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.
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 glutamine with lysine at codon 264 of the NRXN1 protein (p.Gln264Lys). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is present in population databases (rs367919055, ExAC 0.07%) but has not been reported in the literature in individuals with an NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 129817). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance ...
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 ...
The lollipop plot above illustrates recurrent (observed in 3 or more out of 4440 TCGA tumor samples from 15 cancer types) and therefore potentially oncogenic missense mutations (click on Show Cancer Mutations). The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. ...
The lollipop plot above illustrates recurrent (observed in 3 or more out of 4440 TCGA tumor samples from 15 cancer types) and therefore potentially oncogenic missense mutations (click on Show Cancer Mutations). The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. ...
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 ...
The R1195H variant of uncertain significance in the FBN2 gene has not been published as pathogenic or been reported as benign to our knowledge. R1195H is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1195H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals, however, H1195 is the wild-type residue in at least one species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Finally, although located within a calcium-binding EGF-like domain of the FBN2 gene, the R1195H variant does not affect a Cysteine residue. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with ...
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 ...
Author manuscripts deposited to comply with open access mandates are made available in accordance with publisher policies. Please cite only the published version using the details provided on the item record or document. In the absence of an open licence (e.g. Creative Commons), permissions for further reuse of content should be sought from the publisher or author ...
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 ...
Three de novo loss-of-function (LoF) variants in the CHD2 gene were identified in ASD probands from the Simons Simplex Collection (Dong et al., 2014; Iossifov et al., 2014). De novo LoF and missense variants in CHD2 have also been identified in ASD probands from the Autism Sequencing Consortium, the Autism Clinical and Genetic Resources in China (ACGC) cohort, the Autism Genetic Resource Exchange, and the Autism Simplex Collection (De Rubeis et al., 2014; Wang et al., 2016; Stessman et al., 2017).Two additional de novo LoF variants in CHD2 were recently identified in ASD probands from a cohort of 262 Japanese trios in Takata et al., 2018; TADA-Denovo analysis demonstrated that this gene was significantly enriched for damaging de novo mutations in the Japanese ASD cohort, as well as in a combined dataset consisting of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium in addition to the Japanese ASD cohort. De novo loss-of-function and missense ...
Sigma-Aldrich offers abstracts and full-text articles by [A Etxebarria, A Benito-Vicente, M Stef, H Ostolaza, L Palacios, C Martin].
The standalone executable can be used for genome-scale data sets. In addition to the standard MutPred2 input format (see above), the MutPred2 software also supports the output file from ANNOVARs coding_change.pl program. This enables the straightforward movement between VCF files and MutPred2. To install and run MutPred2, you will need about 50 GB of hard disk space and about 8 GB RAM. Click on a link below to download ...
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 ...
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 ...
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 many mutations for W are caused by nonsense mutations, frameshift mutations or DNA deletions, which ...
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 females and nine males' ... 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 ...
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 ...
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 ...
"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 ...
"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 ...
"RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes". The American Journal of Human Genetics. 101 (3): ... Activating mutations in Rac1 have been recently discovered in large-scale genomic studies involving melanoma [22][23][24] and ... Dominant negative or constitutively active germline RAC1 mutations cause diverse phenotypes that have been grouped together as ... Activating or gain-of-function mutations of Rac1 are shown to play active roles in promoting mesenchymal-type of cell movement ...
Daimon M, Gojyou E, Sugawara M, Yamatani K, Tominaga M, Sasaki H (February 1997). "A novel missense mutation in exon 4 of the ... Wiman A, Floderus Y, Harper P (2002). "Two novel mutations and coexistence of the 991C>T and the 1339C>T mutation on a single ... To date, over 50 CPOX mutations causing HCP have been described. Most of these mutations result in substitution of amino acid ... As only patients with mutation in this region (K404E) would develop harderoporphyria, this mutation led to diminishment of the ...
"Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype". Molecular Psychiatry. 8 (11): ... Mutations associated with the gene may result in changes in serotonin transporter function, and experiments with mice have ... It has been examined in connection with obsessive compulsive disorder (OCD). I425V is a rare mutation on the ninth exon. In ... A second variant in the same gene of some patients with this mutation suggests a genetic "double hit", resulting in greater ...
Vastardis H, Karimbux N, Guthua SW, Seidman JG, Seidman CE (Aug 1996). "A human MSX1 homeodomain missense mutation causes ... Frameshift mutations, Ser202Stop mutation, resulting in a protein that lacks the C-terminal end of the homeodomain, impairs not ... Mutations in this gene, which was once known as homeobox 7, have also been associated with Witkop syndrome, Wolf-Hirschhorn ... MSX1 is one of the strongest candidate genes for specific forms of tooth agenesis, mutations in this gene was detected only in ...
This missense mutation occurs in a sequence of seven amino acids that are included in a group of closely related channels ... In affected goats, the CLCN1 gene contains a missense mutation; the amino acid alanine is replaced with a proline residue. This ... The mutation in the goat gene that causes this muscle stiffness was discovered in 1996, several years after the equivalent gene ... The mutation in the goat gene that causes this muscle stiffness was discovered in 1996, several years after the equivalent gene ...
Mazen I, El-Gammal M, Abdel-Hamid M, Amr K (August 2009). "A novel homozygous missense mutation of the leptin gene (N103K) in ... Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD (March 1998). "A leptin missense mutation associated with hypogonadism and ... "A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness". The ... Several mutations of genes involving the melanocortins (used in brain signaling associated with appetite) and their receptors ...
April 2014). "A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta". Human Molecular Genetics. 23 ... Huang XZ, Chen A, Agrez M, Sheppard D (August 1995). "A point mutation in the integrin beta 6 subunit abolishes both alpha v ... While multiple patients with Amelogenesis Imperfecta have since been found to have ITGB6 mutations, there were no other ... April 2014). "ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta". Human Molecular Genetics. 23 ...
September 1996). "Missense mutation of amylin gene (S20G) in Japanese NIDDM patients". Diabetes. 45 (9): 1279-81. doi:10.2337/ ... Cho YM, Kim M, Park KS, Kim SY, Lee HK (May 2003). "S20G mutation of the amylin gene is associated with a lower body mass index ... there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes ...
"Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R". Journal of Inherited Metabolic ... Individuals who are homozygous for a specific mutation (K404E) or compound heterozygous with a null allele in CPOX have a more ... Because of the reduced penetrance of HCP, family members of a patient may carry the same mutation without ever presenting with ... HCP is caused by mutations in CPOX, which codes for the enzyme coproporphyrinogen oxidase. This enzyme is responsible for 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 ... The syndrome is caused by mutations in the RPS6KA3 gene.[1] This gene is located on the short arm of the X chromosome (Xp22.2 ... Mutations in the RPS6KA3 disturb the function of the protein, but it is unclear how a lack of this protein causes the signs and ...
"Identification of a missense mutation in an adult-onset patient with glycogenosis type II expressing only one allele". DNA and ... "Identification of a missense mutation in one allele of a patient with Pompe disease, and use of endonuclease digestion of PCR- ... Hermans MM, de Graaff E, Kroos MA, Wisselaar HA, Oostra BA, Reuser AJ (September 1991). "Identification of a point mutation in ...
2002). „Novel missense mutations in red/green opsin genes in congenital color-vision deficiencies.". Biochem. Biophys. Res. ...
All three siblings were homozygous for a missense mutation in the fifth coding exon of the ESR1 gene.[6] The mutation caused a ... In 2013, an 18-year-old woman with EIS was reported.[5][9] DNA sequencing revealed a homozygous mutation in ESR1, the gene that ... thus each occurrence in humans would have to be a de novo mutation and is not transmitted to offspring.[citation needed] ... "Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man". N. Engl. J. Med. 331 (16): 1056-61. doi: ...
More than 47 disease-causing mutations have been identified for the disorder, all of which lead to absence of functional ... proteins through missense, nonsense, or splicing errors; no hotspots have been identified. Consanguinity is frequent; this ... "Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric ...
Alleles that produce no or truncated protein have more severe effects than missense mutations.[12] Although autoimmune disease ... WAS is associated with mutations in a gene on the short arm of the X chromosome (Xp11.23) that was originally termed the ... The rare disorder X-linked neutropenia has also been linked to a specific subset of WAS mutations.[9] ... Not all patients have a positive family history of the disorder; new mutations do occur. Often, leukemia may be suspected on ...
The mutations include missense, nonsense, and frameshift deletion/insertion mutations that either shorten or disrupt the b-HLH ... These mutations include nonsense, missense, splice site mutation, and intragenic deletions/insertions. Deletion/duplication ... While looking for different mutations in the human TWIST gene, five different types of mutations were discovered in individuals ... two normal parents can have a child with SCS due to a de novo mutation. The exact cause of the de novo mutation is unknown, but ...
Guidelines for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat ... "Standard Mutation Nomenclature in Molecular Diagnostics" The Journal of Molecular Diagnostics 9 (1), 2007 ... Missense. *Nonsense. Kõige tavalisem on transitsioon: üks puriin asendub teisega või üks pürimidiin asendub teisega (C ↔ T, A ...
1997). "Missense mutation of FUT1 and deletion of FUT2 are responsible for Indian Bombay phenotype of ABO blood group system". ... Secretor gene inactivation by a novel single missense mutation A385T in Japanese nonsecretor individuals". J. Biol. Chem. 271 ( ... 2002). "Molecular analysis of mutations and polymorphisms of the Lewis secretor type alpha(1,2)-fucosyltransferase gene reveals ... nonsense mutations in FUT2 and therefore have strong although not absolute protection from the norovirus GII.4.[citation needed ...
2005). "Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene.". Hum. ...
Dominant missense mutations in any of the gene family, which comprises five receptors in Arabidopsis and at least six in tomato ... Mutations in these proteins can lead to heightened salt sensitivity and limit plant growth. The effects of salinity have been ... EIN2, Ethylene insensitive 2, is a protein that activates the pathway and when there is a mutation here the EIN2 will block ... can confer insensitivity to ethylene.[32] Loss-of-function mutations in multiple members of the ethylene-receptor family result ...
Marklund, L.; M. Johansson Moller; K. Sandberg; L. Andersson (1996). "A missense mutation in the gene for melanocyte- ...
Thus, in a sequence of 113 colorectal carcinomas, only four had somatic missense mutations in the DNA repair gene MGMT, while ... Mutation[edit]. Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency ... Cause of mutations[edit]. The likely major underlying cause of mutations in carcinomas is DNA damage.[13] For example, in the ... The high mutation frequencies in carcinomas reflect the genome instability characteristic of cancers.[citation needed] ...
