk1a contributes to normal brain development and adult brain physiology and is one of the candidate genes implicated in the cognitive impairments associated with Down syndrome. (
  • Allopolyploidy greatly expands the range of possible regulatory interactions among functionally redundant homoeologous genes. (
  • Many RNAs are small genes that occur in redundant copies, and RNAs are of course not affected by stop codons or frameshifts, so they are probably somewhat refractory to genetic screens. (
  • The American Society of Gene Therapy has taken lead in fixing this fragmented funding method by making many recommendations including the elimination of redundant regulatory processes and establishment of the National Gene Vector Laboratories (NGVL) to review vector production and toxicology. (
  • In order to overcome these major barriers, an increased number of studies have utilized the following combined analytical methods: well-established rodent models of glaucoma including optic nerve injury models and transcriptomic gene expression profiling, resulting in the successful identification of molecules and signaling pathways relevant to RGC protection. (
  • This chapter presents methods for exploiting the powerful tools available in the nematode worm Caenorhabditis elegans to understand the in vivo functions of cerebral cavernous malformation (CCM) genes and the organization of their associated signaling pathways. (
  • The human DEFA1A3 gene knock-in mouse represents a critical tool to evaluate novel α-defensins 1-3 gene-immune interactions. (
  • Further studies will involve exploring gene-drug interactions under antibiotic prophylaxis settings before UTI challenge. (
  • These mechanisms are thought to result from allele-specific dysgenic interactions between two or more genes [2-5]. (
  • We also discuss the complexities embedded in exploring gene-environment interactions. (
  • Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. (
  • The discovery of the homology of the key sex-determining genes doublesex in Drosophila and mab-3 in C. elegans provided the first evidence for a common evolutionary basis of sex determination in animals. (
  • The selected genes and their polymorphisms are involved in many GWAS associated with cardiovascular disease and variability in warfarin treatment. (
  • Warfarin dose/week was not influenced by each of the MDR1 C3435T, EPHX1 H139R, and PZ A-13G gene polymorphisms when examined separately, but when these single nucleotide polymorphisms (SNPs) were combined, MDR 1 TT/EPHX1 RH,RR/PZ AA subjects showed statistically significant increase in warfarindose/week. (
  • Gene-dose effects have previously been noted for HRAS-l rare alleles and polymorphisms in carcinogen metabolizing enzymes. (
  • IMSEAR at SEARO: Effect of Ava II and NcoI polymorphisms at the low density lipoprotein receptor gene on plasma lipid levels in a group of Thai subjects. (
  • Pongrapeeporn KU, Pimsawat T, Likidlilid A, Poldee S, Yamwong P, Amornrattana A, Ong-Ajyooth S. Effect of Ava II and NcoI polymorphisms at the low density lipoprotein receptor gene on plasma lipid levels in a group of Thai subjects. (
  • Kidney DEFA1A3 +/+ and DEFA1A3 0/0 mouse mRNA expression of Rac (A) and Lyz2 (B) relative to Gapdh gene. (
  • The mRNA vaccinations are a form of gene therapy, according to its definition in many parts of the world, including Europe. (
  • DNA was extracted and the Mass ARRAY™ system was used to genotype four selected SNPs within three genes ( CYP4F2 , ApoE, and CYP2A6 ). (
  • To gain insight into evolutionary origins, we screened a series of genes and SNPs linked to breast or prostate cancer for signatures of historical positive selection. (
  • The emergence of nutrigenomics (how diet effects our genes) and epigenetics (how the environment effects our genes) is demonstrating that people with certain genetic propensities need more or certain nutrients and that environmental influences can modulate disease risk. (
  • The most common mutations in the gene are p.R168X and p.T158M. (
  • Our results strongly confirm that ITPR1 is the causative gene for SCA15 and suggest that we need to investigate the point mutation in ITPR1 in the patients with autosomal dominant cerebellar ataxia and tremor. (
  • As a result, men and women each have two functional copies of these genes. (
