A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
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.
A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.
Biochemical identification of mutational changes in a nucleotide sequence.
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.
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.
An individual having different alleles at one or more loci regarding a specific character.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.
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.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
The number of mutations that occur in a specific sequence, GENE, or GENOME over a specified period of time such as years, CELL DIVISIONS, or generations.
An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.
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.
An individual in which both alleles at a given locus are identical.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Genes that influence the PHENOTYPE only in the homozygous state.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.
Deletion of sequences of nucleic acids from the genetic material of an individual.
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.
A characteristic symptom complex.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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).
A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).
Any method used for determining the location of and relative distances between genes on a chromosome.
The magnitude of INBREEDING in humans.
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.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
Established cell cultures that have the potential to propagate indefinitely.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Proteins produced from GENES that have acquired MUTATIONS.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.
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.
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).
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The 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.
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.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Genotypic differences observed among individuals in a population.
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.
Identification of genetic carriers for a given trait.
Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.
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.
The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
Genetic diseases that are linked to gene mutations on the X CHROMOSOME in humans (X CHROMOSOME, HUMAN) or the X CHROMOSOME in other species. Included here are animal models of human X-linked diseases.
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.
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.
Proteins found in any species of bacterium.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.
DNA present in neoplastic tissue.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
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.
A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).
Congenital absence of or defects in structures of the eye; may also be hereditary.
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.
A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.
Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.
The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.
Proteins prepared by recombinant DNA technology.
Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.
A raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)
The functional hereditary units of BACTERIA.
An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.
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.
The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.
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.
Genes that have a suppressor allele or suppressor mutation (SUPPRESSION, GENETIC) which cancels the effect of a previous mutation, enabling the wild-type phenotype to be maintained or partially restored. For example, amber suppressors cancel the effect of an AMBER NONSENSE MUTATION.
That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.
Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)
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.
The rate dynamics in chemical or physical systems.
Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
Mice bearing mutant genes which are phenotypically expressed in the animals.
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.
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.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
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 phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A mutation named with the blend of insertion and deletion. It refers to a length difference between two ALLELES where it is unknowable if the difference was originally caused by a SEQUENCE INSERTION or by a SEQUENCE DELETION. If the number of nucleotides in the insertion/deletion is not divisible by three, and it occurs in a protein coding region, it is also a FRAMESHIFT MUTATION.
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.
A social group consisting of parents or parent substitutes and children.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.
Abnormal development of cartilage and bone.
The functional hereditary units of FUNGI.
Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Proteins found in any species of fungus.
A general term for the complete loss of the ability to hear from both ears.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.
Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
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.
A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.
Proteins obtained from ESCHERICHIA COLI.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A class of genetic disorders resulting in INTELLECTUAL DISABILITY that is associated either with mutations of GENES located on the X CHROMOSOME or aberrations in the structure of the X chromosome (SEX CHROMOSOME ABERRATIONS).
An essential amino acid that is physiologically active in the L-form.
Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, FOCAL DERMAL HYPOPLASIA, and aplasia cutis congenita.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.
An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single ZYGOTE, as opposed to CHIMERISM in which the different cell populations are derived from more than one zygote.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones.
Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.
The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.
A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.
A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.
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.
Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.
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.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
An infant during the first month after birth.
The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).
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.
Actual loss of portion of a chromosome.
Transmission of gene defects or chromosomal aberrations/abnormalities which are expressed in extreme variation in the structure or function of the eye. These may be evident at birth, but may be manifested later with progression of the disorder.
Tumors or cancer of the human BREAST.
Bilateral hereditary disorders of the cornea, usually autosomal dominant, which may be present at birth but more frequently develop during adolescence and progress slowly throughout life. Central macular dystrophy is transmitted as an autosomal recessive defect.
The appearance of the face that is often characteristic of a disease or pathological condition, as the elfin facies of WILLIAMS SYNDROME or the mongoloid facies of DOWN SYNDROME. (Random House Unabridged Dictionary, 2d ed)
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.
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)
Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)
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.
A cell line derived from cultured tumor cells.

Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b. (1/8732)

Glycogen storage disease type 1b (GSD-1b) is proposed to be caused by a deficiency in microsomal glucose 6-phosphate (G6P) transport, causing a loss of glucose-6-phosphatase activity and glucose homeostasis. However, for decades, this disorder has defied molecular characterization. In this study, we characterize the structural organization of the G6P transporter gene and identify mutations in the gene that segregate with the GSD-1b disorder. We report the functional characterization of the recombinant G6P transporter and demonstrate that mutations uncovered in GSD-1b patients disrupt G6P transport. Our results, for the first time, define a molecular basis for functional deficiency in GSD-1b and raise the possibility that the defective G6P transporter contributes to neutropenia and neutrophil/monocyte dysfunctions characteristic of GSD-1b patients.  (+info)

Genetics of the SCA6 gene in a large family segregating an autosomal dominant "pure" cerebellar ataxia. (2/8732)

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar degeneration caused by the expansion of a CAG trinucleotide repeat in the CACNA1A gene. Mutations in patients are characterised by expanded alleles of between 21 and 30 repeat units and by extreme gonadal stability when transmitted from parents to children. We have investigated the SCA6 mutation in a large Spanish kindred in which previously reported spinocerebellar SCA genes and loci had been excluded. We observed a 23 CAG repeat expanded allele in the 13 clinically affected subjects and in three out of 10 presymptomatic at risk subjects. Transmission of the mutant allele was stable in six parent to child pairs and in 29 meioses through the pedigree. Linkage analysis with the SCA6-CAG polymorphism and marker D19S221 confirmed the location of SCA6 on chromosome 19p13. The molecular findings in this large family confirm the expansion of the CAG repeat in the CACNA1A gene as the cause of SCA6 and the high meiotic stability of the repeat.  (+info)

A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene. (3/8732)

We have identified a novel fibroblast growth factor receptor 3 (FGFR3) missense mutation in four unrelated individuals with skeletal dysplasia that approaches the severity observed in thanatophoric dysplasia type I (TD1). However, three of the four individuals developed extensive areas of acanthosis nigricans beginning in early childhood, suffer from severe neurological impairments, and have survived past infancy without prolonged life-support measures. The FGFR3 mutation (A1949T: Lys650Met) occurs at the nucleotide adjacent to the TD type II (TD2) mutation (A1948G: Lys650Glu) and results in a different amino acid substitution at a highly conserved codon in the kinase domain activation loop. Transient transfection studies with FGFR3 mutant constructs show that the Lys650Met mutation causes a dramatic increase in constitutive receptor kinase activity, approximately three times greater than that observed with the Lys650Glu mutation. We refer to the phenotype caused by the Lys650Met mutation as "severe achondroplasia with developmental delay and acanthosis nigricans" (SADDAN) because it differs significantly from the phenotypes of other known FGFR3 mutations.  (+info)

Cyclic ichthyosis with epidermolytic hyperkeratosis: A phenotype conferred by mutations in the 2B domain of keratin K1. (4/8732)

Bullous congenital ichthyosiform erythroderma (BCIE) is characterized by blistering and erythroderma in infancy and by erythroderma and ichthyosis thereafter. Epidermolytic hyperkeratosis is a hallmark feature of light and electron microscopy. Here we report on four individuals from two families with a unique clinical disorder with histological findings of epidermolytic hyperkeratosis. Manifesting erythema and superficial erosions at birth, which improved during the first few months of life, affected individuals later developed palmoplantar hyperkeratosis with patchy erythema and scale elsewhere on the body. Three affected individuals exhibit dramatic episodic flares of annular, polycyclic erythematous plaques with scale, which coalesce to involve most of the body surface. The flares last weeks to months. In the interim periods the skin may be normal, except for palmoplantar hyperkeratosis. Abnormal keratin-filament aggregates were observed in suprabasal keratinocytes from both probands, suggesting that the causative mutation might reside in keratin K1 or keratin K10. In one proband, sequencing of K1 revealed a heterozygous mutation, 1436T-->C, predicting a change of isoleucine to threonine in the highly conserved helix-termination motif. In the second family, a heterozygous mutation, 1435A-->T, was found in K1, predicting an isoleucine-to-phenylalanine substitution in the same codon. Both mutations were excluded in both a control population and all unaffected family members tested. These findings reveal that a clinical phenotype distinct from classic BCIE but with similar histology can result from K1 mutations and that mutations at this codon give rise to a clinically unique condition.  (+info)

Missense mutations in the gp91-phox gene encoding cytochrome b558 in patients with cytochrome b positive and negative X-linked chronic granulomatous disease. (5/8732)

Chronic granulomatous disease (CGD) is a disorder of host defense due to genetic defects of the superoxide (O2-) generating NADPH oxidase in phagocytes. A membrane-bound cytochrome b558, a heterodimer consisting of gp91-phox and p22-phox, is a critical component of the oxidase. The X-linked form of the disease is due to defects in the gp91-phox gene. We report here biochemical and genetic analyses of patients with typical and atypical X-linked CGD. Immunoblots showed that neutrophils from one patient had small amounts of p22-phox and gp91-phox and a low level of O2- forming oxidase activity, in contrast to the complete absence of both subunits in two patients with typical CGD. Using polymerase chain reactions (PCR) on cDNA and genomic DNA, we found novel missense mutations of gp91-phox in the two typical patients and a point mutation in the variant CGD, a characteristic common to two other patients with similar variant CGD reported previously. Spectrophotometric analysis of the neutrophils from the variant patient provided evidence for the presence of heme of cytochrome b558. Recently, we reported another variant CGD with similar amounts of both subunits, but without oxidase activity or the heme spectrum. A predicted mutation at amino acid 101 in gp91-phox was also confirmed in this variant CGD by PCR of the genomic DNA. These results on four patients, including those with two variant CGD, are discussed with respect to the missense mutated sites and the heme binding ligands in gp91-phox.  (+info)

The major, N2-dG adduct of (+)-anti-B[a]PDE induces G-->A mutations in a 5'-AGA-3' sequence context. (6/8732)

Previously, in a random mutagenesis study, the (+)-anti diol epoxide of benzo[a]pyrene [(+)-anti-B[a]PDE] was shown to induce a complex mutational spectrum in the supF gene of an Escherichia coli plasmid, which included insertions, deletions and base substitution mutations, notably a significant fraction of GC-->TA, GC-->AT and GC-->CG mutations. At some sites, a single type of mutation dominated and to understand individual mutagenic pathways these sites were chosen for study by site-specific means to determine whether the major adduct, [+ta]-B[a]P-N2-dG, was responsible. [+ta]-B[a]P-N2-dG was shown to induce approximately 95% G-->T mutations in a 5'-TGC-3' sequence context and approximately 80% G-->A mutations in a 5'-CGT-3' sequence context. (+)-anti-B[a]PDE induced principally GC-->CG mutations in the G133 sequence context (5'-AGA-3') in studies using both SOS-uninduced or SOS-induced E. coli. Herein, [+ta]-B[a]P-N2-dG is shown to induce principally G-->A mutations (>90%) either without or with SOS induction in a closely related 5'-AGA-3' sequence context (identical over 7 bp). This is the first time that there has been a discrepancy between the mutagenic specificity of (+)-anti-B[a]PDE versus [+ta]-B[a]P-N2-dG. Eight explanations for this discordance are considered. Four are ruled out; e.g. the second most prevalent adduct [+ca]-B[a]P-N2-dG also induces a preponderance of G-->A mutations (>90%), so it also is not responsible for (+)-anti-B[a]PDE-induced G133-->C mutations. The four explanations not ruled out are discussed and include that another minor adduct might be responsible and that the 5'-AGA-3' sequence context differed slightly in the studies with [+ta]-B[a]P-N2-dG versus (+)-anti-B[a]PDE. In spite of the discordance, [+ta]-B[a]P-N2-dG induces G-->A mutations in the context studied herein and this result has proven useful in generating a hypothesis for what conformations of [+ta]-B[a]P-N2-dG are responsible for G-->T versus G-->A mutations.  (+info)

A missense mutation accounts for the defect in the glycerol-3-phosphate acyltransferase expressed in the plsB26 mutant. (7/8732)

The sn-glycerol-3-phosphate acyltransferase (plsB) catalyzes the first step in membrane phospholipid formation. A conditional Escherichia coli mutant (plsB26) has a single missense mutation (G1045A) predicting the expression of an acyltransferase with an Ala349Thr substitution. The PlsB26 protein had a significantly reduced glycerol-3-phosphate acyltransferase specific activity coupled with an elevated Km for glycerol-3-phosphate.  (+info)

How translational accuracy influences reading frame maintenance. (8/8732)

Most missense errors have little effect on protein function, since they only exchange one amino acid for another. However, processivity errors, frameshifting or premature termination result in a synthesis of an incomplete peptide. There may be a connection between missense and processivity errors, since processivity errors now appear to result from a second error occurring after recruitment of an errant aminoacyl-tRNA, either spontaneous dissociation causing premature termination or translational frameshifting. This is clearest in programmed translational frameshifting where the mRNA programs errant reading by a near-cognate tRNA; this error promotes a second frameshifting error (a dual-error model of frameshifting). The same mechanism can explain frameshifting by suppressor tRNAs, even those with expanded anticodon loops. The previous model that suppressor tRNAs induce quadruplet translocation now appears incorrect for most, and perhaps for all of them. We suggest that the 'spontaneous' tRNA-induced frameshifting and 'programmed' mRNA-induced frameshifting use the same mechanism, although the frequency of frameshifting is very different. This new model of frameshifting suggests that the tRNA is not acting as the yardstick to measure out the length of the translocation step. Rather, the translocation of 3 nucleotides may be an inherent feature of the ribosome.  (+info)