Thirumal Kumar D, George Priya Doss C (September 2016). "Role of E542 and E545 missense mutations of PIK3CA in breast cancer: a ... Thirumal Kumar D, George Priya Doss C (September 2016). "Role of E542 and E545 missense mutations of PIK3CA in breast cancer: a ... including the discovery of common activating PIK3CA missense mutations in common human tumors.[8] It has been found to be ... Somatic activating mutations in PIK3CA are found in Klippel-Trenaunay syndrome and venous malformation.[18][19] ...
Figure (2) shows a missense, single point, non silent mutation. Figures (3 and 4) both show frameshift mutations, which is why ... Most mutations have little effect on an organism's phenotype, health, or reproductive fitness.[82] Mutations that do have an ... Mutations occasionally occur within cells in the body as they divide. Although these mutations will not be inherited by any ... somatic mutations). The most frequent mutations are a loss of function of p53 protein, a tumor suppressor, or in the p53 ...
Dolphin CT, Janmohamed A, Smith RL, Shephard EA, Phillips IR (1997). "Missense mutation in flavin-containing mono-oxygenase 3 ... 1999). "Two novel mutations of the FMO3 gene in a proband with trimethylaminuria". Hum. Mutat. 13 (5): 376-9. doi:10.1002/(SICI ... 1998). "Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication". Hum. ... Zhou J, Shephard EA (2006). "Mutation, polymorphism and perspectives for the future of human flavin-containing monooxygenase 3 ...
Marklund, L; Moller MJ; Sandberg K; Andersson L (Dec 1996). "A missense mutation in the gene for melanocyte-stimulating hormone ... In humans, various mutations of the MC1R gene result in red hair, blond hair, fair skin, and susceptibility to sundamaged skin ... Aeumelanic hair coats, associated with mutations of the MC1R gene, have also been identified in mice, cattle, dogs, and horses ... The appearance of mammals with recessive agouti mutations is typically dense black. As with aeumelanism, the difference between ...
These mutations may be frameshift, missense, non-sense, or mutations of other kinds and are likely to cause deletions in the ... Type I and II are known to be caused by mutation of a specific gene. CSA is caused by mutations in the cross-complementing gene ... XP can be caused by mutations in any of these genes: DDB2, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XPC. These genes are all involved ... point mutation p.G608G (GGC , GGT).[64] This mutation causes a splice site within exon 11 of the pre-mRNA to come into action, ...
For instance a frameshift mutation or a missense mutation at the DCX gene location causes a neuronal migration defect also ... Mutations in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological ... Another example is the ROBO3 gene where a mutation alters axon length negatively impacting neuronal connections. Horizontal ... Research in neurogenetics has yielded some promising results, though, in that mutations at specific gene loci have been linked ...
Mazen I, El-Gammal M, Abdel-Hamid M, Amr K (August 2009). "A novel homozygous missense mutation of the leptin gene (N103K) in ... Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD (March 1998). "A leptin missense mutation associated with hypogonadism and ... "A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness". The ... Several mutations of genes involving the melanocortins (used in brain signaling associated with appetite) and their receptors ...
MutationsEdit. The following mutations have been observed: *An exon 3 c.46C,T mutation leading to p.Arg16Stop.[8] This mutation ... Missense (V44D)[9]. *p.R18X and p.Q194X with phenotype altered pigmentation without tumoriginesis.[10] ... Patients without Neurofibromin 1 or SPRED1 mutations may have SPRED2, SPRED3 or SPRY1, SPRY2, SPRY3 or SPRY4 mutations.[9] ... The M4/M5 phenotype of AML are most closely associated with Ras pathway mutations. Ras pathway mutations are also associated ...
"Multisystem disorder associated with a missense mutation in the mitochondrial cytochrome b gene". Ann. Neurol. 50 (4): 540-3. ... Other mutations have been reported to cause septo-optic dysplasia and multisystem disorders. However, mutations in BCS1L, a ... mutations linked to complex III deficiency nuclear type 2 Mutations in complex III-related genes typically manifest as exercise ... mutation linked with mitochondrial complex III deficiency nuclear type 3 UQCRH: hinge protein UQCRC2: Core 2, mutations linked ...
"A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of ... There is a DNA test for the gene which can be used to plan breedings and avoid producing affected foals.[2] The mutation has ... No true albino mutation of the color gene is known among horses, though several varieties of white horse are popularly known as ... Santschi EM, Vrotsos PD, Purdy AK, Mickelson JR (Jan 2001). "Incidence of the endothelin receptor B mutation that causes lethal ...
On exon 3 of the human FABP1 gene an Ala to Thr substitution has been identified leading to a T94A missense mutation. Carriers ... T94A missense mutation on plasma lipoprotein responsiveness to treatment with fenofibrate". Journal of Human Genetics. 49 (8): ...
Both Lowe syndrome (oculocerebrorenal syndrome) and Dent disease can be caused by truncating or missense mutations in OCRL. As ... Dent's disease is a genetic disorder caused by mutations in the gene CLCN5, which encodes a kidney-specific voltage-gated ... About 60% of patients have mutations in the CLCN5 gene (Dent 1), which encodes a kidney-specific chloride/proton antiporter, ... February 2005). "Dent Disease with mutations in OCRL1". Am. J. Hum. Genet. 76 (2): 260-7. doi:10.1086/427887. PMC 1196371 . ...
A missense mutation at the interface of these two proteins can perturb the cell cycle, resulting a greater risk of developing ... Given the complexity of mutation screening for BRCA1, these common mutations may simplify the methods required for mutation ... BRCA1 mutations are only seen in about 18% of ovarian cancers (13% germline mutations and 5% somatic mutations).[68] ... Mutation of BRCA1 in breast and ovarian cancerEdit. Only about 3%-8% of all women with breast cancer carry a mutation in BRCA1 ...
... or splice site mutations that occur at the genetic level.[6] The missense mutations affect the two large luminal loops and ... mutations such as splice site mutations, frame-shifting mutations, and substitutions of a highly conserved residue that ... Mutations of the glucose 6-phosphatase system, to be specific the glucose 6-phosphatase-α subunit (glucose 6-phosphatase-α), ... The specific cause of the GSD-1a stems from nonsense mutations, insertions/deletions with or without a shift in the reading ...
2002). "Novel missense mutations in red/green opsin genes in congenital color-vision deficiencies.". Biochem. Biophys. Res. ... 1993). "Defective colour vision associated with a missense mutation in the human green visual pigment gene.". Nat. Genet. 1 (4 ...
Spanakis E, Milord E, Gragnoli C (2008). „AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense ... mutation significance". J. Cell. Physiol. 217 (3): 605-17. PMID 18726898. doi:10.1002/jcp.21552.. ...
Mutation with respect to structure. Point mutation. *Nonsense mutation. *Missense mutation. *Conservative mutation ... Trinucleotide repeats are classified as insertion mutations[2][3] and sometimes as a separate class of mutations.[4] ... Frameshift mutations will alter all the amino acids encoded by the gene following the mutation. Usually, insertions and the ... Gain-of-Function Mutations. References[edit]. *^ Banavali, Nilesh K. (2013). "Partial Base Flipping is Sufficient for Strand ...
A missense mutation occurs when a gene is altered in a way that results in a different amino acid being substituted for the one ... A missense mutation occurs when a gene is altered in a way that results in a different amino acid being substituted for the one ... A missense mutation in the gene coding for the protein hemoglobin substitutes the base thymine for adenine. This results in the ... What is a silent mutation?. A: A silent mutation occurs when a DNA message changes but the message still codes for the same ...
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 ...
Rapid Detection of Common HIV-1 Drug Resistance Mutations by Use of High-Resolution Melting Analysis and Unlabeled Probes David ... Rapid and Specific Detection of Amantadine-Resistant Influenza A Viruses with a Ser31Asn Mutation by the Cycling Probe Method ... Highly Sensitive and Quantitative Detection of the H274Y Oseltamivir Resistance Mutation in Seasonal A/H1N1 Influenza Virus ... Selection and Counterselection of the rtI233V Adefovir Resistance Mutation during Antiviral Therapy Oliver Schildgen, Cynthia ...
Here we analyzed the efficacy of these inferences in 33 de novo missense mutations … ... Each persons genome sequence has thousands of missense variants. Practical interpretation of their functional significance ... Comparison of predicted and actual consequences of missense mutations Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5189-98. ... Half of all possible missense mutations in the same 23 immune genes were predicted to be deleterious, and most of these appear ...
Some TBK1 mutations are classified as loss of function variants while others are missense mutations with unclear contributions ... ALS-linked missense mutations are distributed throughout the protein, with some mutations disrupting dimerization, kinase ... ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function. Neurobiol. Aging 71, 266.e1-266.e10 ... ALS- and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy. View ORCID ProfileOlivia Harding, View ...
Computational analysis of missense mutations causing Snyder-Robinson syndrome. Human Mutation 31(9): 1043-1049. ... 2013a) A Y328C missense mutation in spermine synthase causes a mild form of Snyder-Robinson syndrome. Human Molecular Genetics ... 2013) Cancer missense mutations alter binding properties of proteins and their interaction networks. PloS One 8(6): e66273. ... 2012) Molecular effect of a novel missense mutation, L266V, on function of ClC‐5 protein in a Japanese patient with Dents ...
Syndromic parkinsonism and dementia associated with OPA1 missense mutations.. Carelli V1,2, Musumeci O3, Caporali L1, Zanna C2 ... We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the ... Twenty‐six control fibroblasts, 21 fibroblasts with the p.G488R mutation, and 34 with the p.A495V mutation were counted in ... Fibroblasts analyzed were from 3 control subjects, 3 subjects with the p.G488R mutation, and 2 with the p.A495V mutation. ...
A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice.. Workman E1, Saieva L, Carrel TL, Crawford TO ... alleles in vivo did not complement each other leading to the possibility that these mutations could affect the same function. ...
Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Alison E Gammie, Naz ... Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Alison E Gammie, Naz ... Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Alison E Gammie, Naz ... Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae Message Subject (Your Name ...
Birben E, Öner C, Öner R, Altay Ç, Gürgey A. Identification of an inframe deletion and a missense mutation in the factor XIIIA ... The first alteration, a missense mutation Leu235Arg in exon 6 of FXIIIA gene, is located in the putative calcium-binding part ... Identification of an inframe deletion and a missense mutation in the factor XIIIA gene in two Turkish patients ... The second mutation is a 3-bp deletion in exon 14 of FXIIIA gene. This deletion is located in beta barrel 2 domain of the ...
mutation. Error bars indicate the SD. P. , 0.05 versus homozygous, by Kruskal-Wallis with Dunns post hoc test. ... We demonstrate that gout can be caused by a mutation in LDHD within the putative catalytic site of the encoded d-lactate ... Notably, the p.R370W mutation had no effect on protein localization. In line with the human phenotype, injection of d-lactate ...
