ORCID Profile
0000-0003-3442-965X
Current Organisation
Oxford Nanopore Technologies Plc
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Publisher: Figshare
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 03-05-2017
Publisher: OMICS Publishing Group
Date: 2014
Publisher: Research Square Platform LLC
Date: 21-08-2019
Abstract: BackgroundEpigenetics plays a fundamental role in cellular development and differentiation epigenetic mechanisms, such as DNA methylation, are involved in gene regulation and the exquisite nuance of expression changes seen in the journey from pluripotency to final differentiation. Thus, DNA methylation has the potential to reveal new insights in to immune cell biology.ResultsWe mined publicly available DNA methylation data with a machine-learning approach to identify differentially methylated loci between different white blood cell types. We then interrogated the DNA methylation and mRNA expression of candidate loci in CD4+, CD8+, CD14+, CD19+ and CD56+ fractions from 12 additional, independent healthy in iduals (6 male, 6 female). ‘Classic’ immune cell markers such as CD8 and CD19 showed expected methylation/expression associations fitting with established dogma that hypermethylation is associated with the repression of gene expression. We also observed large differential methylation at loci which are not considered established immune cell markers, and some of these novel loci showed inverse correlations between methylation and mRNA expression (such as PARK2,DCP2).ConclusionsOur results highlight the value of mining publicly available data, the utility of DNA methylation as a discriminatory marker and the potential value of DNA methylation to provide additional insights into immune cell biology and developmental processes.
Publisher: Impact Journals, LLC
Date: 28-02-2017
Publisher: Figshare
Date: 2019
Publisher: Public Library of Science (PLoS)
Date: 16-10-2015
Publisher: SAGE Publications
Date: 14-05-2013
Abstract: Oestrogen receptor 1 ( ESR1) is located in region 6q25.1 and encodes a ligand-activated transcription factor composed of several domains important for hormone binding and transcription activation. Progesterone receptor ( PGR) is located in 11q22-23 and mediates the role of progesterone interacting with different transcriptional co-regulators. ESR1 and PGR have previously been implicated in migraine susceptibility. Here, we report the results of an association study of these genes in a migraine pedigree from the genetic isolate of Norfolk Island, a population descended from a small number of Isle of Man “Bounty Mutineer” and Tahitian founders. A significant number of molecular markers in the ESR1 (143) and PGR (43) genes were evaluated in a s le of 285 related in iduals (135 males 150 females). A pedigree-based analysis in the GenABEL package was used to analyse the results. A total of 10 markers in the ESR1 gene showed association with migraine ( p 0.05) in the Norfolk Island population. No association was detected with PGR. Three haplotypes in ESR1 were found to be associated with migraine ( p = 0.004, 0.03, 0.005). Future genetic studies in larger populations and expression analysis are required to clarify the role of ESR1 in migraine susceptibility.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2015
Publisher: Springer Science and Business Media LLC
Date: 16-11-2018
DOI: 10.1038/S10038-017-0374-Y
Abstract: Primary open-angle glaucoma (POAG) is influenced by both genetic and environmental factors. Despite significant progress in identifying genetic variants associated with POAG, there remains a substantial amount of unexplained heritability. Study design features that may enhance knowledge of the genetic architecture include focusing on multiple quantitative traits related to ocular disorders (i.e. endophenotypes), targeting genetic variants that directly influence gene expression (i.e. cis-eQTLs) and utilising genetically isolated populations to reduce genetic and environmental noise and thus enhance association signals. In this study we performed heritability and blood-based eQTL association analysis of five key POAG endophenotypes in 330 in iduals from the Norfolk Island (NI) isolate. Results showed evidence of heritability for all five traits, with H
Publisher: Wiley
Date: 24-02-2020
DOI: 10.1002/OBY.22722
Publisher: Zenodo
Date: 2020
Publisher: SAGE Publications
Date: 12-12-2014
Abstract: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk of developing MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation are recognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure and inherited genetic systems. To identify methylation changes associated with MS, we performed a genome-wide DNA methylation analysis of CD4+ T cells from 30 patients with relapsing–remitting MS and 28 healthy controls using Illumina 450K methylation arrays. A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. After prioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of a major effect CpG island in DRB1 in MS cases ( p FDR 3 × 10 −3 ). In addition, we found 55 non-HLA CpGs that exhibited differential methylation, many of which localise to genes previously linked to MS. Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation to MS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.