  • Extra copies of genes from the pseudoautosomal regions of the extra X and Y chromosomes likely contribute to the signs and symptoms of 48,XXYY syndrome. (
  • This apparent redundancy - the presence of several copies of the same gene - is puzzling because it is costly to make and maintain DNA and RNA. (
  • A possible reason for organisms to have many copies of the genes required to make proteins is to allow rapid translation, which allows cells to divide faster, and populations of cells to grow more quickly. (
  • However, this would likely mean that, when nutrients are scarce, carrying and translating many copies of the same gene would become a burden on the cell. (
  • Untreated, babies with their "bubble boy" disease would die in infancy, but in 2010 and 2012, doctors inserted good copies of the gene into their bone marrow cells, restoring the boys' immune systems. (
  • Over the years, scientists have improved the safety of the viruses used to insert good copies of genes into cells. (
  • Though trans-acting effects play major role in expression regulation, the expression dosage of homoeologs is largely influenced by cis-acting variants, which appear to be subjected to selection. (
  • Viswanathan, M., Kim, S. K., Berdichevsky, A. & Guarente, L. A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. (
  • Gene therapies remain under strict regulation and few gene therapeutics have been approved by health authorities because of safety concerns. (
  • The frequency and expression of homoeologous gene alleles showing strong expression dosage bias are predictive of variation in yield-related traits, and have likely been impacted by breeding for increased productivity. (
  • Evolutionary selection of alleles in the melanophilin gene that impacts on prostate organ function and cancer risk. (
  • Curated mutant alleles for the specified gene, listed alphabetically. (
  • Molecular characterization and functional analysis of tyrosine hydroxylase gene in Helicoverpa armigera (Lepidoptera: Noctuidae) [J]. Acta Entomologica Sinica, 2019, 62(3): 294-303. (
  • Gene dosage tests are very important for the molecular diagnosis of diseases caused by either deletion or amplification of a specific DNA region containing certain genes. (
  • GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies ( Molecular Function , Biological Process , and Cellular Component ), a reference, and an evidence code. (
  • Instead, S23 is only interested in increasing the activity of genes which are responsible for making muscle proteins, whilst sending signals to bone-building cells to boost production. (
  • a IL-1 gene manifestation was considerably less pronounced in PKRA7-treated mice (ideals by Mann-Whitney check Discussion In today's study, we exhibited that PKR1 proteins was indicated in infiltrating neutrophils, while PKR2 proteins was within macrophage-like mononuclear cells in the synovial membrane of CIA mice. (
  • We discovered that PKR2 proteins was within macrophage-like cells in the synovial membrane of CIA mice which, unlike PKR1, PKR2 gene manifestation was even more pronounced in swollen joints. (
  • 8, 9, 10 Real-time (kinetic) PCR evaluates product accumulation during the log-linear phase of the reaction and is currently the most accurate and reproducible approach to gene quantification. (
  • In addition to these key regulators, many other genes affect germline proliferation. (
  • MF patient hematopoietic stem/progenitor cells are enriched for a CXCL8/CXCR2 gene signature and display enhanced proliferation and fitness in response to exogenous CXCL8 ligand in vitro. (
  • As the vaccinations begin to spread among the world population, the growth of other gene therapies as a type of vaccination could increase. (
  • As far as we are aware this is the first report of a gene-dose effect for a polymorphism in a tumor suppressor gene. (
  • It works by triggering a genetic pathway starting with a gene called SOX9 which is key for male determination in all vertebrates, although it does not lie on sex chromosomes. (
  • Kuroiwa's team discovered most of the genes on the Y of spiny rats had been relocated to other chromosomes. (
  • Variants within the melanophilin (MLPH) gene fell into this category. (