Purpose: : The specific molecular mechanisms underlying age-related macular degeneration (AMD) are largely unknown. Fibulin 5 is an extracellular matrix protein abundantly expressed in tissues with enriched elastic fibers. This protein plays a critical role in the assembly and crosslinking of tropoelastin. Missense variations of fibulin 5 have been reported to occur exclusively in 1.7 percent of AMD patients (EM Stone et al, 2004, NEJM351:346-53). We characterized the distribution of fibulin 5 in healthy and diseased retina and, in vitro, investigated functional alterations of fibulin 5 due to missense variations found in AMD. Methods: : The expression of fibulin 5 in mouse retina and human macula was assessed by RT-PCR, immunohistochemistry and Western blotting. Expression constructs containing the seven variants (EM Stone et al, 2004, NEJM351:346-53) were generated by site-directed mutagenesis from the human fibulin-5 cDNA (generously provided by B. Schiemann). Secretion rates/levels of the ...
Helicases have important roles in nucleic acid metabolism, and their prominence is marked by the discovery of genetic disorders arising from disease-causing mutations. Missense mutations can yield unique insight to molecular functions and basis for disease pathology. XPB or XPD missense mutations le …
The orthologue of CLN3 in fission yeast is btn1. All disease-causing missense mutations of CLN3 were modelled in Btn1p, and their ability to rescue four defects of fission yeast cells lacking btn1 was assessed. Fission yeast cells deleted for btn1 have multiple defects, including larger vacuoles, a cytokinesis delay under normal growth conditions, cell curving and a failure to initiate polarised growth during growth at higher temperatures. None of the mutations associated with disease rescued all of the phenotypes assayed here, although many had a significant effect on one or more phenotype. Mutations of residues on the lumenal face of the protein almost completely ablated protein function. One of the defects, cell curving, was rescued only by the mutant corresponding to the disease-causing missense mutation p.Glu295Lys. Patients with this mutation have the mildest disease phenotype known for CLN3, with onset of blindness at the normal age but very delayed onset of other symptoms.. ...
Each persons genome sequence has thousands of missense variants. Practical interpretation of their functional significance must rely on computational inferences in the absence of exhaustive experimental measurements. Here we analyzed the efficacy of these inferences in 33 de novo missense mutations revealed by sequencing in first-generation progeny of N-ethyl-N-nitrosourea-treated mice, involving 23 essential immune system genes. PolyPhen2, SIFT, MutationAssessor, Panther, CADD, and Condel were used to predict each mutations functional importance, whereas the actual effect was measured by breeding and testing homozygotes for the expected in vivo loss-of-function phenotype. Only 20% of mutations predicted to be deleterious by PolyPhen2 (and 15% by CADD) showed a discernible phenotype in individual homozygotes. Half of all possible missense mutations in the same 23 immune genes were predicted to be deleterious, and most of these appear to become subject to purifying selection because few persist between
This study reports the results of in-depth analysis of 18 PSSM in samples from VWD patients. The novel and robust procedure used, combining two-step RT-PCR and NGS sequencing, was faster and more sensitive than the method used in our previous article.7 This new approach provides several advantages, such as allele-specific individual sequences, higher sensitivity to detect transcript variants present at low copy numbers, and simplified sample preparation. Moreover, the NGS data on total reads obtained for each transcript is additional information that can provide an approximation of the expression levels of each VWF mRNA. Studies are currently ongoing to confirm that the relative expression of each transcript obtained by NGS is comparable to that provided by real-time RT-PCR.. The proven usefulness of leukocyte analysis to interpret mutations masked by NMD in platelets was seen in relation to the c.3379+1G,A mutation, which had been previously investigated by RT-PCR in platelets.23 In that study, ...
Sigma-Aldrich offers abstracts and full-text articles by [David C A Gaboriau, Pamela J E Rowling, Ciaran G Morrison, Laura S Itzhaki].
The interplay between oxygen and iron is longstanding and central to all or any aerobic lifestyle. have investigated the partnership between iron availability, or insufficiency, and proliferative replies in configurations of relevance to PAH. In a single study the usage of iron chelation via the administration of desferrioxamine to rats was discovered to inhibit chronic hypoxia induced PH and redecorating recommending that iron is certainly essential for vascular proliferation in these situations; an assertion further backed by tests by the same writers which showed an iron chelation technique also inhibited proliferation of cultured PASMCs (Wong et al., 2012). In another scholarly study, usage of plumbagin, an iron chelator, (Padhye et al., 2012) was discovered to limit proliferation in individual PASMCs and lower distal pulmonary artery redecorating within a rat style of PAH (Courboulin et al., 2012). Additionally, iron was discovered to induce redecorating in cultured rat PAECs (Gorbunov et ...
Gefitinib level of resistance remains a main issue in the treatment of lung adenocarcinoma. Inhibition of pAKT by LY294002 or inhibition of pMET by PHA-665752 considerably inhibited SL 0101-1 the …. ...
TY - JOUR. T1 - P4HB recurrent missense mutation causing Cole-Carpenter syndrome. AU - Balasubramanian, Meena. AU - Padidela, Raja. AU - Pollitt, Rebecca C. AU - Bishop, Nicholas J. AU - Mughal, M Zulf. AU - Offiah, Amaka C. AU - Wagner, Bart E. AU - McCaughey, Janine. AU - Stephens, David J. N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.. PY - 2017/12/19. Y1 - 2017/12/19. N2 - BACKGROUND: Cole-Carpenter syndrome (CCS) is commonly classified as a rare Osteogenesis Imperfecta (OI) disorder. This was following the description of two unrelated patients with very similar phenotypes who were subsequently shown to have a heterozygous missense mutation in P4HB.OBJECTIVES: Here, we report a 3-year old female patient with severe OI who on exome sequencing was found to carry the same missense mutation in P4HB as reported in the original cohort. We discuss the ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
We recently described a new autosomal dominant myopathy associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene (MYH2). In this study, we performed mutation analysis of MYH2 in eight Swedish patients with familial myopathy of unknown cause. In two of the eight index cases, we identified novel heterozygous missense mutations in MYH2, one in each case: V970I and L1061V. The mutations were located in subfragment 2 of the MyHC and they changed highly conserved residues. Most family members carrying the mutations had signs and symptoms consisting mainly of mild muscle weakness and myalgia. In addition, we analyzed the extent and distribution of nucleotide variation in MYH2 in 50 blood donors, who served as controls, by the complete sequencing of all 38 exons comprising the coding region. We identified only six polymorphic sites, five of which were synonymous polymorphisms. One variant, which occurred at an allele frequency of 0.01, was identical to the L1061V that was also found ...
Maturity-onset diabetes of the young type 3 (MODY3) is a non-ketotic form of diabetes associated with poor insulin secretion. Over the past years, several studies have reported the association of missense mutations in the Hepatocyte Nuclear Factor 1 Alpha (HNF1A) with MODY3. Missense mutations in the POU homeodomain (POUH) of HNF1A hinder binding to the DNA, thereby leading to a dysfunctional protein. Missense mutations of the HNF1A were retrieved from public databases and subjected to a three-step computational mutational analysis to identify the underlying mechanism. First, the pathogenicity and stability of the mutations were analyzed to determine whether they alter protein structure and function. Second, the sequence conservation and DNA-binding sites of the mutant positions were assessed; as HNF1A protein is a transcription factor. Finally, the biochemical properties of the biological system were validated using molecular dynamic simulations in Gromacs 4.6.3 package. Two arginine residues ...
We report here the results of genetic studies on Müllerian aplasia, namely, results of TBX6 and LHX1 mutation screening in 112 MA patients and CNV analysis in a subset of them.. Sequencing of TBX6 (located in 16p11.2) revealed a splice mutation in two patients and rare missense variants in 15 patients (13.4%). TBX6 is a transcription factor that functions in early embryogenesis. It resides on the minus strand with a full-length transcript of 1806 bp, encoding a 436 aminoacid protein (NP_004599.2). TBX6 is a member of a phylogenetically well-conserved T-box gene family, where all members share the similar N-terminal DNA-binding domain, the T-box [55]. We identified a c.622-2A,T splice site mutation in two patients (one with MRKH and the other with total MA and with ovarian aplasia) and a rare homozygous missense variant in exon 4 and exon 6 in two patients. The splice site mutation is situated in the highly conserved splice acceptor site (AG) of exon 5. According to the in silico prediction ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The p.Arg844Cys variant in the GRIN1 gene has been previously reported de novo in 4 individuals with features consistent with GRIN1-associated neurodevelopmental disorder (Lemke et al., 2016; Vanderver et al., 2016; Wang et al., 2019). This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The GRIN1 gene has fewer missense variants in the general population than expected. A low rate of missense variation may suggest that this gene is intolerant to missense variation. Computational tools predict that the p.Arg844Cys is deleterious; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Arg844Cys variant as pathogenic for autosomal dominant GRIN1-associated neurodevelopmental disorder based on the information above. [ACMG evidence codes used: PS2_VeryStrong; PM2; PP2; PP3 ...
High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ~155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (,1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.. ...
M-CAP is the first pathogenicity classifier for rare missense variants in the human genome that is tuned to the high sensitivity required in the clinic (see Table). By combining previous pathogenicity scores (including SIFT, Polyphen-2 and CADD) with novel features and a powerful model, we attain the best classifier at all thresholds, reducing a typical exome/genome rare (,1%) missense variant (VUS) list from 300 to 120, while never mistaking 95% of known pathogenic variants as benign. Further details can be found here ...
Author Summary Intrinsically unstructured or disordered proteins have been implicated in the etiology of a wide spectrum of diseases. However, the molecular mechanisms that relate mutations in intrinsically disordered regions (IDRs) to disease pathogenesis have not been investigated. Disordered proteins do not conform to the prevailing view of deleterious mutations which equates function, structure and evolutionary conservation - intrinsically disordered regions are functional, but lack a fixed three-dimensional structure and in general have low sequence conservation. Here we demonstrate that |20% of disease-associated missense mutations affect IDRs and interfere with their functions. We further show that 20% of deleterious mutations in IDRs induce predicted disorder-to-order transitions. Our predictions are supported by accelerated molecular dynamics simulations that show an increase in helical propensity of the region harboring a disease disorder-to-order transition mutation of tumor protein p63. Our
In this study we analyzed the spectrum of HNF1A mutations in HCA and showed a significant difference in pattern in comparison with individuals with MODY3, both at the nucleotide and amino acid levels. In HCA, location of the mutations is very restricted because almost all of the truncating mutations led to the loss of the transactivation domain and the missense mutations altered mainly the POU-H domain. When we take into account the two largest series of HNF1A screening in MODY3 (21,25), only 48% of the germline mutations (117 of 720 are missense mutations in POU-H, and 227 of 720 are truncating mutations localized in the first 291 amino acids) fit the features of the HNF1A somatic mutations. This observation suggests that only a part of HNF1A mutations that are associated with diabetes could predispose to the development of a H-HCA.. Previous analysis of the MODY3 mutations showed that the age at onset of diabetes is modulated according to the position of the mutation relative to the HNF1A ...
It is widely accepted that genetic insults are indispensable in the formation of a frank tumor. In the development of human cutaneous SCCs, alterations in ras genes (10%-30% incidence) (3, 4) and the p53tumor suppressor gene (40%-50% incidence) (5, 6) have been most heavily implicated. While the majority of these lesions are missense mutations, the functional assessment of p53 missense mutations is complicated in that some give rise to a loss-of-function or null phenotype classically associated with tumor suppressor genes, whereas the majority of p53 missense mutations appear to result in a gain-of-function phenotype. While the presence of both types of p53 mutations in SCCs denotes a selection advantage to these genetic lesions, whether gain-of-function or loss-of-function mutations are more critical for SCC development is unclear. Therefore, the understanding of p53 phenotype status, i.e., tumor suppressive versus oncogenic, as it relates to SCC formation and progression is of paramount ...
TY - JOUR. T1 - Sarcomeric protein mutations in dilated cardiomyopathy. AU - Chang, Audrey N.. AU - Potter, James D.. N1 - Funding Information: This work was supported by NIH Grants HL67415 and HL-42325 Address for correspondence: Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, 1600 NW 10th Ave (R-189), Miami, Florida 33136. Tel.: 305-243-5874; Fax: 305-324-6024; E-Mail: [email protected] PY - 2005/9. Y1 - 2005/9. N2 - This review aims to provide a concise summary of the DCM associated mutations identified in the proteins of the sarcomere and cytoskeleton, and discuss the reported effects of the mutations, as determined by functional studies, and in relation to the known structure of the protein affected. The mechanisms by which single missense mutations in the proteins of the sarcomere can lead to similar diseases as those caused by mutations in the proteins of the sarcolemma and cytoskeleton, are still unknown. However, a wide variety of ...
Background Rabson Mendenhall syndrome is a rare endocrine condition characterized by severe insulin resistance and hyperglycemia. It occurs due to mutations in the insulin receptor gene. Few mutations...
PAX9, a paired domain transcription factor, has important functions in craniofacial and limb development. Heterozygous mutations of PAX9, including deletion, nonsense, or frameshift mutations that lead to a premature stop codon, and missense mutations, were previously shown to be associated with autosomal dominant oligodontia. Here, we report a novel missense mutation that lies in the highly conserved paired domain of PAX9 and that is associated with non-syndromic oligodontia in one family. The mutation, 83G-->C, is predicted to result in the substitution of arginine by proline (R28P) in the N-terminal subdomain of PAX9 paired domain. To rule out the possibility that this substitution is a rare polymorphism and to test whether the predicted amino acid substitution disrupts protein-DNA binding, we analyzed the binding of wild-type and mutant PAX9 paired domain to double-stranded DNA targets. The R28P mutation dramatically reduces DNA binding of the PAX9 paired domain and supports the hypothesis ...
Intractable severe diarrhea accompanied by phenotypic abnormalities and liver cirrhosis in infants is associated with THES. The prognosis of THES is poor, with ,25% of patients currently reported to succumb to mortality between the ages of 2-5 years, a proportion of which with early-onset cirrhosis. However, case reports have described improved survival rates, with long-term parenteral nutrition (PN)-dependency or PN weaning in certain cases. The patient described in the present study was considered to have THES, based on his intrauterine growth retardation, intractable diarrhea, facial dysmorphism, abnormal scalp hair shafts, trichorrhexis nodosa, immune disorders and liver cirrhosis.. Lee et al (11) isolated genomic clones and mapped the human homolog of the SKI2 gene to 6p21 using fluorescence in situ hybridization. Using genomic sequence analysis, Yang et al (12) determined that SKIV2L is a polymorphic gene, which spans 11 kb and contains 28 exons (11). Fabre et al (10) sequenced the ...
