Trinucleotide Repeat Expansion: An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.Friedreich Ataxia: An autosomal recessive disease, usually of childhood onset, characterized pathologically by degeneration of the spinocerebellar tracts, posterior columns, and to a lesser extent the corticospinal tracts. Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. Most forms of this condition are associated with a mutation in a gene on chromosome 9, at band q13, which codes for the mitochondrial protein frataxin. (From Adams et al., Principles of Neurology, 6th ed, p1081; N Engl J Med 1996 Oct 17;335(16):1169-75) The severity of Friedreich ataxia associated with expansion of GAA repeats in the first intron of the frataxin gene correlates with the number of trinucleotide repeats. (From Durr et al, N Engl J Med 1996 Oct 17;335(16):1169-75)DNA Repeat Expansion: An increase number of repeats of a genomic, tandemly repeated DNA sequence from one generation to the next.Spinocerebellar Degenerations: A heterogenous group of degenerative syndromes marked by progressive cerebellar dysfunction either in isolation or combined with other neurologic manifestations. Sporadic and inherited subtypes occur. Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked.Myotonic Dystrophy: Neuromuscular disorder characterized by PROGRESSIVE MUSCULAR ATROPHY; MYOTONIA, and various multisystem atrophies. Mild INTELLECTUAL DISABILITY may also occur. Abnormal TRINUCLEOTIDE REPEAT EXPANSION in the 3' UNTRANSLATED REGIONS of DMPK PROTEIN gene is associated with Myotonic Dystrophy 1. DNA REPEAT EXPANSION of zinc finger protein-9 gene intron is associated with Myotonic Dystrophy 2.Fragile X Syndrome: A condition characterized genotypically by mutation of the distal end of the long arm of the X chromosome (at gene loci FRAXA or FRAXE) and phenotypically by cognitive impairment, hyperactivity, SEIZURES, language delay, and enlargement of the ears, head, and testes. INTELLECTUAL DISABILITY occurs in nearly all males and roughly 50% of females with the full mutation of FRAXA. (From Menkes, Textbook of Child Neurology, 5th ed, p226)Huntington Disease: A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)Fragile X Mental Retardation Protein: A RNA-binding protein that is found predominately in the CYTOPLASM. It helps regulate GENETIC TRANSLATION in NEURONS and is absent or under-expressed in FRAGILE X SYNDROME.Iron-Binding Proteins: Proteins that specifically bind to IRON.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Spinocerebellar Ataxias: A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)Machado-Joseph Disease: A dominantly-inherited ATAXIA first described in people of Azorean and Portuguese descent, and subsequently identified in Brazil, Japan, China, and Australia. This disorder is classified as one of the SPINOCEREBELLAR ATAXIAS (Type 3) and has been associated with a mutation of the MJD1 gene on chromosome 14. Clinical features include progressive ataxia, DYSARTHRIA, postural instability, nystagmus, eyelid retraction, and facial FASCICULATIONS. DYSTONIA is prominent in younger patients (referred to as Type I Machado-Joseph Disease). Type II features ataxia and ocular signs; Type III features MUSCULAR ATROPHY and a sensorimotor neuropathy; and Type IV features extrapyramidal signs combined with a sensorimotor neuropathy. (From Clin Neurosci 1995;3(1):17-22; Ann Neurol 1998 Mar;43(3):288-96)Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Heredodegenerative Disorders, Nervous System: Inherited disorders characterized by progressive atrophy and dysfunction of anatomically or physiologically related neurologic systems.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Nerve Tissue ProteinsMicrosatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Frontotemporal Dementia: The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.Flap Endonucleases: Endonucleases that remove 5' DNA sequences from a DNA structure called a DNA flap. The DNA flap structure occurs in double-stranded DNA containing a single-stranded break where the 5' portion of the downstream strand is too long and overlaps the 3' end of the upstream strand. Flap endonucleases cleave the downstream strand of the overlap flap structure precisely after the first base-paired nucleotide, creating a ligatable nick.Anticipation, Genetic: The apparent tendency of certain diseases to appear at earlier AGE OF ONSET and with increasing severity in successive generations. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Tandem Repeat Sequences: Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (INVERTED TANDEM REPEATS).Inverted Repeat Sequences: Copies of nucleic acid sequence that are arranged in opposing orientation. They may lie adjacent to each other (tandem) or be separated by some sequence that is not part of the repeat (hyphenated). They may be true palindromic repeats, i.e. read the same backwards as forward, or complementary which reads as the base complement in the opposite orientation. Complementary inverted repeats have the potential to form hairpin loop or stem-loop structures which results in cruciform structures (such as CRUCIFORM DNA) when the complementary inverted repeats occur in double stranded regions.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Minisatellite Repeats: Tandem arrays of moderately repetitive, short (10-60 bases) DNA sequences which are found dispersed throughout the GENOME, at the ends of chromosomes (TELOMERES), and clustered near telomeres. Their degree of repetition is two to several hundred at each locus. Loci number in the thousands but each locus shows a distinctive repeat unit.Pedigree: 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.Cerebellar Ataxia: Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)Age of Onset: 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.Intranuclear Inclusion Bodies: Circumscribed masses of foreign or metabolically inactive materials, within the CELL NUCLEUS. Some are VIRAL INCLUSION BODIES.Chromosome Fragility: Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.Muscular Dystrophy, Oculopharyngeal: An autosomal dominant hereditary disease that presents in late in life and is characterized by DYSPHAGIA and progressive ptosis of the eyelids. Mutations in the gene for POLY(A)-BINDING PROTEIN II have been associated with oculopharyngeal muscular dystrophy.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.Genetic Diseases, Inborn: 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.Polymorphism, Genetic: 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.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Exons: 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.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Amyotrophic Lateral Sclerosis: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.Proteins: 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.Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Genetic Variation: Genotypic differences observed among individuals in a population.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Receptors, Androgen: Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.Cloning, Molecular: 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.Introns: 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.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.DNA Replication: The process by which a DNA molecule is duplicated.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.DNA, Complementary: 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.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Myoclonic Epilepsies, Progressive: A heterogeneous group of primarily familial disorders characterized by myoclonic seizures, tonic-clonic seizures, ataxia, progressive intellectual deterioration, and neuronal degeneration. These include LAFORA DISEASE; MERRF SYNDROME; NEURONAL CEROID-LIPOFUSCINOSIS; sialidosis (see MUCOLIPIDOSES), and UNVERRICHT-LUNDBORG SYNDROME.Blotting, Southern: A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Promoter Regions, Genetic: 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.MutS Homolog 2 Protein: MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.Repetitive Sequences, Amino Acid: A sequential pattern of amino acids occurring more than once in the same protein sequence.Nucleic Acid Heteroduplexes: Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Disease Models, Animal: 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.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.DNA, Satellite: Highly repetitive DNA sequences found in HETEROCHROMATIN, mainly near centromeres. They are composed of simple sequences (very short) (see MINISATELLITE REPEATS) repeated in tandem many times to form large blocks of sequence. Additionally, following the accumulation of mutations, these blocks of repeats have been repeated in tandem themselves. The degree of repetition is on the order of 1000 to 10 million at each locus. Loci are few, usually one or two per chromosome. They were called satellites since in density gradients, they often sediment as distinct, satellite bands separate from the bulk of genomic DNA owing to a distinct BASE COMPOSITION.Open Reading Frames: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).Genome, Bacterial: The genetic complement of a BACTERIA as represented in its DNA.Expressed Sequence Tags: Partial cDNA (DNA, COMPLEMENTARY) sequences that are unique to the cDNAs from which they were derived.Genomic Library: A form of GENE LIBRARY containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns).Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.

*Dictyostelium discoideum

The repeats correspond to repeated sequences of amino acids and are thought to be expanded by nucleotide expansion. Expansion ... Tandem repeats of trinucleotides are very abundant in this genome; one class of the genome is clustered, leading researchers to ... More recent genomic studies have shown that Dictyostelium has maintained more of its ancestral genome diversity than plants and ... of trinucleotide repeats also occurs in humans, in general leading to many diseases. Learning how D. discoideum cells endure ...

*List of MeSH codes (G13)

... dna repeat expansion MeSH G13.920.590.220.865 --- trinucleotide repeat expansion MeSH G13.920.590.300 --- frameshift mutation ... sequence homology, amino acid MeSH G13.810.550 --- sequence homology, nucleic acid MeSH G13.810.550.830 --- synteny MeSH ... MeSH G13.920.590.310 --- gene amplification MeSH G13.920.590.320 --- gene duplication MeSH G13.920.590.335 --- genomic ... sequence deletion MeSH G13.920.590.762.180 --- chromosome deletion MeSH G13.920.590.762.320 --- gene deletion MeSH G13.920. ...

*Trinucleotide repeat disorder

The mutation is a subset of unstable microsatellite repeats that occur throughout all genomic sequences. If the repeat is ... Trinucleotide repeat disorders (also known as trinucleotide repeat expansion disorders, triplet repeat expansion disorders or ... Trinucleotide repeat expansion, also known as triplet repeat expansion, is the DNA mutation responsible for causing any type of ... are a set of genetic disorders caused by trinucleotide repeat expansion, a kind of mutation where trinucleotide repeats in ...

*List of MeSH codes (G14)

... tandem repeat sequences MeSH G14.080.708.800.074 --- dna repeat expansion MeSH G14.080.708.800.074.865 --- trinucleotide repeat ... interspersed repetitive sequences MeSH G14.080.708.330.200 --- dna transposable elements MeSH G14.080.708.330.330 --- genomic ... dna sequence, unstable MeSH G14.340.024.189.220 --- dna repeat expansion MeSH G14.340.024.189.220.865 --- trinucleotide repeat ... trinucleotide repeat expansion MeSH G14.080.708.800.550 --- minisatellite repeats MeSH G14.080.708.850 --- terminal repeat ...

*List of MeSH codes (G06)

... dna repeat expansion MeSH G06.184.603.080.708.800.140.865 --- trinucleotide repeat expansion MeSH G06.184.603.080.708.800.150 ... ankyrin repeat MeSH G06.184.603.080 --- base sequence MeSH G06.184.603.080.040 --- at rich sequence MeSH G06.184.603.080.380 ... genomic islands MeSH G06.184.603.080.708.330.800 --- retroelements MeSH G06.184.603.080.708.330.800.175 --- endogenous ... trinucleotide repeats MeSH G06.184.603.080.708.800.500.850.200 --- trinucleotide repeat expansion MeSH G06.184.603.080.708.800. ...

*List of MeSH codes (G05)

... dna repeat expansion MeSH G05.600.220.865 --- trinucleotide repeat expansion MeSH G05.600.315 --- gene amplification MeSH ... sequence deletion MeSH G05.600.800.180 --- chromosome deletion MeSH G05.600.800.320 --- gene deletion MeSH G05.600.810 --- ... genomic imprinting MeSH G05.315.670 --- protein modification, translational MeSH G05.315.670.600 --- protein processing, post- ...

*Genome instability

... often have an unusual expansion of repeat sequences in DNA, likely attributable to genome instability. Four (ataxia- ... These ubiquitous sites are characterized by trinucleotide repeats, most commonly CGG, CAG, GAA, and GCN. These trinucleotide ... This genomic instability is crucial in ensuring mammalian survival against infection. V, D, J recombination can ensure millions ... such as DNA-repeat expansion. Rare fragile sites can lead to genetic disease such as fragile X mental retardation syndrome, ...

*Myotonin-protein kinase

The 3' untranslated region of this gene contains 5-37 copies of a CTG trinucleotide repeat. Expansion of this unstable motif to ... "Structure and genomic sequence of the myotonic dystrophy (DM kinase) gene". Human Molecular Genetics. 2 (3): 299-304. doi: ... As shown in the figure, as the DMPK repeat is replicated, the hairpin loop that is formed leads to repeat expansion (a) or ... expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member". Cell. 68 (4 ...

*Non-Mendelian inheritance

Trinucleotide repeat disorders also follow a non-Mendelian pattern of inheritance. These diseases are all caused by the ... "Lesson 1: Triplet Repeat Expansion". Retrieved 2007-10-16. "FMR1-Related Disorders". Retrieved 2007-10-29. non-Mendelian ... Genomic imprinting represents yet another example of non-Mendelian inheritance. Just as in conventional inheritance, genes for ... Gene conversion arises during DNA repair via DNA recombination, by which a piece of DNA sequence information is transferred ...