  • UMOD risk variants identified in the above-mentioned GWAS are located in the promoter region of the gene, leading to a theory that they altered UMOD expression. (
  • Annotations from the Clinical Interpretations of Variants in Cancer (CIViC) database are now available as Evidence and within the Gene Viewer. (
  • Worldwide, approximately 20% of cases of familial ALS are due to a mutation in the Cu/Zn superoxide dismutase-1 gene ( SOD1 ). (
  • Recently, a large British pedigree linked to SCA11 has been reported to carry a mutation in the TTBK2-gene. (
  • Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a back mutation , for example, through gene conversion ). (
  • We explored this possibility in DYT1 dystonia, a neurodevelopmental movement disorder caused by a loss-of-function (LOF) mutation in the TOR1A gene encoding torsinA. (
  • This disease, previously referred to as MCKD type 1, is due to a mutation in the variable-number tandem repeat region of the MUC1 (Mucin 1) gene. (
  • In " A New Dawn " (8/19) about Dawn Lesley, who's challenging Lane County Commissioner Jay Bozievich for his west Lane County seat, Eugene Weekly mistakenly reported that Commissioner Jay Bozievich voted against the 2021 county budget because it was going to the Association of Oregon Counties (AOC). (
  • The type and distribution of vertebral column abnormalities in TBX6/Tbx6 compound inheritance implicate subtle perturbations in gene dosage as a cause of spine developmental birth defects responsible for about 10% of CS. (
  • Despite recent progress in finding highly informative mutations in some cases a majority of nonsyndromic birth defects still does not appear to be accounted for by a single gene or chromosomal abnormality. (
  • This strategy produced mice that carried a complete, triplicated Mmu16 segment (TS +/+/+), mice that carried a triplicated Mmu16 segment but were diploid for Dyrk1a (TS +/+/-), and mice that carried the normal, diploid gene dosage (CO +/+). Correction of the Dyrk1a dosage in TS +/+/- mice was validated by karyotyping and immuoblot. (
  • In particular, an interplay of transcriptional regulatory cascades and networks involving CES-1 , CES-2 , HLH-1 / HLH-2 , TRA-1 , and other transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 in cells destined to die. (
  • Interestingly, we found that liposomal formulation significantly altered the transcriptional pattern of a wide range of genes. (
  • The Pseudomonas putida F1 todC1C2BA genes code for toluene dioxygenase, which initiates the degradation of toluene, as well as the catalysis of indan oxidation to (-)-(1R)-indanol and trans-1,3-indandiol. (
  • The xol-1 orthologues of the closely related nematodes C. elegans and C. briggsae are a mere 22% identical, even though genes surrounding xol-1 are much better conserved. (
  • Tissenbaum, H. A. & Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans . (
  • Genetic studies in C. elegans have led to the identification of more than two dozen genes that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. (
  • We developed efficient procedures for targeted, heritable disruption of genes and cis-acting regulatory elements in the model nematode Caenorhabditis elegans and applied them to C. briggsae , a species diverged by 15 to 30 million years. (
  • The todC1C2BA genes were transferred to Escherichia coli and the indan oxidation reaction catalyzed in this system was compared to that in P. putida. (
  • Identification of X-chromosomal genes that drive global X-dosage effects in mammals. (
  • Researchers are working to determine which genes contribute to the specific developmental and physical differences that occur with 48,XXXY syndrome. (
  • The contribution of common genetic variations at the LDL receptor gene in determining interindividual differences in plasma lipid levels in the general population has been observed in several studies. (
  • Whereas some investigators interpret a twofold difference in hybridization intensity as evidence of differential gene expression, others require fourfold differences. (
  • Methods: In the German ADCA cohort the complete coding sequence of the TTBK2-gene was PCR-amplified and screened for mutations by high-resolution-melting (HRM) analysis. (
  • Aspergillus viridinutans , a mold phenotypically resembling A. fumigatus , was identified by gene sequence analyses from 2 patients. (
