A5054470203- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- Bipolar Disorder and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomics and Chromatin Dynamics
- Tryptophan and brain disorders
- Bioinformatics and Genomic Networks
- Genetics and Neurodevelopmental Disorders
- Treatment of Major Depression
- DNA Repair Mechanisms
- Fungal and yeast genetics research
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Diet and metabolism studies
- Autism Spectrum Disorder Research
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Molecular Biology Techniques and Applications
- Ion channel regulation and function
- Health, Environment, Cognitive Aging
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
Cardiff University
2013-2025
University of California, San Diego
2023
Maastricht University
2023
University of California, Los Angeles
2023
California University of Pennsylvania
2023
Centre Hospitalier Universitaire Sainte-Justine
2023
Medical Research Council
1977-2019
The Honourable Society of Lincoln's Inn
1995-2003
University of California, Berkeley
1997
Western Infirmary
1992
The Cdc6 protein is essential for the assembly of pre-replicative complexes (pre-RCs) at origins DNA replication in budding yeast Saccharomyces cerevisiae. This reaction blocked vivo by cyclin-dependent kinase Cdc28p, together with its regulatory subunits, B type cyclins that are present throughout S, G2, and M phases. Because destruction consequent inactivation exit from mitosis, pre-RC formation can only occur after passage through mitosis. Therefore, has been proposed to be coupling S...
Summary The prevalence of an abnormal response to the dexamethasone suppression test (DST) was examined in 119 in-patients suffering from a major depressive disorder and 79 normal controls. Only 11 per cent controls showed DST as against 70 depressed patients. specificity by testing patients with other psychiatric disorders. Abnormal responses were found one-fifth sample schizophrenics, over one-quarter abstinent alcoholics, two-fifths neurotics (including neurotic depressives) almost half...
Abstract Common genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence significant, but not complete, overlap in between the two disorders. It has been hypothesised that variants conferring these disorders do so by influencing brain development, leading to later emergence symptoms. The comparative profile gene expression disorder across development over different regions however remains unclear. Using...
Abstract Ageing underlies functional decline of the brain and is primary risk factor for several neurodegenerative conditions, including Alzheimer’s disease (AD). However, molecular mechanisms that cause during ageing, how these contribute to AD pathogenesis, are not well understood. The objective this study was identify biological processes altered ageing in hippocampus modify Ad lifespan, then putative gene drivers programmes. We integrated common human genetic variation associated with...
Late-onset Alzheimer’s disease (LOAD), the most common cause of dementia, and a huge global health challenge, is neurodegenerative uncertain aetiology. To deliver effective diagnostics therapeutics, understanding molecular basis essential. Contemporary large genome-wide association studies (GWAS) have identified over seventy novel genetic susceptibility loci for LOAD. Most are implicated in microglial or inflammatory pathways, bringing inflammation to fore as candidate pathological pathway....
Abstract Defining the mechanisms involved in aetiology of Alzheimer’s disease from genome-wide association studies alone is challenging since polygenic and most genetic variants are non-coding. Non-coding risk can influence gene expression by affecting miRNA binding those located within enhancers CTCF sites may through alterations chromatin states. In addition, their function be cell-type specific. They specifically microglial thus brain. Hence, transcriptome-wide have been applied to test...
We analyzed the nature of spontaneous mutations at autosomal locus coding for adenine phosphoribosyltransferase in human colorectal carcinoma cell line SW620 to establish whether distinctive mutational pathways exist that might underlie more complex genome rearrangements arising tumor cells. Point occur a low rate aprt hemizygotes derived from SW620, largely as result base substitutions G.C pairs yield transversions and transitions. However, novel pathway is evident form multiple dispersed...
Late onset Alzheimer’s disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim current study to identify novel genes associated with using largest up-to-date reference single nucleotide polymorphism (SNP) panel, accurate imputation software and a gene-based analysis approach tests patterns association within genes, in powerful genome-wide dataset International Genomics Project Consortium, comprising over 7 million genotypes from 17,008...