*Ataxia-telangiectasia

... of the three nucleotide bases GAA from the usual 5-33 repetitions of this trinucleotide sequence to greater than 65 repeats on ... The result is genomic instability which can lead to the development of cancers. Irradiation and radiomimetic compounds induce ... FA is caused by mutation in the frataxin gene, most often an expansion of a naturally occurring repetition ... ATM is located on human chromosome 11 (11q22.3) and is made up of 69 exons spread across 150kb of genomic DNA. The mode of ...

*Microsatellite

Each trinucleotide repeating sequence is transcribed into a repeating series of the same amino acid. In yeasts, the most common ... This involves searching the genomic DNA sequence for microsatellite repeats, which can be done by eye or by using automated ... Length changes in other triplet repeats are linked to more than 40 neurological diseases in humans, notably triplet expansion ... of proteins contain repeating sequences of amino acids encoded by short sequence repeats. Most of the short sequence repeats ...

*Satellite DNA

Microsatellites expansion (trinucleotide repeat expansion) is often found in transcription units. Often the base pair ... The nucleotide sequence of the repeats is fairly well conserved across species. However, variation in the length of the repeat ... band when genomic DNA is separated on a density gradient. Satellite DNA, together with minisatellite and microsatellite DNA, ... Between the strand-biased microsatellite repeats and G:C mononucleotide repeats, all sequence variations retained one or two ...

*Mutation

Trinucleotide repeat expansion Sharma S, Javadekar SM, Pandey M, Srivastava M, Kumari R, Raghavan SC (March 2015). "Homology ... Molecular sequence analysis: With rapid development of DNA sequencing technology, an enormous amount of DNA sequence data is ... If it becomes necessary to differentiate between mutations in genomic DNA, mitochondrial DNA, and RNA, a simple convention is ... Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (June 1993). "Ubiquitous somatic mutations in simple repeated sequences ...

*Flap structure-specific endonuclease 1

DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing ... leading to site-specific trinucleotide expansions. Flap structure-specific endonuclease 1 has been shown to interact with: ... Ottaviani D, LeCain M, Sheer D (2014). "The role of microhomology in genomic structural variation". Trends Genet. 30 (3): 85-94 ... and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. Chem. ...

*Microsatellite

Each trinucleotide repeating sequence is transcribed into a repeating series of the same amino acid. In yeasts, the most common ... This involves searching the genomic DNA sequence for microsatellite repeats, which can be done by eye or by using automated ... and are not usually trinucleotide STRs which could be involved in triplet expansion diseases such as Huntington's disease. ... of proteins contain repeating sequences of amino acids encoded by short sequence repeats.[23] Most of the short sequence ...

*Mutation

Trinucleotide repeat expansion. ReferencesEdit. *^ "mutation , Learn Science at Scitable". www.nature.com. Retrieved 2018-09-24 ... Molecular sequence analysis: With rapid development of DNA sequencing technology, an enormous amount of DNA sequence data is ... Eyre-Walker A (October 2006). "The genomic rate of adaptive evolution". Trends in Ecology & Evolution. 21 (10): 569-75. doi: ... Various methods have been developed to infer the DFE from DNA sequence data.[81][82][83][84] By examining DNA sequence ...

*Chromosomal fragile site

DNA polymerase has been shown to pause at CTG and CGG triplet repeat sequences, which can result in continual expansion via ... Gacy, AM; Goellner, G; Juranić, N; Macura, S; McMurray, CT (May 19, 1995). "Trinucleotide repeats that expand in human disease ... "Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers". Proceedings of the ... Unlike RFSs, common fragile sites (CFSs) are not the result of nucleotide repeat expansion mutations. They are a part of the ...

*CRYGB

Hearne CM, Todd JA (1991). "Trinucleotide repeat polymorphism at the CRYG1 locus". Nucleic Acids Res. 19 (19): 5450. doi: ... 1989). "Nucleotide sequence of the rat gamma-crystallin gene region and comparison with an orthologous human region". Gene. 78 ... 2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome ... are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma- ...

*Medical genetics

DNA sequencing is used to directly analyze the genomic DNA sequence of a particular gene. In general, only the parts of the ... Southern blotting is still useful in the diagnosis of disorders caused by trinucleotide repeats. ... This section needs expansion with: more details and additional citations. You can help by adding to it. (August 2008) ... Short tandem repeats are unique markers that can be used to determine haplotypes and are used in identity testing for maternal ...

*Causes of autism

An expansion of the CGG trinucleotide repeat in the promoter of the gene FMR1 in boys causes fragile X syndrome, and at least ... CNV studies were closely followed by exome sequencing studies, which sequence the 1-2% of the genome that codes for proteins ( ... "Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting". Brain ... Epigenetic changes occur as a result not of DNA sequence changes but of chromosomal histone modification or modification of the ...

