A5062163604- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Genetic Syndromes and Imprinting
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Prenatal Screening and Diagnostics
- Drug Transport and Resistance Mechanisms
- Biomedical Text Mining and Ontologies
- Birth, Development, and Health
- Single-cell and spatial transcriptomics
- Peroxisome Proliferator-Activated Receptors
- Neuroblastoma Research and Treatments
- Pregnancy and preeclampsia studies
- Eicosanoids and Hypertension Pharmacology
- Liver Disease Diagnosis and Treatment
- Telomeres, Telomerase, and Senescence
- Amyotrophic Lateral Sclerosis Research
- Machine Learning in Bioinformatics
- Renin-Angiotensin System Studies
- Genetics, Aging, and Longevity in Model Organisms
- Genetic and phenotypic traits in livestock
- Redox biology and oxidative stress
- Amyloidosis: Diagnosis, Treatment, Outcomes
University of Cambridge
2014-2024
Monash University
2023
Hudson Institute of Medical Research
2023
Jiangsu University
2021
Affiliated Hospital of Jiangsu University
2021
Lymphatic Education & Research Network
2016
Nanjing University
2016
Nanjing General Hospital of Nanjing Military Command
2016
University of Nottingham
2010-2012
Queen's Medical Centre
2010-2011
The nutritional sins of the mother… Prenatal exposures a mother can affect health her offspring, but how? Radford et al. found that male progeny undernourished pregnant mice had altered DNA chemistry in their sperm. In addition, offspring displayed compromised metabolic health. specific affected genes not only lost methylation also lacked normal sperm packaging factors (protamines) and instead were enriched nucleosomes. Thus, when subjected to suboptimal prenatal environment, feel effects...
Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) critical for maintenance of this memory during post-fertilization reprogramming, yet incomplete penetrance ZFP57 mutations in humans and mice suggests additional effectors. We reveal that ZNF445/ZFP445, which we trace to the origins imprinting, binds control regions (ICRs) humans. In mice, ZFP445 act together,...
Abstract Background Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription can distinguish between unmodified and modified bases. Current models of factor binding tend not take modifications into account, while the recent few that do often have limitations. This makes a comprehensive accurate profiling affinities difficult. Results Here, we develop methods identify sites DNA. Our expand standard /// alphabet...
Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary maintaining the DNA methylation memory at multiple imprinting control regions in early mouse embryos and embryonic stem (ES) cells. Maternal-zygotic deletion mice presents highly penetrant phenotype with no animals surviving to birth. Additionally, several cases human...
KRAB zinc finger proteins (KZFPs) represent one of the largest families DNA-binding in vertebrate genomes and appear to have evolved silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting repressive chromatin states. ZFP57 is required maintain post-fertilization DNA methylation memory parental origin at genomic imprints. Here we conduct RNA-seq ChIP-seq analyses normal mutant mouse ES cells understand relative importance imprints, unique...
A key pathological feature of late-onset Alzheimer's disease (LOAD) is the abnormal extracellular accumulation amyloid-β (Aβ) peptide. Thus, altered Aβ degradation could be a major contributor to development LOAD. Variants in gene encoding Aβ-degrading enzyme, angiotensin-1 converting enzyme (ACE) therefore represent plausible candidates for association with LOAD pathology and risk. Following Alzgene meta-analyses all published case-control studies, ACE variants rs4291 rs1800764 showed...
Abstract Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription can distinguish between unmodified and modified bases. Current models of factor binding tend not take modifications into account, while the recent few that do often have limitations. This makes a comprehensive accurate profiling affinities difficult. Here, we developed methods identify sites DNA. Our expand standard A/C/G/T alphabet include...
The missing heritability exhibited by late-onset Alzheimer's disease is unexplained and has been partly attributed to epistatic interaction. Methods available explore this are often based on logistic regression allow for determination of deviation from an expected outcome as a result statistical epistasis. Three such methodologies including Synergy Factor the PLINK modules, -epistasis -fast-epistasis, were applied study interaction between interleukin-6 interleukin-10. models analyzed...
Human embryonic stem cells (hESCs) potentially offer new routes to study, on the basis of Developmental Origins Health and Disease (DOHaD) concept, how maternal environment during pregnancy influences offspring's health can predispose chronic disease in later life. Reactive oxygen species (ROS), antioxidant defences cellular redox status play a key function gene expression regulation are involved diabetes metabolic syndromes as ageing. We have, therefore, designed an vitro cell model...
Abstract Background KRAB-zinc finger proteins (KZFPs) represent one of the largest families DNA binding in vertebrate genomes and appear to have evolved silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting repressive chromatin states. ZFP57 is required maintain post-fertilization methylation memory parental-origin at genomic imprints along with ZFP445 which specific for imprints. However, has multiple methylated targets. Here we conduct...
Apolipoprotein-E (APOE) is the principle apolipoprotein in CNS and haplotypes at rs429358 rs7412 determine which isoforms (e2, 3 or 4) are expressed. Due to process of gene synergism (epistasis), it anticipated that studying single nucleotide polymorphisms (SNPs) combination will uncover new risk genes. Looking all possible two-way SNP combinations raises major computational statistical challenges. We have overcome this by looking 2, way interactions between either e2 e4 allele SNPs (n =...
Genome-wide Association Studies (GWAS) have extensively explored the contribution of common variants (MAF>5%) to heritable human diseases. Whilst these studies offer insight into disease pathways alone, they do not explain entire genetic burden. Consequently, resequencing projects explore role rare variation (MAF<5%) are becoming increasingly popular in post-GWAS era. We recently identified a panel biomarker proteins for late-onset Alzheimer's (LOAD) cerebro-spinal fluid (CSF) which, like...
It is accepted that genetics plays a crucial role in human longevity with up to 30% heritability. Genes implicated age-related diseases might have influencing life-span. In this study, we investigated i) the presence of genes life-span LOAD GWAS data and ii) if known (APOE, CLU, PICALM, CR1 BIN1) also play longevity. Through collaborative effort were able draw upon combined dataset (subject-level genotype data) from 1,385 subjects (before quality control) documented age-at-death (AAD)....