... Hina Iqbal,1 Tayyba Sarfaraz,2 Farida ... Hina Iqbal, Tayyba Sarfaraz, Farida Anjum, Zubair Anwar, and Asif Mir, "Identification of Missense Mutation (I12T) in the BSND ...
Mice with missense and nonsense NF1 mutations display divergent phenotypes compared with human neurofibromatosis type I Kairong ... Summary: Two mouse models carrying NF1 patient-specific mutations have distinct effects on embryonic development, neurofibromin ...
A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype Message Subject (Your Name) has ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ...
Author Summary The purpose of this study was to uncover the molecular basis for the champagne hair color dilution phenotype in horses. Here, we report a DNA base substitution in the second exon of the horse gene SLC36A1 that changes an amino acid in the transmembrane domain of the protein from threonine to arginine. The phenotypic effect of this base change is a diminution of hair and skin color intensity for both red and black pigment in horses, and the resulting dilution has become known as champagne. This is the first genetic variant reported for SLC36A1 and the first evidence for its effect on eye, skin, and hair pigmentation. So far, no other phenotypic effects have been attributed to this gene. This discovery of the base substitution provides a molecular test for horse breeders to test their animals for the Champagne gene (CH).
We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three ... The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the ... Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. *Mike Hutton. 1. na1, ... Hutton, M., Lendon, C., Rizzu, P. et al. Association of missense and 5′-splice-site mutations in tau with the inherited ...
Folate-remedial function of MTHFR impaired by missense mutations [in Japanese] * * 山田 和弘 Yamada Kazuhiro ...
MAFA missense mutation causes familial insulinomatosis and diabetes mellitus Message Subject (Your Name) has sent you a message ... MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. Donato Iacovazzo, Sarah E. Flanagan, Emily Walker ... Strikingly, the missense p.Ser64Phe MAFA mutation was associated with either of two distinct phenotypes, multiple insulin- ... The human phenotypes associated with the p.Ser64Phe MAFA missense mutation reflect both the oncogenic capacity of MAFA and its ...
Enhancers can be disrupted by single nonsense, missense and translationally silent point mutations, without recognition of an ... Some nonsense mutations cause skipping of one or more exons, presumably during pre-mRNA splicing in the nucleus; this ... which may in turn cause phenotypic variability and variable penetrance of mutations elsewhere in a gene. ... Point mutations can generate defective and sometimes harmful proteins. The nonsense-mediated mRNA decay (NMD) pathway minimizes ...
Missense" by people in Harvard Catalyst Profiles by year, and whether "Mutation, Missense" was a major or minor topic of these ... "Mutation, Missense" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Below are the most recent publications written about "Mutation, Missense" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Mutation, Missense". ...
Missense Mutation in Exon 2 of SLC36A1 Responsible for Champagne Dilution in Horses. Table 2. Genotyping Results for c.188(C/G ...
Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes. ... Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes. ...
... and complex III deficiency in skeletal muscle had a missense mutation in the cytochrome b gene of mitochondrial DNA (G15762A). ... The mutation, which leads to the substitution of a highly conserved amino acid (G339E), was heteroplasmic … ... Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy Neurology. 1998 Nov;51(5):1444-7. doi: 10.1212/wnl. ... and complex III deficiency in skeletal muscle had a missense mutation in the cytochrome b gene of mitochondrial DNA (G15762A). ...
A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia, and obesity.. Meyer ... The SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that carries an a--,g missense mutation in exon 5 of ... Mice carrying the mutation are characterized by dwarfism, predominantly due to the reduction (sma1/+) or absence (sma1/sma1) of ...
... ... Missense mutations in the erythroid band 3 protein (Anion Exchanger 1) have been associated with hereditary stomatocytosis. ... Two possibilities that are not exclusive could be envisioned: the missense mutations in AE1 polypeptide change the transport ... transport associated with AE1 missense mutations shows independent movement of Na+ and K+ with a 1 for 1 stoichiometry. ...
... we describe a CHK2 missense mutation (R145W) in another LFS family. This mutation destabilizes the encoded protein, reducing ... Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.. [S B Lee, S H Kim, D W Bell, D C Wahrer, ... In a kindred with LFS without an inherited TP53 mutation, we have previously reported a truncating mutation (1100delC) in CHK2 ... Our observations support the functional significance of CHK2 mutations in rare cases of LFS and suggest that such mutations may ...
Functionally null RAD51D missense mutation associates strongly with ovarian carcinoma. Barbara Rivera, Massimo Di Iorio, ... Functionally null RAD51D missense mutation associates strongly with ovarian carcinoma. Barbara Rivera, Massimo Di Iorio, ... Functionally null RAD51D missense mutation associates strongly with ovarian carcinoma. Barbara Rivera, Massimo Di Iorio, ... Functionally null RAD51D missense mutation associates strongly with ovarian carcinoma Message Subject (Your Name) has forwarded ...
... of cases the mutations are of the missense type. The latter are of particular concern in terms of genetic counselling and ... In that context, our group has contributed to better characterize CDH1 germline missense variants and is now considered a ... Therefore, over the last few years, intensive research has focused on evaluating the functional consequences of CDH1 missense ... Predicting the Functional Impact of CDH1 Missense Mutations in Hereditary Diffuse Gastric Cancer. Soraia Melo 1,2,3. ...
annotations (the reliablity of the annotated protein expression using immunohistochemically (IH) stained on human tissues, the reliablity of the annotated protein expression in immunofluorescently (IF) stained human cell lines, tissue specificity (the distribution of antibody staining or protein expression in human cell types), cell line specificity (the distribution of RNA abundance in cell lines) and subcellular location (based on immunofluorescent staining of cell lines ...
Selected missense mutations impair frataxin processing in Friedreich ataxia Details Written by Jen Farmer Category: Funded ... Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one ... The group found that FXNI154F and FXNG130V missense mutations decrease FXN 81-210 levels compared with FXNWT, FXNR165C, and ... This article reports that selected disease-related FXN missense mutations impair FXN localization, interaction with ...
  • We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5′ splice site of exon 10. (nature.com)
  • Figure 3: 5′-splice-site mutations increase incorporation of tau exon 10 into artificial mRNAs. (nature.com)
  • tau exon-10 5′-splice-site mutations. (nature.com)
  • In vitro splicing of BRCA1 minigene transcripts reproduces the exon-skipping phenotype of a nonsense mutation. (nature.com)
  • Disruption of the splicing enhancer sequence within exon 27 of the dystrophin gene by a nonsense mutation induces partial skipping of the exon and is responsible for Becker muscular dystrophy. (nature.com)
  • A (E139K) PMM2 mutation in carbohydrate-deficient glycoprotein syndrome type Ia disrupting a splicing enhancer resulting in exon 5 skipping. (nature.com)
  • g missense mutation in exon 5 of the GH gene, which translates to a D167G amino acid exchange in the mature protein. (nih.gov)
  • One silent mutation N232N was associated with the skipping of exon 8 from the FAH mRNA. (springer.com)
  • The splice consensus mutations give deletions of complete or small parts of exon sequences from the FAH mRNA. (springer.com)
  • We sequenced cKIT exons from two patients with GIST after the development of imatinib resistance, revealing a point mutation in kinase domain I (exon 13), Val 654 Ala, which has been associated previously with relapse and resistance. (aacrjournals.org)
  • Mutation analysis revealed a heterozygous novel missense mutation, c.204G>T (p.W68C), in exon 2. (ovid.com)
  • D. Sanger sequence of the cDNA reverse transcribed from mRNA (left) and genomic DNA (gDNA) (right) around the exon 7 mutation of the PKLR gene. (haematologica.org)
  • The proband shows a predominantly mutant allele for the exon 7 mutation (top left) in the cDNA whereas an equal signal for mutant and wild type alleles was identified on gDNA (top right), as compared to the mother with only the wild-type allele (bottom) on both cDNA and gDNA (bottom). (haematologica.org)
  • Compound heterozygotes made with Foxo3a-null mice (carrying the targeted deletion of exon 2) displayed complementation with respect to both the activation of the reporter transgene and defects in folliculogenesis similar to those seen in MommeR1 homozygotes, supporting the conclusion that this is the causative mutation. (monash.edu)
  • Only 20% of mutations predicted to be deleterious by PolyPhen2 (and 15% by CADD) showed a discernible phenotype in individual homozygotes. (nih.gov)
  • We conclude that for de novo or low-frequency missense mutations found by genome sequencing, half those inferred as deleterious correspond to nearly neutral mutations that have little impact on the clinical phenotype of individual cases but will nevertheless become subject to purifying selection. (nih.gov)
  • Mice carrying the mutation are characterized by dwarfism, predominantly due to the reduction (sma1/+) or absence (sma1/sma1) of the GH-mediated peripubertal growth spurt, with sma1/+ mice displaying a less pronounced phenotype. (nih.gov)
  • As this protein is also expressed in kidney, a renal phenotype can be associated with SLC4A1 mutations. (hindawi.com)
  • When a red cell phenotype is associated with SLC4A1 mutations, the symptoms are hyperhaemolysis and anaemia, icterus, and splenomegaly. (hindawi.com)
  • Since the initial discovery that 5 point mutations in SLC4A1 gene (responsible for L687P, D705Y, S731P, H734R, or R760Q substitutions in AE1) were associated with increased red cell Na + and K + leak [ 20 ], 4 other point mutations associated with similar red cell phenotype have been reported (G796R, E758K, S762R, and R730C) [ 21 - 24 ]. (hindawi.com)
  • Li Fraumeni Syndrome (LFS) is a multicancer phenotype, most commonly associated with germ-line mutations in TP53. (sigmaaldrich.com)
  • There are few dominant or semidominant Cl- channel mutations in which dominant negative heterodimerization with normal subunits causes the disease phenotype. (thefreelibrary.com)
  • Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. (bioportfolio.com)
  • We confirm that ATP13A2 homozygous mutations are associated with human parkinsonism, and expand the associated genotypic and clinical spectrum, by describing a homozygous missense mutation in this gene in a patient with a phenotype milder than that initially associated with ATP13A2 mutations (Kufor-Rakeb syndrome). (neurology.org)
  • 6 Linkage was recently confirmed in a second pedigree originating from Chile with a similar phenotype, and pathogenic, homozygous, and compound heterozygous loss-of-function mutations in the ATP13A2 gene were identified in these two kindreds. (neurology.org)