*Frameshift mutation

As stated previously, frameshift mutations are more likely to occur in a region of repeat sequence. When DNA mismatch repair ... "Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing". Proc ... "DNA models of trinucleotide frameshift deletions: the formation of loops and bulges at the primer-template junction". Nucleic ... There may be a link between diseases caused by polyglutamine and polyalanine expansion mutations, as frame shifting of the ...
Using the direct identification of repeat expansion and cloning technique, we cloned a novel long CAG/CTG trinucleotide repeat on chromosome 17. Using radiation hybrid panels, the CAG/CTG repeat was mapped to chromosome 17q. The CAG/CTG repeat is hig
Premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are frequent in the general population, with estimated prevalences of 1 per 259 females and 1 per 813 males. Several articles have recently described the presence of late-onset neurological symptoms in male carriers of premutation (FMR1) alleles. The main clinical features described in this newly identified syndrome are cerebellar ataxia and intention tremor. Additional documented symptoms include short-term memory loss, executive functional deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction.To study the penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) among premutation carriers.Family-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. Data were collected (March 2002-April 2003) through ...
Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS. We tested
The need for accessible cellular biomarkers of neurodegeneration in carriers of the fragile X mental retardation 1 (FMR1) premutation (PM) alleles.To assess the mitochondrial status and respiration in blood lymphoblasts from PM carriers manifesting the fragile X-associated tremor/ataxia syndrome (FXTAS) and non-FXTAS carriers, and their relationship with the brain white matter lesions.Oxygen consumption rates (OCR) and ATP synthesis using a Seahorse XFe24 Extracellular Flux Analyser, and steady-state parameters of mitochondrial function were assessed in cultured lymphoblasts from 16 PM males (including 11 FXTAS patients) and 9 matched controls. The regional white matter hyperintensity (WMH) scores were obtained from MRI.Mitochondrial respiratory activity was significantly elevated in lymphoblasts from PM carriers compared with controls, with a 2- to 3-fold increase in basal and maximum OCR attributable to complex I activity, and ATP synthesis, accompanied by unaltered mitochondrial mass and ...
TY - JOUR. T1 - Triplet repeat DNA structures and human genetic disease. T2 - Dynamic mutations from dynamic DNA. AU - Sinden, Richard R.. AU - Potaman, Vladimir N.. AU - Oussatcheva, Elena A.. AU - Pearson, Christopher E.. AU - Lyubchenko, Yuri L.. AU - Shlyakhtenko, Luda S.. PY - 2002/1/1. Y1 - 2002/1/1. N2 - Fourteen genetic neurodegenerative diseases and three fragile sites have been associated with the expansion of (CTG)n•(CAG)n•(CGG)n• (CCG)n, or (GAA)n·(TTC)n repeat tracts. Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, slipped strand DNA, may stably and reproducibly form within triplet repeat sequences. The propensity to form slipped strand DNA is proportional to the length and homogeneity of the repeat ...
TY - JOUR. T1 - Altered hypothalamus-pituitary-adrenal gland axis regulation in the expanded CGG-repeat mouse model for fragile X-associated tremor/ataxia syndrome. AU - Brouwer, J. R.. AU - Severijnen, E.. AU - de Jong, F. H.. AU - Hessl, David R. AU - Hagerman, Randi J. AU - Oostra, B. A.. AU - Willemsen, R.. PY - 2008/7. Y1 - 2008/7. N2 - The human FMR1 gene contains an unstable CGG-repeat in its 5′ untranslated region. The repeat length in the normal population is polymorphic (5-54 CGG-repeats). Individuals carrying lengths beyond 200 CGGs (i.e. the full mutation) show hypermethylation and as a consequence gene silencing of the FMR1 gene. The absence of the gene product FMRP causes the fragile X syndrome, the most common inherited form of mental retardation. Elderly carriers of the premutation (PM), which is defined as a repeat length between 55 and 200 CGGs, can develop a progressive neurodegenerative syndrome: fragile ...
The long-term goal of the project is to understand the mechanisms by which cells maintain trinucleotide repeat (TNR) stability. Expansions of TNR sequences, e.g...
The most common type of DM is called DM1, which is caused by a mutation in a gene called myotonic dystrophy protein kinase (DMPK). The DMPK gene is located on chromosome 19. The specific mutation that causes DM1 is called a trinucleotide repeat expansion. In people who have DM1, a particular unit of the gene is repeated too many times-more than the normal range of five to 38 times-and thus this section of the gene is too big and is unstable. The enlarged section of the gene is called a trinucleotide repeat expansion. People who have repeat numbers in the normal range will not develop DM1 and cannot pass it to their children. Having more than 50 repeats causes DM1. People who have 38-49 repeats have what is called a premutation. They do not develop DM1, but can pass DM1 on to their children. Myotonic dystrophy has an effect called ...
Many human diseases are caused by the expansion of small repeat sequences within genes, including myotonic dystrophy, fragile X syndrome, as well as the class of diseases known as the polyQ diseases, like Huntingtons disease (Gatchel and Zoghbi 2005). Our studies have focused on instability of CAG repeat sequences. Unlike previous studies with a shorter repeat size (SCA3trQ78), the current studies employed ∼270 CAG repeats (UAS-CAG270). With the longer repeat, we observed a significant level of intergenerational repeat instability even in the absence of added gene expression (see Figure 1). This basal level instability showed primarily +1 repeat expansions, consistent with the "replication slippage" model (Kovtun and McMurray 2008). When the CAG repeat was then expressed in germ cells, there was a ...
Dynamic expansions of toxic polyglutamine (polyQ)-encoding CAG repeats in ubiquitously expressed, but otherwise unrelated, genes cause a number of late-onset progressive neurodegenerative disorders, including Huntington disease and the spinocerebellar ataxias. As polyQ toxicity in these disorders increases with repeat length, the intergenerational expansion of unstable CAG repeats leads to anticipation, an earlier age-at-onset in successive generations. Crucially, disease associated alleles are also somatically unstable and continue to expand throughout the lifetime of the individual. Interestingly, the inherited polyQ length mediating a specific age-at-onset of symptoms varies markedly between disorders. It is widely assumed that these inter-locus differences in polyQ toxicity are mediated by protein context effects. Previously, we demonstrated that the tendency of expanded CAG•CTG repeats to undergo ...
An HO endonuclease recognition site was inserted into the LEU2 gene of chromosome III, in strain YFP17. Homology to the HO cleavage site at MAT, HML and HMR was deleted (Pâques et al., 1998). Expression of the HO endonuclease gene was controlled by a galactose‐inducible promoter (Sandell and Zakian, 1993). A DSB is created within the LEU2 gene of chromosome III, such that sequences near the ends of the DSB are homologous to donor sequences located on a plasmid (Figure 1A). Repair of the DSB requires the presence of the homologous sequences on the plasmid. Thus, when HO was expressed in the absence of the donor plasmid, 99.7% of cells died, as they were unable to repair the DSB. However, when a plasmid containing an intact LEU2 gene was introduced to provide homology to the HO‐cleaved LEU2, ∼22% of cells were able to repair the DSB using the plasmid sequence as a template (Pâques et al., 1998, and Figure 1B).. We then supplied different templates in which the ...
Triplet repeat expansion disorders (TRED) are one of the commonest causes of hereditary neuropathy with thirty different heredity diseases due to increased number of trin..
My research is aimed towards understanding the molecular basis of repeat expansion disorders. Several inherited human neurological and muscular disorders like Friedreichs ataxia (FRDA), fragile X syndrome (FXS), myotonic dystrophy (DM1), Huntingtons disease and spinocerebellar ataxia type 7 (SCA7) are caused by a trinucleotide repeat expansion. The mechanism leading to repeat instability is still not known and there is currently no cure for these repeat expansion diseases. One goal of my research is to dissect the DNA replication program at the endogenous disease locus and find molecular components driving repeat expansion in human cells. Therefore we are using a unique technique, called single-molecule analysis of replicated DNA (SMARD), which allows us to visualize the DNA replication at the endogenous genomic locus in ...
Sigma-Aldrich offers abstracts and full-text articles by [Kirin Basuta, Andrea Schneider, Louise Gane, Jonathan Polussa, Bryan Woodruff, Dalyir Pretto, Randi Hagerman, Flora Tassone].
Background Over 40% of male and ∼16% of female carriers of a premutation FMR1 allele (55-200 CGG repeats) will develop fragile X-associated tremor/ataxia syndrome, an adult onset neurodegenerative disorder, while about 20% of female carriers will develop fragile X-associated primary ovarian insufficiency. Marked elevation in FMR1 mRNA transcript levels has been observed with premutation alleles, and RNA toxicity due to increased mRNA levels is the leading molecular mechanism proposed for these disorders. However, although the FMR1 gene undergoes alternative splicing, it is unknown whether all or only some of the isoforms are overexpressed in premutation carriers and which isoforms may contribute to the premutation pathology.. ...
American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) 144B:566 -569 (2007) Brief Research Communication CGG Repeat Length Correlates With Age of Onset of Motor Signs of the Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Flora Tassone,1* John Adams,2 Elizabeth M. Berry-Kravis,3 Susannah S. Cohen,2 Alfredo Brusco,4 Maureen A. Leehey,5 Lexin Li,6 Randi J. Hagerman,2,7 and Paul J. Hagerman1 1 Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis, California M.I.N.D. Institute, University of California, Medical Center, Sacramento, California 3 Departments of Pediatrics, Neurology, and Biochemistry, RUSH University Medical Center, Chicago, Illinois 4 Department of Genetics Biology and Biochemistry, University of Turin, Turin, Italy 5 Department of Neurology, University of Colorado at Denver Health Sciences Center, Denver, Colorado 6 Department of Statistics, North Carolina State University, Raleigh, North Carolina 7 Department ...
TY - JOUR. T1 - Frequency of spinocerebellar ataxia type 1, dentatorubropallidoluysian atrophy, and Machado-Joseph disease mutations in a large group of spinocerebellar ataxia patients. AU - Silveira, I.. AU - Lopes-Cendes, AU - Kish, S.. AU - Maciel, P.. AU - Gaspar, C.. AU - Coutinho, P.. AU - Botez, M. I.. AU - Teive, H.. AU - Arruda, W.. AU - Steiner, C. E.. AU - Pinto-Junior, W.. AU - Maciel, J. A.. AU - Jain, S.. AU - Sack, G.. AU - Andermann, E.. AU - Sudarsky, L.. AU - Rosenberg, R.. AU - MacLeod, P.. AU - Chitayat, D.. AU - Babul, R.. AU - Sequeiros, J.. AU - Rouleau, G. A.. PY - 1996/1. Y1 - 1996/1. N2 - The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders varying in both clinical manifestations and mode of inheritance. Six different genes causing autosomal dominant SCA are mapped: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide ...
Purpose : Fuchs endothelial corneal dystrophy (FECD) is an autosomal dominant disease with assorted variations in expression and penetrance. The expansion of a CTG trinucleotide repeat (TNR) in a different intron of transcription factor 4 (TCF4) has commonly been detected in FECD patients, and the sensitivity and specificity of ,50 repeats was 79% and 96%, respectively (Wieben et al., PloS ONE, 2012). The purpose of this present study was to evaluate the TNR expansion in a larger cohort of Caucasian FECD patients. Methods : We recruited 387 FECD patients (158 males and 229 females; mean age: 69.7±9.2 years; range: 32-92 years) who were scheduled to receive Descemets membrane endothelial keratoplasty (DMEK) at the University of Erlangen-Nürnberg Hospital in order to obtain peripheral blood samples. All patients were diagnosed as FECD due to symptoms such as guttae, corneal edema, and decrease of corneal endothelial cell ...
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Purpose: The strongest genetic association of Fuchs endothelial corneal dystrophy (FECD) is with an expanded trinucleotide repeat (CTG·CAG) in an intron of the TCF4 gene. The same expanded repeat sequence in the 3UTR of the DMPK gene causes Myotonic Dystrophy type 1 (DM1) via a RNA toxicity mechanism. In DM1, poly(CUG) transcripts accumulate in foci and sequester the splicing factor MBNL1, causing missplicing of essential transcripts in skeletal muscle. Our hypothesis is that the same molecular mechanism causes RNA toxicity in the corneal endothelium of FECD patients. Because FECD patients do not present signs or symptoms of DM1, we also ask whether the molecular signature of RNA toxicity is present in muscle cells derived from FECD patients.. Methods: Corneal endothelial tissue was obtained at the time of endothelial keratoplasty, and skin fibroblasts were derived from skin biopsy specimens from patients with FECD. Using fluorescence in situ hybridization ...
Biglan KM, Shoulson I, Kieburtz K, Oakes D, Kayson E, Shinaman MA, Zhao H, Romer M, Young A, Hersch S, Penney J, Marder K, Paulsen J, Quaid K, Siemers E, Tanner C, Mallonee W, Suter G, Dubinsky R, Gray C, Nance M, Bundlie S, Radtke D, Kostyk S, Baic C, Caress J, Walker F, Hunt V, ONeill C, Chouinard S, Factor S, Greenamyre T, Wood-Siverio C, Corey-Bloom J, Song D, Peavy G, Moskowitz C, Wesson M, Samii A, Bird T, Lipe H, Blindauer K, Marshall F, Zimmerman C, Goldstein J, Rosas D, Novak P, Caviness J, Adler C, Duffy A, Wheelock V, Tempkin T, Richman D, Seeberger L, Albin R, Chou KL, Racette B, Perlmutter JS, Perlman S, Bordelon Y, Martin W, Wieler M, Leavitt B, Raymond L, Decolongon J, Clarke L, Jankovic J, Hunter C, Hauser RA, Sanchez-Ramos J, Furtado S, Suchowersky O, Klimek ML, Guttman M, Sethna R, Feigin A, Cox M, Shannon B, Percy A, Dure L, Harrison M, Johnson W, Higgins D, Molho E, Nickerson C, Evans S, Hobson D, Singer C, Galvez-Jimenez N, Shannon K, Comella C, Ross C, Saint-Hilaire MH, ...
Myotonic dystrophy (DM) type 1 is associated with an expansion of (|50) CTG repeats within the 3 untranslated region (UTR) of the dystrophin myotonin protein kinase gene (dmpk). In the corresponding mRNA transcript, the CUG repeats form an extended stem-loop structure. The double-stranded RNA of the stem sequesters RNA binding proteins away from their normal cellular targets resulting in aberrant transcription, alternative splicing patterns, or both, thereby leading to DM. To better understand the structural basis of DM type 1, we determined to 1.58-A resolution the x-ray crystal structure of an 18-bp RNA containing six CUG repeats. The CUG repeats form antiparallel double-stranded helices that stack end-on-end in the crystal to form infinite, pseudocontinuous helices similar to the long CUG stem loops formed by the expanded CUG repeats in DM type 1. The CUG helix is very similar in structure to A-form RNA ...
Polyglutamine (polyQ) diseases are caused by coding expanded (CAG)n repeats in the respective genes.1 Repeat instability, both germ line and somatic, is known to occur in most polyQ diseases and can influence the phenotype. Longer repeats are usually associated with earlier ages at onset (AAO) and/or more severe disease courses. Repeat instability with expansion bias can have severe clinical consequences to patients with these devastating conditions for which there are no disease-modifying treatments available. Several factors, including the size of the repeats (longer repeats are more unstable), and the presence of sequence interruptions (pure repeats are more unstable) are known to have an influence.2. Spinocerebellar ataxia type 6 (SCA6), a late-onset autosomal dominant relatively slowly progressive and pure cerebellar ataxia,3 is one of the six polyQ ...
Fragile X-associated disorders encompass several conditions, which are caused by expansion mutations in the fragile X mental retardation 1 (FMR1) gene. Fragile X syndrome is the most common inherited etiology of intellectual disability and results from a full mutation or ,200 CGG repeats in FMR1. It is associated with developmental delay, autism spectrum disorder, and seizures. Fragile X-associated tremor/ataxia syndrome is a progressive neurodegenerative disease that occurs in premutation carriers of 55-200 CGG repeats in FMR1 and is characterized by kinetic tremor, gait ataxia, parkinsonism, executive dysfunction, and neuropathy ...