Publisher: JMIR Publications Inc.
Date: 10-05-2022
DOI: 10.2196/36858
Abstract: Digital technology and social media use are common among young people in Australia and worldwide. Research suggests that young people have both positive and negative experiences online, but we know little about the experiences of Muslim communities. This study aims to explore the positive and negative experiences of digital technology and social media use among young people and parents from Muslim backgrounds in Melbourne, Victoria, Australia. This study involved a partnership between researchers and a not-for-profit organization that work with culturally and linguistically erse communities. We adopted a participatory and qualitative approach and designed the research in consultation with young people from Muslim backgrounds. Data were collected through in-person and online focus groups with 33 young people aged 16-22 years and 15 parents aged 40-57 years. Data were thematically analyzed. We generated 3 themes: (1) maintaining local and global connections, (2) a paradoxical space: identity, belonging and discrimination, and (3) the digital ide between young Muslims and parents. Results highlighted that social media was an important extension of social and cultural connections, particularly during COVID-19, when people were unable to connect through school or places of worship. Young participants perceived social media as a space where they could establish their identity and feel a sense of belonging. However, participants were also at risk of being exposed to discrimination and unrealistic standards of beauty and success. Although parents and young people shared some similar concerns, there was a large digital ide in online experiences. Both groups implemented strategies to reduce social media use, with young people believing that having short technology-free breaks during prayer and quality family time was beneficial for their mental well-being. Programs that address technology-related harms must acknowledge the benefits of social media for young Muslims across identity, belonging, representation, and social connection. Further research is required to understand how parents and young people can create environments that foster technology-free breaks to support mental well-being.
Publisher: Springer Science and Business Media LLC
Date: 03-09-2015
Publisher: Frontiers Media SA
Date: 05-03-2018
Publisher: Frontiers Media SA
Date: 05-10-2021
DOI: 10.3389/FMICB.2021.752070
Abstract: Acinetobacter baumannii is a multidrug-resistant pathogen that represents a serious threat to global health. A. baumannii possesses a wide range of virulence factors that contribute to the bacterial pathogenicity. Among them, the siderophore acinetobactin is one of the most important, being essential for the development of the infection. In this study we performed an in-depth analysis of the acinetobactin cluster in the strain A. baumannii ATCC 17978. For this purpose, nineteen in idual isogenic mutant strains were generated, and further phenotypical analysis were performed. In idual mutants lacking the biosynthetic genes entA, basG , basC , basD , and basB showed a significant loss in virulence, due to the disruption in the acinetobactin production. Similarly, the gene bauA , coding for the acinetobactin receptor, was also found to be crucial for the bacterial pathogenesis. In addition, the analysis of the Δ basJ/ Δ fbsB double mutant strain demonstrated the high level of genetic redundancy between siderophores where the role of specific genes of the acinetobactin cluster can be fulfilled by their fimsbactin redundant genes. Overall, this study highlights the essential role of entA , basG , basC , basD , basB and bauA in the pathogenicity of A. baumannii and provides potential therapeutic targets for the design of new antivirulence agents against this microorganism.
Publisher: Springer Science and Business Media LLC
Date: 22-04-2020
DOI: 10.1038/S41398-020-0800-3
Abstract: Cannabis use is of increasing public health interest globally. Here we examined the effect of heavy cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study, CHDS). A total of 48 heavy cannabis users were selected from the CHDS cohort, on the basis of their adult exposure to cannabis and tobacco, and DNA methylation assessed from whole blood s les, collected at approximately age 28. Methylation in heavy cannabis users was assessed, relative to non-users ( n = 48 controls) via the Illumina Infinium® MethylationEPIC BeadChip. We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenome-wide significance level ( P 10 −7 ). However, there were 521 sites differentially methylated at P 0.001 which were enriched for genes involved in neuronal signalling (glutamatergic synapse and long-term potentiation) and cardiomyopathy. Further, the most differentially methylated loci were associated with genes with reported roles in brain function (e.g. TMEM190 , MUC3L , CDC20 and SP9 ). We conclude that the effects of cannabis use on the mature human blood methylome differ from, and are less pronounced than, the effects of tobacco use, and that larger s le sizes are required to investigate this further.