Purpose: To study the influence of Crb1 c.3481delC (rd8) mutation on the retinal phentoype of the L-ORD mouse model with heterozygous S163R missense mutation in the C1Q-Tumor Necrosis Factor Related Protein-5 (C1QTNF5/CTRP5) gene.. Methods: Mouse model for L-ORD was generated on C57BL/6J background and the presence of rd8 mutation was observed in this colony. To study the influence of the rd8 mutation on L-ORD phenotype, mouse lines carrying both the Ctrp5 S163R and the rd8 mutation (Ctrp5+/-;rd8/rd8), without the rd8 mutation (Ctrp5+/-;wt/wt); and wild type mice with and without the rd8 mutation (Wtrd8/rd8 and Wtwt/wt, respectively) were generated. Genotyping was carried out by allelic polymerase chain reaction (PCR) or sequencing. Retinal morphology was studied by fundus imaging, histology, light microscopy, electron microscopy and immunohistochemistry.. Results: Genotype analysis of the mice in L-ORD mouse colony detected the rd8 mutation in both the homozygous or heterozygous states. Fundus ...
Thoennissen, N.H., Lasho, T., Thoennissen, G.B., Ogawa, S., Tefferi, A., Koeffler, H.P. (2011-08). Novel CUX1 missense mutation in association with 7q- at leukemic transformation of MPN. American Journal of Hematology 86 (8) : 703-705. [email protected] Repository. https://doi.org/10.1002/ajh. ...
This server predicts the functional impact of amino-acid substitutions in proteins, such as mutations discovered in cancer or missense polymorphisms. The functional impact is assessed based on evolutionary conservation of the affected amino acid in protein homologs. The method has been validated on a large set (60k) of disease associated (OMIM) and polymorphic variants. To explore the functional impact of missense mutations found in The Cancer Genome Atlas please use cBioPortal for Cancer Genomics ...
This sequence change replaces glycine with arginine at codon 85 of the NPPA protein (p.Gly85Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs749353276, ExAC 0.04%) but has not been reported in the literature in individuals with a NPPA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In addition, the arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. However, algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing, but these predictions have not been confirmed by published transcriptional studies. In summary, this is a rare missense change with an ...
Results A novel missense mutation of A to G (p.Q286R) in patients with DDS (n=3/7) was found in the HOOK1 gene, which was inherited from the mother in one patient. This variant was absent in 160 fertile population-matched control individuals. Morphological observation showed that almost all the DDS broke into decaudated heads and headless tails at the implantation fossa or the basal plate. The clinical studies indicated that the mutation might cause reduced FRs on both ART (FR=18.07%) and interspecies ICSI (FR=16.98%). ...
The tiny heat shock protein (sHSP) B-crystallin (B) plays an integral role within the cellular protection system against stress. of the heterogeneity parameter because of this type of program. A system of multimerization into higher-order asymmetric oligomers via the addition as high as six dimeric Lenvatinib products to some 24-mer is suggested. The suggested asymmetric multimers clarify the homogeneous appearance of B in negative-stain EM pictures as well as the known powerful exchange of B subunits. The style of B offers a structural basis for understanding known disease-associated missense mutations and makes predictions regarding substrate binding as well as the reported fibrilogenesis of B. resonances of Tyr48 and Thr63 and between your 13Cresonance of Leu49 as well as the 13Cresonance of Asp62 and Thr63 and 13Cresonance of Phe61 additional corroborate the prediction and reveal an antiparallel orientation between your two strands (Fig.?2and Desk?S1). Even though chemical shift evaluation ...
Background: Escape mutations potentially allow viruses to avoid detection and clearance by the host immune sys-tem and may represent a mechanism through which infections may persist in some patients. The association of the mutations in the HBcAg gene with Hepatitis B asymptomatic carriers (ASC) has not been studied adequately. The current study was aimed to investigate HBcAg18-27 CTL epitope mutations in ASC patients in the South-Eastern region of Iran. Methods: 100 ASC patients were selected for this study and screened for HLA-A2 using flow cytometry. HBV-DNA was extracted from the HLA-A2 positive patients and the HBc gene was amplified using PCR. Direct double sequencing was performed to analyse mutations in the HBc gene of HBV isolates from patients with ASC. Results: Overall, 25 (25%) of individuals were HLA-A2 positive. Direct double sequencing indicated no mutations in the HBcAg18-27 epitope. However, four mutations within the T helper and three mutations within the B cell epitopes of ASC ...
Previous VHL mutation testing of germline DNA from the proband of family NCI-1326 was negative. However, the VHL and BAP1 genes are both on chromosome 3p so we asked whether somatic mutations in VHL could be detected in the tumors. VHL mutation analysis (Supplementary Materials and Methods) showed VHL mutation in some tumors (IV:1, Tumor 1 and IV:4, Tumor 1), but not in others (IV:1, Tumors 3 and 4; Supplementary Fig. S2 and data not shown). Thus, mutations in VHL and BAP1 may cooperate in the development of at least some tumors.. Together, these data suggest that the novel BAP1 p.L14H missense variant is the cause of the underlying cancer phenotype in the family described. First, the variant cosegregated with the RCC phenotype. Second, the variant targets the catalytic domain, which is a common site of missense mutations including pathogenic somatically-acquired mutations in neighboring residues pG13V and p.H144N. Third, L14 is highly conserved across species, and in silico analyses suggest ...
The steady advances in machine learning and accumulation of biomedical data have contributed to the development of numerous computational models that assess the impact of missense variants. Different methods, however, operationalize impact differently. Two common tasks in this context are the predic …
Predicting the deleteriousness of missense variants is extremely difficult. Variants whithin sites essential to protein function is an important criterion for variant pathogenicity prediction. However, for many proteins these essential sites have not been identified due to lack of statistical power and experimental data.. Here, we have developed a novel statistical framework to identify missense pathogenic enriched regions (PERs). We compare missense variant density identified in individuals of the general population (gnomAD, n= 2,219,811) against missense variant density retrieved from patient variant databases (ClinVar/HGMD, n = 76,153). To gain power, we grouped 9,990 genes into 2,871 gene families and evaluated the density of pathogenic variants across all members of the gene family.. We identified 464 PERs spanning 41,463 amino acids in 1,252 genes. In addition, gene-wise analysis was able to identify 251 additional PERs involving 2,639 amino acids. These regions can be effectively ...
These are internal identifiers that are unique to a mutation on a particular transcript and are displayed in the URL of the mutation pages. Therefore, several of these internal ids could be associated with a single genomic COSV id where the mutation has been mapped to all overlapping genes and transcripts. Similarly, since every COSM id is mapped to one COSV id (where genomic coordinates are known), each COSM id can also be associated with several alternative (internal) identifiers. These ids are expected to change between assemblies (GRCh37 and GRCh38) and between the releases ...
These are internal identifiers that are unique to a mutation on a particular transcript and are displayed in the URL of the mutation pages. Therefore, several of these internal ids could be associated with a single genomic COSV id where the mutation has been mapped to all overlapping genes and transcripts. Similarly, since every COSM id is mapped to one COSV id (where genomic coordinates are known), each COSM id can also be associated with several alternative (internal) identifiers. These ids are expected to change between assemblies (GRCh37 and GRCh38) and between the releases ...
Valve upřesnilo, jak je to s Mutations u nov ho DLC s n zvem The Sacrifice, kter vych z jak pro Left 4 Dead 2, tak i pro prvn d l. Mutations budou exkluzivn pro druh d l hry. PC hr či budou m t pět nov ch Mutations, zat mco majitel X360 verze je dostanou pouze v př padě, e maj tak DLC The Passing. Valve zat m nechce prozradit, jak tyto nov koly budou, ale alespoň naznačili: Hr li jste někdy m d Versus a př li jste si b t Tankem? Př li jste si někdy b t jenom v hradně Tankem? A kdy jste umřeli, zase byste se jako Tank nejraději zjevili? A v ichni va i kamar di byli tak Tanky? Nov mutace Taaannnk!! je přesně takov . Abychom vysvětlili Tank je gigantick zmutovan př era v Left 4 Dead (v ce info např klad zde). Mutace jsou zase t denn speci ln m dy v Left 4 Dead jako realistick Versus m d (nevyznačen předměty, silněj zomb ci atd.) nebo Chainsaw Massacre (m te pouze jednu zbraň a tou je řetězov pila). Po t dnu zase konč a nahrazuj je jin m dy. ...
10,12 This could be a novel therapeutic strategy to target Aβ neurotoxicity in AD. Presenilin APP mutations result in only a small proportion of autosomal dominant inherited types of AD, which is why there have been so many linkage selleck kinase inhibitor studies of other loci with FAD. The observation of linkage with chromosomal region 14q in some FAD families eventually led to the discovery of a novel gene, namely presenilin 1 (PS1).73-76 The first PS1 mutation. associated with FAD was reported in 1995.73,77,78 Since then about 120 kinds of PS1 mutation have been reported in about 260 families around the world. Almost all of the reported PS1 mutations are missense and give rise to the Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical substitution of a single amino acid. So far, only two splicing defect mutations have been reported79,82; these change the topography of the protein in membranes. In addition, the mutations are most frequently observed in exon 5 (28 ...
TY - JOUR. T1 - Compound heterozygosity for a hemizygous rare missense variant (rs141999351) and a large CNV deletion affecting the FSTL5 gene in a patient with schizophrenia. AU - Gardella, Rita. AU - Sacchetti, Emilio. AU - Legati, Andrea. AU - Magri, Chiara. AU - Traversa, Michele. AU - Gennarelli, Massimo. PY - 2016/10/29. Y1 - 2016/10/29. N2 - HighlightsWe identified a potential damaging variant in the FSTL5 gene of a schizophrenia patient.The patient was also a carrier of a CNV deleting almost the whole FSTL5 gene.Our findings are consistent with the double-hit hypothesis of schizophrenia.FSTL5 may be a candidate gene in schizophrenia.. AB - HighlightsWe identified a potential damaging variant in the FSTL5 gene of a schizophrenia patient.The patient was also a carrier of a CNV deleting almost the whole FSTL5 gene.Our findings are consistent with the double-hit hypothesis of schizophrenia.FSTL5 may be a candidate gene in schizophrenia.. UR - ...
Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and carries substantial morbidity despite treatment. We performed a genome-wide association study (GWAS) of CoA among 120 Icelandic cases and 355,166 controls and found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio (OR) = 44.2, P = 5.0x10-22), encoding an essential sarcomere protein. Approximately 20% of CoA cases in Iceland carry p.Arg721Trp. This is the first mutation associated with non-familial or sporadic CoA at a population level. P.Arg721Trp also associates with risk of bicuspid aortic valve (BAV) and other CHDs and has been reported to have a broad effect on cardiac electrical function and to associate strongly with sick sinus syndrome (SSS) and atrial fibrillation (AF). These findings suggest that p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity, and emphasize the major importance of sarcomere integrity for cardiac development ...
Notch1 has been regarded as a fundamental regulator in tissue differentiation and stem cell properties. Recently, Notch1 mutations have been reported intensively both in solid tumors and in hematopoietic malignancies. However, little is known about the biological effect and the clinical implication of these reported mutations. Previously, we discovered several missense mutations in the Notch1 receptor in a Chinese population with oral squamous cell carcinoma (OSCC). We selected a hotspot mutation in the Abruptex domain (C1133Y). The expression of Notch1 was determined by western blot and real-time qPCR in OSCC cell lines transfected with pcDNA3.1-Notch1WT, pcDNA3.1-Notch1C1133Y, or pcDNA3.1 empty vector. CCK-8 assays were used to assess cell proliferation. Flow cytometry and western blot were used to confirm the alteration of cell cycle after transfection. Transwell assays and the detection of Epithelial-to-mesenchymal transition (EMT) markers were used to determine the invasive ability. The effects
A Novel Heterozygous Missense Variant (c.667G,T;p.Gly223Cys) in USH1C That Interferes With Cadherin-Related 23 and Harmonin Interaction Causes Autosomal Dominant Nonsyndromic Hearing Loss. ...
We describe a novel homozygous missense glucokinase mutation (R397L) resulting in insulin-treated neonatal diabetes in an infant from a consanguineous Asian family. Both parents were heterozygous for R397L and had mild hyperglycemia. Glucokinase mutations should be considered in infants of all ethnic groups with neonatal diabetes and consanguinity.
Author: Mohamed, Salah A. et al.; Genre: Journal Article; Published in Print: 2006-07-14; Keywords: NOTCH1; Bicuspid aortic valve; Valve calcification; Missense mutations; Title: Novel missense mutations (p.T596M and p.P1797H) in NOTCH1 in patients with bicuspid aortic valve
Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to MED13L haploinsufficiency syndrome. Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that
In contrast to the typical Pierson syndrome phenotype, which has been associated primarily with null mutations in LAMB2,1,4 missense mutations, such as R246Q and C321R, cause mild variants of Pierson syndrome, in which congenital nephrotic syndrome is the predominant manifestation and extrarenal features are less pronounced.18 LAMB2 missense mutation is one of the most common disease-causing mutations in early onset nephrotic syndrome.39 Previously, we investigated the mechanisms whereby the R246Q mutation causes congenital nephrotic syndrome19; here, we determined how the C321R mutation causes proteinuria.. Our results suggest that the mechanisms responsible for nephrotic syndrome in patients harboring the C321R-LAMB2 mutation involve both severely impaired laminin secretion and concomitant podocyte ER stress-associated injury. Our hypothesis is supported by both in vivo and in vitro data. In vivo, we generated three lines of transgenic mice, in which C321R-LAMB2 mRNA was expressed in podocytes ...
Mutations in SLC6A1, encoding γ-aminobutyric acid (GABA) transporter 1 (GAT-1), have been recently associated with a spectrum of epilepsy syndromes, intellectual disability and autism in clinic. However, the pathophysiology of the gene mutations is far from clear. Here we report a novel SLC6A1 missense mutation in a patient with epilepsy and autism spectrum disorder and characterized the molecular defects of the mutant GAT-1, from transporter protein trafficking to GABA uptake function in heterologous cells and neurons. The heterozygous missense mutation (c1081C to A (P361T)) in SLC6A1 was identified by exome sequencing. We have thoroughly characterized the molecular pathophysiology underlying the clinical phenotypes. We performed EEG recordings and autism diagnostic interview. The patient had neurodevelopmental delay, absence epilepsy, generalized epilepsy, and 2.5-3 Hz generalized spike and slow waves on EEG recordings. The impact of the mutation on GAT-1 function and trafficking was evaluated by 3H
article{ad4911a9-fa37-43c8-88dd-95a7ab3e310d, abstract = {,p,ABHD12 mutations have been linked to neurodegenerative PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract), a rare, progressive, autosomal, recessive disease. Although ABHD12 is suspected to play a role in the lysophosphatidylserine and/or endocannabinoid pathways, its precise functional role(s) leading to PHARC disease had not previously been characterized. Cell and zebrafish models were designed to demonstrate the causal link between an identified new missense mutation p.T253R, characterized in ABHD12 from a young patient, the previously characterized p.T202I and p.R352* mutations, and the associated PHARC. Measuring ABHD12 monoacylglycerol lipase activity in transfected HEK293 cells demonstrated inhibition with mutated isoforms. Both the expression pattern of zebrafish abhd12 and the phenotype of specific antisense morpholino oligonucleotide gene knockdown morphants were consistent with human ...
