A5061678104- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Genomic variations and chromosomal abnormalities
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Congenital heart defects research
- RNA Research and Splicing
- Neurological disorders and treatments
- Neuroscience and Neuropharmacology Research
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Animal Genetics and Reproduction
- Genetics, Bioinformatics, and Biomedical Research
- MicroRNA in disease regulation
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Bioinformatics and Genomic Networks
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Radiopharmaceutical Chemistry and Applications
- Circular RNAs in diseases
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
The Open University
2003-2024
Huntington's Disease Association
2006-2016
National Fragile X Foundation
1999
John Radcliffe Hospital
1989-1998
Guy's Hospital
1997
Salisbury University
1995
Churchill Hospital
1995
Institute of Molecular Medicine
1991-1993
Mayo Clinic
1992
Western General Hospital
1988-1991
Blood–brain barrier (BBB) dysfunction is a hallmark of neurological conditions such as multiple sclerosis (MS) and stroke. However, the molecular mechanisms underlying neurovascular during BBB breakdown remain elusive. MicroRNAs (miRNAs) have recently emerged key regulators pathogenic responses, although their role in central nervous system (CNS) microvascular disorders largely unknown. We identified miR-155 critical miRNA neuroinflammation at BBB. expressed unit individuals with MS mice...
Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive motor, psychiatric and cognitive decline. Marked neuronal loss occurs in the cortex striatum. HD inherited an autosomal dominant fashion caused trinucleotide repeat expansion (CAG) gene encoding protein huntingtin. Predictive genetic testing has revealed early deficits asymptomatic carriers at time when there little evidence for cell death, suggesting that impaired cognition results from cellular or...
Fragile X syndrome is one of 14 trinucleotide repeat diseases. It arises due to expansion a CGG which present in the 5′-untranslated region FMR1 gene, disruption leads mental retardation. The mechanisms involved are poorly understood and date, transgenic mouse models containing expanded repeats have failed reproduce instability seen humans. As both cis-acting factors genomic context thought play role expansion, we now generated knock-in Fmr1 gene murine (CGG)8 has been exchanged with human...
Journal Article Precursor arrays for triplet repeat expansion at the fragile X locus Get access Mark C. Hirst, Hirst Molecular Genetics Group, Institute of Medicine, John Radcliffe HospitalHeadington, Oxford OX3 9DU, UK Search other works by this author on: Academic PubMed Google Scholar Prabhjit K. Grewal, Grewal Kay E. Davies * *To whom correspondence should be addressed Human Genetics, Volume 3, Issue 9, September 1994, Pages 1553–1560, https://doi.org/10.1093/hmg/3.9.1553 Published: 01...
Predictive genetic testing for Huntington's disease (HD) has revealed early cognitive deficits in asymptomatic gene carriers, such as altered working memory, executive function and impaired recognition memory. The perirhinal cortex processes aspects of memory the underlying mechanism is believed to be long-term depression (LTD) excitatory neurotransmission, converse potentiation (LTP). We have used R6/1 mouse model HD assess synaptic plasticity cortex. report here a progressive derailment...
Pro-inflammatory cytokine-induced activation of nuclear factor, NF-κB has an important role in leukocyte adhesion to, and subsequent migration across, brain endothelial cells (BECs), which is crucial for the development neuroinflammatory disorders such as multiple sclerosis (MS). In contrast, microRNA-146a (miR-146a) emerged anti-inflammatory molecule by inhibiting activity various cell types, but its effect BECs during neuroinflammation remains to be evaluated. Here, we show that miR-146a...
The fragile X syndrome is an X-linked disorder which has been shown to be associated with the length variation of a DNA fragment containing CGG trinucleotide repeat element at or close site. Phenotypically normal carriers generally have smaller than affected individuals. We cloned region in cosmids and defined area amplified sequence. used probes from analyse mutation families. show that evolves different ways individuals same family. In addition we not all positive this amplification...
Expanded trinucleotide repeats underlie a growing number of human diseases.The FMR1 (CGG) n array can exhibit genetic instability characterized by progressive expansion over several generations leading to gene silencing and the development fragile X syndrome.While is dependent upon length uninterrupted , occurs in limited germ line early developmental window, suggesting that lineage-specific expression other factors determines cellular environment permissive for expansion.To identify these...