Publisher: Figshare
Date: 2019
Publisher: Public Library of Science (PLoS)
Date: 13-04-2012
Publisher: Zenodo
Date: 2021
Publisher: Zenodo
Date: 2021
Publisher: Zenodo
Date: 2020
Publisher: Wiley
Date: 19-07-2022
Abstract: Sanger sequencing of the mitochondrial DNA (mtDNA) control region was previously the only method available for forensic casework involving degraded s les from skeletal remains. The introduction of Next Generation Sequencing (NGS) has transformed genetic data generation and human identification using mtDNA. Whole mitochondrial genome (mtGenome) analysis is now being introduced into forensic laboratories around the world to analyze historical remains. Research into large pedigrees using the mtGenome is critical to evaluate currently available interpretation guidelines for mtDNA analysis, which were developed for comparisons using the control region. This study included mtGenomes from 225 in iduals from the last four generations of the Norfolk Island (NI) genetic isolate pedigree consisting of 49 distinct maternal lineages. The data from these in iduals were arranged into 2339 maternally related pairs separated by up to 18 meioses. Our results show that 97.3% of maternally related pairs were concordant at all nucleotide positions, resulting in the correct interpretation of “Cannot Exclude” 2.7% of pairs produced an “Inconclusive” result, and there were no instances of false exclusion. While these results indicate that existing guidelines are suitable for multigenerational whole mtGenome analysis, we recommend caution be taken when classifying heteroplasmic changes as differences for human identification. Our data showed the classification of heteroplasmic changes as differences increases the prevalence of inconclusive identification by 6%, with false exclusions observed in 0.34% of pairs examined. Further studies of multigenerational pedigrees, however, are needed to validate mtGenome interpretation guidelines for historical case work to more fully utilize emerging advancements.
Publisher: Wiley
Date: 21-08-2017
DOI: 10.1002/OBY.21950
Publisher: Cambridge University Press (CUP)
Date: 20-09-2013
DOI: 10.1017/THG.2013.63
Abstract: Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNFα, lymphotoxin α (LTA), and lymphotoxin β (LTB), has been implicated to influence the intensity and duration of local inflammation. It is thought that sterile inflammation mediated by LTA, LTB, and TNFα contributes to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Previous studies have investigated variants within the TNF gene cluster region in relation to migraine susceptibility, with largely conflicting results. The aim of this study was to expand on previous research and utilize a large case-control cohort and range of variants within the TNF gene cluster to investigate the role of the TNF gene cluster in migraine. Nine single nucleotide polymorphisms (SNPs) were selected for investigation as follows: rs1800683, rs2229094, rs2009658, rs2071590, rs2239704, rs909253, rs1800630, rs1800629, and rs3093664. No significant association with migraine susceptibility was found for any of the SNPs tested, with further testing according to migraine subtype and gender also showing no association for disease risk. Haplotype analysis showed that none of the tested haplotypes were significantly associated with migraine.
Publisher: JMIR Publications Inc.
Date: 02-2022
Abstract: igital technology and social media use are common among young people in Australia and worldwide. Research suggests that young people have both positive and negative experiences online, but we know little about the experiences of Muslim communities. his study aims to explore the positive and negative experiences of digital technology and social media use among young people and parents from Muslim backgrounds in Melbourne, Victoria, Australia. his study involved a partnership between researchers and a not-for-profit organization that work with culturally and linguistically erse communities. We adopted a participatory and qualitative approach and designed the research in consultation with young people from Muslim backgrounds. Data were collected through in-person and online focus groups with 33 young people aged 16-22 years and 15 parents aged 40-57 years. Data were thematically analyzed. e generated 3 themes: (1) maintaining local and global connections, (2) a paradoxical space: identity, belonging and discrimination, and (3) the digital ide between young Muslims and parents. Results highlighted that social media was an important extension of social and cultural connections, particularly during COVID-19, when people were unable to connect through school or places of worship. Young participants perceived social media as a space where they could establish their identity and feel a sense of belonging. However, participants were also at risk of being exposed to discrimination and unrealistic standards of beauty and success. Although parents and young people shared some similar concerns, there was a large digital ide in online experiences. Both groups implemented strategies to reduce social media use, with young people believing that having short technology-free breaks during prayer and quality family time was beneficial for their mental well-being. rograms that address technology-related harms must acknowledge the benefits of social media for young Muslims across identity, belonging, representation, and social connection. Further research is required to understand how parents and young people can create environments that foster technology-free breaks to support mental well-being.