  • [2] While this constitutes only 0.000165% of the human genome's approximately 6 billion bases, unrepaired lesions in critical genes (such as tumor suppressor genes ) can impede a cell's ability to carry out its function and appreciably increase the likelihood of tumor formation and contribute to tumour heterogeneity . (
  • But this can't happen in humans or other mammals because we have at least 30 crucial "imprinted" genes that work only if they come from the father via sperm. (
  • The new finding supports an alternative possibility - that humans can evolve a new sex determining gene. (
  • The aim was to determine the lethal concentrations LC100 of temephos for the most susceptible populations and to define the discriminating dosage as the double of this value. (
  • This report, expanded to include more women and using a new analytic approach, contains data that suggest a strong gene-dose effect of the p53 variant on breast cancer risk. (
  • The gene expression profiles of Hamsl 1 in different developmental stages of H. armigera were detected by qPCR. (
  • After many years of research, it became clear that some autosomal, recessive forms of Parkinson's are caused by mutations in genes that affect mitochondrial function or quality control. (
  • For both cohorts, the gene-dosage alterations were assessed using a customized multiplex ligation probe amplification (MLPA) assay. (
  • Gene dosage alterations were not detected in the TTBK2-gene. (
  • Extensive research on the effects of green tea has suggested that this natural product, which is used in so many cultures, in so many different ways, shows that the neuroprotective/neurodegenerative effects of green tea catechins not only act as antioxidants metal chelators, but also as modulators of intracellular neuronal signaling and metabolism, cell survival/death genes, and mitochondrial function. (
  • Table 3 Results of exon dosage analysis for the nine PD patients with exon deletions and duplications. (
  • The technique, in which doctors "infect" patients' cells with viruses engineered to carry useful genes, has matured and evolved. (
  • Nous avons examiné les dossiers de 56 patients ayant eu un diagnostic de fièvre méditerranéenne familiale et suivis au Centre médical Roi Hussein en Jordanie sur une période de 4 ans afin d'étudier leur profil clinique, l'évolution de la maladie, le génotype, le traitement et les complications. (
  • En ce qui concerne le traitement, 97 % des patients répondaient bien à la colchicine et une amyloïdose n'a été documentée chez aucun des patients après un suivi de 5 ans. (
  • The translocation affects the gene responsible for development of a fetus into a male (the SRY gene). (
  • Mutations in the C9orf72 gene are responsible for 30-40% of familial ALS cases in the United States and Europe. (
  • Beutler et al (Proc Nat Acad Sci 95:8170-8174, 1998) described the variant in the promoter of the UGT1A1 gene that is responsible for most cases of Gilbert syndrome as the presence of 7 instead of 6 thymine-adenine (TA) repeats in the promoter region of the gene. (
  • The gene responsible for FMF is designated MEFV and was recently cloned [8]. (
  • The Dyrk1a gene dosage was genetically normalized in TS mice via repeatedly backcrossing TS females to C57BL/6EixC3H/HeSNJ (B6EiCSN) F1 hybrid ( 003647 ) males. (
  • Normalization of Dyrk1a dosage restores the LTP response in TS +/+/- mice. (
  • TS +/+/- mice, by comparison, exhibit GAD65/67 and VGLUT expression levels similar to CO +/+ mice, indicating that correction of Dyrk1a dosage restores the balance between excitatory and inhibitory neuronal signaling to that of wild type mice. (
  • This study aims to compare bacterial burden and antimicrobial gene expression between human DEFA1A3 gene knock-in mice under a pyelonephritis model. (
  • Notice milder inflammatory cell infiltration and synovial thickening Open up in another windows Fig. 6 Assessment of cytokine gene manifestation in the bones of PKRA7-treated and neglected CIA mice on Day time 35. (
  • The method was robust enough to validate relative changes in the expression of a number of genes with varying abundance of transcripts. (
  • The dosage was the equivalent of 0.04 mg EGCG/g body weight/day. (