• Mutations
  • There are many types of SCAs as there are various gene mutations that can cause this disease. (biomedcentral.com)
  • Using the CRISPR/Cas system, I engineered isogenic cell lines with p63 SAM domain mutations and used the cell models in proteomic-based experiments to identify candidate SAM domain-interacting proteins. (vanderbilt.edu)
  • no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations. (wikipedia.org)
  • When they examined MECP2 in patients with other neurological disorders, they found that mutations in the gene can result in other phenotypes ranging from learning disabilities to autism spectrum disorders. (wikipedia.org)
  • Mutations of this gene can lead to fragile X syndrome, intellectual disability, premature ovarian failure, autism, Parkinson's disease, developmental delays and other cognitive deficits. (wikipedia.org)
  • Fewer than 1% of all cases of fragile X syndrome are caused by mutations that delete part or all of the FMR1 gene, or change a base pair, leading to a change in one of the amino acids in the gene. (wikipedia.org)
  • These mutations disrupt the 3-dimensional shape of FMRP or prevent the protein from being synthesized, leading to the signs and symptoms of fragile X syndrome. (wikipedia.org)
  • This gene suffers mutations that cause the PABPN1 protein to have extra alanine (amino acids), this manifests itself physically in the symptoms of this MD. The expansion caused by the mutations on the PABPN1 gene ultimately interrupts the cellular mechanics of poly(A) RNA. (wikipedia.org)
  • nuclear
  • Like other nuclear receptors, the AR protein consists of several functional domains: the transactivation domain (also called the transcription-regulation domain or the amino / NH2-terminal domain), the DNA-binding domain, the hinge region, and the steroid-binding domain (also called the carboxyl-terminal ligand-binding domain). (wikipedia.org)
  • Despite the prominence of iron-sulfur cluster (ISC) proteins in bioenergetics, intermediary metabolism, and redox regulation of cellular, mitochondrial, and nuclear processes, these proteins have been given scarce attention in Drosophila . (springer.com)
  • Polyadenylate-binding protein 2 (PABP-2) also known as polyadenylate-binding nuclear protein 1 (PABPN1) is a protein that in humans is encoded by the PABPN1 gene. (wikipedia.org)
  • https://www.ncbi.nlm.nih.gov/gene/8106 "PABPN1 poly(A) binding protein, nuclear 1 [ Homo sapiens (human) ]"]11 OCT 2014. (wikipedia.org)
  • symptoms
  • In general, the more repeats in the affected range that someone has, the earlier the age of onset of symptoms and the more severe the symptoms. (thefreedictionary.com)
  • It is not possible to look at a person's repeat number and predict at what age they will begin to have symptoms or how their condition will progress. (thefreedictionary.com)
  • In general, the more repeats above 38 an individual has, the earlier the age of onset of symptoms and the more severe the symptoms. (healthofchildren.com)
  • MJD is an autosomal dominant disease, meaning that if either parent gives the defective gene to a child, the child will show symptoms of the disease. (wikipedia.org)
  • A limitation to this test is that if the number of CAG repeats in an individual being tested falls between the healthy and pathogenic ranges (45-60 repeats), then the test cannot predict whether an individual will have MJD symptoms. (wikipedia.org)
  • citation needed] For many of the loci, trinucleotide expansion is harmless,[citation needed] but in some areas expansion has detrimental effects that cause symptoms. (wikipedia.org)
  • Less commonly, OPMD can be inherited in an autosomal recessive pattern, which means that two copies of the mutated gene need to be present in each cell, both parents need to be carriers of the mutated gene, and usually show no signs or symptoms. (wikipedia.org)
  • transcriptional
  • My research tests the hypothesis that the p63 SAM domain is required to regulate key protein-protein interactions involved in transcriptional regulation of p63 target genes required during development. (vanderbilt.edu)
  • The CGG expansion is associated with hypermethylation of the surrounding DNA, chromatin condensation, and subsequent transcriptional silencing of the fmr-1 gene, resulting in the loss of expression of fragile X mental retardation protein (FMRP) [ 7 ]. (pubmedcentralcanada.ca)