  • This is the first study demonstrating a severe BPES phenotype resulting from a FOXL2 missense mutation outside the forkhead domain, expanding our knowledge about the phenotypic consequences of missense mutations outside the forkhead domain in BPES. (molvis.org)
  • Missense Mutations in Plakophilin-2 Cause Sodium Current Deficit and Associate with a Brugada Syndrome Phenotype. (ca.gov)
  • Home › About CIRM › Our Publications › Grantee publications › Missense Mutations in Plakophilin-2 Cause Sodium Current Deficit and Associate with a Brugada Syndrome Phenotype. (ca.gov)
  • The findings in the present study, which are associated with phenotype and the new point mutation in the SKIV2L gene, will increase our understanding of the characteristics of THES in the Chinese population. (spandidos-publications.com)
  • In this study, we show that an SMN A2G missense mutation rescues the severe SMA phenotype in low copy SMN2;Smn − / − mice but is unable to rescue Smn − / − embryonic lethality in the absence of the SMN2 gene. (rupress.org)
  • Here, we describe the first homozygous missense mutation in TRHR , associated with a typical phenotype. (endocrine-abstracts.org)
  • The lipodystrophy mutation R482Q, which causes a different phenotype and is believed to act through an emerin-independent mechanism, was indistinguishable from wild-type in its localization and its ability to trap emerin at the nuclear rim. (biologists.org)
  • To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. (whiterose.ac.uk)
  • Though both mutations affected mitochondrial ISC enzymes activities and mitochondria ultrastructure, the hFXN(I154F) mutant presented a more severe phenotype with affected cytosolic and nuclear ISC enzyme activities, mitochondrial iron accumulation and an increased sensitivity to oxidative stress. (inserm.fr)
  • In contrast to the classic phenotype of the Andermann syndrome linked to truncating KCC3 mutations the phenotype and the course of the disease linked to the missense mutation appeared to be different (i.e., showing additional features like diffuse and widespread white matter abnormalities). (uni-regensburg.de)
  • Molecular mechanisms of pathogenic mutations refer to the disease‐causing change of the wild‐type properties of the corresponding macromolecules and networks. (els.net)
  • The magnitude of change of the wild‐type characteristics alone cannot be used to predict whether a mutation is pathogenic. (els.net)
  • Frequently, a detailed knowledge of the biological reactions that are involved is needed to discriminate the pathogenic mutations from harmless variations. (els.net)
  • T;p.S207L as the first bona fide pathogenic RAD51D missense cancer susceptibility allele and supports the use of targeted PARP-inhibitor therapies in OC patients carrying deleterious missense RAD51D mutations. (aacrjournals.org)
  • Identification of a novel pathogenic missense mutation in using whole exome sequencing: a case report. (bioportfolio.com)
  • Pathogenic variants (mutations) in the Abelson helper integration site 1 ( AHI1 ) gene are known to be associated with Joubert syndrome, a developmental disorder causing visual, cognitive and motor deficits. (bmj.com)
  • These mutations therefore have the potential to be pathogenic in humans. (arvojournals.org)
  • It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. (haematologica.org)
  • The pathogenic events leading to the progressive muscle weakness in patients with a E706K mutation in the head of the myosin heavy chain (MyHC) IIa were analyzed at the muscle cell and motor protein levels. (diva-portal.org)
  • Using transfection of lamin-A/C-deficient fibroblasts, we have studied the effects of nine pathogenic mutations on the ability of lamin A to assemble normally and to localize emerin normally at the nuclear rim. (biologists.org)
  • Next-generation sequencing poses, therefore, a significant clinical challenge: the capability to assess variants as pathogenic lags significantly behind variant identification, especially for nonsynonymous point mutations. (ahajournals.org)
  • Pathogenic function was suggested by bioinformatic mutation search. (iospress.com)
  • Furthermore, two Italian cases with YOPD without atypical features carried a novel missense mutation (Thr12Met, Gly533Arg) in single heterozygous state. (neurology.org)
  • Missense mutation refers to a change in one amino acid in a protein, arising from a point mutation in a single nucleotide. (wikipedia.org)
  • Two other types of nonsynonymous substitution are the nonsense mutations - in which a codon is changed to a premature stop codon that results in truncation of the resulting protein -, and the nonstop mutations - in which a stop codon erasement results in a longer, nonfunctional protein. (wikipedia.org)
  • Missense mutations can render the resulting protein nonfunctional, and such mutations are responsible for human diseases such as Epidermolysis bullosa, sickle-cell disease, and SOD1 mediated ALS. (wikipedia.org)
  • Thus, the 6th amino acid glutamic acid is substituted by valine-notated as an "E6V" mutation-and the protein is sufficiently altered to cause the sickle-cell disease. (wikipedia.org)
  • Not all missense mutations lead to appreciable protein changes. (wikipedia.org)
  • DNA: 5' - AAC AGC CTG CGT ACG GCT CTC - 3' 3' - TTG TCG GAC GCA TGC CGA GAG - 5' mRNA: 5' - AAC AGC CUG CGU ACG GCU CUC - 3' Protein: Asn Ser Leu Arg Thr Ala Leu LMNA missense mutation (c.1580G>T) introduced at LMNA gene - position 1580 (nt) in the DNA sequence (CGT) causing the guanine to be replaced with the thymine, yielding CTT in the DNA sequence. (wikipedia.org)
  • The resulting transcript and protein product is: DNA: 5' - AAC AGC CTG CTT ACG GCT CTC - 3' 3' - TTG TCG GAC GAA TGC CGA GAG - 5' mRNA: 5' - AAC AGC CUG CUU ACG GCU CUC - 3' Protein: Asn Ser Leu Leu Thr Ala Leu Cancer associated missense mutations can lead to drastic destabilisation of the resulting protein. (wikipedia.org)
  • Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? (wikipedia.org)
  • A missense mutation in the gene coding for the protein hemoglobin substitutes the base thymine for adenine. (reference.com)
  • A silent mutation occurs when a DNA message changes but the message still codes for the same amino acid and produces the correct protein. (reference.com)
  • Although human deoxyribonucleic acid (DNA) variations and rare mutations may be manifested at different levels and different magnitudes, a single nucleotide polymorphism (SNP) to a missing chromosome or a single amino acid mutation to a truncated protein, the pathological effect is the malfunction of the cell or the corresponding organ. (els.net)
  • Illustration of different types of mutations at (a) DNA and protein sequence level and (b) chromosomal level. (els.net)
  • 2012) Molecular effect of a novel missense mutation, L266V, on function of ClC‐5 protein in a Japanese patient with Dent's disease. (els.net)
  • Notably, the p.R370W mutation had no effect on protein localization. (jci.org)
  • Missense mutations in the erythroid band 3 protein (Anion Exchanger 1) have been associated with hereditary stomatocytosis. (hindawi.com)
  • It appears that the SLC4A1 mutations can be divided into two classes according to the way they impair AE1 function: (1) those that prevent correct folding of the protein so that it is not addressed to plasma membrane. (hindawi.com)
  • This mutation destabilizes the encoded protein, reducing its half-life from >120 min to 30 min. (sigmaaldrich.com)
  • Here, we examined 23 patient missense mutations covering a spectrum of exonic/structural regions, clinical phenotypes, and ethnic populations in order to determine their influence on protein stability, using two recombinant expression systems and a thermostability assay, and enzymatic function by measuring MUT activity and affinity for its cofactor and substrate. (sigmaaldrich.com)
  • Our data stratify MUT missense mutations into categories of biochemical defects, including (1) reduced protein level due to misfolding, (2) increased thermolability, (3) impaired enzyme activity, and (4) reduced cofactor response in substrate turnover. (sigmaaldrich.com)
  • The deleterious effects of missense mutations are commonly attributed to their impact on primary amino acid sequence and protein structure . (humpath.com)
  • Missense meanderings in sequence space: a biophysical view of protein evolution . (humpath.com)
  • To understand whether MECP2 mutations are associated with schizophrenia, we systematically screen for mutations at the protein-coding regions of the MECP2 gene in a sample of 404 schizophrenic patients (171 females, 233 males) and 390 non-psychotic controls (171 females, 218 males). (frontiersin.org)
  • Mutations in either protein cause inner ear disorders in mice and humans. (jneurosci.org)
  • Both missense as well as nonsense mutations result in an altered protein product which is unlikely to function as it should. (enotes.com)
  • In a missense mutation, an entirely new amino acid is produced as the codon responsible for the protein is altered. (enotes.com)
  • Missense mutations of the protein p53, which have been detected in approximately 42% of cancer cases, not only lose the tumor suppression activity of wild-type p53, but also gain oncogenic functions promoting tumor progression and drug-resistance. (aacrjournals.org)
  • Our previous works showed that cellular Cer can eradicate cancer cells that carry a p53 deletion-mutation by modulating alternative pre-mRNA splicing, restoring wild-type p53 protein expression. (aacrjournals.org)
  • A previous computational analysis of missense mutations linked to monogenic disease found a high proportion of missense mutations affect protein stability, rather than other aspects of protein structure and function. (proteopedia.org)
  • The purpose of the present study is to relate the presence of such stability damaging missense mutations to the levels of a particular protein present under in vivo like conditions, and to test the reliability of the computational methods. (proteopedia.org)
  • Experimental data on a set of missense mutations of the enzyme phenylalanine hydroxylase (PAH) associated with the monogenic disease phenylketonuria (PKU) have been compared with the expected in vivo impact on protein function, obtained using SNPs3D, an in silico analysis package. (proteopedia.org)
  • For these mutations, destabilization of protein three dimensional structure is the major molecular mechanism leading to PKU, and results in a substantial reduction of in vivo PAH protein concentration. (proteopedia.org)
  • Shi Z, Sellers J, Moult J. Protein stability and in vivo concentration of missense mutations in phenylalanine hydroxylase. (proteopedia.org)
  • Thus, the G863V point mutation provides the first evidence that the triglyceride and phospholipid transfer functions of a vertebrate MTP protein can be separated, arguing that selective inhibition of the triglyceride transfer activity of MTP may be a feasible therapeutic approach for dyslipidemia. (biorxiv.org)
  • Constructs expressing wild-type VSX1 or one of the seven mutations were used to investigate transcriptional activity and protein stability in vitro . (arvojournals.org)
  • instead, most mutations are monoallelic missense changes involving specific arginine residues at β-sheet propellor tips that allow the FBXW7 protein to recognise its substrates. (bmj.com)
  • The mutant protein carrying this missense mutation showed an approximately 80% decrease in POMGNT1 enzyme activity compared with the wild type. (arvojournals.org)