Nearly 30 genetic diseases are caused by the repetition of a short sequence of 2-9 base pairs, known as microsatellites. These microsatellite repeats occur in humans normally; however disease symptoms become apparent once a certain repeat threshold is reached. Usually, these diseases follow a phenomenon known as genetic anticipation, in which each subsequent generation experiences increased diseas... read moree severity and earlier onset, which was found to correlate with microsatellite repeat length. To study these expansions, budding yeast (S. cerevisiae) strains were used in genetic experiments to determine a proteins effect on CAG repeat expansion. Preliminary data suggest that Rmi1 is required for expansions to occur, Los1 protects against expansions, and Gpb1 does not have a role in expansion Submitted in partial fulfillment of the grant requirement of ...
Looking for online definition of oculopharyngeal muscular dystrophy in the Medical Dictionary? oculopharyngeal muscular dystrophy explanation free. What is oculopharyngeal muscular dystrophy? Meaning of oculopharyngeal muscular dystrophy medical term. What does oculopharyngeal muscular dystrophy mean?
Spinocerebellar ataxia type 2 (SCA2) is a condition characterized by progressive problems with movement. SCA2 results from a mutation in the ATXN2 gene known as a trinucleotide repeat expansion. This mutation increases the length of the repeated CAG segment in the ATXN2 gene. People with 32 or more repeats CAG repeats in the ATXN2 gene develop SCA2.. It is unclear how the abnormally long CAG segment affects the function of the ataxin-2 protein. The abnormal protein apparently leads to cell death, as people with SCA2 show a loss of brain cells. Certain brain cells called Purkinje cells seem to be particularly sensitive to the presence of abnormal ataxin-2. Purkinje cells are located in the part of the brain that coordinates movement (cerebellum) and are involved in chemical signaling between nerve cells (neurons). It is unknown how the abnormal ataxin-2 protein leads to the death of Purkinje and other brain ...
The National Institutes of Health (NIH) has awarded a five-year grant of more than $9 million to Emory researchers to study fragile X syndrome-associated disorders and work toward developing effective treatments.. The grant is one of three nationally to support the Centers for Collaborative Research in Fragile X, and a renewal of Emorys National Fragile X Syndrome Research Center that has been continuously funded by NIH since the inception of such centers ten years ago.. Fragile X syndrome is the most common form of inherited intellectual and developmental disabilities and often results in emotional and behavioral problems; as many as 30 to 50 percent of people with fragile X syndrome also have features of autism spectrum disorders.. Fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency (FXPOI) result from a variety of mutations in the FMR1 gene.. FMR1 normally makes a protein that helps create and maintain connections ...
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a dynamic GAA repeat expansion mutation within intron 1 of the FXN gene. Studies of mouse models for other trinucleotide repeat (TNR) disorders have revealed an important role of mismatch repair (MMR) proteins in TNR instability.. Read More: The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model. ...
Triplet-repeat expansions cause several inherited human diseases. Expanded triplet-repeats are unstable in somatic cells, and tissue-specific somatic instability contributes to disease pathogenesis. In mammalian cells instability of triplet-repeats is dependent on the location of the origin of replication relative to the repeat tract, supporting the fork-shift model of repeat instability.. Role of transcript and interplay between transcription and replication in triplet-repeat instability in mammalian cells. ...
Nowak NT, Diamond MP, Land SJ, Moffat SD. Contributions of sex, testosterone, and androgen receptor CAG repeat number to virtual Morris water maze performance. Psychoneuroendocrinology. 2014 Mar;41:13-22. doi: 10.1016/j.psyneuen.2013.12.003. Epub 2013 Dec 13. PubMed PMID: 24495604.. Senut MC, Sen A, Cingolani P, Shaik A, Land SJ, Ruden DM. Lead Exposure Disrupts Global DNA Methylation in Human Embryonic Stem Cells and Alters Their Neuronal Differentiation. Toxicol Sci. 2014 Feb 20. [Epub ahead of print] PubMed PMID: 24519525.. Cingolani P, Platts A, Wang le L, Coon M, Nguyen T, Wang L, Land SJ, Lu X, Ruden DM. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin). 2012 Apr-Jun;6(2):80-92. doi: 10.4161/fly.19695. PubMed PMID: 22728672; PubMed Central PMCID: PMC3679285.. Cingolani P, Patel VM, Coon M, Nguyen T, Land SJ, Ruden DM, Lu X. Using Drosophila melanogaster ...
TY - JOUR. T1 - Mosaic FMR1 deletion causes fragile X syndrome and can lead to molecular misdiagnosis. T2 - A case report and review of the literature. AU - Coffee, Bradford. AU - Ikeda, Morna. AU - Budimirovic, Dejan B. AU - Hjelm, Lawrence N.. AU - Kaufmann, Walter E.. AU - Warren, Stephen T.. PY - 2008/5/15. Y1 - 2008/5/15. N2 - The most common cause of fragile X syndrome is expansion of a CGG trinucleotide repeat in the 5′UTR of FMR1. This expansion leads to transcriptional silencing of the gene. However, other mutational mechanisms, such as deletions of FMR1, also cause fragile X syndrome. The result is the same for both the expansion mediated silencing and deletion, absence of the gene product, FMRP. We report here on an 11-year-old boy with a cognitive and behavioral profile with features compatible with, but not specific to, fragile X syndrome. A mosaic deletion of 1,013,395 bp was found using high-density X ...
To date, 43 types of Spinocerebellar Ataxias (SCAs) have been identified. A subset of the SCAs are caused by the pathogenic expansion of a CAG repeat tract within the corresponding gene. Ethnic and geographic differences are evident in the prevalence of the autosomal dominant SCAs. Few descriptions of the clinical phenotype and molecular genetics of the SCAs are available from the African continent. Established studies mostly concern the South African populations, where there is a high frequency of SCA1, SCA2 and SCA7. The SCA7 mutation in South Africa (SA) has been found almost exclusively in families of indigenous Black African ethnic origin. To present the results of the first clinical description of seven Zambian families presenting with autosomal dominant SCA, as well as the downstream molecular genetic analysis of a subset of these families. The study was undertaken at the University Teaching Hospital in Lusaka, Zambia. Ataxia was quantified with the Brief Ataxia ...
Spontaneous 46,XX primary ovarian insufficiency (POI) is a cause of decreased fertility in approximately 1% of women before age 40. The most common known genetic cause of 46,XX POI is a pre -mutation in the Fragile X Mental Retardation (FMR1) gene. The FMR1 gene is located on the X-chromosome and contains a CGG repeat in the un-translated region; this CGG repeat is normally present in less than 55 copies, but has a tendency to expand across generations. Greater than 200 CGG copies results in Fragile X Syndrome (FXS), the most common form of heritable mental retardation. A pre-mutation in the FMR1 gene, defined as between 55 and 199 CGG repeats, is associated with POI in women and carries a risk of expanding to the full mutation in a woman s offspring, resulting in a child with FXS. POI that is associated with the FMR1 pre-mutation is known as Fragile X-associated POI ( FXPOI ). Approximately 20% of women with an FMR1 pre-mutation develop FXPOI. Importantly, ...
Allen EG, He W, Yadav-Shah M and Sherman SL (2004). A study of the distributional characteristics of FMR1 transcript levels in 238 individuals. Hum. Genet. 114: 439-447. http://dx.doi.org/10.1007/s00439-004-1086-x PMid:14758538 Bakker CE, Kooy RF, DHooge R and Tamanini F (2000). Introduction of a FMR1 transgene in the fragile X knockout mouse. Neurosc. Res. Communic. 26: 265-277. http://dx.doi.org/10.1002/1520-6769(200005/06)26:3,265::AID-NRC13,3.0.CO;2-T Brouwer JR, Mientjes EJ, Bakker CE, Nieuwenhuizen IM, et al. (2007). Elevated Fmr1 mRNA levels and reduced protein expression in a mouse model with an unmethylated fragile X full mutation. Exp. Cell Res. 313: 244-253. http://dx.doi.org/10.1016/j.yexcr.2006.10.002 PMid:17150213 PMCid:1852528 Brouwer JR, Huizer K, Severijnen LA, Hukema RK, et al. (2008). CGG-repeat length and neuropathological and molecular correlates in a mouse model for fragile X-associated tremor/ataxia syndrome. J. Neurochem. 107: 1671-1682. ...
Background: The androgen receptor (AR) is an essential gene in prostate cancer pathogenesis and progression. Genetic variation in AR exists, including a polymorphic CAG repeat sequence that is inversely associated with transcriptional activity. Experimental data suggest that heightened AR activity facilitates formation of TMPRSS2:ERG, a gene fusion present in approximately 50 percent of tumors of prostate cancer patients. Methods: We undertook a nested case-control study to investigate the hypothesis that shorter CAG repeat length would be associated with prostate cancer risk defined by TMPRSS2:ERG status. The study included 291 men with prostate cancer (147 ERG-positive) and 1,221 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Results: Median CAG repeat length (Interquartile range) among controls was 22 (20-24). Men with shorter CAG repeats had an increased risk of ...
Trinucleotide repeats sequences (TRS) represent a common type of genomic DNA theme whose enlargement is connected with a lot of individual diseases. demonstrate the fact that patterns of opportunities of varied TRSs depend on NSC 74859 the duration specifically. The collective propensity for DNA strand parting of repeated sequences acts as a precursor for outsized intermediate bubble expresses independently from the G/C-content. We record that repeats possess the to hinder the binding of transcription elements with their consensus series by changed DNA inhaling and exhaling dynamics in closeness from the binding sites. These observations might impact ongoing tries to make use of LMD and MCMC simulations for TRS-related modeling of genomic DNA efficiency in elucidating the common denominators of the dynamic TRS expansion mutation with potential therapeutic ...
To develop and evaluate a new method for determination of the CAG repeat length in Exon 1 of the androgen receptor gene. DESIGN AND METHODS: The method is based on PCR amplification of a DNA region encompassing the repeats and analysis of the length of the PCR product on a sequencing gel. One of the PCR primers was labeled with Cy5.5 fluorescent dye to facilitate detection after laser excitation. We used a fully automated system for electrophoretic separation of the PCR product and accurate sizing of the length of the PCR product using fragment analysis. RESULTS: The major advantages of the new technique are its simplicity, speed, accuracy, and reproducibility. Analysis of the CAG repeats in genomic DNAs from 18 males indicated that they were all hemizygous with a mean CAG repeat number of 22 (range 20-30 repeats). Among 60 DNAs from females, 16 were homozygous and 44 were heterozygous. The ...
Researchers at UC Davis have identified a new feature of the genetic mutation responsible for the progressive neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS) — the formation of “R-loops,” which they believe may be associated with the disorder’s neurological symptoms, such as tremors, lack of balance, features of parkinsonism, and cognitive decline.
Huntingtons disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and ...
Mutagenesis is incredibly frequent at trinucleotide repeats in families with certain hereditary neurological diseases. These site-specific expansions, or gains of triplet repeats, occur in cells that appear otherwise normal.. ...
(2005) Del Carratore et al. Biochimica et Biophysica Acta - Molecular Cell Research. Human myotonic dystrophy protein kinase (DMPK), the product of the myotonic dystrophy (DM) locus, is a member of a novel class of multidomain serine-threonine protein kinases, which interacts with members of the ...
Short repeat lengths of the CAG polymorphism in exon 1 of the AR gene have been hypothesized to predispose to prostate cancer (18) . It is speculated that relatively small enhancements of AR activity mediated through increased transactivation and/or mRNA levels promote prostate carcinogenesis over time. However, we failed to detect an association between short AR CAG alleles and prostate cancer incidence when we compared our familial prostate cancer patients to a Caucasian control population. Furthermore, we observed no effect of short CAG alleles and the age of prostate cancer diagnosis nor on the development of high-grade cancer.. There are a number of possible factors that may have contributed to the lack of an observed association between short AR CAG alleles and prostate cancer in our study. The effect of short AR CAG alleles on prostate cancer risk, as determined in two case-control studies, is relatively small, if present at all (relative risk, ≤1.5; Refs. 5 and 6 ). Lack of a uniform ...
1) Sydenham chorea and 2) Topic of the month: Historical interviews. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Jeff Waugh interviews Dr. Fabienne Brilot-Turville about her paper on antibody binding to neuronal surface in Sydenham chorea. In the next segment, Dr. Stacey Clardy is reading our e-Pearl of the week about fragile X-associated tremor ataxia syndrome. In the next part of the podcast Dr. Farrah Mateen completes our historical interviews for the month by interviewing Dr. Read More 1) Sydenham chorea and 2) Topic of the month: Historical interviews. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Jeff Waugh interviews Dr. Fabienne Brilot-Turville about her paper on antibody binding to ...
Our results demonstrate that CUG repeat RNA expression can elicit toxicity in zebrafish embryos. This toxicity manifests with limited CUG RNA foci formation, morphologic abnormalities, early behavioral abnormalities and significant transcriptional changes. Coexpression of MBNL2 with GFP(CUG)91 mRNA suppresses the observed morphologic, behavioral and transcriptional alterations, suggesting a role for MBNL in these phenotypes. Lastly, embryos that survive the initial developmental period during which the expanded CUG repeat RNA is present have seemingly normal late development and motor function, as measured by swim speed at 1 and 31 weeks of age. Our results establish zebrafish as a model system for studying DM1 pathogenesis and provide insights into this disorder and into RNA-mediated toxicity.. One goal of this work was to establish a system for studying early developmental effects of CUG repeat RNA-mediated toxicity. Congenital myotonic dystrophy is ...
Holmes SE, OHearn E, Callahan C, Hwang HS, Rosenblatt A, Ingersoll-Ashworth RG, Fleisher A, Stevanin G, Brice A, Potter NT, Ross CA, Margolis RL. A CTG trinucleotide repeat expansion in Junctophilin 3 is associated with Huntingtons Disease-Like 2 (HDL2). Nature Genetics, 29 (2001): 377-378, 2001.. Chung DW, Rudnicki DD, Yu L, Margolis RL. A natural antisense transcript at the Huntingtons disease repeat locus regulates HTT expression. Human Molecular Genetics, 20 (2011):3467-77.. Chiang C-H, Su Y, Wen Z, Yoritomo N, Ross CA, Margolis RL (co-corresponding author), Song H, Ming G-l. Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Molecular Psychiatry 16 (2011):358-60.. Seixas AI, Holmes SE, Takeshima H, Pavlovich A, Sachs N, Pruitt JL, Silveira I, Ross CA, Margolis RL, Rudnicki DD. Loss of junctophilin-3 contributes to Huntingtons Disease-like 2 pathogenesis, Annals of Neurology, ...
Hsing AW, Gao YT, Wu G., Wang X., Deng J., Chen YL, Sesterhenn IA, Mostofi FK, Benichou J., Chang C.. Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. Cancer Res. 2000;60: 5111-5116 ...
Trinucleotide repeat-containing gene 6A protein is a protein that in humans is encoded by the TNRC6A gene. This gene encodes a member of the trinucleotide repeat containing 6 protein family. The protein functions in post-transcriptional gene silencing through the RNA interference (RNAi) and microRNA pathways. The protein associates with messenger RNAs and Argonaute proteins in cytoplasmic bodies known as GW-bodies or P-bodies. Inhibiting expression of this gene delocalizes other GW-body proteins and impairs RNAi and microRNA-induced gene silencing. GRCh38: Ensembl release 89: ENSG00000090905 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000052707 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (Jul 1997). "cDNAs with long CAG trinucleotide repeats from human ...
... , one of the two types of myotonic dystrophy, is an inherited type of muscular dystrophy that affects the muscles and other body systems (e.g., heart, eyes, pancreas). Myotonic dystrophy type 1 has been categorized into three somewhat overlapping subtypes: mild, classic, and congenital (present at birth). Symptoms of the mild form are the least severe with a normal life span. The classic form is characterized by muscle weakness and wasting, prolonged muscle tensing (myotonia), cataract, and often abnormal heart function; adults may become physically disabled and may have a shortened life span. The congenital form is characterized by severe generalized weakeness at birth (hypotonia), often causing complications with breathing and early death. The condition is inherited in an autosomal dominant pattern and is caused by mutations in the DMPK gene ...