ATM is the gene mutated in the autosomal recessive disorder Ataxiatelangiectasia (A-T). Female relatives of A-T patients carrying a heterozygous A-T mutation have an increased breast cancer risk but it was not known if ATM mutations that were not pathogenic for A-T were associated with breast cancer risk. In a large combined analysis, Fletcher and colleagues genotyped 5 polymorphic missense ATM SNPs in 26,101 breast cancer cases from 23 different studies. The authors report that the 5 missense ATM SNPs were associated with a small increased risk of breast cancer. This study illustrates how testing the combined effects of rare missense variants in known breast cancer genes can help clarify their overall contribution to breast cancer susceptibility. ...
In this study, systematic inhibitor response to ErbB missense mutations in gastric cancer (GC) is investigated by combining computational analysis and experimental assay. The response profile is created for 6 ATP-competitive, reversible inhibitors against 9, 17, 5 and 17 GC-associated missense mutations of ErbB1, ErbB2, ErbB3 and ErbB4 kinase domains, respectively. From the profile a number of p...
Homozygous mutations in TREM2 are known to cause rare, autosomal recessive forms of dementia with an early onset and presenting with[6] or without[8] bone cysts and fractures. A rare missense mutation (rs75932628-T) in the gene encoding TREM2, (predicted to result in an R47H substitution), confers a significant risk of Alzheimers disease. Given the reported antiinflammatory role of TREM2 in the brain, it is suspected of interfering with the brains ability to prevent the buildup of plaque.[9][10] TREM2 mutations increase the risk of neurodegenerative conditions such as Alzheimers disease, amyotrophic lateral sclerosis, and Parkinsons disease. TREM2 interacts with DAP12 in microglia to trigger phagocytosis of amyloid beta peptide and apoptotic neurons without inflammation. Mutations in TREM2 impair the normal proteolytic maturation of the protein which in turn interferes with phagocytosis and may therefore contribute to the pathogenesis of Alzheimers disease.[11] Soluble TREM2 has been ...
ACTB encodes β-actin, an abundant cytoskeletal housekeeping protein. In humans, postulated gain-of-function missense mutations cause Baraitser-Winter syndrome (BRWS), characterized by intellectual disability, cortical malformations, coloboma, sensorineural deafness, and typical facial features. To date, the consequences of loss-of-function ACTB mutations have not been proven conclusively. We describe heterozygous ACTB deletions and nonsense and frameshift mutations in 33 individuals with developmental delay, apparent intellectual disability, increased frequency of internal organ malformations (including those of the heart and the renal tract), growth retardation, and a recognizable facial gestalt (interrupted wavy eyebrows, dense eyelashes, wide nose, wide mouth, and a prominent chin) that is distinct from characteristics of individuals with BRWS. Strikingly, this spectrum overlaps with that of several chromatin-remodeling developmental disorders. In wild-type mouse embryos, β-actin expression ...
Although improvements in genetic analysis have greatly enhanced our understanding of the mechanisms behind pancreatitis, it continues to afflict many families for whom the hereditary factors remain unknown. Recent evaluation of a patient with a strong family history of pancreatitis prompted us to reexamine a large kindred originally reported over 50 years ago with an autosomal-dominant inheritance pattern of chronic pancreatitis, diabetes, and pancreatic adenocarcinoma. Whole-exome sequencing analysis identified a rare missense mutation in the gene encoding pancreas-specific protease elastase 3B (CELA3B) that cosegregates with disease. Studies of the mutant protein in vitro, in cell lines, and in CRISPR-Cas9-engineered mice indicate that this mutation causes translational upregulation of CELA3B, which, upon secretion and activation by trypsin, leads to uncontrolled proteolysis and recurrent pancreatitis. Although lesions in several other pancreatic proteases have been previously linked to ...
Although improvements in genetic analysis have greatly enhanced our understanding of the mechanisms behind pancreatitis, it continues to afflict many families for whom the hereditary factors remain unknown. Recent evaluation of a patient with a strong family history of pancreatitis prompted us to reexamine a large kindred originally reported over 50 years ago with an autosomal-dominant inheritance pattern of chronic pancreatitis, diabetes, and pancreatic adenocarcinoma. Whole-exome sequencing analysis identified a rare missense mutation in the gene encoding pancreas-specific protease elastase 3B (CELA3B) that cosegregates with disease. Studies of the mutant protein in vitro, in cell lines, and in CRISPR-Cas9-engineered mice indicate that this mutation causes translational upregulation of CELA3B, which, upon secretion and activation by trypsin, leads to uncontrolled proteolysis and recurrent pancreatitis. Although lesions in several other pancreatic proteases have been previously linked to ...
Although improvements in genetic analysis have greatly enhanced our understanding of the mechanisms behind pancreatitis, it continues to afflict many families for whom the hereditary factors remain unknown. Recent evaluation of a patient with a strong family history of pancreatitis prompted us to reexamine a large kindred originally reported over 50 years ago with an autosomal-dominant inheritance pattern of chronic pancreatitis, diabetes, and pancreatic adenocarcinoma. Whole-exome sequencing analysis identified a rare missense mutation in the gene encoding pancreas-specific protease elastase 3B (CELA3B) that cosegregates with disease. Studies of the mutant protein in vitro, in cell lines, and in CRISPR-Cas9-engineered mice indicate that this mutation causes translational upregulation of CELA3B, which, upon secretion and activation by trypsin, leads to uncontrolled proteolysis and recurrent pancreatitis. Although lesions in several other pancreatic proteases have been previously linked to ...
Congenital heart defects (CHDs) are the most common birth defect worldwide and are a leading cause of neonatal mortality. Nonsyndromic atrioventricular septal defects (AVSDs) are an important subtype of CHDs for which the genetic architecture is poorly understood. We performed exome sequencing in 13 parent-offspring trios and 112 unrelated individuals with nonsyndromic AVSDs and identified five rare missense variants (two of which arose de novo) in the highly conserved gene NR2F2, a very significant enrichment (p = 7.7 × 10(-7)) compared to 5,194 control subjects. We identified three additional CHD-affected families with other variants in NR2F2 including a de novo balanced chromosomal translocation, a de novo substitution disrupting a splice donor site, and a 3 bp duplication that cosegregated in a multiplex family. NR2F2 encodes a pleiotropic developmental transcription factor, and decreased dosage of NR2F2 in mice has been shown to result in abnormal development of atrioventricular septa. Via
BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 ...
The consequences of base substitution mutations in protein coding regions of a gene depend on the substitution and its location. They may be silent, not resulting in a new amino acid in the protein sequence, eg. GCA or GCG codons in mRNA both mean arginine [this is often true in the third position of a codon, especially with transitions because of wobble base pairing]. A base substitution could also result in an amino acid substitution; this is referred to as a missense mutation. For example, CTC in the DNA sense strand [GAG in mRNA] will specify a glutamate residue in the protein; this is altered to CAC in the DNA or GUG in the mRNA, resulting in a valine residue in the beta-globin protein chain causing sickle-cell anemia. Missense mutations may have very serious consquences, as in the case of sickle-cell anemia, mild consequences as in the case of hemoglobin C (a different amino acid substitution in position 6 of beta-globin) or no phenotype as in the case of two known amino acid ...
We developed a sequence context based model of de novo mutations to create per-gene probabilities of mutation. We noticed a high correlation (0.94) between the probability of a synonymous mutation in a gene and the number of rare synonymous variants identified in that same gene first using the NHLBI. s Exome Sequencing Project data (evs.gs.washington.edu), then with 25,000 exomes analyzed simultaneously (see abstract by MacArthur et al). We predicted the number of variants that we would expect to see in the dataset and, in order to quantify deviations, created a Z score of the chi-squared difference between observation and expectation for both synonymous and missense variation. While the distribution of these Z scores for the synonymous variants was normal, there is a marked shift in the missense distribution towards having fewer variants than predicted ...
With increasing use of multi-gene panel tests, one of the genes in which mutations are frequently detected among breast cancer patients and others is the CHEK2 gene. This gene has been shown to have a 2-3 fold excess risk for breast cancer. There are many CHEK2 mutations that have been identified that generally fall into two broad categories: those that prematurely shorten the protein that is made from the gene (called truncating mutations) and those that change a single base pair within the gene that impairs it from working normally (called missense mutations). Most completed studies have focused on a specific truncating mutation called 1100delC, as it is a relatively common change particularly among European populations.. A few studies have tried to assess if breast cancers associated with CHEK2 mutations may have specific characteristics, although results have not been consistent. For example, a study from 2014 which included 3 CHEK2 truncating mutations (including the 1100delC ...
The horizontal axis represents time, and the vertical axis represents a percentage of the population. When a mutation enters the population, it occurs in only one individual and is plotted as a point somewhere on the x axis. If the mutation is passed on, for example to four new offspring, then it will be in a higher percentage of the population at the next time step. Most mutations will soon drop out of the population. Either the individual where the mutation originates will not survive, or if it does survive and mate, by chance it may not pass the mutation to its children. Even then the children may not pass the mutation any further. Mutations that eventually die out show up as inverted ``V shapes in the figure: they are introduced, they are passed on to some proportion of the population in the next few generations, and eventually the percentage drops to 0 as the mutation disappears. Some small percentage of new mutations are passed on successfully. If by chance the mutation continues to ...
Six novel missense mutations (H29D, L35P, G84R, C96S, S101C, and Y103C) were identified in seven families. Three of these mutations involve cysteine residues within the insulin A chain and are therefore predicted to affect the normal folding of the proinsulin molecule. S101C was identified in two families: in ISPAD180 the finding that both children are heterozygous for the mutation but neither parent is a carrier suggests that the mutation has arisen de novo in one parent who must be a germline mosaic (Fig. 2). In the second family, the mutation was not present in the unaffected father, but DNA was not available from the mother.. The novel C96S mutation occurs at the site of a previously reported mutation (C96Y) identified in a patient with PND (10) and in the Akita mouse model (11). The same amino acid substitution (Cys,Ser) is present at the adjacent residue (C95S) in the Munich mouse model (23). Studies of these mice indicate that mutant proinsulin is trapped and accumulated in the ER, ...
sage -t --long devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py ********************************************************************** File devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py, line 1259, in sage.combinat.cluster_algebra_quiver.mutation_type._mutation_type_test Failed example: _mutation_type_test(2) # long time Expected: True (A, 2) True (A, (1, 1), 1) True (B, 2) True (BC, 1, 1) True (G, 2) Got: True (A, (1, 1), 1) True (A, 2) True (B, 2) True (BC, 1, 1) True (G, 2) ********************************************************************** File devel/sage/sage/combinat/cluster_algebra_quiver/mutation_type.py, line 1266, in sage.combinat.cluster_algebra_quiver.mutation_type._mutation_type_test Failed example: _mutation_type_test(3) # long time Expected: True (A, 3) True (A, (2, 1), 1) True (B, 3) True (BB, 2, 1) True (BC, 2, 1) True (C, 3) True (CC, 2, 1) True (G, 2, -1) True (G, 2, 1) Got: True (A, (2, 1), 1) ...
Description of disease Gain-of-function mutation. Treatment Gain-of-function mutation. Symptoms and causes Gain-of-function mutation Prophylaxis Gain-of-function mutation
Family history showed that the patients father had developed muscle weakness and atrophy in his upper extremities at 50 years of age, and died of pneumonia at 72 years of age. However, her mother was healthy and died of chronic renal failure at 80 years of age. Her elder sister was, at the time of writing, 73 years of age and healthy. Her elder brother displayed muscle weakness and wasting in his upper limbs and was diagnosed with ALS at 46 years of age. He also had mild cognitive impairment 10 years after onset. He died from respiratory failure 15 years after symptom onset. Her younger sister developed weakness in her right hand at 50 years of age. She was diagnosed with ALS at 58 years of age. There are no affected members in the third generation of this family; however, they are all younger than 35 years of age.. A novel missense mutation (C to A codon 41 in exon 2) that resulted in an amino acid substitution of glycine to aspartate (G41D) was identified in participants II-2, II-3, II-4, ...
Description: Goniodysgenesis (GG) is caused by abnormal development of the anterior chamber of the eye. Due to abnormal development of intraocular fluid egress channels inside the eye the iridocorneal angle (ICA), through which the excessive chamber fluid is filtered and drained. Within dog, population goniodysgenesis is considered as a congenital disease, which can often cause glaucoma or blindness. For first was GG detected in Border Collies in the late 90s in Australia, after that it spread to Europe and USA.. Goniodysgenesis has two forms: severe and mild. The severe form of this disease is caused by the mutation in the gene encoding for olfactomedin-like 3 (OLFML3). This encoded protein facilitates protein-protein interactions, cell adhesion, and intracellular interactions and has a general supporting function. It seems that the mild form of the disease is not associated with this mutation and can be caused by other genetic predispositions. GG is caused by a missense mutation c.590G,A ...
On Fri, Jul 22, 2011 at 2:08 AM, Dave Raggett ,[email protected], wrote: , On 22/07/11 02:26, Adam Klein wrote: ,, ,, This is only complex because youre coalescing the mutations, right? ,, In Rafaels original proposal, each mutation would result in a single ,, immutable mutation record, so the semantics would be to deliver (by ,, appending to a queue associated with each observer) a mutation record ,, to any currently-registered observers. ,, ,, Or is there some other concern with beginning notifications partway ,, through a task? , , I would suggest avoiding coalescing mutations altogether! , , But if you are going to, *dont* coalesce mutations when the resulting DOM , tree is dependent on the order in which those mutations took place. This is , critical to distributed editing applications. The DOM should have no such behavior. The only exception to this rule that I know of is ,script, elements. They execute their contained script the first time they are inserted into a Document, but dont undo ...
For position 29 only BLOSSUM62 says that this mutation is not likely. The 9 other sources show that this mutation wont have a damaging influence on the function or structure of the protein. This is perspicuous since the conservation of this position is not very high. The amino acid on position 125 is quite good conserved with 96%. SNAP and SIFT says that this mutation will have an influence on the protein whereas Polyphen2 says that this mutation is ether not (HumVar) or hardly damaging (HumDiv). Since this position is quite good conserved it is more likely that this mutation will have an influence on the function or structure of the protein. back to Maple_syrup_urine_disease main page go back to Task 5 Mapping SNPs ...
