Karen Morrison
A5089453718- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Renal cell carcinoma treatment
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Renal and related cancers
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Cancer-related gene regulation
- RNA regulation and disease
- Alzheimer's disease research and treatments
- Cell Adhesion Molecules Research
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Neurological disorders and treatments
- Monoclonal and Polyclonal Antibodies Research
- Prion Diseases and Protein Misfolding
- Chemical Reactions and Isotopes
- Cancer Cells and Metastasis
- Platelet Disorders and Treatments
- Peptidase Inhibition and Analysis
- bioluminescence and chemiluminescence research
- 14-3-3 protein interactions
Queen's University Belfast
2019-2025
Inserm
2022-2024
Centre de recherche en Epidémiologie et Santé des Populations
2022-2024
Université de Versailles Saint-Quentin-en-Yvelines
2022-2024
Université Paris-Saclay
2022-2024
Center for Human Genetics
2024
University Hospital Southampton NHS Foundation Trust
2017-2023
University of Southampton
2016-2023
Motor Neurone Disease Association
2023
Royal Victoria Hospital
2022-2023
We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with large proportion cases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).We screened 4448 patients diagnosed ALS (El Escorial criteria) 1425 FTD (Lund-Manchester from 17 regions worldwide for GGGGCC using repeat-primed PCR assay. assessed familial disease status on basis self-reported family history similar neurodegenerative diseases at time sample...
Background: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak. Objectives: To provide evidence‐based or expert recommendations ALS based on a literature search consensus an panel. Methods: All available medical reference systems were searched, original papers, meta‐analyses, review book chapters guidelines reviewed. final was performed in February 2011. Recommendations reached by consensus. Recommendations: Patients with symptoms suggestive...
Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants other lysosomal storage disorder genes is more broadly associated with disease susceptibility. The sequence kernel association test was used to interrogate variant among 54 genes, leveraging whole exome sequencing data from 1156 cases and 1679 control subjects. discovered significant rare, likely damaging risk....
Mutation in the CHMP2B gene has been implicated frontotemporal dementia. The authors screened patients with ALS and several cohorts of control samples. They identified mutations (Q206H; I29V) two non-SOD1 ALS. Neuropathology Q206H case showed lower motor neuron predominant disease ubiquitylated inclusions neurons. Antibodies to p62 (sequestosome 1) novel oligodendroglial cortex.
Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free data, can genotype at the locus interest, even if expanded repeat larger than read length. applied our algorithm data...
Annexin A11 mutations, implicated in ALS, prevent binding to calcyclin and induce the formation of cytoplasmic inclusions.
Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of TDP-43 is a major component, characteristic pathological feature most ALS FTD patients. Here we use genome-wide linkage analysis large ALS/FTD kindred to identify novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified CCNF missense mutation...
Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization investigate over 3,000 genes encode druggable proteins predict their efficacy as targets for disease. expression protein quantitative trait loci mimic exposure medications, we examine the causal effect on risk (in two large cohorts), age at onset progression. propose 23...
Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes...
Background Despite several studies suggesting a potential oligogenic risk model in amyotrophic lateral sclerosis (ALS), case–control statistical evidence implicating oligogenicity with disease or clinical outcomes is limited. Considering its direct and therapeutic implications, we aim to perform large-scale robust investigation of ALS the course. Methods We leveraged Project MinE genome sequencing datasets (6711 cases 2391 controls) identify associations between known genes risk, as well...
Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation CHMP2B was recently identified Danish pedigree autosomal dominant FTD. Subsequently, two unrelated patients familial ALS, one whom also showed features FTD, were shown to carry missense mutations CHMP2B. The initial aim this study determine whether contribute more broadly ALS pathogenesis.Sequencing 433 cases from the North...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons that results in progressive weakness and death from respiratory failure, commonly within about 3 years. Previous studies have shown association locus on chromosome 9p with ALS linkage ALS-frontotemporal dementia. We aimed to test whether this genomic region also associated an independent set UK samples, identify risk factors further genome-wide study combined data the analysis those other countries.We...
Mutations in the progranulin gene (GRN) are a major cause of frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) but distinguishing clinical and anatomical features this subgroup remain unclear. In large UK cohort we found five different frameshift premature termination mutations likely to be causative FTLD 25 affected family members. A previously described 4-bp insertion mutation GRN exon 2 comprised majority cases our (20/25), four novel being...
We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 controls, the largest sample size so far for PD GWAS. Replication was attempted an additional cohort of 1039 French cases 1984 controls 27 regions showing strongest evidence (P< 10−4). replicated published associations 4q22/SNCA 17q21/MAPT chromosome 10−10) found independent 4q22/SNCA. A detailed analysis haplotype structure at 17q21 showed that there are three separate risk groups...