Genes encoding the mRNA targets of fragile X mental retardation protein (FMRP) are enriched for genetic association with psychiatric disorders. However, many FMRP possess functions that themselves genetically associated disorders, including synaptic transmission and plasticity, making it unclear whether risk is truly related to binding by or alternatively mediated sampling genes better characterised another trait functional annotation. Using published common variant, rare coding variant copy...
BackgroundRecent breakthroughs in psychiatric genetics have implicated biological pathways onto which genetic risk for disorders converges. However, these studies do not reveal the developmental time point(s) at are relevant.MethodsWe aimed to determine relationship between and gene expression relating discrete pathways. We used postmortem RNA sequencing data (BrainSeq BrainSpan) from brain tissue multiple prenatal postnatal points, with summary statistics recent genome-wide association of...
Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are genetic disorders with lifespan risk for neuropsychiatric disorders. Microdeletions duplications associated neurocognitive deficits, yet few studies compared these groups using the same measures to address confounding measurement differences. We report a prospective international collaboration applying computerized assessment, Penn Computerized Neurocognitive Battery (CNB), administered in multi-site study...
Summary The 1 mg dexamethasone suppression test (DST) was carried out in patients with a major depressive illness order to establish whether the results of this test, given before antidepressant or ECT treatment, could predict eventual therapeutic outcome. No significant difference be detected overall improvement between those normal abnormal DST response respectively, based on 50 ng/ml cortisol cut-off point. However, using 100 as point it found that an (i.e. post-DST plasma concentration ⩾...
The rise in serum gastrin and pepsinogen I after 5 days' treatment with the proton pump inhibitor pantoprazole (40 mg/day) was examined eight duodenal ulcer patients Helicobacter pylori infection compared whom it had been eradicated. Before treatment, post-prandial concentrations were higher H. pylori-positive than -eradicated (p < 0.05). median pre-prandial on similar (41%) (45%). also py/on'-positive (81%) (69%), resulting significantly during former. greater (114%) (8%), These...
The dexamethasone suppression test (DST) was carried out on 143 patients with a major depressive disorder, who were classified into those history of weight loss (n = 89) and without 54). Seventy-three per cent 61% had an abnormal DST; this difference not statistically significant. Of the receiving prophylactic lithium therapy, 13 found to have changed their DST status retesting after period 14 months, but there no significant in weight. It is concluded that necessary condition for illness.
The nature of recessive mutations at the autosomal locus encoding purine salvage enzyme adenine phosphoribosyl transferase (APRT) was analyzed in a highly malignant human tumor cell line (the colorectal carcinoma SW620). Mutant strains resistant to analog 8-azaadenine were obtained two steps. first step selection for partial drug resistance produced hemizygous APRT as result high frequency loss one allele. In second selection, low base substitutions, small deletions, or insertions complete...
Ageing is the greatest global healthcare challenge, as it underlies age-related functional decline and primary risk factor for a range of common diseases, including neurodegenerative conditions such Alzheimer's disease (AD). However, molecular mechanisms defining chronological age versus biological age, how these underlie AD pathogenesis, are not well understood. The objective this study was to integrate human genetic variation associated with lifespan or from Genome-Wide Association Studies...
Scientific Report29 April 2019Open Access Transparent process Nucleosome dynamics of human iPSC during neural differentiation Janet C Harwood orcid.org/0000-0002-3225-0069 MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, UK Search more papers by this author Nicholas A Kent orcid.org/0000-0002-4114-1307 School Biosciences, D Allen orcid.org/0000-0003-4009-186X Adrian J Corresponding Author [email protected] orcid.org/0000-0003-3124-5169 Neuroscience and Mental...
Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are among the most common rare genetic disorders associated with significant risk for neuropsychiatric across lifespan. Microdeletions duplications in these neurocognitive deficits, yet there few studies comparing groups using same measures. We address this gap a prospective international collaboration applying computerized assessment. The Penn Computerized Neurocognitive Battery (CNB) was administered...