OBJECTIVES: To serially assess changes in lumbar CSF biogenic amines, radiographic characteristics, and neurological signs in 34 patients with dominantly inherited ataxia. METHODS: Mutational analysis was used to identify genetic subgroups. Annual assessment of lumbar CSF monoamine metabolites using a gas chromatographic/mass spectrometric method and morphometric measurements of the cerebellum, pons, and the cervical spinal cord on MRI were analysed for each patient and compared with normal controls. RESULTS: Patients with CAG trinucleotide repeat expansions on chromosome 6p (mutSCA1) and chromosome 14q (mutSCA3) had only about one half the normal concentrations of lumbar CSF homovanillic acid (HVA) whereas, 5-hydroxyindoleacetic acid (5-HIAA) concentrations were similar to those in age matched normal subjects. The HVA and 5-HIAA concentrations in clinically similar patients without mutSCA1 or mutSCA3 were normal. One year after the first study, HVA ...
TY - JOUR. T1 - CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles. AU - Pretto, Dalyir I.. AU - Mendoza-Morales, Guadalupe. AU - Lo, Joyce. AU - Cao, Ru. AU - Hadd, Andrew. AU - Latham, Gary J.. AU - Durbin-Johnson, Blythe. AU - Hagerman, Randi J. AU - Tassone, Flora. PY - 2014. Y1 - 2014. N2 - Background: Greater than 200 CGG repeats in the 5UTR of the FMR1 gene lead to epigenetic silencing and lack of the FMR1 protein, causing fragile X Syndrome. Individual carriers of a premutation (PM) allele with 55-200 CGG repeats are typically unmethylated and can present with clinical features defined as FMR1-associated conditions. Methods: Blood samples from 17 male PM carriers were assessed clinically and molecularly by Southern blot, western blot, PCR and QRT-PCR. Blood and brain tissue from an additional 18 PM males were also similarly examined. Continuous outcomes were modelled using linear regression and binary outcomes were modelled using logistic ...
Fragile X syndrome (FXS OMIM # 300624) is the most common inherited mental retardation syndrome, affecting approximately 1:4000 males and approximately 1:8000 females. The disease is caused by the expansion of a trinucleotide CGG repeat in the 5-untranslated (UTR) region of the FMR1 gene. Methylation of the expanded CGG tract leads to silencing of expression of the FMR1 gene. The American College of Medical Genetics defines a normal repeat length as between 5 and 44. Intermediate alleles of between 45-54 repeats almost never expand to full mutations in a single meiosis. Premutation alleles are defined as 55-200 CGG. Premutation alleles of less than 90 repeats have a variable risk for expansion to full mutations whereas larger premutation alleles almost always expand when inherited through a female. Full mutation alleles are defined as >200 repeats. FXS in an X-linked ...
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The gene responsible for Fragile X syndrome, fragile X mental retardation‐1 (FMR1), contains an unstable sequence of CGG trinucleotide repeats in its promoter region
In most regions and when doing a comparison of the whole genomes, Arabidopsis shows a great affinity for mononucleotide repeats compared to rice (Figures 1 to 5). The comparison between the whole genomes of rice and Arabidopsis clearly shows that Arabidopsis has a higher percentage of mononucleotide repeats (33.9%) than rice (18.3%). The only regions where mononucleotide repeats are not as high are the 5UTR and coding regions. Rice seems to have a greater affinity for trinucleotide repeats, with an exceptionally high density of approximately 1,670/MB in the 5UTR, even higher than in exon regions (approximately 421.4/MB). In fact, trinucleotide SSRs are the major type of SSR in all regions except 3UTRs (Figures 1 to 5).. Yet despite these differences in which type of SSR is most common for each organism, rice and Arabidopsis show similar distribution of the SSR types (period) in their coding regions. Both ...
Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by inheriting a CAG repeat expansion in the coding region of the...
TY - JOUR. T1 - A design thinking approach to primary ovarian insufficiency. AU - Martin,Lisa Arndt. AU - Porter,Alison Gatewood. AU - Pelligrini,Vincent A.. AU - Schnatz,Peter F.. AU - Jiang,Xuezhi. AU - Kleinstreuer,Nicole. AU - Hall,Janet E.. AU - Verbiest,Sarah. AU - Olmstead,Jill. AU - Fair,Ryan. AU - Falorni,Alberto. AU - Persani,Luca. AU - Rajkovic,Aleksandar. AU - Mehta,Khanjan. AU - Nelson,Lawrence M.. AU - Rachels Well Primary Ovarian Insufficiency Community of Practice Group. PY - 2017/3/1. Y1 - 2017/3/1. N2 - Most clinicians are not prepared to provide integrated personal care to address all the clinical needs of women with primary ovarian insufficiency. Design thinking is an engineering methodology used to develop and evaluate novel concepts for systems operation. Here we articulate the need for a seamlessly integrated mobile health system to support genomic research as well as patient care. We also review the pathophysiology and management of primary ovarian insufficiency. ...
FMR1 Full-Length MS Protein Standard (NP_002015), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5 UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene.
top contents. Introduction. Fragile X Syndrome is an example of a triplet repeat expansion disorder. Other expansion disorders include Huntingdon s disease and Spinal Muscular Atrophy. The most important clinical feature of Fragile X is that it causes moderate to severe mental retardation. It has a prevalence of 1 in 4000 and therefore is the second most common genetic cause of mental retardation after Down s syndrome. Fragile X Syndrome is an X linked disorder therefore it mainly affects males, however females are affected although much less frequently and less severely. top contents. Prevalence. Until recently fragile X syndrome was believed to have a prevalence of 1/1000. This is now thought to be an over-estimation, thanks to new accurate DNA analysis technologies we now believe that a prevalence of 1/4000 is much more likely. Until screening programmes are established allowing us to better diagnose patients we are unable to calculate an accurate ...
George Huntingtons description of Huntingtons disease (HD) in 1872 (at the age of 22 years) remains the basic pillar of diagnosis: A hereditary chorea, tendency to insanity and suicide and its manifesting itself as a grave disease in adulthood.1 HD is a progressive autosomal dominant disorder, characterised by involuntary choreiform movements, psychiatric manifestations with cognitive decline and, rarely, a bradykinetic rigidity. A G8 HD probe developed in Boston for preclinical and prenatal screening of HD using molecular genetics was first acquired in South Africa in the late 1980s.2 The disease has been shown to be due to an increased number of trinucleotide repeats in the IT 15 gene on chromosome 4p 16.3. Measurement of the CAG trinucleotide expansion has been found to be a highly sensitive and specific marker for the diagnosis of HD (sensitivity 98.8%; 95% confidence interval (CI) 97.7 - 99.4%; specificity 100%, 95% CI 95.2 - 100%).3 In ...
Can genital herpes be caught from a cold sore? 4. I took a Q tip push on it, a little blood came out, pushed on it again greenish yellowish watery pus, came out, pushed on it again a little more blood, came out, and nothing more. Hypothyroidism: A deficiency of thyroid hormone due to an underactive thyroid gland. w zmianach o małym nasileniu wystarcza leczenie miejscowe osuszające i odkażające (np. This young woman had the cyst squeezed before, and it slowly began to grow back. Research continues on the common elements of various neurodevelopmental disorders, including the hereditary ataxias, caused by gene mutations called trinucleotide repeat expansions, in which symptoms appear earlier and more severely from generation to generation.. Please take a moment and let us know what you think of these plucking moments. They tend to show both sides of the vagina or lips, especially at the bottom. If the lump was herpes it would become a blister with a whitish ...
Looking for online definition of spinocerebellar ataxia, autosomal recessive type 11 in the Medical Dictionary? spinocerebellar ataxia, autosomal recessive type 11 explanation free. What is spinocerebellar ataxia, autosomal recessive type 11? Meaning of spinocerebellar ataxia, autosomal recessive type 11 medical term. What does spinocerebellar ataxia, autosomal recessive type 11 mean?
The Blog. Youve reached this site as you may be the one of nearly one million people affected by Myotonic Dystrophy Worldwide. This site aggregates and publishes all information on Myotonic Dystrophy Myotonic Dystrophy is a disease that is genetically based and inherited from one generation to the next. One out of two children of a person with myotonic dystrophy will most likely have the disease. Unlike most diseases, the symptoms that a person with this disease varies from person to person. Some people are just mildly affected others are severely affected. This makes it hard to tell you exactly how the disease will affect a particular person.. Four treatments that have potential have now surfaced about Myotonic Dystrophy. These are three approved Drugs by FDA and "off label use" may assist some people with DM1. (As always check with your Doctor) . The other is a drug that is not FDA approved in the USA for human use. Three off label uses have showed promise in mice studies but as yet there is ...
Huntingtons disease (HD) is an autosomal dominant neurodegenerative disorder, caused by a CAG-repeat expansion in the HTT-gene. Today there are no disease-modifying therapies (DMTs), but several promising clinical trials are underway, including therapies that reduce mutant huntingtin expression.. Reliable biomarkers could empower such trials and guide the timing for initiation of future DMTs.. Neurofilament light (NFL) and tau, which are cerebrospinal fluid markers of neuronal death, have been implicated as markers of disease progression. Increased levels of the inflammatory marker YKL-40 have also been reported in HD.. The aim was to validate and compare the above biomarker candidates by targeted analyses, while explorative liquid chromatography-mass spectrometry (LC-MS) was used to identify new candidates. Clinically well-characterized HD patients, premanifest gene expansion carriers (pGECs), and controls were enrolled from Uppsala University Hospital in ...
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The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of dominantly inherited progressive ataxia disorders. More than 30 different gene loci have been identified so far. The most common SCAs, which together account for more than half of all affected families, are SCA1, SCA2, SCA3, and SCA6. Each of these disorders is caused by a translated CAG repeat expansion mutation. SCA1, SCA2, and SCA3 usually have an onset between 30 and 40, and SCA6 usually begins at the age of 50 to 60. In addition to progressive ataxia, SCA1, SCA2, and SCA3 frequently present with additional non-ataxic symptoms, including parkinsonism. Carbidopa/levodopa was found to have a good therapeutic effect on parkinsonism.. The SCA6 used to be considered a pure cerebellar disorder. However, a recent large study on natural history of SCAs found that patients with SCA6 often had nonataxia symptoms, an observation that challenges the view that SCA6 is a purely cerebellar disorder. ...
Spinocerebellar ataxia type 6 (SCA6) is a rare, late-onset, autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, oculomotor disorders, peripheral neuropathy, and ataxia of the gait, stance, and limbs due to cerebellar dysfunction. Unlike other types, SCA 6 is not fatal. This cerebellar function is permanent and progressive, differentiating it from episodic ataxia type 2 (EA2) where said dysfunction is episodic. In some SCA6 families, some members show these classic signs of SCA6 while others show signs more similar to EA2, suggesting that there is some phenotypic overlap between the two disorders. SCA6 is caused by mutations in CACNA1A, a gene encoding a calcium channel α subunit. These mutations tend to be trinucleotide repeats of CAG, leading to the production of mutant proteins containing stretches of 20 or more consecutive glutamine residues; these proteins have an increased tendency to form intracellular agglomerations. Unlike ...
Fragile X syndrome is caused by dynamic mutation of FMR1 gene CpG island CGG repeats. The underlying mutational mechanism is not fully understood. Different microsatellite markers and SNP have previously been reported as markers associated with FMR1 CGG repeat instability. The aim of the present study was to identify specific haplotypes among Latvian FXS patients and the control group with respect to allelic stability. Eleven male FXS patients and 122 control male patients participated in the study. In total, 27 different DXS548-FRAXAC1-ATL1-FRAXAC2 haplotypes were found. The prevalent haplotype in the control group was 7-4-A-5+ (rel. frequency 0.327). The prevalent haplotype associated with the FXS group was 2-2-G-4 (rel. frequency 0.818; p , 0.0001). Grey zone alleles with a long uninterrupted CGG tract at the 3 end were significantly associated with the 2-2-G-4 haplotype (p = 0.0022). Our findings suggest that, for the Latvian population, the haplotype 2-2-G-4 is a marker ...
Spinocerebellar ataxia type 5 (SCA5) is an autosomal dominant neurodegenerative disease that primarily affects the cerebellum. Affected patients have progressive cerebellar cortical atrophy and profound Purkinje cell loss. Similar clinical presentations reported in three different SCA5 families include upper and lower limb incoordination, slurred speech, and eye movement abnormalities. Age of onset typically occurs during the third or fourth decade of life, and symptoms worsen over time (Liquori et al., 2002). SCA5 is caused by mutations in the SPTBN2 gene, which encodes β-III-spectrin, a cytoskeletal protein highly expressed in Purkinje cells (Ikeda et al., 2006). An American and a French SCA5 family have distinct, nonoverlapping in-frame deletions in the third of the 17 spectrin repeats, and both of these deletions are predicted to disrupt the triple α-helical structure of the spectrin repeat and the conformation of the spectrin tetramer. A third reported SCA5 family, from ...
Medicine for primary ovarian insufficiency - What are the tests for primary ovarian insufficiency? Many tests, see REI. Reproductive endocrinology md will confirm poi - pregnancy test, fsh, lh, estradiol, amh, thyroid and prolactin tests, pelvic ultrasound. Test for genetic causes: karyotype looking for turners syndrome, fragile x premutation testing, fish test for sry (y-chromosome material). Test adrenal antibodies which cause addisons disease. Screen for diabetes, thyroid antibodies, and parathyroid disease.
Nucleotide repeat expansions underlie a heterogeneous groups of neurological and neuromuscular disorders with various disease mechanisms depending on the gene function, structure and location of the expansion. Hexanucleotide repeat expansion in the C9orf72 gene is the most frequent inherited cause of both ALS and FTD. A leading hypothesis for disease mechanism is gain of toxicity from the expanded repeats, which are transcribed in both sense and antisense directions and give rise to distinct sets of intranuclear RNA foci. This could sequester certain RNA-binding proteins and lead to their loss of function. An alternative but not mutually exclusive mechanism is the aberrant accumulation of dipeptide repeat proteins produced by repeat-associated non-ATG (RAN) translation in all six reading frames (poly-GA, poly-GR, poly-PA, poly-PR and poly-PG) of both strands. A third ...
NUB1 suppression of Huntington toxicity: mechanistic insights Yao Yao, Boxun Lu Department of Biophysics, School of Life Sciences, Fudan University, Shanghai, Peopleâ s Republic of China Abstract: Huntingtonâ s disease (HD) is an autosomal dominant neurodegenerative disorder marked by chorea, dystonia, incoordination, and cognitive and motor disturbance. The major cause of HD is the cytotoxicity of the mutant huntingtin protein (mHTT), encoded by the mutant HTT gene. The mechanism by which mHTT leads to cytotoxicity and neuronal death is unclear, and thus enhancing clearance of the mHTT protein is likely to be an effective approach to treat HD. We have recently identified NUB1 (negative regulator of ubiquitin-like proteins 1) as a modifier of mHTT levels via enhancement of its proteasomal degradation. In this review, we will discuss the mechanism of NUB1-mediated mHTT clearance and potential targeting strategies. Keywords: drug target discovery, Huntingtonâ s disease, NEDD8, ubiquitination
Myotonin-protein kinase (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase (DMK) is an enzyme that in humans is encoded by the DMPK gene. The dmpk gene product is a Ser/Thr protein kinase homologous to the MRCK p21-activated kinases and the Rho family of kinases. Data obtained by using antibodies that detect specific isoforms of DMPK indicate that the most abundant isoform of DMPK is an 80-kDa protein expressed almost exclusively in smooth, skeletal, and cardiac muscles. This kinase exists both as a membrane-associated and as a soluble form in human left ventricular samples. The different C termini of DMPK that arise from alternative splicing determine its localization to the endoplasmic reticulum, mitochondria, or cytosol in transfected COS-1 cells. Among the substrates for DMPK proposed by in vitro studies are phospholemman, the dihydropyridine receptor, and the myosin phosphatase targeting subunit. However, an in vivo demonstration of the ...