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Investigation Dna Proteins And Mutations Answer Key. Point mutations that occur in dna sequences encoding proteins are either silent, missense or nonsense. Copying errors when dna replicates or is transcribed into rna can cause changes in the sequence of bases which makes up the genetic code. Mutations mutations the genes encoded in your dna result […]
Get an answer for Which of the two types of mutations, nonsense or missense, would be more harmful to an organism? and find homework help for other Biology questions at eNotes
Supplementary MaterialsS1 Fig: Verification of ER-resident E3 ubiquitin ligases for SLO-1 degradation. a known ER stress inducer. Data are means SEM; NS, not significant, One-way ANOVA; Tukeys post hoc test). (level pub = 10 m).(TIF) pgen.1008829.s002.tif (593K) GUID:?DBE63996-C89E-4F82-881B-7FFAF2BF049C S3 Fig: A mutation reverses the reduced SLO-1 function in the absence of ERG-28. A mutation raises aldicarb resistance in animals. Aldicarb-induced paralysis was analyzed using Kaplan-Meier success evaluation.(TIF) pgen.1008829.s003.tif (330K) GUID:?27E62CCF-E0A9-4960-B343-65FD7739843D S4 Fig: An mutation will not impede the trafficking of overexpressed SLO-1. (A) Consultant pictures and quantification of SLO-1 on the dorsal cable of mutant pets. No aggregated puncta had been observed (range club = 10 m).(TIF) pgen.1008829.s004.tif (1.0M) GUID:?AB4CE45E-2E16-4600-9923-5ABFB0F9CBFE S5 Fig: The deletion mutation recovers higher degrees of SLO-1 on the dorsal cord compared to the missense mutation. ...
In this rar are the contents of the hdd mutation sits on. It contains the current (non-functioning) source code as well as multiple source backups I had made throughout its development. The current source code is capable of importing tags from other projects, but when I last touched it I was in the middle of writing code to explode the sound_diagnostics tag at decompile time, and rebuilding it at compile time from the sound tags. So in its current state it will not work for anything, if it even compiles without errors. I would check the last source backup to see if it can import tags, since it could prove useful to some people. I would also like to say that this project is the result of many years of work, coding styles, and ideas. It is a mess and does not reflect my current coding ability. My only request is that if you choose to do anything to Mutation and release it, please release it under another name with credit to the mutation source code. I have a vision in my head of what Mutation ...
A) in a published family with nonsyndromic MR, MRX13. This change occurs in a highly conserved amino acid, with proline (P) being substituted by threonine (T) (p.P544T). Functional analysis shows that this amino-acid substitution compromises both tri- and didemethylase activity of the JARID1C protein. We conclude that the two novel changes impair JARID1C protein function and are disease-causing mutations in these families ...
In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a ... Missense mutation refers to a change in one amino acid in a protein, arising from a point mutation in a single nucleotide. ... Missense mutations can render the resulting protein nonfunctional, and such mutations are responsible for human diseases such ... Not all missense mutations lead to appreciable protein changes. An amino acid may be replaced by an amino acid of very similar ...
A missense mRNA arises from a missense mutation, in the event of which a DNA nucleotide base pair in the coding region of a ... Missense mRNA molecules are created when template DNA strands or the mRNA strands themselves undergo a missense mutation in ... Missense mRNAs may be detected as a result of two different types of point mutations - spontaneous mutations and induced ... Induced mutations caused by mutagens can give rise to missense mutations. Nucleoside analogues such as 2-aminopurine and 5- ...
Several mutations in the THOC2 gene, part of the THO complex, are associated with disease. For example, missense mutations, or ... "Missense Mutation". Genome.gov. Retrieved 2022-10-24. "What is ALS?". The ALS Association. Retrieved 2022-10-25. (Pages with ... Mutations on this gene leads to the incorrect localization of the protein in the cytoplasm, an essential process for neural and ... Mutations in other genes can also have an indirect dependence on the TREX complex and lead to disease, including familial ...
Missense mutations code for a different amino acid. A missense mutation changes a codon so that a different protein is created ... For example, sickle-cell disease is caused by a single point mutation (a missense mutation) in the beta-hemoglobin gene that ... These are both examples of a non-conservative (missense) mutation. Silent mutations code for the same amino acid (a "synonymous ... Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of mutation may be increased ...
The POLD1 missense mutation p. S478N, in the exonuclease domain, has been validated as damaging and pathogenic. Other POLD1 ... Another recent study showed that mutations affecting Polδ and Polε mutations can co-occur along with MMR mutations. This ... POLD1 mutations have been studied in cell lines and mouse models. For example, a homozygous Polδ mutation in mice that disrupts ... For families with known mutations, single site testing is also available to confirm the presence of a mutation. The ...
Donnelly P, Menet H, Fouanon C, Herbert O, Moisan JP, Le Roux MG, Pascal O (1994). "Missense mutation in the choroideremia gene ... Mutations in this gene are a cause of choroideremia; also known as tapetochoroidal dystrophy (TCD). This X-linked disease is ... Schwartz M, Rosenberg T, van den Hurk JA, van de Pol DJ, Cremers FP (1993). "Identification of mutations in Danish ... "Detection and characterization of point mutations in the choroideremia candidate gene by PCR-SSCP analysis and direct DNA ...
Codon degeneracy Neutral mutation Genealogical DNA test Missense mutation Nonsense mutation Point mutation Synonymous ... Conversely, silent mutations are mutations in which the amino acid sequence is not altered. Silent mutations lead to a change ... The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are ... Mutations in the Multi-Drug Resistance Gene 1 show how silent mutations can have an effect on the outcome of the phenotype. ...
It is a type of missense mutation. C allele homozygosity is associated with black hair in people of European descent, although ...
Azuma N, Nishina S, Yanagisawa H, Okuyama T, Yamada M (June 1996). "PAX6 missense mutation in isolated foveal hypoplasia". ... Martha A, Strong LC, Ferrell RE, Saunders GF (1995). "Three novel aniridia mutations in the human PAX6 gene". Human Mutation. 6 ... Prosser J, van Heyningen V (1998). "PAX6 mutations reviewed". Human Mutation. 11 (2): 93-108. doi:10.1002/(SICI)1098-1004(1998) ... Mutations of the PAX6 gene in mammalian species can produce a drastic effect on the phenotype of the organism. This can be seen ...
... point mutation, with an expansion in one allele and a point mutation in the other. A missense point mutation can have milder ... The condition is caused by mutations in the FXN gene on chromosome 9, which makes a protein called frataxin. In FRDA, cells ... Depending on the point mutation, cells can produce no frataxin, nonfunctional frataxin, or frataxin that is not properly ... March 2016). "Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia". Annals of Neurology. 79 (3): 485- ...
Three novel truncating mutations and one novel missense mutation in the CACNA1A gene". J Neurol. 249 (11): 1515-9. doi:10.1007/ ... "Detection of a novel missense mutation and second recurrent mutation in the CACNA1A gene in individuals with EA-2 and FHM". Hum ... Yue Q, Jen J, Nelson S, Baloh R (1997). "Progressive ataxia due to a missense mutation in a calcium-channel gene". Am J Hum ... Knight M, Storey E, McKinlay Gardner R, Hand P, Forrest S (2000). "Identification of a novel missense mutation L329I in the ...
2006). "Muscle cell and motor protein function in patients with a IIa myosin missense mutation (Glu-706 to Lys)". Neuromuscul. ... 2001). "Autosomal dominant myopathy: missense mutation (Glu-706 --> Lys) in the myosin heavy chain IIa gene". Proc. Natl. Acad ... 2005). "Mutations and sequence variation in the human myosin heavy chain IIa gene (MYH2)". Eur. J. Hum. Genet. 13 (5): 617-22. ... 2002). "Myosin heavy chain IIa gene mutation E706K is pathogenic and its expression increases with age". Neurology. 58 (5): 780 ...
Missense)". "Mutation overview page ZNF439 - p.R457H ( Substitution - Missense)". "Rs1057868 - SNPedia". "Mutation overview ... For example, POR Missense mutations A287P and R457H lead to reductions in the activity of CYP2C19 and CYP2C9, respectively, ... whereas A503V and Q153R missense mutations lead to small increases in the activity of CYP2C9. While these and other POR genetic ... page SLC22A2 - p.Q153R ( Substitution - Missense)". (Articles with short description, Short description matches Wikidata, All ...
It is a missense mutation identical to the second missense mutation in W17. The horses with W30 are white or almost fully white ... The mutation (c.856G>A) is thought to have occurred spontaneously in this horse. It is a missense mutation on exon 5. W7 is ... This mutation is an SNP (c.1805C>T) which produces a missense mutation replacing alanine with valine in the kinase domain, on ... The reason for this is that several mutations of W are caused by nonsense mutations, frameshift mutations or DNA deletions, ...
Three patients showed heterozygous de-novo missense mutation. Six patients were found with de-novo missense mutation and one ... De novo mutation is a mutation that occurs in the germ cell of one parent. Neither parent has the mutation, but it is passed to ... The cause of alternating hemiplegia of childhood is the mutation of ATP1A3 gene. In a study of fifteen female and nine male ... September 2012). "De novo mutations in ATP1A3 cause alternating hemiplegia of childhood". Nature Genetics. 44 (9): 1030-1034. ...
Bengtson P, Larson C, Lundblad A, Larson G, Påhlsson P (August 2001). "Identification of a missense mutation (G329A;Arg(110 ...
ENU introduces missense point mutations; screening for mutations in a particular exon of DISC1 can produce mouse models with ... Sdy mice have homozygous mutations to DTNBP1, and lack the ability to produce dysbindin, heterozygous mutants can be produced ... PPP3CC PPP3CC is a gene in which mutations are risk factors for schizophrenia; knockout animal models have social deficits. ...
Missense mutations c.164 G > C, p.Arg55Pro and c.170 G > A, p.Gly57Glu, homozygous transversion 169G-C, p. Gly57-Arg, ... homozygous non sense mutation c.103G>T (p.Glu35X), and homozygous nonsense mutation c.22C > T, p.Gln8X have been associated ... SDHAF1 is a chaperone protein involved in the assembly of the succinate dehydrogenase (SDH) complex (complex II). Mutations in ... "Disease-Causing SDHAF1 Mutations Impair Transfer of Fe-S Clusters to SDHB". Cell Metabolism. 23 (2): 292-302. doi:10.1016/j. ...
"A missense T (Brachyury) mutation contributes to vertebral malformations". Journal of Bone and Mineral Research. 23 (10): 1576- ... "Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6". Human Molecular Genetics. 22 (8): 1625-31. doi: ...
Five missense mutations (A287P, R457H, V492E, C569Y, and V608F) and a splicing mutation in the POR genes have been found in ... Another POR missense mutation Y181D has also been identified. Fifteen of nineteen patients having abnormal genitalia and ... The role of POR mutations beyond CAH are being investigated; and questions such as how POR mutations cause bony abnormalities ... April 2020). "Molecular Basis of CYP19A1 Deficiency in a 46,XX Patient With R550W Mutation in POR: Expanding the PORD Phenotype ...
de Vries L, Gat-Yablonski G, Dror N, Singer A, Phillip M (2014). "A novel MKRN3 missense mutation causing familial precocious ... Schreiner F, Gohlke B, Hamm M, Korsch E, Woelfle J (2014). "MKRN3 mutations in familial central precocious puberty". Horm Res ... "Central precocious puberty in a girl and early puberty in her brother caused by a novel mutation in the MKRN3 gene". J. Clin. ... "Central precocious puberty caused by mutations in the imprinted gene MKRN3". N. Engl. J. Med. 368 (26): 2467-75. doi:10.1056/ ...
No effects have been observed with this missense mutation. Figure III. STRING Predicted Protein Interactions for Human CXorf66 ...
"MAFA missense mutation causes familial insulinomatosis and diabetes mellitus". Proceedings of the National Academy of Sciences ... Mutation of these residues is perinatally lethal in mice, and mutation of the Ser64Phe priming site was reported to induce ...
"Leptin receptor missense mutation in the fatty Zucker rat". Nature Genetics. 13 (1): 18-19. doi:10.1038/ng0596-18. PMID 8673096 ... "De Novo Mutations in FOXP1 in Cases with Intellectual Disability, Autism, and Language Impairment". The American Journal of ...
"Identification of a SACS gene missense mutation in ARSACS". Neurology. 62 (1): 107-9. doi:10.1212/01.wnl.0000099371.14478.73. ... Takado Y, Hara K, Shimohata T, Tokiguchi S, Onodera O, Nishizawa M (April 2007). "New mutation in the non-gigantic exon of SACS ... Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative ... Mercier J, Prévost C, Engert JC, Bouchard JP, Mathieu J, Richter A (2001). "Rapid detection of the sacsin mutations causing ...
Missense mutations are nonsynonymous substitutions that arise from point mutations, mutations in a single nucleotide that ... and provides support for theories that include advantageous mutations. Missense mutation Nonsense mutation Ting Hu and Wolfgang ... Another type of mutation that deals with stop codons is known as a nonstop mutation or readthrough mutation, which occurs when ... Nonsense mutations are nonsynonymous substitutions that arise when a mutation in the DNA sequence causes a protein to terminate ...
Missense mutations in SNCA are rare. On the other hand, multiplications of the SNCA locus account for around 2% of familial ... Missense mutations of the gene (in which a single nucleotide is changed), and duplications and triplications of the locus ... In patients with Parkinson's disease, the OR for carrying a GBA mutation was 5·43 (95% CI 3·89-7·57), confirming that mutations ... A significant number of autosomal-dominant Parkinson's disease cases are associated with mutations in the LRRK2 gene Mutations ...
"Functional consequences of PRODH missense mutations". American Journal of Human Genetics. 76 (3): 409-20. doi:10.1086/428142. ... Mutations in the PRODH gene are associated with Proline Dehydrogenase deficiency. Many case studies have reported on this ... All patients had biallelic mutations in the PRODH gene, often with several variants on the same allele. Residual enzyme ... "PRODH mutations and hyperprolinemia in a subset of schizophrenic patients". Human Molecular Genetics. 11 (19): 2243-9. doi: ...
No missense mutations occur in TSC1. In TSC2, the gene abnormalities are on chromosome 16p13. This gene encodes tuberin, a ... Once a particular mutation is identified in someone with TSC, this mutation can be used to make confident diagnoses in other ... If such a pathogenic mutation is found then this alone is sufficient to diagnose TSC. However, some mutations are less clear in ... In TSC2, all types of mutations have been reported; new mutations occur frequently. Few differences have yet been observed in ...
... each with developmental delays believed to be attributable in part to the mutations. All documented mutations are missense ... Tunovic S, Barkovich J, Sherr EH, Slavotinek AM (July 2014). "De novo ANKRD11 and KDM1A gene mutations in a male with features ... De novo mutations to KDM1A have been reported in three patients, ... "LSD1/KDM1A mutations associated to a newly described form of ...
Examination of SARS-CoV-2 sequences collected during the Covid-19 pandemic found that missense mutations were most common in ... the central linker region of the protein, suggesting this relatively unstructured region is more tolerant of mutations than the ...
... is caused by a novel missense mutation in GJB2". J. Invest. Dermatol. 123 (5): 856-63. doi:10.1111/j. ...
"A common missense mutation in the adhalin gene in three unrelated Brazilian families with a relatively mild form of autosomal ... "Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy". Cell. 78 (4): 625-33. doi:10.1016/ ... LOVD mutation database: SGCA (Articles with short description, Short description matches Wikidata, Genes on human chromosome 17 ... Duggan DJ, Gorospe JR, Fanin M, Hoffman EP, Angelini C (Feb 1997). "Mutations in the sarcoglycan genes in patients with ...