Expansion and methylation of CGG repeat sequences is associated with Fragile X syndrome in humans. We have examined the consequences expansion for nucleosome assembly positioning on Mental Retardation gene 1(FMR1) gene. Short unmethylated repeats are not particularly favored terms affinity histone octamer or reconstituted nucleosome. However, upon their increases a highly positioned assembles found adjacent to nucleosomal dyad. these abolishes preferential due methylation. Thus, triplet can...
Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neuroinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers molecular cargo that involved cell-to-cell communication. Circulating endothelial EVs increased plasma patients with neurological disorders, and immune cell-derived known to modulate cerebrovascular functions. However, little about whether brain cell (BEC)-derived themselves contribute BBB dysfunction. Human cerebral...
Three fragile sites, FRAXA, FRAXE and FRAXF lie in the Xq27-28 region of human X chromosome. The expression FRAXA is associated with syndrome, most prevalent form inherited mental retardation whilst a rarer comparatively milder handicap. Both sites have been cloned site found to be due expansion analogous CGG/GCC trinucleotide repeat arrays. We describe here cloning third site, FRAXF, demonstrate that it involves (GCCGTC)n(GCC)n compound array. PCR analyses across normal individuals show...
Journal Article The identification of a third fragile site, FRAXF, in Xq27 — q28 distal to both FRAXA and FRAXE Get access M.C. Hirst, Hirst Molecular Genetics Group, John Radcliffe HospitalHeadington, Oxford OX3 9DU Search for other works by this author on: Academic PubMed Google Scholar A. Barnicoat, Barnicoat 2Guy's St Thomas's United Medical Dental School, Division Paediatrics, Guy's HospitalLondon Bridge, London, UK G. Flynn, Flynn Q. Wang, Wang M. Daker, Daker V.J. Buckle, Buckle 1MRC...
<i>Background:</i> The introduction of gene testing for Huntington’s disease (HD) has enabled the neuropsychiatric and cognitive profiling human carriers prior to onset overt motor symptoms. Such studies reveal an early decline in working memory executive function, altered EEG a loss striatal dopamine receptors. Working is processed prefrontal cortex modulated by extrinsic dopaminergic inputs. <i>Objective:</i> We sought study excitatory synaptic function plasticity...
Chromosome fragility in two families not exhibiting amplification of the CGG trinucleotide associated with fragile X site has been examined. Fluorescence situ hybridisation cosmid DNA from loci immediately flanking FRAXA and other distal have confirmed that cytogenetic these subjects is result expression a new folate sensitive site, FRAXE.
The normal human FMR1 gene contains a genetically stable (CGG)n trinucleotide repeat which usually carries interspersed AGG triplets. An increase in number and the loss of interspersions results array instability, predominantly expansion, leading to silencing. Instability is directly related length uninterrupted widely assumed be an increased propensity form G-rich secondary structures lead expansion through replication slippage. In order investigate this we have cloned arrays with internal...
The fragile X syndrome is a common cause of mental impairment. In view the low reproductive fitness affected males, high incidence has been suggested to be result rate new mutations occurring exclusively in male germline. Extensive family studies, however, have failed identify any cases mutation. Alternatively, it that selective advantage unaffected heterozygotes may, part, explain syndrome. Molecular investigations shown caused by amplification CGG trinucleotide repeat FMR-1 gene which...
Journal Article A YAC contig across the fragile X site defines region of fragility Get access M.C. Hirst, Hirst Search for other works by this author on: Oxford Academic PubMed Google Scholar K. Rack, Rack 1MRC Molecular Haematology Unit, Institute Medicine, John Radcliffe HospitalOxford, 0X3 9DU Y. Nakahori, Nakahori A. Roche, Roche M.V. Bell, Bell G. Flynn, Flynn Z. Christadoulou, Christadoulou R.N. MacKinnon, MacKinnon M. Francis, Francis A.J. Littler, Littler 2Biotechnology Dept, ICI...