Publisher: Elsevier BV
Date: 12-2013
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Public Library of Science (PLoS)
Date: 04-11-2020
Publisher: Springer Science and Business Media LLC
Date: 27-08-2016
Publisher: Springer Science and Business Media LLC
Date: 29-07-2015
DOI: 10.1007/S00439-015-1587-9
Abstract: Migraine has been defined as a common disabling primary headache disorder. Epidemiology studies have provided with the undeniable evidence of genetic components as active players in the development of the disease under a polygenic model in which multiple risk alleles exert modest in idual effects. Our objective was to test the contribution of a polygenic effect to migraine risk in the Norfolk Island population using a panel of SNPs reported to be disease associated in published migraine GWAS. We also investigated whether in idual SNPs were associated with gene expression levels measured in whole blood. Polygenic scores were calculated in a total of 285 related in iduals (74 cases, 211 controls) from the Norfolk Island using 51 SNPs previously reported to be associated with migraine in published GWAS. The association between polygenic score and migraine case-control status was tested using logistic regression. Results indicate that a migraine polygenic risk score was associated with migraine case-control status in this population (P = 0.016). This supports the hypothesis that multiple SNPs with weak effects collectively contribute to migraine risk in this population. Amongst the SNPs included in the polygenic model, four were associated with the expression of the USMG5 gene, including rs171251 (P = 0.012). Results from this study provide evidence for a polygenic contribution to migraine risk in an isolated population and highlight specific SNPs that regulate the expression of USMG5, a gene critical for mitochondrial function.
Publisher: Springer Science and Business Media LLC
Date: 26-04-2022
DOI: 10.1038/S41598-022-10530-3
Abstract: Estimates of mutation rates for various regions of the human mitochondrial genome (mtGenome) vary widely, depending on whether they are inferred using a phylogenetic approach or obtained directly from pedigrees. Traditionally, only the control region, or small portions of the coding region have been targeted for analysis due to the cost and effort required to produce whole mtGenome Sanger profiles. Here, we report one of the first pedigree derived mutation rates for the entire human mtGenome. The entire mtGenome from 225 in iduals originating from Norfolk Island was analysed to estimate the pedigree derived mutation rate and compared against published mutation rates. These in iduals were from 45 maternal lineages spanning 345 generational events. Mutation rates for various portions of the mtGenome were calculated. Nine mutations (including two transitions and seven cases of heteroplasmy) were observed, resulting in a rate of 0.058 mutations/site/million years (95% CI 0.031–0.108). These mutation rates are approximately 16 times higher than estimates derived from phylogenetic analysis with heteroplasmy detected in 13 s les (n = 225, 5.8% in iduals). Providing one of the first pedigree derived estimates for the entire mtGenome, this study provides a better understanding of human mtGenome evolution and has relevance to many research fields, including medicine, anthropology and forensics.
Publisher: Cold Spring Harbor Laboratory
Date: 20-02-2020
DOI: 10.1101/2020.02.20.957340
Abstract: Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n=62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but nine nuclear encoded variants in eight separate genes were found to be associated with exercise responses (FDR .05) (rs11061368: DIABLO, rs113400963: FAM185A, rs6062129 and rs6121949: MTG2, rs7231304: AFG3L2, rs2041840: NDUFAF7, rs7085433: TIMM23, rs1063271: SPTLC2, rs2275273: ALDH18A1). Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities. Previous exercise genetic studies contain many flaws that impede the growth in knowledge surrounding change in exercise outcomes. In particular, exercise studies looking at mtDNA variants have looked at very small portions of the mitochondrial genome. Mitochondria are the ‘power house’ of the cell and therefore understanding the mitochondrial genetics behind adaptations to training can help us fill knowledge gaps in current research. Here, we utilised a new mitochondrial genetic sequencing technique to examine all mitochondrial and mitochondrial related genetic variations. We have shown that there were no mitochondrial specific variants that influenced exercise training however there were 9 related variants that were significantly associated with exercise phenotypes. Additionally, we have shown that building composite traits increased the significance of our association testing and lead to novel findings. We will be able to understand why response to training is so varied and increase the effectiveness of exercise training on a host of metabolic disorders.