Cook, D; Brooks S; Bellone R; Bailey E (2008). Barsh, Gregory S. (ed.). "Missense Mutation in Exon 2 of SLC36A1 Responsible for ...
Sanger sequencing or the use of WES of parental samples confirmed the de novo status of the truncating and missense mutations ... Other mutations observed include a nonsense mutation, an in-frame deletion of amino acids and an entire gene deletion. De novo ... Parental DNA has confirmed that de novo mutations are common in patients with ZTTK syndrome. De novo LoF mutations and ... As an autosomal dominant disease, children with parents carrying a SON mutation have a 50% risk of inheriting the mutation. ...
A beta cardiac myosin heavy chain gene missense mutation". Cell. 62 (5): 999-1006. doi:10.1016/0092-8674(90)90274-i. PMID ... Several mutations in MYH7 have been associated with inherited cardiomyopathies. Lowrance et al. were the first to identify the ... Park JM, Kim YJ, Yoo JH, Hong YB, Park JH, Koo H, Chung KW, Choi BO (July 2013). "A novel MYH7 mutation with prominent ... Harris SP, Lyons RG, Bezold KL (March 2011). "In the thick of it: HCM-causing mutations in myosin binding proteins of the thick ...
"Missense mutations in the AFG3L2 proteolytic domain account for ~1.5% of European autosomal dominant cerebellar ataxias". Human ... "Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28". Nature Genetics. 42 (4): 313-321. ... a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation". European Journal of Human Genetics. 18 ... "Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m ...
April 2002). "Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene". The Journal of ... pathological and in vitro mutations and polymorphisms". Human Mutation. 21 (6): 557-568. doi:10.1002/humu.10213. PMID 12754700 ... February 1991). "Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid ... Kucera T, Waltner-Law M, Scott DK, Prasad R, Granner DK (July 2002). "A point mutation of the AF2 transactivation domain of the ...
Multiple mutations have been identified in RPS6KA3 that can give rise to the disorder, including missense mutations, nonsense ... These cases are caused by new mutations in the RPS6KA3 gene (de novo mutations). A new mutation means that neither parent has ... Mutations in the RPS6KA3 disturb the function of the protein, but it is unclear how a lack of this protein causes the signs and ... Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase ...
August 1996). "Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in ... Although the genetic defect was not known for many years, it was identified in the year 2000 as a mutation in the gene MERTK. ... This mutation results in defective retinal pigment epithelium phagocytosis of photoreceptor outer segments. The shaking rat ... Festing MF, May D, Connors TA, Lovell D, Sparrow S (July 1978). "An athymic nude mutation in the rat". Nature. 274 (5669): 365- ...
These mutations are mainly missense mutations that result in amino acid substitutions, and while some of them result in G6PD ... Many variants of G6PD, mostly produced from missense mutations, have been described with wide-ranging levels of enzyme activity ... Vulliamy T, Beutler E, Luzzatto L (1993). "Variants of glucose-6-phosphate dehydrogenase are due to missense mutations spread ... More than 40 severe class I mutations involve mutations near the structural site, thus affecting the long term stability of ...
"Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17". Nature. 393 (6686): 702-705. ... "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease". Nature. 349 (6311 ... and the Potamkin Prize for his work in describing the first genetic mutations in the amyloid gene in Alzheimer's disease, in ...
"A homozygous missense mutation in the ciliary gene TTC21B causes familial FSGS". J. Am. Soc. Nephrol. 25 (11): 2435-43. doi: ... Mutations in this gene are associated with various ciliopathies, nephronophthisis 12, and asphyxiating thoracic dystrophy 4. [ ... "Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing ... "Expanding the phenotype of CRB2 mutations - A new ciliopathy syndrome?". Clin. Genet. 90 (6): 540-544. doi:10.1111/cge.12764. ...
2000). "Identification of missense mutations in the SRD5A2 gene from patients with steroid 5alpha-reductase 2 deficiency". Clin ... 1999). "Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los ... Nordenskjöld A, Magnus O, Aagenaes O, Knudtzon J (1999). "Homozygous mutation (A228T) in the 5alpha-reductase type 2 gene in a ... Anwar R, Gilbey SG, New JP, Markham AF (1997). "Male pseudohermaphroditism resulting from a novel mutation in the human steroid ...
April 2019). "Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in ...
... missense mutations in the IRAK1 gene which causes overactivation of its product protein, interleukin-1 receptor-associated ... These alterations include mutations (i.e. changes in nucleic acid sequences), chromosomal rearrangements (i.e. deletions, ...
In Old Order Amish families, a homozygous proline to leucine missense mutation within the first RLD domain has been implicated ... "A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder". Human ... This genotype is present in almost all people with blue eyes and is hypothesised as being the founder mutation of blue eyes in ... HERC2 frameshift mutations have also been described in colorectal cancers. In accordance to its role in facilitating p53 ...
... deficits in reading and spelling associated with a missense mutation". Molecular Psychiatry. 15 (12): 1190-6. doi:10.1038/mp. ...
These results suggest that PGLYRP3 protects humans from these diseases, and that mutations in PGLYRP3 gene are among the ... have significantly more frequent missense variants in PGLYRP3 gene (and also in the other three PGLYRP genes) than healthy ...
... both nonsense and missense mutations are possible. However, the subsequent transformations differ between nonsense and missense ... Another method to reduce mismatch repair is to bury the mutations of interest within other silent mutations. Since silent ... Finally, long segments of mutations will be less affected by short segments of mutations. Transformed oligonucleotides are ... 1989). "Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)". Nucleic Acids Res. 17 (7 ...
"A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis". American Journal of Human ... However, because mutations in the TERF2 dimerization domain destabilize the protein, it has not been possible to test the ...
1995). "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease". Nature. 375 (6534): 754-60. ...
Loss-of-function mutations, nonsense mutations, and missense mutations are three of the most common. Nonsense and missense ... Although FMO3 mutations account for most known cases of trimethylaminuria, some cases are caused by other factors. A fish-like ... If the enzyme is missing or its activity is reduced because of a mutation in the FMO3 gene, trimethylamine is not broken down ... 1998). "Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication". Human ...
Multiple mutations including truncation and missense mutations are known to cause the disease from multiple families based on ... In addition, mutations in ELAC2 are known to cause combined oxidative phosphorylation deficiency 17 (COXPD17), a rare autosomal ... 2003). "Association of common missense changes in ELAC2 ( HPC2) with prostate cancer in a Japanese case-control series". J. Hum ... "ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy". Am. J. Hum. Genet. 93 ...
... twofold degenerate codons can withstand silence mutation rather than Missense or Nonsense point mutations at the third position ... Since transition mutations (purine to purine or pyrimidine to pyrimidine mutations) are more likely than transversion (purine ... The degeneracy of the genetic code is what accounts for the existence of synonymous mutations.: Chp 15 Degeneracy of the ... For example, in theory, fourfold degenerate codons can tolerate any point mutation at the third position, although codon usage ...
"Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients" (PDF). J. Biol. Chem ... "Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients". J. Biol. Chem. 276 ...
"Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone ... Mutations in LRP5 can lead to considerable changes in bone mass. A loss-of-function mutation causes osteoporosis pseudoglioma ... Mice with the same Lrp5 gain-of-function mutations as also have high bone mass. The high bone mass is maintained when the ... Mutations in this gene also cause familial exudative vitreoretinopathy. A glial-derived extracellular ligand, Norrin, acts on a ...
February 2007). "Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome". The New England Journal of ... Pathogenic mutations have included R45C, R56X, T50A, R73C, P99L, R155P, V353M, G129R, R183C, F368I, and S277N. These mutations ... Pathogenic mutations have included Y301N, R184C, G35R, R114W, R183H, Q302E, and R306H. These mutations tend to affect the ... Mutations in this gene are associated with mitochondrial complex III deficiency (nuclear, 1), GRACILE syndrome, and Bjoernstad ...
Sequencing of NC101 showed it has a missense mutation in nadA, a gene that encodes for quinolinate synthase A, which is ... Lopez, Lacey R.; Barlogio, Cassandra J.; Broberg, Christopher A.; Wang, Jeremy; Arthur, Janelle C. (2021). "A nadA Mutation ...
A missense mutation on the NET gene (SLC6A2) was discovered in which an alanine residue was replaced with a proline residue ( ... This notation for missense mutations, take Val69Ile for example, indicates that amino acid Val69 was changed to Ile. An ... Thirteen NET missense mutations have been discovered so far. Abbreviations: TMD, transmembrane domain; n/a, non-applicable. For ... However, 40 other OI patients did not have the same missense mutation, indicating other factors contributed to the phenotype in ...
... Front Genet. 2020 Feb 27;11:61. doi: ... However, mutations in KIF1A have not been detected in patients with epilepsy. In our study, we conducted customized sequencing ... and phenotype testing in zebrafish showed that this rare mutation results in epileptic seizure-like activity. These results ... of a family with six patients with generalized epilepsy over three generations and identified a rare heterozygous mutation (c. ...
A method and server for predicting damaging missense mutations. Nat Methods 2010; 7: 248-249. ... Extended haplotype association study in Crohns disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the ... Crohn disease: frequency and nature of CARD15 mutations in Ashkenazi and Sephardi/Oriental Jewish families. Am J Hum Genet 2004 ... A frameshift mutation in NOD2 associated with susceptibility to Crohns disease. Nature 2001; 411: 603-606. ...
Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families. K. Hara, A. Shiga, H. Nozaki, J. Mitsui, Y. ... Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families ... results strongly confirm that ITPR1 is the causative gene for SCA15 and suggest that we need to investigate the point mutation ...
Genomic Mutation ID Genomic mutation identifier (COSV) to indicate the definitive position of the variant on the genome. This ... It describes the source of the mutation i.e gene name/sample name/tissue name with unique ID, and also shows the mutation ... Legacy mutation identifier (COSM) represents existing COSM mutation identifiers. This identifier remains the same between ... CDS mutation. c.692C>T (Substitution, position 692, C➠T) Nucleotides inserted. n/a Genomic coordinates. GRCh38, 4:86101090.. ...
Exome sequencing identified a missense mutation of EPS8L3 in Marie Unna Hereditary Hypotrichosis. Posted on October 25, 2012. ...
Disease-causing missense mutations in Jouberin. (A) Localisation of the missense mutations in Jouberin. Open box depicts coiled ... thus representing a null mutation. The missense mutation, c.2258A,T; p.Asp753Val, was previously unreported in JBTS and absent ... Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss. Am J Hum Genet 2000; ... Patients in all three of the above families carried at least one AHI1 allele with a missense mutation in the WD40 domain (WD40 ...
Microdeletions and point mutations in ASA may cause MLD. Milder cases usually have missense mutations that allow some residual ... The patient was found to be a compound heterozygote for two novel missense mutations in ASA, G293D in exon 5, and C489G ... The pathological nature of the two novel missense mutations we identified in our patient was supported by the non-conservative ... Despite the confounding effect of the associated pseudodeficiency, it is clear that the patients missense mutations led to a ...
"ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia" has been published in Neurology ... Home » JPND Publications » ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia ...
Genomic Mutation ID Genomic mutation identifier (COSV) to indicate the definitive position of the variant on the genome. This ... It describes the source of the mutation i.e gene name/sample name/tissue name with unique ID, and also shows the mutation ... Legacy mutation identifier (COSM) represents existing COSM mutation identifiers. This identifier remains the same between ... CDS mutation. c.1133C>T (Substitution, position 1133, C➠T) Nucleotides inserted. n/a Genomic coordinates. GRCh38, 4:86029202.. ...
A missense mutation causes aspartase deficiency in Yersinia pestis * Ronald E. Viola1, Lyudmyla Yerman1, Janet M. Fowler2, ... A missense mutation causes aspartase deficiency in Yersinia pestis. Microbiology 154, 1271 (2008); https://doi.org/10.1099/mic. ... Rosqvist R., Skurnik M., Wolf-Watz H. 1988; Increased virulence of Yersinia pseudotuberculosis by two independent mutations. ... A differential plating medium for the estimation of the mutation rate to avirulence. J Bacteriol 81:605-608 ...
In this study, we generated a new knock-in mouse strain that carries an ECEL1/DINE pathogenic G607S missense mutation, based on ... Our mutant mouse data suggest that ECEL1/DINE G607S and C760R mutations both lead to motor innervation defects as primary ... However, the functional consequences of the two mutations are distinct, with loss of axonal transport of ECEL1/DINE in C760R ... Until now, the consequences of the identified pathogenic mutations have remained incompletely understood because of a lack of ...
From: A missense mutation of plastid RPS4 is associated with chlorophyll deficiency in Chinese cabbage (Brassica campestris ssp ... Table 2 Mutation sites in chlorophyll-deficient mutant (cdm) and wild-type (WT) compared with the reference genome. ...
Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation ... Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation ...
Two GORAB missense mutations identified in gerodermia osteodysplastica patients fall within this IGRAB domain. GORAB carrying ... In contrast, the p.Ser175Phe mutation displaced GORAB from the Golgi compartment to vesicular structures and selectively ... and bone that is caused by loss-of-function mutations in GORAB. The golgin, RAB6-interacting (GORAB) protein localizes to the ... the mutation p.Ala220Pro had a cytoplasmic distribution and failed to interact with both RAB6 and ARF5. ...
Missense mutations in the human β fibrinogen gene cause congenital afibrinogenemia by impairing fibrinogen secretion. In: Blood ... Missense mutations in the human β fibrinogen gene cause congenital afibrinogenemia by impairing fibrinogen secretion. Blood. ... Missense mutations in the human β fibrinogen gene cause congenital afibrinogenemia by impairing fibrinogen secretion. / Duga, ... title = "Missense mutations in the human β fibrinogen gene cause congenital afibrinogenemia by impairing fibrinogen secretion", ...
深入研究「A germline missense mutation in COQ6 is associated with susceptibility to familial schwannomatosis」主題。共同形成了獨特的指紋。 ... A germline missense mutation in COQ6 is associated with susceptibility to familial schwannomatosis. ...
Missense Mutation 2. Pannychida - Mental Thromb 3. Pannychida - Harmonious Mechanism 4. Pannychida - Subsistence Will 5. ... SAT211: Pannychida - Missense Mutation (2018) by Satanath Records, released 31 October 2018 1. Pannychida - ... supported by 123 fans who also own "SAT211: Pannychida - Missense Mutation (2018)" ... supported by 119 fans who also own "SAT211: Pannychida - Missense Mutation (2018)" ...
A missense mutation results in a codon change, which leads to a change in amino acids. ... A silent mutation is a codon mutation, which does not result in a change of amino acid. ... a-definition-and-an-example-of-each-of-the-following-mutations-silent-nonsense-missense-and-frameshift-mutation-aug-gug-cca-uuc ... a-definition-and-an-example-of-each-of-the-following-mutations-silent-nonsense-missense-and-frameshift-mutation-aug-gug-cca-uuc ...
Return to Article Details A case of Kallmann syndrome associated to a novel missense mutation of the FGFR1 gene Download ...