  • It appears to be involved in regulating gene expression based on its location in the nucleus of the cell, its association with promoter regions of several genes, and its interactions with transcriptional regulators and parts of the RNA splicing machinery. (wikipedia.org)
  • interacts
  • The Htt protein is involved in vesicle trafficking as it interacts with HIP1, a clathrin-binding protein, to mediate endocytosis, the trafficking of materials into a cell. (wikipedia.org)
  • 1993
  • On the same day in April 1993, both Zoghbi and Orr identified ATXN1 as the gene responsible for SCA1. (wikipedia.org)
  • fragile
  • Fragile X syndrome (FXS) results from deficiency of fragile X mental retardation protein (FMRP). (jneurosci.org)
  • Fragile X mental retardation protein (FMRP) is a cytoplasmic mRNA binding protein whose expression is lost in fragile X syndrome. (pubmedcentralcanada.ca)
  • We have established that translation of amyloid precursor protein (APP), which is cleaved to generate neurotoxic βamyloid, is normally repressed by the fragile X mental retardation protein (FMRP) in the dendritic processes of neurons. (pubmedcentralcanada.ca)
  • Wan, Dockendorff, Jongens, Dreyfuss: Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein. (antikoerper-online.de)
  • Callan, Clements, Ahrendt, Zarnescu: Fragile X Protein is required for inhibition of insulin signaling and regulates glial-dependent neuroblast reactivation in the developing brain. (antikoerper-online.de)
  • fragile X) or many genes through a dominant negative effect (ex. (wikipedia.org)
  • FMR1 (fragile X mental retardation 1) is a human gene that codes for a protein called fragile X mental retardation protein, or FMRP. (wikipedia.org)
  • Minor expansions of CGG repeats that do not cause fragile X syndrome are associated with an increased risk for premature ovarian aging, also called occult primary ovarian insufficiency, a condition in which women prematurely deplete their ovarian function. (wikipedia.org)
  • Fragile X syndrome is caused by the loss of production of fragile X mental retardation protein (FMRP) in response to FMR1 gene silencing. (wikipedia.org)
  • While there, she was part of the team that identified the fragile-X syndrome gene. (wikipedia.org)
  • sequence
  • SCA types 1-3, 6-10, 12, and 17 result from a trinucleotide repeat expansion in the DNA-coding sequence. (biomedcentral.com)
  • Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. (abnova.com)
  • If these repeats are found in coding regions then the variations to the polynucleotide sequence can result in the formation of abnormal proteins in eukaryotes. (wikipedia.org)
  • There is a CAG repeat in the coding sequence which is longer in humans than other species (6-38 uninterrupted CAG repeats in healthy humans versus 2 in the mouse gene). (wikipedia.org)
  • The first complete DNA sequence of the repeat expansion in someone with the full mutation was generated by scientists in 2012 using SMRT sequencing. (wikipedia.org)
  • A CGG sequence in the FMR1 gene that is repeated between 55 and 200 times is described as a premutation. (wikipedia.org)
  • The 5' end of the HD gene has a sequence of three DNA bases, cytosine-adenine-guanine (CAG), coding for the amino acid glutamine, that is repeated multiple times. (wikipedia.org)
  • The protein has no sequence homology with other proteins and is highly expressed in neurons and testes in humans and rodents. (wikipedia.org)
  • The nucleotide sequence of the repeats is fairly well conserved across species. (wikipedia.org)
  • This was demonstrated in the land crab Gecarcinus lateralis, whose genome contains 3% of a GC-rich sequence consisting of repeats of a ~2100 base pair (bp) sequence called RU. (wikipedia.org)
  • Between the strand-biased microsatellite repeats and G:C mononucleotide repeats, all sequence variations retained one or two base pairs with A (purine) interrupting the pyrimidine-rich strand and T (pyrimidine) interrupting the purine-rich strand. (wikipedia.org)
  • One RU sequence was shown to have multiple copies of an Alu sequence element inserted into a region bordered by inverted repeats where most copies contained just one Alu sequence. (wikipedia.org)
