ORCID Profile
0000-0003-3759-2145
Current Organisations
University of Southampton
,
Australian National University
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2013
Publisher: Springer Science and Business Media LLC
Date: 14-10-2009
Abstract: Epigenetic modification of DNA via methylation is one of the key inventions in eukaryotic evolution. It provides a source for the switching of gene activities, the maintenance of stable phenotypes and the integration of environmental and genomic signals. Although this process is widespread among eukaryotes, both the patterns of methylation and their relevant biological roles not only vary noticeably in different lineages, but often are poorly understood. In addition, the evolutionary origins of DNA methylation in multicellular organisms remain enigmatic. Here we used a new 'epigenetic' model, the social honey bee Apis mellifera , to gain insights into the significance of methylated genes. We combined microarray profiling of several tissues with genome-scale bioinformatics and bisulfite sequencing of selected genes to study the honey bee methylome. We find that around 35% of the annotated honey bee genes are expected to be methylated at the CpG dinucleotides by a highly conserved DNA methylation system. We show that one unifying feature of the methylated genes in this species is their broad pattern of expression and the associated 'housekeeping' roles. In contrast, genes involved in more stringently regulated spatial or temporal functions are predicted to be un-methylated. Our data suggest that honey bees use CpG methylation of intragenic regions as an epigenetic mechanism to control the levels of activity of the genes that are broadly expressed and might be needed for conserved core biological processes in virtually every type of cell. We discuss the implications of our findings for genome-scale regulatory network structures and the evolution of the role(s) of DNA methylation in eukaryotes. Our findings are particularly important in the context of the emerging evidence that environmental factors can influence the epigenetic settings of some genes and lead to serious metabolic and behavioural disorders.
Publisher: Wiley
Date: 14-09-2016
DOI: 10.1111/ALL.12949
Publisher: Springer Science and Business Media LLC
Date: 21-04-2015
Publisher: BMJ
Date: 05-02-2014
Publisher: Elsevier
Date: 2016
Publisher: MDPI AG
Date: 10-06-2014
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/2615348
Abstract: Screening cytosine-phosphate-guanine dinucleotide (CpG) DNA methylation sites in association with some covariate(s) is desired due to high dimensionality. We incorporate surrogate variable analyses (SVAs) into (ordinary or robust) linear regressions and utilize training and testing s les for nested validation to screen CpG sites. SVA is to account for variations in the methylation not explained by the specified covariate(s) and adjust for confounding effects. To make it easier to users, this screening method is built into a user-friendly R package, ttScreening , with efficient algorithms implemented. Various simulations were implemented to examine the robustness and sensitivity of the method compared to the classical approaches controlling for multiple testing: the false discovery rates-based (FDR-based) and the Bonferroni-based methods. The proposed approach in general performs better and has the potential to control both types I and II errors. We applied ttScreening to 383,998 CpG sites in association with maternal smoking, one of the leading factors for cancer risk.
Publisher: Institute of Mathematical Statistics
Date: 12-2015
DOI: 10.1214/15-AOAS865
Publisher: Springer Science and Business Media LLC
Date: 21-08-2015
Publisher: Springer Science and Business Media LLC
Date: 15-04-2014
Publisher: Wiley
Date: 29-03-2016
DOI: 10.1111/ALL.12882
Publisher: Future Medicine Ltd
Date: 12-2013
DOI: 10.2217/EPI.13.68
Abstract: Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment.
Publisher: American Society for Clinical Investigation
Date: 23-04-2020
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.ANAI.2015.11.016
Abstract: Thymic stromal lymphopoietin (TSLP) polymorphisms influence atopy risk. TSLP might constitute a key interface between the environment and the allergic immune response. However, whether the effects of TSLP polymorphisms on atopic dermatitis (AD) are modified by allergic sensitization is not clear. To evaluate the joint effect of allergic sensitization and TSLP polymorphisms on AD and to test whether TSLP polymorphisms increase the risk of asthma in children with AD. A total of 1,520 kindergarten children (375 with AD and 1,145 controls) selected from the Childhood Environment and Allergic Diseases Study cohort in 2010 were enrolled. Information about allergic diseases and environmental exposures was collected by questionnaire. Skin prick tests were performed to measure allergic sensitization. TSLP polymorphisms were genotyped by TaqMan assay. Logistic regressions were conducted to estimate the association among TSLP polymorphisms, allergic sensitization, and AD. For replication, a subs le of the British Isle of Wight birth cohort was used. The TSLP rs2289278 CC genotype increased the risk of AD (odds ratio 1.90, 95% confidence interval 1.12-3.22). In children sensitized to certain allergens, a genetic predisposition (rs2289278 genotype CC) significantly increased the risk of AD. These findings were replicated in the British subs le using rs2289276 genotypes TT and TC, which are in linkage disequilibrium with rs2289278. In subjects with AD, the rs2289278 C allele also significantly increased the risk of developing asthma (odds ratio 8.31, 95% confidence interval 1.08-64.13). The association of rs2289278 with AD was stronger in children with allergic sensitization than in children without atopy. TSLP polymorphisms also increased the risk of asthma in children with AD.
Publisher: Wiley
Date: 27-07-2015
DOI: 10.1111/PAI.12408
Abstract: It has been recognized for centuries that allergic disease runs in families, implying a role for genetic factors in determining in idual susceptibility. More recently, a range of evidence shows that many of these genetic factors, together with in utero environmental exposures, lead to the development of allergic disease through altered immune and organ development. Environmental exposures during pregnancy including diet, nutrient intake and toxin exposures can alter the epigenome and interact with inherited genetic and epigenetic risk factors to directly and indirectly influence organ development and immune programming. Understanding of these factors will be essential in identifying at-risk in iduals and possible development of therapeutic interventions for the primary prevention of allergic disease. In this review, we summarize the evidence that suggests allergic disease begins in utero, together with possible mechanisms for the effect of environmental exposures during pregnancy on allergic disease risk, including epigenetics.
Publisher: Springer Science and Business Media LLC
Date: 19-09-2014
Publisher: Springer Science and Business Media LLC
Date: 21-07-2015
Publisher: Wiley
Date: 24-11-2011
Publisher: Wiley
Date: 21-01-2016
DOI: 10.1111/ALL.12833
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-10-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-08-2010
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Gabrielle A. Lockett.