HFE missense mutations. Homozygosity for a missense mutation, with substitution of a cysteine residue for a tyrosine residue at ... This missense mutation, converting alanine to aspartic acid at residue 77 (A77D mutation), was not identified in samples from ... HFE gene missense mutations. The gene most recognized as responsible for the disease is called HFE, and it is located within ... SLC11A3 gene missense mutation and autosomal dominant hemochromatosis. A large family was described with autosomal dominant ...
A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly.. ... A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly. ...
He was homoallelic for the CPOX missense mutation, c.980A > G (p.H327R), and had massively increased urinary uroporphyrins I ... a rare variant due to specific CPOX mutations that alter enzyme residues D400-K404, most patients described to date having at ...
Copyright © 2022 Effect of BET Missense Mutations on Bromodomain Function - OnePress theme by FameThemes ... We found that RIP1 interacted with some of these enzymes and KK-AT mutation had no effect on these interactions (Supplementary ... We found that RIP1 interacted with some of these enzymes and KK-AT mutation had no effect on these interactions (Supplementary ...
Molecular evaluation of a novel missense mutation & an insertional truncating mutation in SUMF1 gene. Indian Journal of Medical ... Molecular evaluation of a novel missense mutation & an insertional truncating mutation in SUMF1 gene. ... The bioinformatic analysis of the missense mutation revealed no apparent effect on the overall structure. However, the mutated ... Conclusions: The two mutations identified in the present case were novel. This is perhaps the first report of an insertion ...
The familial dementia gene revisited: a missense mutation revealed by whole-exome sequencing identifies ITM2B as a candidate ... a missense mutation revealed by whole-exome sequencing identifies ITM2B as a candidate gene underlying a novel autosomal ...
A missense mutation in the androgen receptor gene causing androgen insensitivity syndrome in a Chinese family ...
Missense mutation. Silent mutation. Missense mutation. Silent mutation. Missense mutation. Silent mutation. Missense mutation. ... Silent mutation. mxf. ofx. cip. Lev. 109. 19F. D. ST156 Spain 9V-3. S81F. -. -. V381, G384, L386. S79Y. Q41. -. -. 6, R. ,32, R ... Boldface font indicates mutations from the literature that conferred fluoroquinolone resistance; underline indicates mutation ... regular font indicates silent mutations, all are transition: V381 (gtA-gtG), G384 (ggA-ggG), L386 (ttG-ttA), N461 (aaC aaT), ...
Erythrocytosis associated with a novel missense mutation in the BPGM gene Petousi N., Copley RR., Lappin TRJ., Haggan SE., ... Transcript and description for the "Dance you PhD 2016: Cancer, mutations and DNA modifications" video ...
ObjectiveTo understand how the novel L130F mutation, found in 2 patients with Axenfeld-Rieger syndrome, disrupts function of ... Analyses of a Novel L130F Missense Mutation in FOXC1. Yoko A. Ito, BSc; Tim K. Footz, MSc; Tara C. Murphy, MSc; et al Winnie ... 21 An R121H missense mutation in helix 3 of the FOXC2 FHD displayed a similar migration pattern to that of the L130F mutation ... 21 The L130F FOXC1 mutation is one of the most disruptive FOXC1 mutations studied because this mutation disrupts nuclear ...
  • Therefore, several of these internal ids could be associated with a single genomic COSV id where the mutation has been mapped to all overlapping genes and transcripts. (sanger.ac.uk)
  • Although several mutations in the fibrinogen genes associated with dysfibrinogenemia and hypofibrinogenemia have been described, the genetic defects of congenital afibrinogenemia are largely unknown, except for a recently reported 11-kb deletion of the fibrinogen Aα-chain gene. (elsevier.com)
  • Sequencing of the fibrinogen genes in the 2 probands detected 2 different homozygous missense mutations in exons 7 and 8 of the Bβ-chain gene, leading to amine acid substitutions Leu353Arg and Gly400Asp, respectively. (elsevier.com)
  • NLRP7 gene mutations can also prevent proper imprinting of multiple genes that contribute to a developing embryo, leading to abnormal gene activity (expression). (medlineplus.gov)
  • Causative mutations can occur in any of the three genes, but FGB mutations are the least common. (medscape.com)
  • As it have been described in other oligogenic diseases with a specific major gene involved in their development, mutations in other genes within the same pathway should be considered31. (emlinhibitor.com)
  • Total mutational load has been described for other pathologies, involving mutations in several genes that codify for proteins belonging to the same or related pathways, in the same individual34,35. (emlinhibitor.com)
  • BACKGROUND: Mutations in genes encoding desmosomal proteins have been reported to cause arrhythmogenic right ventricular cardiomyopathy (ARVC), an autosomal dominant disease characterised by progressive myocardial atrophy with fibro-fatty replacement. (ox.ac.uk)
  • Mutations in genes can have no effect, alter the product of a gene , or prevent the gene from functioning properly or completely. (wikipedia.org)
  • [8] Due to the damaging effects that mutations can have on genes, organisms have mechanisms such as DNA repair to prevent or correct mutations by reverting the mutated sequence back to its original state. (wikipedia.org)
  • [16] [17] Other types of mutation occasionally create new genes from previously noncoding DNA . (wikipedia.org)
  • The gene predictions selected here will be used to determine the effect of each variant on genes, for example intronic, missense, splice site, intergenic etc. (ucsc.edu)
  • however, mutations in other cohesin complex genes have also been implicated, particularly in atypical and mild CdLS cases. (wustl.edu)
  • Procesos que se dan en distintos organismos, por el que surgen nuevos genes. (bvsalud.org)
  • Background Recent findings suggesting that Abelson helper integration site 1 ( AHI1 ) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. (bmj.com)
  • The effects of the identified missense variants in AHI1 were predicted by three-dimensional structure homology modelling. (bmj.com)
  • All four missense variants were present in the conserved WD40 domain of Jouberin, the ciliary protein encoded by AHI1 , with variable predicted implications for the domain structure. (bmj.com)
  • Moreover, it structurally and functionally validates the effect of the RP-associated AHI1 variants on protein function, thus proposing a new genotype-phenotype correlation for AHI1 mutation associated retinal ciliopathies. (bmj.com)
  • Includes genetic variants for which the available evidence indicates likelihood, but not proof, that the mutation is deleterious. (cdc.gov)
  • Specific and designated deleterious mutations or variants of uncertain clinical significance are not present in the individual being tested. (cdc.gov)
  • Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. (alzforum.org)
  • What is more, the lack of awareness about deleterious synonymous mutations can lead to misclassification of pathogenic variants. (hindawi.com)
  • Variants of concern (VOC) carrying mutations in the RBD or other regions of S reduce the effectiveness of many nAbs and vaccines by evading neutralization. (bvsalud.org)
  • NLRP7 gene mutations account for recurrent hydatidiform mole in about 55 percent of women with this condition. (medlineplus.gov)
  • The NLRP7 gene mutations that cause recurrent hydatidiform mole lead to production of a protein with reduced function or prevent production of any protein at all. (medlineplus.gov)
  • In women with NLRP7 gene mutations, a hydatidiform mole will develop in every pregnancy that occurs with her egg cells. (medlineplus.gov)
  • Additionally, NLRP7 gene mutations result in slowed release of interleukin-1 beta. (medlineplus.gov)
  • The iron status in these subjects was studied and correlated with the HFE gene mutations. (who.int)
  • Our study has shown that the HFE gene mutations are common in Egypt among β-thalassaemia carriers compared with normal controls. (who.int)
  • The aim of this study was to assess the prevalence of glucokinase gene mutations in Italian children with MODY and to investigate genotype/phenotype correlations of the mutants. (nih.gov)
  • " ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia" has been published in Neurology Genetics . (neurodegenerationresearch.eu)
  • Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα). (ox.ac.uk)
  • Genomic mutation identifier (COSV) to indicate the definitive position of the variant on the genome. (sanger.ac.uk)
  • To date, only a few homozygous HCP patients have been described, most having Harderoporphyria, a rare variant due to specific CPOX mutations that alter enzyme residues D400-K404, most patients described to date having at least one K404E allele. (gazi.edu.tr)
  • positive for a deleterious mutation negative for a deleterious mutation genetic variant (three types - suspected deleterious, favor polymorphism, and uncertain clinical significance). (cdc.gov)
  • There are three possible categories of results for full DNA sequencing: 1) positive for deleterious mutation, 2) negative for deleterious mutation, and 3) genetic variant (three types - suspected deleterious, favor polymorphism and uncertain clinical significance). (cdc.gov)
  • We characterize variant diversity, amino acid mutation frequency, functionality and associations with COVID-19 infections in one of the largest datasets of SARS-CoV-2 genome sequences collected from wastewater in the New York metropolitan area. (bvsalud.org)
  • The results show that Syntool score can discriminate synonymous disease causing mutations in Human Gene Mutation Database (HGMD Professional) and ClinVar database much better than others. (hindawi.com)
  • However, mutations in KIF1A have not been detected in patients with epilepsy. (nih.gov)
  • 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. (neurology.org)
  • 8 No mutation data are available about the extremely rare patients that presented without peripheral neuropathy. (bmj.com)
  • Two GORAB missense mutations identified in gerodermia osteodysplastica patients fall within this IGRAB domain. (ox.ac.uk)
  • Nevertheless, mutation mechanisms other than the deletion of a fibrinogen gene are likely to exist because patients with afibrinogenemia showing no gross alteration within the fibrinogen cluster have been reported. (elsevier.com)
  • Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly. (jamanetwork.com)
  • Patients with mutations that changed the charge of the altered amino acid (such as that from arginine to glutamine at nucleotide 403 or from arginine to cysteine at nucleotide 453) had a significantly shorter life expectancy (mean age at death, 33 years), whereas patients with the one mutation that did not produce a change in charge (Val606Met) had nearly normal survival. (ox.ac.uk)
  • However, patients with different mutations did not differ appreciably in their clinical manifestations of familial hypertrophic cardiomyopathy. (ox.ac.uk)
  • We detected not only missense mutations in ENG, but also mutations affecting the splicing process, and interestingly a high proportion of patients with ENG mutations harbouring an additional mutation in BMPR2 gene. (emlinhibitor.com)
  • Rodr uez-Viales et al.32 published a study of two PAH families in which index patients PD173074 price showed one mutation in the 5UTR region of BMPR2 gene described by Wang et al.33 in an IPAH patient, along with another mutation in the coding region of BMPR2 or in the ENG gene, respectively. (emlinhibitor.com)
  • Graphical representation of pathogenic mutations type found in patients with more than one pathogenic mutation. (emlinhibitor.com)
  • Missense mutations are the most CEP-37440 web frequent in our patients, unlike nonsense mutations.could not discard an oligogenic inheritance model for PAH as described for others diseases, with a major gene being BMPR2. (emlinhibitor.com)
  • Thirteen of our patients were carriers of a mutation in BMPR.Ants.differences compared to wild-type, considering these ENG missense mutations as rare benign variants30. (emlinhibitor.com)
  • 8] A study of patients in Turkey revealed the presence of the prothrombin 20210a mutation in 0.7% of subjects. (medscape.com)
  • 12] A study of cancer patients in the Netherlands found that the presence of the prothrombin 20210a mutation in these patients may increase the risk of venous thrombosis to a level greater than that attributable to the malignancy alone. (medscape.com)
  • Treatment with oral anticoagulants is useful in preventing recurrence in patients with the mutation who have already experienced a thrombotic event. (medscape.com)
  • Finally, we show that the proportion of TBK1 that is active (phosphorylated) is reduced in 5 lymphoblastoid cell lines derived from patients harboring heterozygous missense or in-frame deletion TBK1 mutations. (ox.ac.uk)
  • Patients with gemistocytic astrocytoma with oligodendroglial differentiation, IDH1 samples from a Li-Fraumeni family with and secondary glioblastoma with RRAS mutation, and 1p/19q loss, suggesting a TP53 germline mutation and multiple deletion tended to have shorter survival that FUBP1 immunohistochemistry is nervous system tumours revealed times than those without deletion. (who.int)
  • A nonsense mutation in a corresponding region of KRT5 has been found in Dowling-Degos disease and a missense mutation in the V1 domain of KRT5 has been described in patients with epidermolysis bullosa with mottled pigmentation. (medscape.com)
  • The purpose of this study was to identify recessive TSPAN12 mutations in FEVR patients. (ox.ac.uk)
  • Further screening in a cohort of 10 retinal dysplasia/severe FEVR patients identified an additional three cases with recessive TSPAN12 mutations. (ox.ac.uk)
  • In all examined cases, single mutation carriers were mildly affected compared to patients harboring two TSPAN12 mutations. (ox.ac.uk)
  • FHH3 patients have heterozygous AP2S1 missense Arg15 mutations (p.Arg15Cys, p.Arg15His or p.Arg15Leu) with hypercalcaemia, which may be marked and symptomatic, and occasional hypophosphataemia and osteomalacia. (birmingham.ac.uk)
  • We report the first intragenic deletion and frameshift mutations identified in RAD21 in two patients presenting with atypical CdLS. (wustl.edu)
  • This study expands the spectrum of RAD21 mutations and emphasizes the clinical utility of performing RAD21 mutation analysis in patients presenting with atypical forms of CdLS. (wustl.edu)
  • Moreover, the variability of clinical presentation within families and low penetrance of mutations as well as the significance of performing molecular genetic testing in mildly affected patients are discussed. (wustl.edu)
  • Recent evidence has shown that Dasatinib has been also recently associated with promising clinical activity in patients with advanced GIST carrying exon 18 mutation of the PDGFRA gene (including the D842V mutation). (cornell.edu)
  • A frameshift mutation is a change of codon reading frame through insertion or deletion of one nucleotide or nucleotides. (academic.tips)
  • Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements . (wikipedia.org)
  • One patient had an in-frame deletion of exon 13, while the second patient had a c.592_593dup frameshift mutation. (wustl.edu)
  • The in-frame deletion mutation was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems. (wustl.edu)
  • Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. (ox.ac.uk)
  • First reported in 1996 as a familial cause of venous thromboembolism, the prothrombin 20210a mutation results in increased levels of plasma prothrombin and a concurrent increased risk for the development of thrombosis. (medscape.com)
  • Recessive mutations in TSPAN12 cause retinal dysplasia and severe familial exudative vitreoretinopathy (FEVR). (ox.ac.uk)
  • Mutations of CaSR, Gα11 and AP2σ2, encoded by AP2S1, cause familial hypocalciuric hypercalcaemia types 1-3 (FHH1-3), respectively. (birmingham.ac.uk)
  • Whole-cell recordings from primary cultured neurons revealed that the mutant KIF1A increases the excitatory synaptic transmission but not the intrinsic excitability of neurons, and phenotype testing in zebrafish showed that this rare mutation results in epileptic seizure-like activity. (nih.gov)
  • Mutations may or may not produce detectable changes in the observable characteristics ( phenotype ) of an organism. (wikipedia.org)
  • A central challenge in interpreting personal genomes data is how to identify pathogenic mutations by using their prior information or other phenotype information. (hindawi.com)
  • To further characterize the phenotypic spectrum and calcitropic pathophysiology of FHH3, we used CRISPR/Cas9 genome editing to generate mice harboring the AP2S1 p.Arg15Leu mutation, which causes the most severe FHH3 phenotype. (birmingham.ac.uk)