  • B. In silico analysis of all three intronic mutations using SpliceAid2 predicts unique protein binding motifs in WT (left) as compared to mutant (right) RNA. (haematologica.org)
  • Results: Sequencing identified a homozygous mutation (P81R) in TRHR , substituting arginine for a proline residue in transmembrane helix 2 (TM2) which is highly conserved amongst G-protein coupled receptors (GPCRs). (endocrine-abstracts.org)
  • T), predicted to cause a missense mutation (T158M) within the methylcytosine binding domain of the methyl-CpG binding protein. (bmj.com)
  • In X-linked EDMD, most emerin mutations result in complete absence of emerin protein (Manilal et al. (biologists.org)
  • A missense mutation in the giant protein titin is the only plausible disease-causing variant that segregates with disease among the 7 surviving affected individuals, with interrogation of the entire genome excluding other potential causes. (ahajournals.org)
  • This A178D missense mutation, affecting a conserved residue in the second immunoglobulin-like domain of titin, was introduced in a bacterially expressed recombinant protein fragment and biophysically characterized in comparison to its wild-type counterpart. (ahajournals.org)
  • The MTRR A66G mutation alters isoleucine into a methionine residue in the protein chain and subsequently disrupts the methionine/homocysteine cycle. (springermedizin.de)
  • The mutation, expected to affect the ligand-binding domain of the androgen receptor protein, led to complete androgen insensitivity of XY SRY+, testicular DSD individuals. (up.ac.za)
  • Missense mRNA molecules are created when template DNA strands or the mRNA strands themselves undergo a missense mutation in which a protein coding sequence is mutated and an altered amino acid sequence is coded for. (wikipedia.org)
  • Such selective substitutions of uridine for cytidine, and inosine for adenosine in RNA editing can produce differential isoforms of missense mRNA transcripts, and confer transcriptome diversity and enhanced protein function in response to selective pressures. (wikipedia.org)
  • In human, many different mutations in SLC4A1 gene coding for AE1 have been reported [ 11 ]. (hindawi.com)
  • Nine different mutations were identified, of which six are novel. (springer.com)
  • 5) Although the only culprit in this disorder is CLNC1, different mutations in this gene can cause autosomaldominant (Thomsen disease, OMIM 160800) or recessive trait (recessive generalized myotonia or Becker myotonia, OMIM 255700). (thefreelibrary.com)
  • 250 different mutations. (haematologica.org)
  • We identified 8 different mutations and 6 (g.-323A1/A2, g.-122T→C, g.73G→A, g.7880C→T, g.10523G→A, g.10976G→A) previously reported polymorphisms 1 in the 11 patients. (haematologica.org)
  • Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements. (nature.com)
  • Give difference between gene mutations and genomatic mutations. (enotes.com)
  • DDHD1 gene mutations have been reported to be associated with the SPG28 subtype of autosomal recessive HSP but have never been reported in jALS patients. (frontiersin.org)
  • Approximately 10% of cases are familial (fALS).The frequency of SOD1 gene mutations in patients with fALS varies among populations, from 0% in Ireland to 13.6% in Italy and 23.5% in Scandinavia. (bmj.com)
  • We sequenced the complete ATP13A2 coding region in 46 patients with parkinsonism of juvenile or young onset, and we identified three novel ATP13A2 missense mutations, including one homozygous mutation. (neurology.org)
  • Patient 106 had a second homozygous mutation (p.Trp364Cys) that had been previously reported. (haematologica.org)
  • Results A homozygous mutation, G257A, was identifiedPEX7 in the genome of patient while the parents were compound heterozygous. (sid.ir)
  • Labelle Y, Phaneuf D, Leclerc B, Tanguay RM (1993) Characterization of the human fumarylacetoacetae hydrolase gene and identification of a missense mutation abolishing enzymatic activity. (springer.com)
  • Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency. (sigmaaldrich.com)
  • This in-depth mutation study illustrates the tools available for MUT enzyme characterization, guides future categorization of further missense mutations, and supports the development of alternative, chaperone-based therapy for patients not responding to current treatment. (sigmaaldrich.com)
  • Generation and characterization of a human iPSC line from an ALS patient carrying the Q66K-MATR3 mutation. (bioportfolio.com)
  • Functional characterization of bestrophin-1 missense mutations associated with autosomal recessive bestrophinopathy. (semanticscholar.org)
  • Biophysical characterization of M1476I, a sodium channel founder mutation associated with cold-induced myotonia in French Canadians. (semanticscholar.org)
  • Both 1100delC and R145W germ-line mutations in CHK2 are associated with loss of the wild-type allele in the corresponding tumor specimens, and neither tumor harbors a somatic TP53 mutation. (sigmaaldrich.com)
  • Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one allele and a GAA repeat expansion on the other. (curefa.org)
  • The second allele carried a missense mutation (G649A) resulting in replacement of Glu217, an amino acid involved in the catalytic site, by Lys and predicting a major alteration in charge. (jimmunol.org)
  • APOE ε4 allele frequency was greater in sEOAD and sLOAD compared to APPdup, missense APP mutations, DS and controls, and varied between each of the CAA phenotypes with APOE ε4 homozygosity being more commonly associated with type 3 CAA than types 1 and 2 CAA in sLOAD and sEOAD. (unboundmedicine.com)
  • When present on the same cKIT allele as an oncogenic mutation, the Val 654 Ala mutation abolishes imatinib-mediated inhibition of cKIT phosphoactivation in vitro . (aacrjournals.org)
  • Conditional expression of a heterozygous propellor tip missense Fbxw7 allele in the mouse intestines causes tumorigenesis. (bmj.com)
  • We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P= 1.2 × 10−4). (nottingham.ac.uk)
  • METHODOLOGY: We have developed a new strategy to generate murine cellular models for FRDA: cell lines carrying a frataxin conditional allele were used in combination with an EGFP-Cre recombinase to create murine cellular models depleted for endogenous frataxin and expressing missense-mutated human frataxin. (inserm.fr)
  • Furthermore, we detected a novel double-missense mutation P376S-P419R in a male patient. (frontiersin.org)
  • We have identified a heterozygous FOXL2 missense mutation c.650C→G (p.Ser217Cys) co-segregating with disease in members of a three-generation family with BPES type II. (molvis.org)
  • In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. (wikipedia.org)
  • A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. (harvard.edu)
  • We have previously reported that a missense mutation at the preceding codon is similarly associated with neonatal onset ADA- SCID and accumulation of extremely high deoxyATP. (jimmunol.org)
  • Mutation screening in already known candidate genes by sequence analyses revealed proline to threonine substitution at codon 23 (p.Pro23Thr) in CRYGD for aculeiform type cataract in family A. The family B with four members affected by granular nuclear cataract, however, could not be linked with any of these analyzed 23 candidate genes. (springer.com)
  • G mutation at codon 12 of this gene, which results in the substitution of proline with alanine (Pro12Ala) in subjects with type 1 (n = 522) and type 2 (n = 503) diabetes compared to that in healthy controls (n = 310) and found no differences between these groups. (drsharma.ca)
  • The point mutation is nonsynonymous because it alters the RNA codon in the mRNA transcript such that translation results in amino acid change. (wikipedia.org)
  • If the resulting mRNA codon is one that changes the amino acid, a missense mRNA would be detected. (wikipedia.org)
  • Nonsense mutation Start codon Stop codon Jameson JL. (wikipedia.org)
  • 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. (nih.gov)
  • 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 separate mouse substrains, rodents, or primates. (nih.gov)
  • Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in postmitotic tissues. (nih.gov)
  • 2) Hereditary pure myotonia is caused by mutations in two different genes coding for the voltage-dependent skeletal muscle specific Cl- and Na+ channels. (thefreelibrary.com)
  • The examination of large numbers of tumors can provide helpful information for classification of drivers versus passengers, but the ability of sequencing alone to provide definitive results is limited by the marked variation in mutation frequency among individual tumors and individual genes. (aacrjournals.org)
  • 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)
  • 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). (bioportfolio.com)
  • Mutations in MMR (DNA mismatch repair) genes underlie HNPCC (hereditary non-polyposis colon cancer) and also a significant proportion of sporadic colorectal cancers. (portlandpress.com)
  • METHODS AND RESULTS: We searched for PKP2 variants in genomic DNA of 200 patients with BrS diagnosis, no signs of AC, and no mutations in BrS-related genes SCN5A, CACNa1c, GPD1L and MOG1. (ca.gov)
  • No coding sequence mutations were found in LPL and APOC2 genes encoding, respectively, lipoprotein lipase and apolipoprotein (apo) C-II. (biomedcentral.com)
  • We investigated how ALS-associated mutations in TBK1 affect Parkin-dependent mitophagy using imaging to dissect the molecular mechanisms involved in clearing damaged mitochondria. (pnas.org)
  • It has been proposed that the molecular mechanism accounting for cation leaky red cells in these hereditary stomatocytoses was a change in AE1 transport properties induced by the point mutations. (hindawi.com)
  • Genomeand molecular structures and mutations of CD38. (intechopen.com)
  • A mutation that results in an increase in a gene's activity or in acquiring a new molecular function or a new pattern of gene expression. (bioportfolio.com)
  • Molecular modeling of cKIT-imatinib complexes shows that this residue is located in the drug-binding site and that the Val 654 Ala mutation disrupts drug binding by removing hydrophobic contacts with the central diaminophenyl ring of imatinib. (aacrjournals.org)
  • Molecular analysis revealed compound heterozygosity for two novel missense mutations affecting conserved residues in the arylsulphatase A (ASA) sulphatase and carboxyterminal domains, resulting in an 89% loss of enzymatic activity. (bmj.com)
  • PKP2 mutations may be a molecular substrate leading to the diagnosis of Brugada syndrome. (ca.gov)
  • These mutations were considered to be causative of disease because of their nature, evolutionary conservation and molecular modeling. (haematologica.org)
  • Future identification of other, naturally-occurring, TRHR mutations may map the molecular basis of ligand binding and activation of TRHR which are poorly understood. (endocrine-abstracts.org)
  • Additionally, design of a PCR-RFLP technique provided an accurate molecular test for identification of horses carrying the mutation. (up.ac.za)
  • Berger R, Faassen H van, Taanman JW, Vries H de, Agsteribbe E (1988) Different types of mutations in the chronic and acute forms of type I tyrosinemia (abstract). (springer.com)
  • Which of the two types of mutations, nonsense or missense, would be more harmful to an organism? (enotes.com)