  • alleles
  • The alleles, which are a variant form of a gene involved in this form of MD are: PABPN1, (GCG)n EXPANSION, (GCG)8-13, PABPN1, (GCG)n EXPANSION, (GCG)7 and PABPN1, GLY12ALA. (wikipedia.org)
  • specifically, the length differences observed between microsatellite alleles are generally multiples of the repeat unit length. (wikipedia.org)
  • mRNA
  • In Cryptococcus neoformans , mRNAs encoding ribosomal proteins (RP) are rapidly and specifically repressed during cellular stress, and the bulk of this repression is mediated by deadenylation-dependent mRNA decay. (asm.org)
  • These proteins regulate the polysome association of the target mRNA but perform functions related to sterol homeostasis which appear independent of ribosomal protein mRNAs. (asm.org)
  • FMRP has been suggested to play roles in nucleocytoplasmic shuttling of mRNA, dendritic mRNA localization, and synaptic protein synthesis. (wikipedia.org)
  • Molecular
  • Our data support a growing consensus that FMRP binds to guanine-rich domains of some dendritic mRNAs, suppressing their translation and suggest that AD (neurodegenerative disorder) and FXS (neurodevelopmental disorder) may share a common molecular pathway leading to the overproduction of APP and its protein-cleaving derivatives. (pubmedcentralcanada.ca)
  • Moreover, biosynthesis and delivery of ISCs to target proteins requires a highly regulated molecular network that spans different cellular compartments. (springer.com)
  • Heat shock proteins (HSPs) function as molecular chaperones that aid in protein folding and the degradation of misfolded proteins. (readbyqxmd.com)
  • The lab's current projects include: locating human sleep genes, uncovering the molecular mechanisms of human sleep regulation and human circadian rhythms, investigating mouse models with de/dys-myelinating disease, and classifying miRNAs that contribute to healthy myelin. (wikipedia.org)
  • homologous
  • A second, homologous protein, Gis2, was identified in the genome of C. neoformans and also bound the 3′-UTR probe, and deletion of both genes resulted in loss of binding in cell extracts. (asm.org)
  • Type I strains are specified by the gene called MatA, Type II stains have three different genes: MatB (homologous to Mat A), Mat C, and Mat D, and Type III strains have Mat S and Mat T genes (which are homologous to Mat C and Mat D). These sexes can only mate with the two different sexes and not with its own. (wikipedia.org)
  • humans
  • Knock-out of the Fmr1 gene in mice removes FMRP and mimics FXS in humans ( O'Donnell and Warren, 2002 ). (jneurosci.org)
  • This elongation is variable in length, with as few as 6 and as many as 81 repeats reported in humans. (wikipedia.org)
  • Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform is an enzyme that in humans is encoded by the PPP2R2B gene. (wikipedia.org)
  • They cloned the causative gene/mutation and studied the in vitro biochemical consequences of the mutation, culminating in a 2001 paper An hPer2 phosphorylation site mutation in familial advanced sleep-phase syndrome, reporting the first circadian gene mutation in humans. (wikipedia.org)
  • Fu traced the phenotype back to a point mutation in a gene called DEC2 that is associated with short sleep phenotype in humans. (wikipedia.org)
  • Some types of satellite DNA in humans are: A repeated pattern can be between 1 base pair long (a mononucleotide repeat) to several thousand base pairs long[citation needed], and the total size of a satellite DNA block can be several megabases without interruption. (wikipedia.org)
  • polymerase
  • When DNA polymerase encounters a direct repeat, it can undergo a replication slippage. (wikipedia.org)
  • Slippage occurs through five main stages: In the first step, DNA polymerase encounters the direct repeat during the replication process. (wikipedia.org)
  • DNA polymerase reassembles its position on the template strand and resumes normal replication, but during the course of reassembling, the polymerase complex backtracks and repeats the insertion of deoxyribonucleotides that were previously added. (wikipedia.org)