  • Thus, our studies have established a mouse model that is representative for FHH3 in humans, and demonstrated that the AP2S1 p.Arg15Leu mutation causes a predominantly calcitropic phenotype, which can be ameliorated by treatment with cinacalcet. (birmingham.ac.uk)
  • G (p.K151E) substitution in exon 3 and a single base insertion mutation (c.690_691 InsT) in exon 5 in the SUMF1 gene. (who.int)
  • All were missense mutations (i.e., causing the substitution of a single amino acid) clustered in the head and head-rod junction regions of the molecule. (ox.ac.uk)
  • The prothrombin 20210a mutation involves the substitution of an adenine for a guanine at position 20210 within the 3' untranslated region of the prothrombin gene. (medscape.com)
  • Here we defined synonymous and missense variation as single nucleotide substitution variation. (hindawi.com)
  • The D842V mutation results in an amino acid substitution at position 842 in PDGFRA, from an aspartic acid (D) to a valine (V). This mutation occurs within the TK2 domain. (cornell.edu)
  • De Novo Missense Mutations in DHX30 Impair Global Translation and Cause a Neurodevelopmental Disorder. (bvsalud.org)
  • Here we identified six different de novo missense mutations in DHX30 in twelve unrelated individuals affected by global developmental delay (GDD), intellectual disability ( ID ), severe speech impairment and gait abnormalities . (bvsalud.org)
  • Paternity testing indicated that the latter mutations have arisen de novo. (nih.gov)
  • ERCC1 were absent in other low-grade in lowgrade diffuSe glioMaS schwannomas also carried the MSH4 diffuse gliomas and in primary (de novo) germline mutation and, in addition, a glioblastomas (Ohta et al. (who.int)
  • A missense mutation results in a codon change, which leads to a change in amino acids. (academic.tips)
  • Disruptive mutations (i.e. nonsense, frameshifts, splice-site) were equally represented in Groups 1 and 2 and were not clearly associated with an impaired first-phase insulin response. (nih.gov)
  • The defect is caused by mutations (frameshift, nonsense, missense, or splice-site) in the CHD7 (Chromodomain [ chr omatin o rganisation mo difier] Helicase DNA-Binding Protein 7) gene, which has been mapped to chromosome 8q12.2. (mhmedical.com)
  • useful for glioma diagnosis (Baumgarten additional germline mutations. (who.int)
  • These findings demonstrated that missense mutations in the Bβ fibrinogen gene could cause congenital afibrinogenemia by impairing fibrinogen secretion. (elsevier.com)
  • To assess the importance of this gene in non-syndromic childhood or congenital deafness in Turkey, we screened for mutations affected members of 25 unrelated Turkish families. (sdu.edu.tr)
  • Includes all mutations (nonsense, insertions, deletions) that prematurely terminate (truncate) the protein product of BRCA1 at least 10 amino acids from the C-terminus, or the protein product of BRCA2 at least 110 amino acids from the C-terminus (based on documentation of deleterious mutations in BRCA1 and BRCA2 ). (cdc.gov)
  • Pathogenic mutations in TMPRSS3, which encodes a transmembrane serine protease, cause non-syndromic deafness DFNB8/10. (sdu.edu.tr)
  • Also includes mutations in the protein-coding region that neither alter the amino acid sequence nor are predicted to significantly affect exon splicing, and base pair alterations in non-coding portions of the gene that have been demonstrated to have no deleterious effect on the length or stability of the mRNA transcript. (cdc.gov)
  • Arie Perry has researched Mutation in several fields, including DNA methylation and Exon. (research.com)
  • The results from our study suggest that there are relatively understudied mutations in the spike protein (H655Y, T95I) and understudied mutations occurring in non-spike proteins (N, ORF1b, ORF9b and ORF9c), that are enhancing transmissibility and infectivity among human populations, warranting further investigation. (bvsalud.org)
  • A missense mutation of plastid RPS4 is associated with chlorophyll deficiency in Chinese cabbage (Brassica campestris ssp. (biomedcentral.com)
  • Homocystinuria due to MTHFR deficiency caused by compound heterozygous mutations composed of the MTHFR gene in this family may be associated with cerebral atrophy and cerebral dysplasia. (biomedcentral.com)
  • METHODS: Mutation screening was performed by denaturing high-performance liquid chromatography and direct sequencing. (ox.ac.uk)
  • Nevertheless, there are still rarely synonymous mutation prediction methods. (hindawi.com)
  • The methods of deleterious prediction could be helpful in identifying candidate disease causing mutations. (hindawi.com)
  • METHODS: Mutation screening was performed by directly sequencing PCR products generated from genomic DNA with primers designed to amplify the coding sequence of TSPAN12. (ox.ac.uk)
  • T can predict nonsynonymous mutations or missense mutations pathogenicity but can not predict synonymous mutations pathogenicity. (hindawi.com)
  • We collected the family history and detailed clinical information, then performed whole-exome sequencing, and analyzed the pathogenicity of the candidate mutations. (biomedcentral.com)
  • Missense mutations and whole gene deletions in RAD21 have been identified in children with growth retardation, minor skeletal anomalies and facial features that overlap findings in individuals with CdLS. (wustl.edu)
  • This is perhaps the first report of an insertion mutation in SUMF1 causing premature truncation of the protein. (who.int)
  • A nonsense mutation is a mutation that leads to a premature stop of protein synthesis or translation. (academic.tips)
  • The L130F mutation in the FOXC1 (forkhead box C1) gene does not affect protein stability. (jamanetwork.com)
  • The L130F mutation in the FOXC1 (forkhead box C1) gene alters phosphorylation of wild-type (WT) FOXC1 protein. (jamanetwork.com)
  • The L130F mutation in the FOXC1 (forkhead box C1) gene disrupts efficient nuclear localization of the FOXC1 protein. (jamanetwork.com)
  • Missense mutations map in the low density-lipoprotein receptor A (LDLRA), scavenger-receptor cysteine-rich (SRCR), and protease domains of the protein, indicating that all domains are important for its function. (sdu.edu.tr)
  • p.His202Asp) in a highly conserved amino acid position (even across kingdoms), which disrupts the first copper-binding site (CuA) of functional protein, was identified in the homozygous condition (G/G or D/D) in all Asinara white albino donkeys and in the albino son of a trio (the grey parents had genotype C/G or H/D), supporting the recessive mode of inheritance of this mutation. (unibo.it)
  • A 2007 study on genetic variations between different species of Drosophila suggested that, if a mutation changes a protein produced by a gene, the result is likely to be harmful, with an estimated 70% of amino acid polymorphisms that have damaging effects, and the remainder being either neutral or marginally beneficial. (wikipedia.org)
  • Recent increase in our knowledge suggests that synonymous mutations could cause changes in protein expression, conformation, and function [ 2 , 3 ]. (hindawi.com)
  • The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. (phosphosite.org)
  • Co-immunoprecipitation studies showed that the AP2S1 p.Arg15Leu mutation impaired protein-protein interactions between AP2σ2 and the other AP2 subunits, and also with the CaSR. (birmingham.ac.uk)
  • Strikingly, over 60% of the most frequently occurring mutations were found in regions other than the spike (S) protein, and nearly 50% remain uncharacterized for functional impacts warranting further investigation. (bvsalud.org)
  • Conclusions This report confirms that mutations in AHI1 can underlie autosomal recessive RP. (bmj.com)
  • CONCLUSIONS: Different missense mutations in the beta cardiac myosin heavy-chain gene can be identified in approximately 50 percent of families with hypertrophic cardiomyopathy. (ox.ac.uk)
  • CONCLUSIONS: We report for the first time recessive mutations in TSPAN12 and describe the first genetic cause for the clinical variation seen in FEVR families. (ox.ac.uk)
  • The identification of the causative mutation of the albinism in the Asinara white donkeys might open new perspectives to study the dynamics of this putative deleterious allele in a feral population and to manage this interesting animal genetic resource. (unibo.it)
  • Identification of additional DSC2 mutations associated with ARVC may result in increased diagnostic accuracy with implications for genetic counseling. (ox.ac.uk)
  • Mutation is the ultimate source of all genetic variation , providing the raw material on which evolutionary forces such as natural selection can act. (wikipedia.org)
  • Mutations can involve the duplication of large sections of DNA, usually through genetic recombination . (wikipedia.org)
  • Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8. (bvsalud.org)
  • The purpose of this study is to expand the mutation site of the MTHFR gene and provide genetic counseling for this family. (biomedcentral.com)
  • For example clicking on "Chemically induced" box, will limit the search to those strains where the genetic mutation was induced by a chemical being administered to the mouse strain. (edu.au)
  • To date, approximately 30 different mutations have been identified in the causative gene, sulfatase modifying factor 1 (SUMF1). (who.int)
  • In this study, we analysed the donkey TYR gene as a strong candidate to identify the causative mutation of the albinism of these donkeys. (unibo.it)
  • Molecular models and scatterplot of in silico analysis of the L130F mutation in the FOXC1 (forkhead box C1) gene. (jamanetwork.com)
  • The lack of correlation between the molecular severity of glucokinase mutations, insulin secretion at intravenous glucose tolerance test and differences in glucose tolerance suggests that factors outside the beta cell are also involved in determining post-load glucose concentrations in these subjects. (nih.gov)
  • However, more recent pedigree analysis showed that the nonsynonymous mutation was not pathogenic, and one synonymous mutation was pathogenic [ 6 ]. (hindawi.com)
  • Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by mutations in the arylsulphatase A ( ASA ) gene. (bmj.com)
  • Mutations in BEST1 cause five distinct retinal degenerative diseases, including adult vitelliform macular dystrophy (AVMD), autosomal recessive bestrophinopathy (ARB), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and retinitis pigmentosa (RP). (ox.ac.uk)
  • Transient transfection experiments with plasmids expressing wild-type and mutant fibrinogens demonstrated that the presence of either mutation was sufficient to abolish fibrinogen secretion. (elsevier.com)
  • Synonymous mutation is the single nucleotide change that does not cause an amino acid change but can affect the rate and efficiency of translation. (hindawi.com)
  • There is general lack of awareness about synonymous mutations, which is sometimes called "silent" mutations, due to no effect on amino acid change. (hindawi.com)
  • A case-control study aimed to determine the prevalence of C282Y, H63D and S65C mutations of the HFE gene in β-thalassaemia carriers and investigate their influence on iron absorption. (who.int)
  • A total of 41 β-thalassaemia carriers and 40 control subjects without haemoglobinopathies were screened for the C282Y, H63D and S65C mutations by polymerase chain reaction-restriction fragment-length polymorphism. (who.int)
  • La présente étude cas-témoins visait à déterminer la prévalence des mutations C282Y, H63D et S65C du gène HFE chez les porteurs d'une β-thalassémie et à rechercher leur influence sur l'absorption du fer. (who.int)
  • Au total, 41 porteurs d'une β-thalassémie et 40 sujets témoins ne présentant aucune hémoglobinopathie ont participé à cette étude visant à examiner les mutations C282Y, H63D et S65C du gène HFE par la méthode du polymorphisme de longueur des fragments de restriction d'ADN amplifié. (who.int)
  • Includes all missense mutations and mutations that occur in analyzed intronic regions whose clinical significance has not yet been determined, as well as chain-terminating mutations that truncate BRCA1 and BRCA2 distal to amino acid positions 1853 and 3308, respectively. (cdc.gov)
  • Neither missense is IP7 to the convergent reaction as IL7R assembles produced by the MSH2 for wide extracellular complex( TSLP) while IL2RG activates involved with the residues for IL2, IL4, IL9, IL15 and IL21. (erik-mill.de)
  • We screened 54 ARVC probands for mutations in desmocollin-2 (DSC2), the only desmocollin isoform expressed in cardiac tissue. (ox.ac.uk)
  • and (d) validating the candidate gene as a tumor suppressor through the identification of truncating or missense mutations as well as by growth and tumor suppressing assays. (cdc.gov)
  • His study in Cancer research is interdisciplinary in nature, drawing from both Tumor suppressor gene, Oncogene and Mutation. (research.com)
  • His Cancer research research incorporates themes from Mutation and Tumor suppressor gene. (research.com)
  • Question 9: How often is a test positive when a mutation is present (analytic sensitivity)? (cdc.gov)
  • 17%) gemistocytic astrocytomas and in mutation with a sensitivity of 100% and 3 of 24 (13%) secondary glioblastomas. (who.int)
  • A silent mutation is a codon mutation, which does not result in a change of amino acid after the alteration. (academic.tips)
  • Since the location of a mutation or its DNA-sequence alteration (or both) appears to influence survival, we suggest that the precise definition of the disease-causing mutation can provide important prognostic information about affected members. (ox.ac.uk)
  • In biology , a mutation is an alteration in the nucleic acid sequence of the genome of an organism , virus , or extrachromosomal DNA . (wikipedia.org)
  • Is BRCA1/2 mutation testing qualitative or quantitative? (cdc.gov)
  • While four mutations are recurrent, two are unique with one affecting the codon of one recurrent mutation . (bvsalud.org)
  • More than 75 mutations in the NLRP7 gene have been found to cause a pregnancy-related condition called recurrent hydatidiform mole. (medlineplus.gov)
  • In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). (yeastgenome.org)
  • For example, UGG change to UGA would be a nonsense mutation, as shown below. (academic.tips)
  • Different mutations in the beta cardiac myosin heavy-chain gene have been identified in three affected families. (ox.ac.uk)
  • RESULTS: Seven mutations in the beta cardiac myosin heavy-chain gene were identified in 12 of the 25 families. (ox.ac.uk)
  • We conclude that missense mutations in functional domains of TBK1 impair the binding and phosphorylation of its normal targets, implicating a common loss of function mechanism, analogous to truncation mutations. (ox.ac.uk)
  • We investigated whether a relationship between telomerase and p53 could be demonstrated in a human sarcoma cell line containing a missense p53 mutation and several stable transfectants that express the wild- type p53 gene or a temperature-sensitive mutant of p53. (elsevier.com)
  • You may also limit the search to a chromosome or mutation type. (edu.au)
  • If you perform further searches make sure you clear the text boxes as any existing text, selected chromosome or mutation type will influence the new search. (edu.au)
  • Identification of the L130F mutation in the FOXC1 (forkhead box C1) gene. (jamanetwork.com)
  • RESULTS: TSPAN12 screening in a large dominant FEVR family unexpectedly led to the identification of homozygous mutations in severely affected family members, whereas mildly affected family members were heterozygous. (ox.ac.uk)
  • It describes the source of the mutation i.e gene name/sample name/tissue name with unique ID, and also shows the mutation syntax at the amino acid and nucleotide sequence level. (sanger.ac.uk)
  • however, many other mutations are missense with unknown functional effects. (ox.ac.uk)
  • High prevalence of glucokinase mutations in Italian children with MODY. (nih.gov)
  • So recent increase in our knowledge has revealed a substantial contribution of synonymous mutations to human disease risk and other complex traits. (hindawi.com)
  • Therefore, a corollary of this perception was that synonymous mutations would have no effect on the fitness of an organism and would be "neutral" during evolution [ 1 ]. (hindawi.com)
  • For example, a number of studies show that synonymous mutations result in aberrant mRNA splicing, which can lead to human disease [ 4 - 6 ]. (hindawi.com)
  • For synonymous and missense variation, Lek et al. (hindawi.com)
  • Mutations in TANK binding kinase 1 (TBK1) have been linked to amyotrophic lateral sclerosis. (ox.ac.uk)
  • The D842V mutation is known to be associated with tyrosine kinase inhibitor resistance. (cornell.edu)
  • MD results indicate substantial conformational alterations in SGK1, thus its functional loss, particularly upon T256A mutation. (frontiersin.org)