Publisher: Zenodo
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 06-07-2020
DOI: 10.1038/S41598-020-67870-1
Abstract: Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n = 62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but eight nuclear encoded variants in seven separate genes were found to be associated with exercise responses (FDR 0.05) ( rs11061368 : DIABLO , rs113400963 : FAM185A , rs6062129 and rs6121949 : MTG2 , rs7231304 : AFG3L2 , rs2041840 : NDUFAF7 , rs7085433 : TIMM23 , rs1063271 : SPTLC2 ) . Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities.
Publisher: Wiley
Date: 17-01-2017
DOI: 10.1002/MGG3.270
Publisher: LIDSEN Publishing Inc
Date: 12-04-2018
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 07-2015
DOI: 10.1038/NATURE14618
Publisher: Springer Science and Business Media LLC
Date: 19-07-2015
Publisher: Public Library of Science (PLoS)
Date: 28-09-2017
Publisher: Figshare
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 07-10-2015
Publisher: Wiley
Date: 23-01-2013
DOI: 10.1002/GCC.22044
Abstract: We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin's lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.
Publisher: Cold Spring Harbor Laboratory
Date: 26-06-2019
DOI: 10.1101/682070
Abstract: Epigenome-wide studies are often performed using heterogeneous methylation s les, especially when there is no prior information as to which cell-types are disease associated. While much work has been done in ascertaining cell-type fractions and removing cell-type heterogeneity variation, relatively little work has been done in identifying cell-type specific variation in heterogeneous s les. In this paper, we present a Bayesian model-based approach for making cell-type specific inferences in heterogeneous settings, by using a logit-Normal s ling distribution and incorporating a priori knowledge of cell-type lineage. The method is applied to the detection of cell-type specific sex effects in methylation, where cell-type information is present as an independent verification of the results. Panels derived from this method contained more loci where CD8+T, CD19+B and Natural Killer cell-types were differentially methylated. The analysis suggests that an ensemble approach with this method included could be used for discovering cell-type specific methylation changes. anwkenn/Bayes_CDM
Publisher: Springer Science and Business Media LLC
Date: 18-07-2017
Publisher: Cold Spring Harbor Laboratory
Date: 04-11-2019
DOI: 10.1101/829598
Abstract: Cannabis use is of increasing public health interest globally. Here we examined the effect of cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study). We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenomewide significance level (P −7 ). However, there were 521 sites differentially methylated at P .001 which were enriched for genes involved in cardiomyopathy and neuronal signalling. Further, the most differentially methylated loci were associated with genes with reported roles in brain function (e.g. TMEM190, MUC3L, CDC20 and SP9 ). We conclude that the effects of cannabis use on the mature human blood methylome differ from, and are less pronounced than, the effects of tobacco use, and that larger s le sizes are required to investigate this further.
Publisher: Frontiers Media SA
Date: 07-02-2018
Publisher: Springer Science and Business Media LLC
Date: 27-11-2018
DOI: 10.1038/S41598-018-35603-0
Abstract: Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. The inflammatory process in MS is driven by both T and B cells and current therapies are targeted to each of these cell types. Epigenetic mechanisms may provide a valuable link between genes and environment. DNA methylation is the best studied epigenetic mechanism and is recognized as a potential contributor to MS risk. The objective of this study was to identify DNA methylation changes associated with MS in CD19 + B-cells. We performed an epigenome-wide association analysis of DNA methylation in the CD19 + B-cells from 24 patients with relapsing-remitting MS on various treatments and 24 healthy controls using Illumina 450 K arrays. A large differentially methylated region (DMR) was observed at the lymphotoxin alpha ( LTA ) locus. This region was hypermethylated and contains 19 differentially methylated positions (DMPs) spanning 860 bp, all of which are located within the transcriptional start site. We also observed smaller DMRs at 4 MS-associated genes: SLC44A2 , LTBR , CARD11 and CXCR5 . These preliminary findings suggest that B-cell specific DNA-methylation may be associated with MS risk or response to therapy, specifically at the LTA locus. Development of B-cell specific epigenetic therapies is an attractive new avenue of research in MS treatment. Further studies are now required to validate these findings and understand their functional significance.
Publisher: Informa UK Limited
Date: 11-08-2014
DOI: 10.4161/EPI.33066
Publisher: Public Library of Science (PLoS)
Date: 29-05-2012
Location: New Zealand
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
Start Date: 2016
End Date: 2018
Funder: Wellington Medical Research Foundation
View Funded Activity