The length of the CGG repeat in the 5′ untranslated region of FMR1 is polymorphic in the healthy population and ranges from 6 to 54 repeats. Some individuals carry alleles with an intermediate number (55 - 200) of repeats. These are referred to as pre-mutation alleles, as they do not result in a fragile X syndrome phenotype. However, premutation alleles are prone to expand to a larger number of repeats during meiosis, especially in females. When the number of repeats exceeds 200, the expansion is referred to as a full mutation allele and results in the full syndrome.. At the molecular level, the large number of CGG repeats results in epigenetic changes in the promoter and 5′ untranslated region of FMR1, which in turn cause the gene not to be transcribed. Although most known cases are caused by the expansion of the CGG repeat to a full mutation, a small ...
BACKGROUND: Patients with myotonic dystrophy type 1 (DM1) have a three-fold higher risk of sudden cardiac death (SCD) than age-matched healthy controls. Despite numerous attempts to define the cardiac phenotype and natural history, existing literature suffers from low power, selection-bias and lack of controls. Thus, the optimal strategy for assessing cardiac involvement in DM1 is unclear. METHOD: In this large single-centre study, we evaluated 129 unselected DM1 patients (49.6% men), mean (SD) age 44 (14.7) years with family history, physical examination, electrocardiogram (ECG), echocardiography, Holter-monitoring and muscle strength testing. RESULTS: Cardiac involvement was found in 71 patients (55%) and included: 1) Conduction abnormalities: atrio-ventricular block grade I (AVB grade I) (23.6%), AVB grade II (5.6%), right/left bundle branch block (5.5/3.2%) and prolonged QTc (7.2%); 2) arrhythmias: atrial fibrillation/flutter (4.1%), other supraventricular tachyarrhythmia (7.3%) and ...
Huntingtons disease (HD) is a fatal neurodegenerative disease caused by expansion of CAG repeats in the Huntingtin gene (HTT). Neither its pathogenic mechanisms nor the normal functions of HTT are well understood. To model HD in humans, we engineered a genetic allelic series of isogenic human embryonic stem cell (hESC) lines with graded increases in CAG repeat length. Neural differentiation of these lines unveiled a novel developmental HD phenotype: the appearance of giant multinucleated telencephalic neurons at an abundance directly proportional to CAG repeat length, generated by a chromosomal instability and failed cytokinesis over multiple rounds of DNA replication. We conclude that disrupted neurogenesis during development is an important, unrecognized aspect of HD pathogenesis. To address the function of normal HTT protein we generated HTT+/- and HTT-/- lines. Surprisingly, the same phenotype emerged in HTT-/- but not HTT+/- lines. We ...
The aim of this study was to explore perceived fatigue, experienced functional limitations due to fatigue and clinical correlates in patients with Myotonic Dystrophy type 1 (DM1). In total, 32 consecutive patients with DM1 (14 women and 18 men) and 30 sex, age and education matched healthy control subjects participated. Perceived fatigue was rated on the Fatigue Impact Scale (FIS). Patients also completed a set of assessments aimed to characterize CTG-repeat size, muscle impairment, depression and cognitive functions. Non-parametric analysis were performed as appropriate, including Mann-Whitney U-test and Spearman correlation test. DM1 patients had higher FIS total score than healthy controls, suggesting higher fatigue levels. More specifically, DM1 patients scored higher on the FIS physical and psychosocial subscales than controls but not on the FIS cognitive scale. Scores on fatigue correlated significantly with muscle impairment and depression. Perceived fatigue is significantly more ...
BACKGROUND AND PURPOSE: Patients with myotonic dystrophy type 1 (DM1) have an increased incidence of endocrine dysfunction. In this study, the temporal evolution of endocrine dysfunction in patients with DM1 was investigated. METHODS: Endocrine function was assessed in 68 patients with DM1, in whom endocrine function had been followed, on average, for 8 years. The endocrine function was assessed by measuring the concentration of hormones and metabolites in blood and by validating libido with questionnaires. RESULTS: At baseline, 30 of the 68 patients presented with at least one hormonal dysfunction. When re-evaluated after 8 years, 57 of 68 patients had endocrine dysfunction. Diabetic patients had increased from one to four. At follow-up, hyperparathyroidism occurred in 25% and abnormal thyroid-stimulating hormone in 21%, compared with 14% and 9% at baseline. Sixteen of 33 men had increased luteinizing hormone levels compared with seven at baseline. CONCLUSIONS: Our findings show that endocrine ...
Purpose: To investigate the effects of a hand-training programme on grip, pinch and wrist force, manual dexterity and activities of daily living, in adults with myotonic dystrophy type 1 (DM1). Method: In this randomised controlled trial with a crossover design, 35 adults with DM1 were, after stratification for grip force, assigned by lot to two groups. Group A started with 12 weeks of hand training, while group B had no intervention. After a wash-out period of 12 weeks, where none received training, the order was reversed. The Grippit® was used as primary outcome measure and the hand-held Microfet2™ myometer, the Purdue Pegboard, the Canadian Occupational Performance Measure (COPM) and the Assessment of Motor and Process Skills (AMPS) were secondary outcome measures. Assessments were performed before and after training and control periods, i.e. four times altogether. Results: Ten persons dropped out and 13 had acceptable adherence. Intention-to-treat analyses revealed significant ...
Huntingtin is a 350 kDa protein of 3144 amino acids that is altered in Huntingtons disease (HD). The expanded trinucleotide CAG repeat of the HD…
From NCBI Gene:. This gene is an antisense transcript to the KLHL1 gene (homolog to the Drosophila KELCH gene); it does not itself appear to be protein coding. A TAC/TGC trinucleotide repeat expansion that is incorporated into this gene transcript, but not the KLHL1 transcript, causes spinocerebellar ataxia type 8. Presumably the expansion interferes with normal antisense function of this transcript. [provided by RefSeq, Oct 2008]. ...
, Research Paper Protein Binding Studies for Expanded Poly-A Repeats and Mutant PABP2 resulting from Oculopharyngeal Muscular Dystrophy INTRODUCTION:
Friedreichs ataxia (FRDA) represents a rare neurodegenerative disease caused by expansion of GAA trinucleotide repeats in the first intron of the FXN gene. The number of GAA repeats in FRDA patients varies from approximately 60 to ,1000 and is tightly correlated with age of onset and severity of the disease symptoms. The heterogeneity of Friedreichs ataxia stresses the need for a large cohort of patient samples to conduct studies addressing the mechanism of disease pathogenesis or evaluate novel therapeutic candidates. Herein, we report the establishment and characterization of an FRDA fibroblast repository, which currently includes 50 primary cell lines derived from FRDA patients and seven lines from mutation carriers Read the entire article HERE. ...
How is Friedreichs ataxia inherited?. Friedreichs ataxia is an autosomal recessive disease, which means the patient must inherit two affected genes, one from each parent, for the disease to develop. A person who has only one abnormal copy of a gene for a recessive genetic disease such as Friedreichs ataxia is called a carrier. A carrier will not develop the disease but could pass the affected gene on to his or her children. If both parents are carriers of the Friedreichs ataxia gene, their children will have a 1 in 4 chance of having the disease and a 1 in 2 chance of inheriting one abnormal gene that they, in turn, could pass on to their children. About one in 90 Americans of European ancestry carries one affected gene.. Humans have two copies of each gene - one inherited from the mother and one from the father. Genes are located at a specific place on each of an individuals 46 chromosomes, which are tightly coiled chains of DNA containing millions of chemicals called bases. These bases - ...
The human P1 middle latency evoked potential is postulated to be generat- ed in the thalamus by a cholinergic component of the ascending reticular activating system. To test the midbrain function of dentatorubral-pallidoluysian atrophy (DRPLA), recording of middle latency response to click stimuli were carried out in a DRPLA family which was detected with the aid of molecular diagnosis. Comparisons between the DRPLA members and the normal members indicated normal Pa responses but P1 component is abnormal in DRPLA. This P1 abnormality suggests that the midbrain cholinergic cells in DRPLA may be dysfunctional ...
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TY - JOUR. T1 - A female compound heterozygote (pre- and full mutation) for the CGG FMR1 expansion. AU - Milà, Montserrat. AU - Castellví-Bel, Sergi. AU - Giné, Ramon. AU - Vazquez, Carlos. AU - Badenas, Cèlia. AU - Sánchez, Aurora. AU - Estivill, Xavier P.. PY - 1996. Y1 - 1996. N2 - Fragile X syndrome is the most common cause of inherited mental retardation. The incidence has been estimated to be 1 in 1250 males and 1 in 2000 females. Molecular studies have shown that 95% of fragile X syndrome cases are caused by the expansion of a CGG triplet in the FMR1 gene with hypermethylation of the adjacent CpG island. In spite of the high incidence of this syndrome, a female with both FMR1 genes in the expanded form has never been reported. We present here a female from the Canary Islands presenting mental retardation and attention problems. Molecular analysis has revealed that both of her FMR1 genes have the CGG expansion, one with a premutation and the other with ...
Myotonic dystrophy is an inherited type of muscular dystrophy that affects the muscles and other body systems. People who have myotonic dystrophy have muscle wasting and weakness in their lower legs, hands, neck and face that get worse over time. Signs and symptoms of myotonic dystrophy usually develop when a person is in his or her twenties or thirties. The severity of myotonic dystrophy varies widely among those who have it, even among family members.. The weakness and muscle wasting that occurs slowly progress to the point of disability. Usually, disability does not become severe until fifteen to twenty years after the symptoms appear. The progression of muscle weakness is slower and is less serious in people who are older when the muscle weakness is first noticed.. There are two types of myotonic dystrophy: Type 1 and Type 2. The two types are caused by alterations (mutations) in two different genes. The symptoms of Type 2 myotonic dystrophy are usually milder than those of Type 1. A severe ...
TY - JOUR. T1 - The DNA Replication Program Is Altered at the FMR1 Locus in Fragile X Embryonic Stem Cells. AU - Gerhardt, Jeannine. AU - Tomishima, Mark J.. AU - Zaninovic, Nikica. AU - Colak, Dilek. AU - Yan, Zi. AU - Zhan, Qiansheng. AU - Rosenwaks, Zev. AU - Jaffrey, Samie R.. AU - Schildkraut, Carl L.. PY - 2014/1/9. Y1 - 2014/1/9. N2 - Fragile X syndrome (FXS) is caused by a CGG repeat expansion in the FMR1 gene that appears to occur during oogenesis and during early embryogenesis. One model proposes that repeat instability depends on the replication fork direction through the repeats such that (CNG)n hairpin-like structures form, causing DNA polymerase to stall and slip. Examining DNA replication fork progression on single DNA molecules at the endogenous FMR1 locus revealed that replication forks stall at CGG repeats in human cells. Furthermore, replication profiles of FXS human embryonic stem cells (hESCs) compared ...
Spinocerebellar ataxia type 14 autosomal dominant (PRKCG) Test Cost INR 30000.00 Surat Pune Jaipur Lucknow Kanpur Nagpur Visakhapatnam Indore Thane Bhopal Patna Vadodara Ghaziabad Ludhiana Coimbatore Madurai Meerut Ranchi Allahabad Trivandrum Pondicherry Mysore Aligarh best offer discount price
Neurodegenerative diseases (see 6.08 Neurodegeneration) include: AD; Parkinsons disease; amyotrophic lateral sclerosis (ALS); demyelinating diseases, e.g., multiple sclerosis: neuropathies, e.g., diabetic, HIV, and chemotoxin-induced; Downs syndrome (DS); prion diseases, e.g., Creutzfeldt-Jakob disease; tauopathies, e.g., Picks disease, frontal temporal dementia with Parkinsonism (FTDP); trinucleotide repeat or polyglutamine (polyQ) diseases, e.g., Huntingtons disease (HD); spinocerebellar ataxias (SCA); dentatorubral-pallidolysian atrophy (DRPLA); Friedreichs ataxia; multiple systems atrophy (MSA); stroke and traumatic brain injury.. Current treatment strategies for all neurodegenerative disorders, where available, are palliative.. ...
Myotonic Dystrophy (DM) a multi-systemic disorder, is the most common adult muscular dystrophy form. Among the pathological manifestations observed in the skeletal musculature include non-muscle defects as insulin resistance. Aberrant regulation has postulated involvement in the disease progression of DM1 specific insulin resistance characteristic of the disorder. RNA binding proteins involved in alternative splicing affect inclusion of spliced exons by binding to sequence specific cis-acting elements in pre-mRNA. The MBNL as well as the CELF class of proteins regulate alternative splicing of pre-mRNA insulin receptor (IR) by working antagonistically as a result of their distinct pre-mRNA binding sites. Of the two isoforms of insulin receptor (IR), the expression of the B isoform is affected to yield the non-muscle, low signaling isoform A. Here attempts are made to demonstrate a relationship between the muscleblind proteins and alternatively spliced insulin receptor by which protein-RNA binding ...
Myotonic Dystrophy (DM) a multi-systemic disorder, is the most common adult muscular dystrophy form. Among the pathological manifestations observed in the skeletal musculature include non-muscle defects as insulin resistance. Aberrant regulation has postulated involvement in the disease progression of DM1 specific insulin resistance characteristic of the disorder. RNA binding proteins involved in alternative splicing affect inclusion of spliced exons by binding to sequence specific cis-acting elements in pre-mRNA. The MBNL as well as the CELF class of proteins regulate alternative splicing of pre-mRNA insulin receptor (IR) by working antagonistically as a result of their distinct pre-mRNA binding sites. Of the two isoforms of insulin receptor (IR), the expression of the B isoform is affected to yield the non-muscle, low signaling isoform A. Here attempts are made to demonstrate a relationship between the muscleblind proteins and alternatively spliced insulin receptor by which protein-RNA binding ...
Funding This work was supported by the Canadian Institutes of Health Research (CIHR) (CEP), the Muscular Dystrophy Canada (CEP), by the University of Rochester Paul Wellstone Muscular Dystrophy Cooperative Research Center with support from the NIH (grant U54NS48843) (CEP and CAT), The Muscular Dystrophy Association USA (MDAUSA) (CAT), a Doctoral Training Award from the CIHR Collaborative Graduate Training Program in Molecular Medicine (MMA), and an Ontario Graduate Scholarship (MMA), a postdoctoral fellowship from The Hospital for Sick Children Research Training Centre (ALC), and a postdoctoral fellowships from the MDAUSA and the Cell Science Research Foundation and the Uehara Memorial Foundation (MN). Mutant sequences were deposited to GenBank (accession numbers JF697199, JF697200and JF697201). ...
Huntingtons disease results in massive loss of cells in the brain, particularly in regions called the cortex and striatum. The cells depicted are from a patient with Huntingtons disease that have been genetically corrected. They are striatal neurons with expression of DARPP-32 and beta-III-tubulin, markers of neurons lost in Huntingtons disease.. June 28, 2012 Novato, California Researchers at the Buck Institute have corrected the genetic mutation responsible for Huntingtons disease (HD) using a human induced pluripotent stem cell (iPSC) that came from a patient suffering from the incurable, inherited neurodegenerative disorder. Scientists took the diseased iPSCs, made the genetic correction, generated neural stem cells and then transplanted the mutation-free cells into a mouse model of HD where they are generating normal neurons in the area of the brain affected by HD. Results of the research are published in the June 28, 2012 online edition of the journal Cell Stem Cell.. iPSCs are ...
Researchers at Mayo Clinic have identified the specific genetic defect in the TCF4 gene - the expansion of the TGC repeat - that appears to be responsible for Fuchs endothelial corneal dystrophy (FECD).
From NCBI Gene:. The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the pure cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive ...