  • It isn't possible to say which of the two types of mutations would be more harmful to an organism as both forms affect the functioning of proteins in organisms in adverse ways and result in serious ailments. (enotes.com)
  • Can someone please explain what types of mutations that affect chromosomes are least likely to be. (enotes.com)
  • We localized the genetic defect to a point mutation in the tubulin - specific chaperone E ( Tbce ) gene affecting an evolutionary conserved amino acid residue. (pubmedcentralcanada.ca)
  • Sequencing of the Foxo3a gene in MommeR1 mice revealed a point mutation that causes an amino acid substitution in the highly conserved Forkhead DNA-binding domain. (monash.edu)
  • In vitro transcription assays showed that the point mutation causes loss of FOXO3a transactivation activity. (monash.edu)
  • The consecutive round of replication would result in a point mutation. (wikipedia.org)
  • Coding-region single-nucleotide polymorphisms 7 (cSNPs) within exonic splicing enhancers or silencers may affect the patterns or efficiency of mRNA splicing, which may in turn cause phenotypic variability and variable penetrance of mutations elsewhere in a gene. (nature.com)
  • Analysis of the effect of the respective mutations on the FAH mRNA showed a strong reduction of FAH mRNA levels in association with the nonsense mutations, and normal levels with the missense mutations. (springer.com)
  • This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. (haematologica.org)
  • Missense mRNA is a messenger RNA bearing one or more mutated codons that yield polypeptides with an amino acid sequence different from the wild-type or naturally occurring polypeptide. (wikipedia.org)
  • A missense mRNA arises from a missense mutation, in the event of which a DNA nucleotide base pair in the coding region of a gene is changed such that it results in the substitution of one amino acid for another. (wikipedia.org)
  • While homologous recombination has been widely used to generate single-base substitutions, novel technologies that co-inject gRNA and hCas9 mRNA of the CRISPR/Cas9 system, in conjunction with single-strand oligodeoxynucleotide (ssODN) donor sequences have shown efficiency in generating point mutations in the genome. (wikipedia.org)
  • 42% of mutations predicted by PolyPhen2 to be deleterious (and 45% by CADD) had little measurable consequence for TP53-promoted transcription. (nih.gov)
  • Disease-causing missense (and other in-frame) mutations can exert their deleterious effects at the cellular level through multiple mechanisms. (humpath.com)
  • Some missense mutations are deleterious because they disturb cis-acting splicing elements-so-called "exonic splicing enhancers" (ESEs). (humpath.com)
  • For some of these mutations, the novel glycans have been shown to be both necessary and sufficient to account for the deleterious impact of the mutation. (humpath.com)
  • Deleterious mutations of MECP2 are responsible for Rett syndrome, a severe X-linked childhood neurodevelopmental disorder predominates in females, male patients are considered fatal. (frontiersin.org)
  • Conclusion: We describe the first deleterious, missense TRHR defect associated with moderate CCH. (endocrine-abstracts.org)
  • G (p.Met495Val) missense mutation of the DDHD1 gene could be a causative mutation of autosomal recessive jALS. (frontiersin.org)
  • Further investigation, however, is needed to determine whether VSX1 mutations found in disease populations are in fact causative for corneal dystrophies. (arvojournals.org)
  • Genetic heterogeneity in THES has previously been documented, with causative mutations also identified in the SKIV2L gene ( 9 ). (spandidos-publications.com)
  • However, there is only a single report of an androgen receptor mutation causative of such a DSD syndrome in a horse pedigree. (up.ac.za)
  • A patient with progressive exercise intolerance, proximal weakness, and complex III deficiency in skeletal muscle had a missense mutation in the cytochrome b gene of mitochondrial DNA (G15762A). (nih.gov)
  • The G1571R mutation is of particular interest as mutations of the orthologous residue (G1306) in the human skeletal muscle sodium channel gene SCN4A are associated with cases of periodic paralysis and myotonia, including the human cold-sensitive disorder paramyotonia congenita . (genetics.org)
  • A study of a novel R133W β-tropomyosin mutation on regulation of skeletal muscle contraction in the skinned single fiber prepration and single fiber in vitro motility assay suggested that the mutation induced alteration in myosin-actin kinetics causing a reduced number of myosin molecules in the strong actin binding state, resulting in overall muscle weakness in the absence of muscle wasting. (diva-portal.org)
  • 1. Missense mutations in the alpha-subunit of the human skeletal muscle sodium channel (hSkM1) have been detected in some heritable forms of myotonia. (semanticscholar.org)
  • Missense mutation is a type of nonsynonymous substitution in a DNA sequence. (wikipedia.org)
  • this would be a synonymous substitution and not a missense mutation. (wikipedia.org)
  • The mutation, which leads to the substitution of a highly conserved amino acid (G339E), was heteroplasmic (85%) in the patient's muscle and was not present in 100 individuals of different ethnic backgrounds. (nih.gov)
  • Here we report a novel Nav1.9 mutation, a glycine 699 substitution by arginine (G699R) in the domain II S4-S5 linker, identified in a patient with painful small fiber neuropathy. (springer.com)
  • DNA analysis revealed a novel missense mutation involving substitution of proline for leucine at position 173 (P173L), which was reported to be important for stabilizing the hydrogen bond between tyrosine at position 205 and leucine at position 169. (degruyter.com)
  • For example, a SUBSTITUTION MUTATION in the first base of a triplet might produce the following missense mutation: CCU (pro) → ACU (thr). (thefreedictionary.com)
  • t heterozygous missense mutation of SOD1 gene leading to a substitution of cysteine for glycine (p.G147C). (bmj.com)
  • The C677T mutation is the substitution of base C at the 677 site with T, leading to the substitution of alanine with valine, which results in a thermolabile variant with reduced activity. (springermedizin.de)
  • The mutation of MTHFR A1298C is the substitution of base A to C at the 1298 site, leading to the substitution of glutamic acid with alanine, which reduces enzyme activity. (springermedizin.de)
  • For example, in knock-in studies, human orthologs are identified in model organisms to introduce missense mutations, or a human gene with a substitution mutation is integrated into the genome of the model organism. (wikipedia.org)
  • Importantly, while in most cases CDH1 alterations result in the complete loss of E-cadherin associated with a well-established clinical impact, in about 20% of cases the mutations are of the missense type. (mdpi.com)
  • Finally, clinical data from patients with FXNG130V and FXNI154F mutations demonstrates a lower severity compared with other individuals with Friedreich ataxia. (curefa.org)
  • These data suggest that the effects on processing associated with FXNG130V and FXNI154F mutations lead to higher levels of partially processed FXN, which may contribute to the milder clinical phenotypes in these patients. (curefa.org)
  • However, increasing reports indicate that some MECP2 mutations may also present various neuropsychiatric phenotypes, including intellectual disability, autism spectrum disorder, depression, cocaine addiction, and schizophrenia in both males and females, suggesting varied clinical expressivity in some MECP2 mutations. (frontiersin.org)
  • However, there is an increasing appreciation that the clinical presentations of MECP2 mutations are not limited to typical Rett syndrome. (frontiersin.org)
  • These neuropsychiatric manifestations were found in both male and female patients, indicating MECP2 mutations have a high level of clinical heterogeneity. (frontiersin.org)
  • This case, with clinical data including the water deprivation test and P173L mutation, will facilitate understanding the structure and function of the AVPR2. (degruyter.com)
  • Here we report a very late onset adult MLD patient with no clinical or neurophysiological evidence of peripheral neuropathy, who is a compound heterozygote for two previously unreported missense mutations in the ASA gene. (bmj.com)
  • 1 MECP2 mutations are now associated with a widening range of clinical presentations, including Angelman syndrome and X linked and non-specific mental retardation. (bmj.com)
  • Conclusion Taken together, clinical presentation and peroxisome profile of the patient suggested a missense mutation led to formation of a pathogenicPEX7, responsible for incidence of RCDP. (sid.ir)
  • Different types of KCC3 mutations may determine different clinical phenotypes. (uni-regensburg.de)
  • In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, between APP genetic causes of AD (APPdup, APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer's disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). (unboundmedicine.com)
  • Genetic studies revealed a homozygous missense mutation in the Insulin receptor gene confirming the diagnosis of Rabson Mendenhall syndrome. (springer.com)
  • Genetic analysis of his family was also performed, and his parents appeared to be healthy, but carried heterozygous mutations. (spandidos-publications.com)
  • We identified a novel mutation in POMGNT1 that causes nonsyndromic autosomal recessive retinitis pigmentosa, adding to the genetic heterogeneity of this retinal disease. (arvojournals.org)
  • Genomic DNA was screened for mutations in FVII gene by PCR ( Table 2 ), conformation sensitive gel electrophoresis (CSGE) 2 and DNA sequencing (ABI 310 genetic analyzer, Applied Biosystems, Foster city, CA, USA). (haematologica.org)
  • We localized the genetic defect in pmn mice to a missense mutation in the tubulin - specific chaperone E (Tbce) gene on mouse chromosome 13. (pubmedcentralcanada.ca)
  • Thus, the pmn gene mutation provides the first genetic evidence that alterations in tubulin assembly lead to retrograde degeneration of motor axons, ultimately resulting in motoneuron cell death. (pubmedcentralcanada.ca)
  • Conclusions- Here we present genetic and functional evidence implicating the novel A178D missense mutation in titin as the cause of a highly penetrant familial cardiomyopathy with features of left ventricular noncompaction. (ahajournals.org)
  • In a patient with early onset dementia, strategic diagnostic workup including genetic assessment revealed an adult-onset metachromatic leukodystrophy with a novel mutation in the arylsulfatase A gene. (iospress.com)
  • Missense mRNAs may be applied synthetically in forward and reverse genetic screens used to interrogate the genome. (wikipedia.org)
  • A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice. (nih.gov)
  • Mapping and sequencing showed that noddy mutant mice harbor an isoleucine-to-asparagine (I108N) mutation in the EC1 repeat of PCDH15. (jneurosci.org)
  • These studies in mice indicate that, although the increased mutation rates caused by MMR defects are sufficient to drive tumorigenesis, both functions co-operate in tumour suppression. (portlandpress.com)
  • Our mild SMA mice will be useful in (a) determining the effect of missense mutations in vivo and in motor neurons and (b) testing potential therapies in SMA. (rupress.org)
  • Our study further refines the model for TBK1 function in mitophagy, demonstrating that some ALS-linked mutations likely contribute to disease pathogenesis by inducing mitochondrial stress or inhibiting mitophagic flux. (pnas.org)
