A5043197316- Genetics and Neurodevelopmental Disorders
- Genetic Neurodegenerative Diseases
- DNA Repair Mechanisms
- Autism Spectrum Disorder Research
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Endoplasmic Reticulum Stress and Disease
- Genetic factors in colorectal cancer
- Genomics and Phylogenetic Studies
- Advanced biosensing and bioanalysis techniques
- Chromatin Remodeling and Cancer
- Genomics and Rare Diseases
- Metabolism and Genetic Disorders
- RNA regulation and disease
- Connective tissue disorders research
National Institutes of Health
2016-2025
National Institute of Diabetes and Digestive and Kidney Diseases
2016-2025
Université Bourgogne Franche-Comté
2025
National Hospital for Neurology and Neurosurgery
2024
McGill University
2024
Montreal Neurological Institute and Hospital
2024
The University of Texas Southwestern Medical Center
2024
University College London
2024
Hokkaido University
2012
Morgan State University
2012
Journal Article CGG repeats associated with DNA instability and chromosome fragility form structures that block synthesis in vitro Get access K. Usdin, Usdin * Section on Genomic Structure Function, National Institute of Diabetes Kidney Diseases, Institutes HealthBethesda, MD 20892–0830, USA To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Woodford Nucleic Acids Research, Volume 23, Issue 20, 25 October 1995, Pages...
Friedreich ataxia (FRDA), the most common hereditary ataxia, is caused by mutations in frataxin (FXN) gene. The vast majority of FRDA involve expansion a GAA*TTC-repeat tract intron 1, which leads to an FXN mRNA deficit. Bisulfite mapping demonstrates that region adjacent repeat was methylated both unaffected and affected individuals. However, methylation more extensive patients. Additionally, three residues were almost completely methylation-free individuals but always those with FRDA. One...
We report an inborn error of metabolism caused by expansion a GCA-repeat tract in the 5' untranslated region gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The observed three unrelated patients who presented early-onset delay overall development, progressive ataxia, elevated levels glutamine. In addition to one patient also showed cerebellar atrophy. associated relative deficiency GLS messenger...
Despite recent advances in sequencing, complete finishing of large genomes and analysis novel proteins they encode typically require cloning specific regions. However, many these fragments are extremely difficult to clone current vectors. Superhelical stress circular plasmids can generate secondary structures that substrates for deletion, particularly regions contain numerous tandem or inverted repeats. Common vectors also induce transcription translation inserted fragments, which select...
Expansion of a GAA · TTC repeat in the first intron frataxin (FXN) gene causes an mRNA deficit that results Friedreich ataxia (FRDA). The region flanking on FRDA alleles is associated with more extensive DNA methylation than seen normal and histone modifications typical repressed genes. However, whether these changes are responsible for controversial. Using chromatin immunoprecipitation cell lines from affected unaffected individuals, we show certain marks active also reduced promoter FXN...
Fragile X-associated tremor and ataxia syndrome, primary ovarian insufficiency, X syndrome are Repeat Expansion Diseases caused by expansion of a CGG•CCG-repeat microsatellite in the 5 UTR FMR1 gene. To help understand mechanism responsible for these disorders, we have crossed mice containing∼147 CGG•CCG repeats endogenous murine Fmr1 gene with containing null mutation encoding mismatch repair protein MSH2. MSH2 mutations associated elevated levels generalized instability. However, show here...
: Fragile X syndrome (FXS), the most common form of inherited cognitive disability, is caused by a deficiency fragile mental retardation protein (FMRP). In patients, absence FMRP due to an aberrant transcriptional silencing 1 (FMR1) gene. FXS has no cure, and available treatments only provide symptomatic relief. Given that FMR1 gene in patient cells can be partially reversed treatment with compounds target repressive epigenetic marks, restoring expression could one approach for FXS. We...
We show here that a K+-dependent block to DNA synthesis is sensitive and specific indicator of intrastrand tetraplex formation can be used, both identify sequences with tetraplex-forming potential examine parameters affect formation. determined by complex combination factors including the size base composition its constituent loops stems. In process carrying out this study we have found number ability form tetraplexes larger than previously thought, such are ubiquitous in eukaryote genomes.
We have found that a strong DNA synthesis arrest site forms in the chicken beta-globin promoter vitro under physiological conditions. The is located G+C-rich region which guanines are predominately on top strand and pyrimidines bottom strand. This non-palindromic has no mirror symmetry. Arrest of only observed when G-rich used as template, shows an absolute requirement for K+. sequence G16CG(GGT)3 necessary sufficient to synthesis. template concentration independent eliminated by blocking N7...
Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and known autism. Most cases FXS result from expansion a CGG·CCG repeat in 5′ UTR FMR1 gene that leads to silencing. It has previously been shown silenced alleles are associated with histone H3 dimethylated at lysine 9 (H3K9Me2) trimethylated 27 (H3K27Me3), modified histones typical developmentally repressed genes. We show here these also elevated levels (H3K9Me3) H4 20 (H4K20Me3). All four present on exon...
Expansion of the CGG.CCG-repeat tract in 5' UTR FMR1 gene to >200 repeats leads heterochromatinization promoter and silencing. This results Fragile X syndrome (FXS), most common heritable form mental retardation. The mechanism silencing is unknown. We report here that a Class III histone deacetylase, SIRT1, plays an important role this process show inhibition enzyme produces significant reactivation. contrasts with much smaller effect inhibitors like trichostatin A (TSA) inhibit I, II IV...
Repeat expansion diseases result from of a specific tandem repeat. The three fragile X-related disorders (FXDs) arise germline expansions CGG•CCG repeat tract in the 5' UTR (untranslated region) X mental retardation 1 (FMR1) gene. We show here that addition to expansion, also occurs somatic cells both mice and humans carriers premutation alleles. Expansion primarily affects brain, testis, liver with very little heart or blood. Our data would be consistent simple two-factor model for organ...
FMR1 premutation (PM) alleles have 55–200 CGG·CCG-repeats in their 5′ UTR. PM carriers are at risk of fragile X–associated tremor and ataxia syndrome (FXTAS). Females also for FX primary ovarian insufficiency (FXPOI). pathology is generally attributed to deleterious properties transcripts with long CGG-tracts. For FXPOI, hormone changes suggest a reduced residual follicle pool. Whether this due smaller than normal original pool or an increased rate depletion unclear. A FX-PM mouse the...
We hypothesized that the mitochondria of granulosa cells (GC) and/or oocytes might be abnormal in a mouse model fragile X premutation (FXPM).Mice heterozygous and homozygous for FXPM have increased death (atresia) large ovarian follicles, fewer corpora lutea with gene dosage effect manifesting decreased litter size(s). Furthermore, mice mitochondrial content, structurally mitochondria, reduced expression critical genes. Because this allele produces mutant Fragile mental retardation 1 (Fmr1)...