Disease-specific induced pluripotent stem cells.  - PubMed - NCBIDisease-specific induced pluripotent stem cells. - PubMed - NCBI

Huntington disease (HD) is caused by a tri-nucleotide repeat expansion within the huntingtin locus. DNA sequencing shows that ... 54 repeats). The control is genomic DNA from a healthy volunteer. ... Sequence Analysis*BLAST (Basic Local Alignment Search Tool). * ... Mutated alleles identical to the original specimens were verified by DNA sequencing. Adenosine deaminase deficiency line ADA- ... DMD2 is a patient control (exon 4 deletion). The control is genomic DNA from a healthy volunteer. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/18691744?dopt=Abstract

Dictyostelium discoideum - WikipediaDictyostelium discoideum - Wikipedia

The repeats correspond to repeated sequences of amino acids and are thought to be expanded by nucleotide expansion. Expansion ... Tandem repeats of trinucleotides are very abundant in this genome; one class of the genome is clustered, leading researchers to ... More recent genomic studies have shown that Dictyostelium has maintained more of its ancestral genome diversity than plants and ... of trinucleotide repeats also occurs in humans, in general leading to many diseases. Learning how D. discoideum cells endure ...
more infohttps://en.wikipedia.org/wiki/Dictyostelium_discoideum

Trinucleotide repeat disorder - WikipediaTrinucleotide repeat disorder - Wikipedia

The mutation is a subset of unstable microsatellite repeats that occur throughout all genomic sequences. If the repeat is ... Trinucleotide repeat disorders (also known as trinucleotide repeat expansion disorders, triplet repeat expansion disorders or ... Trinucleotide repeat expansion, also known as triplet repeat expansion, is the DNA mutation responsible for causing any type of ... are a set of genetic disorders caused by trinucleotide repeat expansion, a kind of mutation where trinucleotide repeats in ...
more infohttps://en.wikipedia.org/wiki/Trinucleotide_repeat_disorder

JoVE | Peer Reviewed Scientific Video Journal - Methods and ProtocolsJoVE | Peer Reviewed Scientific Video Journal - Methods and Protocols

Repeat length was determined by direct sequencing, short tandem repeat (STR) assay and Southern blotting. Genomic Southern ... The TGC trinucleotide repeat expansion in TCF4 is strongly associated with FECD, and a repeat length ,50 is highly specific for ... A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy. ... We tested for an association between an intronic TGC trinucleotide repeat in TCF4 and FECD by determining repeat length in 66 ...
more infohttps://www.jove.com/visualize/abstract/23185296/a-common-trinucleotide-repeat-expansion-within-transcription-factor-4

Our novel findings on poly(Q) diseases and Insulin Signalling | Department of BiotechnologyOur novel findings on poly(Q) diseases and Insulin Signalling | Department of Biotechnology

... "expansion" refers to the increased number of trinucleotide repeats (such as increased number of CAG repeats in DNA sequence of ... generally over 40 repeats), it overrides all genomic safeguards and leads to toxicity due to abnormal folding of the encoded ... In over 50% of the trinucleotide repeat disorders known till date, the expansion is found to be of the CAG trinucleotide that ... "trinucleotide repeat expansion" in the coding DNA sequence of the affected gene (such as huntingtin gene in case of ...
more infohttp://www.dbtindia.nic.in/our-novel-findings-on-polyq-diseases-and-insulin-signalling/

Dictyostelium discoideumDictyostelium discoideum

The repeats correspond to repeated sequences of amino acids and are thought to be expanded by nucleotide expansion.[2] ... Expansion of trinucleotide repeats also occurs in humans, generally leading to many diseases. Learning how D. discoideum cells ... Comparative genomic studies allows for comparison of eukaryotic genomes. A phylogeny based on the proteome showed that the ... Tandem repeats of trinucleotides are very abundant in this genome; one class of the genome is clustered leading researchers to ...
more infohttps://en.academic.ru/dic.nsf/enwiki/8589209/Dictyostelium_discoideum

Trinucleotide repeat in TCF4 responsible for Fuchs endothelial corneal dystrophy - Para profesionales médicos - Mayo ClinicTrinucleotide repeat in TCF4 responsible for Fuchs' endothelial corneal dystrophy - Para profesionales médicos - Mayo Clinic

... the expansion of the TGC repeat - that appears to be responsible for Fuchs endothelial corneal dystrophy (FECD). ... Repeat length was determined by direct sequencing, short tandem repeat (STR) assay. Genomic Southern blots were used to ... "The TGC trinucleotide repeat expansion in TCF4 is strongly associated with FECD. A repeat length , 50 is highly specific for ... A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy. ...
more infohttps://www.mayoclinic.org/es-es/medical-professionals/clinical-updates/ophthalmology/trinucleotide-repeat-in-tcf4-responsible-for-fuchs-endothelial-corneal-dystrophy

Interactive Fly, DrosophilaInteractive Fly, Drosophila

... genomic instability, increased tri-nucleotide repeat expansion, and destabilization of telomeric repeats. These data highlight ... Examination of the human PCNA promoter DNA sequence reveals a site with homology to the consensus DNA sequence bound by p53. ... FEN-1 mutations altering PCNA binding should reduce activity during replication, likely causing DNA repeat expansions as seen ... mutations in and around a repeat sequence are found to abolish Tax transactivation. Multimerized copies of either half of the ...
more infohttp://www.sdbonline.org/sites/fly/polycomb/pcna2a.htm

Trinucleotide repeat expansion and TCF4 gene expression in Fuchs endothelial corneal dystrophy | IOVS | ARVO JournalsTrinucleotide repeat expansion and TCF4 gene expression in Fuchs endothelial corneal dystrophy | IOVS | ARVO Journals

TNR was also confirmed by DNA sequencing of the PCR product. Results : Genomic DNA from the blood of the FECD patient expressed ... 50 repeats, 2) a heterozygous CTG expansion of ,50 repeats, and 3) a homozygous CTG expansion of ,50 repeats. Of the total 387 ... 50 repeats, and 27 (14 males and 13 females, 7.0%) harbored a homozygous CTG expansion of ,50 repeats. TNR expansion determined ... Purification of genomic DNA from each patients blood sample was carried out and the expansion of CTG repeats in the third ...
more infohttp://iovs.arvojournals.org/article.aspx?articleid=2561188

DiVA - Search resultDiVA - Search result

Until today, nineteen trinucleotide repeat expansions larger than forty repeat copies have been found in the human genome. Of ... Sequencing of the two fragments showed sequence identities with two disease genes, the Huntington gene and the ataxin 3 gene, ... Large family materials are not required and as little as 10 microg genomic DNA from a single individual is sufficient for this ... A cloning strategy for identification of genes containing trinucleotide repeat expansions2001In: International Journal of ...
more infohttp://uu.diva-portal.org/smash/resultList.jsf?p=246851&fs=false&language=en&searchType=SIMPLE&query=&af=%5B%5D&aq=%5B%5B%5D%5D&aq2=%5B%5B%5D%5D&aqe=%5B%5D&noOfRows=50&sortOrder=author_sort_asc&sortOrder2=title_sort_asc&onlyFullText=false&sf=all

IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister | Reproductive Biology and...IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister | Reproductive Biology and...