  • One hypothesis is that the increasing number of repeats influence the overall shape of the DNA, which can have an effect on its interaction with DNA polymerase and thus the expression of the gene. (wikipedia.org)
  • mediate
  • In model organisms, SAM domains have been shown to mediate important protein-protein interactions. (vanderbilt.edu)
  • Thus the AR activates these genes to mediate the effects of androgens in the human body, including the development and maintenance of the male sexual phenotype and generalized anabolic effects. (wikipedia.org)
  • mass spectrometry
  • Znf9, a small zinc knuckle RNA binding protein identified by mass spectrometry, was found to interact specifically with the RPL2 3′-UTR probe. (asm.org)
  • aberrant
  • There is evidence for aberrant thiol oxidation within mHTT and other proteins in HD models. (plos.org)
  • N-terminal mHTT results in HD through accumulation in cells and aberrant interactions with numerous proteins 9 , 10 and possibly direct production of reactive oxygen species 11 . (plos.org)
  • Mitochondria
  • Efficient transportation of mitochondria depends on multiple factors, including their own energy production, the integrity of the cytoskeleton and its protein components (tubulin, etc.), and adequate myelination of the axons. (wikipedia.org)
  • causative gene
  • In August 1999, 16 years after meeting her first patient with Rett syndrome, Zoghbi and collaborators identified MECP2 as the causative gene. (wikipedia.org)
  • accumulation
  • Reduced FXN protein results in mitochondrial dysfunction and iron accumulation leading to increased oxidative stress and cell death in the nervous system and heart. (curefa.org)
  • Amyloid precursor protein (APP) facilitates synapse formation in the developing brain, while beta-amyloid (Aβ) accumulation, which is associated with Alzheimer disease, results in synaptic loss and impaired neurotransmission. (pubmedcentralcanada.ca)
  • localization
  • Often, cis elements in the 3′ untranslated regions (UTRs) of mRNAs encode proteins with roles in the fates of the mRNAs, including stability, translatability, and localization. (asm.org)
  • found
  • This results in some repeats found in the template strand being replicated twice into the daughter strand. (wikipedia.org)
  • The HD gene is found in all human genomes. (wikipedia.org)
  • TNR expansion in TCF4 , which we have previously found to be present in the majority of FECD patients, was lacking in DM1 families. (arvojournals.org)
  • We previously found that the degradation of mutated Htt with polyQ expansion (Htt103QP) depends on both ubiquitin proteasome system and autophagy. (readbyqxmd.com)
  • The test will show positive for MJD if this region contains 61-87 repeats, as opposed to the 12-44 repeats found in healthy individuals. (wikipedia.org)
  • in this case, the germ cells produced have a greater number of repeats than are found in the somatic tissues. (wikipedia.org)
  • When the repeat is present in an untranslated region, it could affect the expression of the gene in which the repeat is found (ex. (wikipedia.org)
  • This protein, most commonly found in the brain, is essential for normal cognitive development and female reproductive function. (wikipedia.org)
  • Several alternatively spliced transcripts encoding different isoforms have been found for this gene. (wikipedia.org)
  • The lab studied the genomes of people with this trait and found a point mutation in the PER2 gene that likely causes the behavioral phenotype. (wikipedia.org)
  • Huntingtin has been found to interact directly with at least 19 other proteins, of which six are used for transcription, four for transport, three for cell signalling, and six others of unknown function (HIP5, HIP11, HIP13, HIP15, HIP16, and CGI-125). (wikipedia.org)
  • Over 100 interacting proteins have been found, such as huntingtin-associated protein 1 (HAP1) and huntingtin interacting protein 1 (HIP1), these were typically found using two-hybrid screening and confirmed using immunoprecipitation. (wikipedia.org)
  • FMRP
  • The important role of mGluRs in both eCB and protein synthesis, together with evidence that certain cognitive deficits may result from disordered CB1-mediated signaling, suggests that FMRP deficiency could alter Gp1 mGluR-dependent eCB mobilization. (jneurosci.org)