A5107558944- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Birth, Development, and Health
- Prenatal Screening and Diagnostics
- Renal and related cancers
- RNA modifications and cancer
- Heavy Metal Exposure and Toxicity
- RNA Research and Splicing
- Pancreatic function and diabetes
- Chromosomal and Genetic Variations
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Gestational Diabetes Research and Management
- Stress Responses and Cortisol
- Liver Disease Diagnosis and Treatment
- Children's Rights and Participation
- ICT in Developing Communities
- Neuroendocrine regulation and behavior
- Genomic variations and chromosomal abnormalities
- Mercury impact and mitigation studies
- MicroRNA in disease regulation
- Obesity, Physical Activity, Diet
- Health, Environment, Cognitive Aging
- Congenital heart defects research
- Assisted Reproductive Technology and Twin Pregnancy
University of Bath
2009-2024
North Carolina State University
2015-2023
King's College London
2010-2021
Guy's Hospital
2011-2020
Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific exists very scarcely at midgestation. We reveal two forms of oocyte-specific inheritance: limited preimplantation, or longer duration, i.e. maternally imprinted loci. Transient and maternal germline DMRs (gDMRs) are indistinguishable gametes...
Imprinted genes – critical for growth, metabolism, and neuronal function are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs established before tissue specification, these marks similar across cell types. Thus, they attractive investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate in humans by performing...
Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as DNA methylation (DNAm), are a hypothesized link; however, epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites cord blood leukocytes associated with pre-pregnancy 187 mother-female and 173 mother-male offsprings. DNAm was measured using Illumina...
Imprinted genes are defined by their preferential expression from one of the two parental alleles. This unique mode gene is dependent on allele-specific DNA methylation profiles established at regulatory sequences called imprinting control regions (ICRs). These loci have been used as biosensors to study how environmental exposures affect and transcription. However, a critical unanswered question whether they more, less, or equally sensitive stressors rest genome.Using cadmium exposure in...
Abstract Cadmium (Cd) is a toxic heavy metal ubiquitous in the environment. Maternal exposure to Cd associated with fetal growth restriction, trace element deficiencies, and congenital malformations. during adulthood cardiovascular disease (CVD); however, effects of maternal on offspring development are not well-understood. Utilizing mouse model exposure, we show that born Cd-exposed mothers have increased heart weights at birth susceptibility hypertension adulthood. Despite inefficient...
Alternative polyadenylation increases transcriptome diversity by generating multiple transcript isoforms from a single gene.It is thought that this process can be subject to epigenetic regulation, but few specific examples of have been reported.We previously showed the Mcts2/H13 locus genomic imprinting and alternative H13 transcripts occurs in an allele-specific manner, regulated mechanisms.Here, we demonstrate allelespecific at another imprinted with similar features.Nap1l5 retrogene...
Despite being a fundamental biological problem the control of body size and proportions during development remains poorly understood, although it is accepted that insulin-like growth factor (IGF) pathway has central role in regulation, probably all animals. The involvement imprinted genes also attracted much attention, not least because two earliest discovered were shown to be oppositely antagonistic their regulation growth. Igf2 gene encodes paternally expressed ligand promotes growth,...
Abstract Cadmium (Cd) is a ubiquitous toxic heavy metal of major public concern. Despite inefficient placental transfer, maternal Cd exposure impairs fetal growth and development. Increasing evidence from animal models humans suggests negatively impacts neurodevelopment; however, the underlying molecular mechanisms are unclear. To address this, we utilized multiple -omics approaches in mouse model to identify pathways altered developing brain. Offspring maternally exposed presented with...
Imprinted retrotransposed genes share a common genomic organization including promoter-associated differentially methylated region (DMR) and position within the intron of multi-exonic 'host' gene. In mouse, at least one transcript host gene is also subject to imprinting. Human retrogene orthologues are imprinted we reveal that human not imprinted. This coincides with rearrangements occurred during primate evolution, which increase separation between DMRs genes. To address mechanisms...
Cadmium (Cd) is a toxic heavy metal found throughout the environment and one of top ten toxicants major public health concern identified by World Health Organization. In utero Cd exposure causes fetal growth restriction, malformation, spontaneous abortion; however, mechanisms which impacts these outcomes are poorly understood. accumulates in placenta, suggesting that negative may be consequence disrupted placental function insufficiency. To understand impact on gene expression within we...
Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with imprinted, maternally (outside of central nervous system) Grb10 gene on chromosome 11, but little else known about expression Ddc_exon1a. Fluorescent immunostaining localizes DDC to myocardium pre-natal heart, susceptible abnormal development and implicated congenital...
Abstract Background and Aims Within the next decade, NAFLD is predicted to become most prevalent cause of childhood liver failure in developed countries. Predisposition juvenile can be programmed during early life response maternal metabolic syndrome (MetS), but underlying mechanisms are poorly understood. We hypothesized that imprinted genes, defined by expression from a single parental allele, play key role MetS‐induced NAFLD, due their susceptibility environmental stressors functions...
Cadmium (Cd) is a toxic metal ubiquitous in the environment. In utero, Cd inefficiently transported to foetus but causes foetal growth restriction (FGR), likely through impairment of placenta where accumulates. However, underlying molecular mechanisms are poorly understood. can modulate expression imprinted genes, defined by their transcription from one parental allele, which play critical roles placental and growth. The genes governed DNA methylation at Imprinting Control Regions (ICRs),...
Alternative splicing (AS) and alternative polyadenylation (APA) generate diverse transcripts in mammalian genomes during development differentiation. Epigenetic marks such as trimethylation of histone H3 lysine 36 (H3K36me3) DNA methylation play a role generating transcriptome diversity. Intragenic CpG islands (iCGIs) their corresponding host genes exhibit dynamic epigenetic gene expression patterns between different tissues. We hypothesise that iCGI-associated H3K36me3, transcription can...
Abstract Cadmium (Cd) exposure in adulthood is associated with nonalcoholic fatty liver disease (NAFLD), characterized by steatosis, inflammation, and fibrosis. The prevalence of NAFLD children increasing, suggesting a role for the developmental environment programming susceptibility. However, Cd underlying mechanisms remain unclear. We have proposed that imprinted genes are strong candidates connecting early life later disease. In support this, we previously identified roles Imprinted Gene...
Genomic imprinting is a form of gene dosage regulation in which expressed from only one the alleles, manner dependent on parent origin. The mechanisms governing imprinted expression have been investigated detail and greatly contributed to our understanding genome general. Both DNA sequence features, such as CpG islands, epigenetic methylation non-coding RNAs, play important roles achieving expression. However, relative importance these factors varies depending locus question. Defining...
The behaviour of a nursing dam influences the development, physiology, and her offspring. Maternal behaviours can be modulated both by environmental factors, including diet, physical or behavioural characteristics In most studies effects environment on maternal behaviour, F0 dams nurse their own F1 Because are indirectly exposed to stressor in utero these studies, it is not possible differentiate between from direct exposure those mediated changes as consequence exposure. this study, we used...
Abstract Background The growth factor receptor bound 7 (Grb7) family of signalling adaptor proteins comprises Grb7, Grb10 and Grb14. Each can interact with the insulin other tyrosine kinases, where Grb14 inhibit activity. In cell culture studies they mediate functions including survival, proliferation, migration. Mouse knockout (KO) have revealed physiological roles for in glucose-regulated energy homeostasis. Both KO mice exhibit increased peripheral tissues, glucose sensitivity a modestly...