... contains an unstable sequence of CGG trinucleotide repeats in its promoter region, with expansions of ,200 trinucleotide ... any genomic anomaly linked to POF would be expected to negatively affect reproductive outcome in both siblings. The present ... and ongoing counselling resources were available throughout the IVF sequence. ... repeats typically leading to abnormal methylation and silencing of FMR1 expression [4]. Therefore, in monozygotic (identical) ...
more infohttps://rbej.biomedcentral.com/articles/10.1186/1477-7827-8-31

Prion diseasePrion disease

... we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these ... containing trinucleotide repeats should aid in the identification of genes that may contain expansions of trinucleotide repeats ... The characterization and sequence analysis of thirty CTG-repeat containing genomic cosmid clones.. Eur J Hum Genet 1998 Jan;6(1 ... The sequenced cosmids contain repeats that are between three and 19 perfect units (average 10 perfect repeats). The cosmids map ...
more infohttp://www.mad-cow.org/apr99_sci.html

The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants | CMAJThe Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants | CMAJ

66 or trinucleotide repeat expansions). We analyzed 1 variant at a time and did not consider genetic networks.67 This approach ... Unlike lower-resolution genomic tests, such as karyotyping, microarrays and exome sequencing, whole genome sequencing captures ... We used the Illumina HiSeq X system to sequence DNA extracted from whole blood (median sequence depth of 38× across all 56 ... Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first- ...
more infohttp://www.cmaj.ca/content/190/5/E126.full.print

Combinatorial cell-specific regulation of GSK3 directs cell differentiation and polarity in Dictyostelium | DevelopmentCombinatorial cell-specific regulation of GSK3 directs cell differentiation and polarity in Dictyostelium | Development

1A), although there is an AAT, tri-nucleotide expansion in ZAK1 that is absent in ZAK2. This repeat encodes an asparagine block ... Given its sequence and functional kinship with ZAK1, we suggest that ZAK2 is a more consistent nomenclature. ... ZAK2 disruption was confirmed by genomic Southern (data not shown) and northern blot hybridizations (Fig. 1D) and RT-PCR (Fig. ... Consistent with the expansion of ecmA-expressing cells in zak2 nulls, we see a dramatic increase in global levels of ecmA mRNA ...
more infohttp://dev.biologists.org/content/138/3/421

Free Medical Flashcards about BF - MM2Free Medical Flashcards about BF - MM2

... such as those with trinucleotide repeat expansions Position-independent DNA sequence knowledge - How is sequence identified? ... Single nucleotide polymorphism (unique genomic marker). Linkeage analysis - Use of SNPSs?. Find an SNP near gene of interest. ... Triplet repeat expansions lead to what? Instability. Insertions - What are substantial repeat insertions called? Tandem repeats ... 1. Isolate protein product of a disease gene 2. Determine a.a. sequence of protein and therefore cDNA sequence 3. Synthesize ...
more infohttps://www.studystack.com/flashcard-1231498

Community Academic Profiles - Faculty & Researchers - Stanford MedicineCommunity Academic Profiles - Faculty & Researchers - Stanford Medicine

Rapid cloning of expanded trinucleotide repeat sequences from genomic DNA NATURE GENETICS Koob, M. D., Benzow, K. A., Bird, T. ... Trinucleotide repeat expansions have been shown to cause a number of neurodegenerative diseases. A hallmark of most of these ... The involvement of trinucleotide repeat expansions in a number of other diseases--including familial spastic paraplegia, ... 10)--is suggested both by the presence of anticipation and by repeat expansion detection (RED) analysis of genomic DNA samples ...
more infohttps://med.stanford.edu/profiles/id/john-day

Community Academic Profiles - Faculty & Researchers - Stanford MedicineCommunity Academic Profiles - Faculty & Researchers - Stanford Medicine

Rapid cloning of expanded trinucleotide repeat sequences from genomic DNA NATURE GENETICS Koob, M. D., Benzow, K. A., Bird, T. ... Trinucleotide repeat expansions have been shown to cause a number of neurodegenerative diseases. A hallmark of most of these ... The involvement of trinucleotide repeat expansions in a number of other diseases--including familial spastic paraplegia, ... 10)--is suggested both by the presence of anticipation and by repeat expansion detection (RED) analysis of genomic DNA samples ...
more infohttps://med.stanford.edu/profiles/pulmonary/john-day

Preclinical and clinical advances in transposon-based gene therapy | Bioscience ReportsPreclinical and clinical advances in transposon-based gene therapy | Bioscience Reports

... with CRISPR/Cas9 system potentially supports gene therapy in genetic disorders caused by expansion of trinucleotide repeats. As ... TNA sequence [51,157]. Comparative analysis of genomic insertion indicated that the PB transposon displayed the highest ... a) SB transposon is ~1.6 kb in total length and consists of two inverted repeat/direct repeats (IR/DRs) flanking DNA encoding ... two sgRNAs were designed to remove CAG repeat expansion in exon 1 of HTT locus under Cas9 nuclease activity. Homology-directed ...
more infohttp://www.bioscirep.org/content/37/6/BSR20160614

Dictionary | Fragile XDictionary | Fragile X

Trinucleotide repeat disorders - A set of genetic disorders caused by trinucleotide repeat expansion, a kind of mutation where ... The mutation is a subset of unstable microsatellite repeats that occur throughout all genomic sequences. If the repeat is ... Strong amplification of the sequence of unstable trinucleotide repeats (CGG) or other mutations turn off FMR-1 gene expression ... is the name of the gene characterized by numerous repeats of single trinucleotide sequences on the fragile part of X chromosome ...
more infohttp://www.fragilex.eu/translation/english-glossary/

Neuroprotection with Beta-Lactam Compounds - Johns Hopkins UniversityNeuroprotection with Beta-Lactam Compounds - Johns Hopkins University

Neurological disorders include, but are not limited to, amyotrophic lateral sclerosis (ALS), trinucleotide repeat expansion ... 1 is sequence listings for SEQ ID NOs: 1-4, which are EAAT2 promoter sequences. ... As used herein, the term "promoter" generally refers a region of genomic DNA, usually found 5′ to an mRNA transcription start ... Previous studies document that sequence, 5′ of EAAT2 coding region, has promoter motifs and can be activated in vitro. The ...
more infohttp://www.freepatentsonline.com/y2007/0238717.html

nature.com searchnature.com search

Rapid cloning of expanded trinucleotide repeat sequences from genomic DNA *Michael D. Koob ... Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP *Todd R. Klesert ... Rights & permissionsfor article Rapid cloning of expanded trinucleotide repeat sequences from genomic DNA . Opens in a new ... Rights & permissionsfor article Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of ,i,DMAHP,/ ...
more infohttps://www.nature.com/search?author=%22Thomas%20D.%20Bird%22&error=cookies_not_supported&code=9048795c-9bd2-46f2-bac9-7afaa8fcf4b0

The What is Mismatch Repair Mechanism? MMR is a - Free dissertations databaseThe What is Mismatch Repair Mechanism? MMR is a - Free dissertations database

MMR proteins are further involved in expansion of trinucleotide repeat (the process which forms the basis of various hereditary ... Nucleotide Excision Repair: removes a sequence of nucleotides including the damaged ones and replaces by a new sequence of DNA ... Genomic instability is induced when mutation occurs in MMR genes. Loss of MMR results in elevated levels of frameshift mutation ... The DNA sequence provides the blue print for the proteins that our cells need to function and thus their damage causes n number ...
more infohttps://southlaketimes.com/the-what-is-mismatch-repair-mechanism-mmr-is-a/

TATA Box-Binding Protein - CAGSTATA Box-Binding Protein - CAGS

SCA17 is caused by the heterozygous expansion of the CAG/CAA trinucleotide repeat in the gene increasing it from 25-42 in the ... Whole exome sequencing helped identify a homozygous mutation (c.171delG, p.Q57 fs) in exon 2 of the patients TBP gene. As TBP ... 2017) described the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, ... Its coding sequence is contained within 8 exons and it encodes a 37.6 kDa protein product composed of 339 amino acids. An ...
more infohttp://www.cags.org.ae/ctga/details.aspx?id=2369&pg=10&se=Latest

Processing and transcriptome expansion at the mRNA 3′ end in health and disease: finding the right end | SpringerLinkProcessing and transcriptome expansion at the mRNA 3′ end in health and disease: finding the right end | SpringerLink

It is caused by short trinucleotide repeat [(GCG)8-13] expansions in the coding region of the nuclear poly(A)binding protein 1 ... Ultimately, ongoing genome sequencing activities will most likely grant us further insights into genomic variations resulting ... accessory sequences can function as upstream sequence elements (USE) [17, 32, 36, 66, 67, 75, 98, 128, 129, 132, 193] to ... How about other sequence elements?. 3′ end processing depends on various canonical and non-canonical (auxiliary) sequence ...
more infohttps://link.springer.com/article/10.1007%2Fs00424-016-1828-3

Frontiers | RNA-Seq of Guar (Cyamopsis tetragonoloba, L. Taub.) Leaves: De novo Transcriptome Assembly, Functional Annotation...Frontiers | RNA-Seq of Guar (Cyamopsis tetragonoloba, L. Taub.) Leaves: De novo Transcriptome Assembly, Functional Annotation...

A total of 5,773 potential simple sequence repeats (SSRs) and 3,594 high-quality single nucleotide polymorphisms (SNPs) were ... A total of 5,773 potential simple sequence repeats (SSRs) and 3,594 high-quality single nucleotide polymorphisms (SNPs) were ... Sequence similarity analyses and annotation of the unigenes against non-redundant protein (Nr) and Gene Ontology (GO) databases ... Sequence similarity analyses and annotation of the unigenes against non-redundant protein (Nr) and Gene Ontology (GO) databases ...
more infohttps://www.frontiersin.org/articles/10.3389/fpls.2017.00091/full
  • The specificity and efficiency of this process are determined by the binding of two core multi-protein complexes (CPSF and CSTF, for "cleavage and polyadenylation specificity factor" and "cleavage stimulation factor") to sequences surrounding the poly(A) site as soon as the nascent pre-mRNA transcript emerges from the elongating RNA polymerase II (POL2). (springer.com)
  • With the advent of next-generation RNA sequencing technologies, it became apparent that not only the "body" of transcripts but also the mRNA 3′ end is affected by enormous diversity. (springer.com)
  • It involves more than 50 proteins [ 160 ], which are loaded onto more or less highly conserved sequence motifs to catalyze this step of pre-mRNA maturation. (springer.com)
  • We describe genomic variation identified in the initial recruitment cohort of 56 volunteers. (cmaj.ca)
  • This can be achieved by isolation of the genomic domain into a vector (see item) followed by the multiple reproduction of this vector. (fragilex.eu)
  • The DNA sequence provides the blue print for the proteins that our cells need to function and thus their damage causes n number of problems, fortunately our cells use various enzyme mediated ways to fix such problems. (southlaketimes.com)
  • Then they bind to the base that has been mispaired and another set of complex proteins chops the strand near this sequence. (southlaketimes.com)
  • Therefore, in monozygotic (identical) twin sisters, any genomic anomaly linked to POF would be expected to negatively affect reproductive outcome in both siblings. (biomedcentral.com)
  • 2017) described the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. (cags.org.ae)
  • This analysis is performed by Next Generation Sequencing (NGS) and is designed to examine coding regions and splicing junctions. (fulgentgenetics.com)
  • Genomic Southern blots were used to evaluate samples for which only a single allele was identified by STR analysis. (jove.com)
  • Clone (en) - A clone is a group of unicellular organisms (bacteria, yeasts, vertebrates) derived from a common parent cell. (fragilex.eu)