  • The association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of defective mitochondrial dynamics, mtDNA multiple deletions, and altered mitophagy with parkinsonism. (nih.gov)
  • In this report, we describe a jALS patient with a novel missense mutation in the DDHD1 gene, which is a member of the intracellular phospholipase A1 gene family and involved in the regulation of mitochondrial function. (frontiersin.org)
  • 4) About 130 mutations have been found in this gene, which cause autosomal-dominant as well as autosomal-recessive forms of this disorder. (thefreelibrary.com)
  • BPES is essentially an autosomal dominant disease, due to mutations in the forkhead box L2 ( FOXL2 ) gene, encoding a forkhead transcription factor. (molvis.org)
  • Mutations are usually autosomal dominant, but the p.D90A and the p.D96N may be autosomal recessive. (bmj.com)
  • Vanita V, Singh D, Robinson PN, Sperling K, Singh JR (2006) A novel mutation in the DNA-binding domain of MAF at 16q23.1 associated with autosomal dominant "cerulean cataract" in an Indian family. (springer.com)
  • In autosomal dominant EDMD, most mutations are mis-sense and evenly spread throughout the helical rod and globular tail domains common to lamins A and C. It seems likely that these mutations exert a dominant-negative effect on the function of the multisubunit lamin filaments ( Morris, 2001 ). (biologists.org)
  • Our observations support the functional significance of CHK2 mutations in rare cases of LFS and suggest that such mutations may substitute for inactivation of TP53. (sigmaaldrich.com)
  • Therefore, over the last few years, intensive research has focused on evaluating the functional consequences of CDH1 missense variants and in assessing E-cadherin pathogenicity. (mdpi.com)
  • Large-scale sequencing of cancer genomes has uncovered thousands of DNA alterations, but the functional relevance of the majority of these mutations to tumorigenesis is unknown. (aacrjournals.org)
  • We have developed a computational method, called Cancer-specific High-throughput Annotation of Somatic Mutations (CHASM), to identify and prioritize those missense mutations most likely to generate functional changes that enhance tumor cell proliferation. (aacrjournals.org)
  • We chose to focus on missense mutations as they account for the majority of somatic mutations found in the exons of tumor-derived DNA ( 6 ), and because their functional significance is more difficult to infer than that of nonsense or frameshift mutations. (aacrjournals.org)
  • The use of techniques that produce a functional MUTATION or an effect on GENE EXPRESSION of a specific gene of interest in order to identify the role or activity of the gene product of that gene. (bioportfolio.com)
  • These results highlight some of the structural and functional consequences of the Val 654 Ala mutation in relapsing imatinib-resistant GIST and emphasize the importance of tumor genetics in drug development and patient-specific cancer treatment regimens. (aacrjournals.org)
  • By recording Na+ currents from cells transfected with cDNA encoding either wild-type or mutant hSkM1, we characterized the functional consequences of two myotonia-associated mutations that lie at the cytoplasmic end of the sixth transmembrane segment in domain II (S804F) or domain III (V1293I). (semanticscholar.org)
  • CONCLUSIONS: These new cellular models, which are the first to spontaneously reproduce all the biochemical phenotypes associated with FRDA, are important tools to gain new insights into the in vivo consequences of pathological missense mutations as well as for large-scale pharmacological screening aimed at compensating frataxin deficiency. (inserm.fr)
  • 2014) A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation. (els.net)
  • They failed to produce active enzyme toward either substrate upon transfection into COS-1 cells, demonstrating that these mutations caused CAH. (uniprot.org)
  • Expression of the mutant cDNA in Cos cells confirmed that the mutation abolished enzyme activity. (jimmunol.org)
  • Analysis of novel missense ATR mutations reveals new splicing defects underlying Seckel Syndrome. (bioportfolio.com)
  • Surprisingly, this pex1-1 mutation ameliorated the metabolic and physiological defects of pex6-1 without restoring PEX5 levels. (rice.edu)
  • The first cellular models based on frataxin missense mutations that reproduce spontaneously the defects associated with Friedreich ataxia. (inserm.fr)
  • Human sodium channel gating defects caused by missense mutations in S6 segments associated with myotonia: S804F and V1293I. (semanticscholar.org)
  • Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. (whiterose.ac.uk)
  • Each person's genome sequence has thousands of missense variants. (nih.gov)
  • In that context, our group has contributed to better characterize CDH1 germline missense variants and is now considered a worldwide reference centre. (mdpi.com)
  • however, the abundance of variation in the human genomes makes the identification of a disease-causing mutation on a background of benign rare variants challenging. (ahajournals.org)
  • It furthermore highlights that rare titin missense variants, currently often ignored or left uninterpreted, should be considered to be relevant for cardiomyopathies and can be identified by the approach presented here. (ahajournals.org)
  • By performing WGS in 2 family members, filtering against variants seen in normal population cohorts and using linkage information derived from single nucleotide polymorphism (SNP) arrays of 13 family members, we could identify a missense variant in the titin gene ( TTN ) as the most plausible cause of disease in the family. (ahajournals.org)
  • Numerous missense mutations in the globular head of slow/beta-cardiac MyHC are associated with familial hypertrophic cardiomyopathy. (diva-portal.org)
  • Here, we present a new familial AR mutation in horses. (up.ac.za)
  • We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the guanosine triphosphatase domain, each segregating with affected individuals. (nih.gov)
  • 2013). De novo mutations in epileptic encephalopathies. (springer.com)
  • Most of the MECP2 mutations are private de novo mutations. (frontiersin.org)
  • thus we assumed this mutation to be either inherited from her father or acquired de novo . (haematologica.org)
  • The case of a male infant with neonatal encephalopathy and a de novo MECP2 mutation is reported. (bmj.com)
  • A novel missense mutation in CLCN1 gene in a family with autosomal recessive congenital myotonia. (thefreelibrary.com)
  • FOXA2 gene mutation in a patient with congenital complex pituitary hormone deficiency. (bioportfolio.com)
  • Homozygous SLC26A3 mutations cause congenital chloride diarrhea with male subfertility, while homozygous CFTR mutations cause cystic fibrosis with male infertility. (physiciansweekly.com)
  • Some tumours have biallelic loss of function mutations but most have monoallelic missense mutations involving specific arginine residues at β-propellor tips involved in substrate recognition. (bmj.com)
  • RHOBTB2 Mutations Expand the Phenotypic Spectrum of Alternating Hemiplegia of Childhood. (harvard.edu)
  • The high resolution human 1j8u structure was used to model catalytic domain mutations. (proteopedia.org)
  • Regulatory domain mutations were modeled using a homology model of the human domain, based on the rat 1phz structure, as were three catalytic domain mutations, R261Q, R413P, and Y414C, that are in contact with the regulatory domain across a subunit interface. (proteopedia.org)
  • Catalytic domain mutations R408W and R408Q are in contact with the tetramerization domain of another subunit and were modeled using 2pah . (proteopedia.org)
  • Other novel mutations detected in this study were nonsense (p.Gln227X and p.Gln382X) mutations in catalytic domain that result in PTCs. (haematologica.org)
  • Genomic mutation identifier (COSV) to indicate the definitive position of the variant on the genome. (sanger.ac.uk)
  • Missense mutations in TANK-binding kinase 1 (TBK1) have diverse biophysical and biochemical effects on the molecule and are associated with the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia. (pnas.org)
  • Mutations that abolish either TBK1 dimerization or kinase activity were insufficient to fully inhibit mitophagy, while mutations that reduced both dimerization and kinase activity were more disruptive. (pnas.org)
  • In a kindred with LFS without an inherited TP53 mutation, we have previously reported a truncating mutation (1100delC) in CHK2, encoding a kinase that phosphorylates p53 on Ser(20). (sigmaaldrich.com)
  • CHASM substantially outperformed previously described missense mutation function prediction methods at discriminating known oncogenic mutations in P53 and the tyrosine kinase epidermal growth factor receptor. (aacrjournals.org)
  • Several activating mutations in the cKIT receptor tyrosine kinase are associated with the development and progression of gastrointestinal stromal tumors (GIST). (aacrjournals.org)
  • Oncogenic mutations in the transmembrane receptor tyrosine kinase (RTK) cKIT are implicated as an important event in the pathogenesis of up to 90% of all GIST ( 2 , 3 ) and are also associated with the development of mast cell leukemia ( 4 ) and testicular seminoma ( 5 ). (aacrjournals.org)
  • Numerous reports have described unique mutations in cKIT, which cause constitutive activation of the cKIT kinase domain ( 6 ). (aacrjournals.org)
  • 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. (medworm.com)
  • It is suggested that most ErbB mutations have only a modest effect on inhibitor binding, but few that are located around the kinase active site can influence the binding significantly. (medworm.com)
  • These mutations are scattered throughout the kinase domain in a pattern similar to that described in gastrointestinal stromal tumors (GISTs), except that mis-sense mutations are predominant and deletions and insertion/duplications are rare. (thefreedictionary.com)
  • More recently, mutations of sodium channel Nav1.9 have been linked to human pain disorders, with two gain-of-function mutations found in patients with painful small fiber neuropathy. (springer.com)
  • Some mutations cause severe dysregulation of the pathway, while others induce limited disruption. (pnas.org)
  • Novel deletion and a new missense mutation (Glu 217 Lys) at the catalytic site in two adenosine deaminase alleles of a patient with neonatal onset adenosine deaminase- severe combined immunodeficiency. (jimmunol.org)
  • Mutations at the adenosine deaminase (ADA) locus result in a spectrum of disorders, encompassing a fulminant neonatal onset severe combined immunodeficiency (SCID) and childhood onset immunodeficiency, as well as apparently normal immune function. (jimmunol.org)
  • Conversely, CAA was more severe in APPdup and missense APP mutations, and in DS, compared to sEOAD and sLOAD. (unboundmedicine.com)
  • Here, we report on a very severe form of BPES resulting from a missense mutation outside the forkhead domain. (molvis.org)
  • Rabson Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance due to mutations in insulin receptor gene (INSR gene). (springer.com)
  • Haghighi A, Verdin H, Haghighi-Kakhki H, Piri N, Gohari NS, De Baere E. Missense mutation outside the forkhead domain of FOXL2 causes a severe form of BPES type II. (ugent.be)
  • Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. (whiterose.ac.uk)
  • One patient with severe type 5 hyperlipoproteinemia (MIM 144650), fasting chylomicronemia and relapsing pancreatitis resistant to standard therapy was found to be homozygous for a novel GPIHBP1 missense variant, namely G56R. (biomedcentral.com)
  • Thus, a very rare GPIHBP1 missense mutation appears to be associated with severe hypertriglyceridemia and chylomicronemia. (biomedcentral.com)
  • The present study describes identification of p.Pro23Thr mutation in CRYGD for aculeiform type cataract in an ADCC family of Indian origin. (springer.com)
  • The chemical complementation of cells from patients in vitro with various modifiers of glycosylation has been demonstrated and raises the possibility of specific chemical treatments for patients bearing gain-of-glycosylation mutations . (humpath.com)
  • Residue I108 interacts with CDH23 EC2 in the handshake and its mutation impairs the interaction in vitro . (jneurosci.org)
  • To address this issue, we utilized a variety of in vitro techniques to studying seven mutations found in disease populations spanning two highly conserved domains, the homeodomain (HD) and CVC domain. (arvojournals.org)
  • Vsx1 mutations spanning the HD and CVC domains altered transcriptional repression in vitro and visual signaling in vivo . (arvojournals.org)
  • More than one hundred unique FOXL2 mutations have been described in BPES in different populations, many of which are missense mutations in the forkhead domain. (molvis.org)
  • Only few missense mutations have been reported outside the forkhead domain so far. (molvis.org)
  • Missense mutation outside the forkhead domain o. (ugent.be)
  • Sequencing the Ocd lines revealed mutations within highly conserved regions of the para coding sequence, in the transmembrane segment S6 of domain III (I1545M and T1551I), and in the linker between domains III and IV (G1571R), the location of the channel inactivation gate. (genetics.org)
  • Since no human mutations in GPIHBP1 have yet been reported, we screened the genomic DNA of 160 unrelated adults with fasting chylomicronemia to search for coding sequence mutations in this gene. (biomedcentral.com)
  • Determining which mutations are drivers and which are passengers is one of the most pressing challenges in cancer genetics. (aacrjournals.org)
  • abstract = "An N-ethyl-N-nitrosourea random mutation screen was used to identify recessive modifiers of gene silencing in the mouse using an epigenetically sensitive reporter transgene. (monash.edu)
  • We identified a missense mutation, Arg1845Trp, in the rod region of slow/beta-cardiac MyHC in patients with a skeletal myopathy from two different families. (diva-portal.org)
  • We identified six rare missense mutations in this sample, including T197M in one male patient and two female controls, L201V in nine patients (three males and six females) and 4 controls (three females and one male), L213V in one female patient, A358T in one male patient and one female control, P376S in one female patient, and P419S in one male patient. (frontiersin.org)
  • These mutations had been reported to be present in patients with various neuropsychiatric disorders other than Rett syndrome in the literature. (frontiersin.org)
  • Our findings suggest that rare MECP2 mutations exist in some schizophrenia patients and the MECP2 gene could be considered a risk gene of schizophrenia. (frontiersin.org)
  • Rett syndrome is predominant in females because male patients with similar mutations are considered fatal. (frontiersin.org)
  • Associations have been reported between mutations in the DDHD1 gene and the SPG28 subtype of autosomal recessive HSP but have never been reported in jALS patients. (frontiersin.org)
  • Our data also suggest that ATP13A2 single heterozygous mutations might be etiologically relevant for patients with YOPD and further studies of this gene in Parkinson disease are warranted. (neurology.org)
  • When stratified by CAA subtype from 1 to 4, there were no differences in plaque scores between the groups, though in patients with APPdup, APP mutations and sEOAD, types 2 and 3 CAA were more common than type 1. (unboundmedicine.com)
  • Many patients in this group could not be identified genetically until GOF heterozygous mis-sense mutations in the STAT1 molecule were defined in this decade [10,11]. (thefreedictionary.com)
  • 8 No mutation data are available about the extremely rare patients that presented without peripheral neuropathy. (bmj.com)
  • Previous studies showed inherited mutations in desmosomal proteins lead to sodium current deficits in hearts of patients diagnosed with arrhythmogenic cardiomyopathy (or arrhythmogenic right ventricular dysplasia/ cardiomyopathy). (ca.gov)
  • In this study, we identified 5 patients with PKP2 mutations from 200 patients with Brugada syndrome. (ca.gov)
  • This is the first report of mutations in patients with FVII deficiency from southern India. (haematologica.org)
  • This mutation was absent from the genomes of 600 control subjects and 610 patients with hyperlipidemia. (biomedcentral.com)
  • This missense mutation was absent from the genomes of 600 normolipidemic Caucasian control subjects and 610 Caucasian patients with hyperlipidemia. (biomedcentral.com)
  • RESULTS: The authors detected four novel mutations within the KCC3 gene in their patients: two different truncating mutations in the first patient, a homozygous truncating mutation in the second, and a homozygous missense mutation in the third patient. (uni-regensburg.de)
  • However, a paucity of appropriate animal models has slowed our understanding both of the interaction and of how mutations of residues within the predicted interface compromise tip link integrity. (jneurosci.org)
  • Driver mutations may have characteristics similar to those causing Mendelian disease when inherited in the germ line ( 7 ) and may be identifiable by constraints on tolerated amino acid residues at the mutated positions ( 3 , 7 - 9 ). (aacrjournals.org)
  • Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. (sigmaaldrich.com)
  • We describe a novel mutation in the ND6 gene (T14487C) in a patient with Leigh syndrome. (wiley.com)
  • Few mutations which are associated with Rabson Mendenhall syndrome have been identified and reported in the past. (springer.com)
  • Mutations in the gene for the transcriptional repressor, MECP2, have been well characterised in girls with Rett syndrome. (bmj.com)
  • 2- 4 There are also reports of males with fatal and non-fatal neonatal encephalopathy caused by an MECP2 mutation identified because of recurrence among siblings or the occurrence of a close female relative with Rett syndrome. (bmj.com)
  • Recently, truncating mutations of the KCC3 gene (also known as SLC12A6) have been associated with Andermann syndrome. (uni-regensburg.de)
  • CONCLUSIONS: Not only truncating but also missense mutations of the KCC3 gene are associated with Andermann syndrome. (uni-regensburg.de)
  • RNA editing-dependent amino acid substitutions can produce missense mRNA's of which occur through hydrolytic deaminase reactions. (wikipedia.org)
  • A novel homozygous missense mutation (Gly504Arg) was identified in one sporadic case from Brazil with juvenile parkinsonism. (neurology.org)
  • We demonstrate that gout can be caused by a mutation in LDHD within the putative catalytic site of the encoded d-lactate dehydrogenase, resulting in augmented blood levels of d-lactate, a stereoisomer of l-lactate, which is normally present in human blood in miniscule amounts. (jci.org)
  • These results offer new insights into the interaction between PCDH15 and CDH23 and help explain the etiology of human deafness linked to mutations in the tip-link interface. (jneurosci.org)
  • In order to analyse the most common mutations in human tumours, we created a Fbxw7 fl(R482Q) /+ mouse and conditionally expressed this mutation in the intestines using Vill -Cre. (bmj.com)
  • These findings explain the FBXW7 mutation spectrum found in human cancers, and emphasise the need for animal models faithfully to reflect human disease. (bmj.com)
  • To date, mouse models carry Fbxw7 null alleles, but these do not faithfully recapitulate the mutations most commonly present in human cancers. (bmj.com)
  • A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR. (physiciansweekly.com)
  • Mechanisms of a Human Skeletal Myotonia Produced by Mutation in the C-Terminus of NaV1.4: Is Ca2+ Regulation Defective? (semanticscholar.org)
  • Factor VII (FVII) (OMIM: 227500) deficiency is a rare (1:500,000) autosomal recessive disorder of blood coagulation caused by heterogeneous mutations (~140) in FVII gene. (haematologica.org)
  • Our investigation utilizes disease-linked mutations to further refine the current model of mitophagy, identifying regulatory crosstalk between the kinases TBK1 and ULK1, and providing insights into the roles of TBK1 in neurodegenerative pathogenesis. (pnas.org)
  • This article reports that selected disease-related FXN missense mutations impair FXN localization, interaction with mitochondria processing peptidase, and processing. (curefa.org)
  • Up to 1.4% of known disease-causing missense mutations are predicted to give rise to gains-of-glycosylation. (humpath.com)
  • Several diseases including Epidermolysis bullosa, sickle-cell disease, and SOD1 mediated ALS are the result of missense mutation. (enotes.com)
  • Could a disease caused by mutation in a gene found on the X chromosome affect a male? (enotes.com)
  • Could a disease caused by a mutation in a gene found on the Y chromosome affect a female? (enotes.com)
  • Co-segregation of this mutation with the disease was demonstrated by direct sequencing of the fragment in affected as well as unaffected members of this family. (thefreelibrary.com)
  • Although of limited scale, the results support the view that destabilization is the most common mechanism by which missense mutations cause monogenic disease. (proteopedia.org)
  • Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by mutations in the arylsulphatase A ( ASA ) gene. (bmj.com)
  • 7 , 8 Using our novel PCR-CSGE strategy, 7 out of 8 disease causing mutations were detected with a comparable sensitivity (88% vs. 91%) to DGGE. (haematologica.org)
  • Mutations in an almost identical copy gene, SMN2 , do not cause disease. (rupress.org)
  • Differential effects of Best disease causing missense mutations on bestrophin-1 trafficking. (semanticscholar.org)
  • Mutations in bestrophin-1 (Best1) cause Best vitelliform macular dystrophy (BVMD), a dominantly inherited retinal degenerative disease. (semanticscholar.org)
  • Disease-associated missense mutations in bestrophin-1 affect cellular trafficking and anion conductance. (semanticscholar.org)
  • The mechanisms by which sodium channel mutations cause cold sensitivity are not well understood. (genetics.org)
  • A sodium channel myotonia due to a novel SCN4A mutation accompanied by acquired autoimmune myasthenia gravis. (semanticscholar.org)
  • A mutation in a rare type of intron in a sodium-channel gene results in aberrant splicing and causes myotonia. (semanticscholar.org)
  • Targeted next‑generation sequencing and Sanger DNA sequencing showed compound heterozygous mutations of the SKIV2L gene. (spandidos-publications.com)
  • The present study was the first, to the best of our knowledge, to report a case of a boy with THES resulting from compound heterozygous mutations of the SKIV2L gene in China. (spandidos-publications.com)
  • The present study reported the case of a Chinese boy with THES resulting from compound heterozygous mutations of the SKIV2L gene. (spandidos-publications.com)