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Raúl Alelú-Paz, Francisco J Carmona, José V Sanchez-Mut, Ariel Cariaga-Martínez, Ana González-Corpas, Nadia Ashour, Maria J Orea, Ana Escanilla, Alfonso Monje, Carmen Guerrero Márquez, Jerónimo Saiz-Ruiz, Manel Esteller, Santiago Ropero
Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450K) DNA methylation array. We identified 139 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences which functions remain unknown...
2016: Frontiers in Psychology
Brooke Rhead, Calliope Holingue, Michael Cole, Xiaorong Shao, Hong L Quach, Diana Quach, Khooshbu Shah, Elizabeth Sinclair, John Graf, Thomas Link, Ruby Harrison, Elior Rahmani, Eran Halperin, Wei Wang, Gary S Firestein, Lisa F Barcellos, Lindsey A Criswell
Objectives Our study aimed to determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients were also differentially methylated in peripheral blood samples. Methods We measured 371 genome-wide DNA methylation profiles from 63 RA cases and 31 controls, in CD14+ monocytes, CD19+ B cells, CD4+ memory T cells and CD4+ naïve T cells, using Illumina HumanMethylation450 (450k) BeadChips. Results We found that of 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naïve T cells of RA cases compared to controls...
October 9, 2016: Arthritis & Rheumatology
Oliver Kaut, Ina Schmitt, Jörg Tost, Florence Busato, Yi Liu, Per Hofmann, Stephanie H Witt, Marcella Rietschel, Holger Fröhlich, Ullrich Wüllner
Numerous studies have elucidated the genetics of Parkinson's disease; however, the aetiology of the majority of sporadic cases has not yet been resolved. We hypothesized that epigenetic variations could be associated with PD and evaluated the DNA methylation pattern in PD patients compared to brothers or twins without PD. The methylation of DNA from peripheral blood mononuclear cells of 62 discordant siblings including 24 monozygotic twins was characterized with Illumina DNA Methylation 450K bead arrays and subsequently validated in two independent cohorts: 221 PD vs...
October 6, 2016: Neurogenetics
Cristina Camprubí, Albert Salas-Huetos, Riccardo Aiese-Cigliano, Anna Godo, Maria-Carme Pons, Giancarlo Castellano, Mark Grossmann, Walter Sanseverino, José I Martin-Subero, Nicolás Garrido, Joan Blanco
The influence of aberrant sperm DNA methylation on the reproductive capacity of couples has been postulated as a cause of infertility. This study compared the DNA methylation of spermatozoa of 19 fertile donors and 42 infertile patients using the Illumina 450K array. Clustering analysis of methylation data arranged fertile and infertile patients into two groups. Bivariate clustering analysis identified a differential distribution of samples according to the characteristics of seminogram and age, suggesting a possible link between these parameters and specific methylation profiles...
September 15, 2016: Reproductive Biomedicine Online
Olivia M de Goede, Pascal M Lavoie, Wendy P Robinson
AIM: To provide insight into fetal nucleated red blood cell (nRBC) development using genome-wide DNA methylation (DNAm) profiling. MATERIALS & METHODS: The DNAm profile (Illumina 450K array) of cord blood (n = 7) derived nRBCs was compared with B cells, CD4 and CD8 T cells, natural killer cells, granulocytes, monocytes and placenta (n = 5). RESULTS: nRBCs and placenta had similarly low array-wide DNAm compared with white blood cells, but their patterns of hypomethylation differed at biologically relevant subsets of the array...
September 30, 2016: Epigenomics
Christian Trolle, Morten Muhlig Nielsen, Anne Skakkebæk, Philippe Lamy, Søren Vang, Jakob Hedegaard, Iver Nordentoft, Torben Falck Ørntoft, Jakob Skou Pedersen, Claus Højbjerg Gravholt
Adults with 45,X monosomy (Turner syndrome) reflect a surviving minority since more than 99% of fetuses with 45,X monosomy die in utero. In adulthood 45,X monosomy is associated with increased morbidity and mortality, although strikingly heterogeneous with some individuals left untouched while others suffer from cardiovascular disease, autoimmune disease and infertility. The present study investigates the leukocyte DNAmethylation profile by using the 450K-Illumina Infinium assay and the leukocyte RNA-expression profile in 45,X monosomy compared with karyotypically normal female and male controls...
September 30, 2016: Scientific Reports
James M Flanagan, Angela Wilson, Chail Koo, Nahal Masrour, John Gallon, Erick Loomis, Kirsty Flower, Charlotte Wilhelm-Benartzi, Alexander Hergovich, Paula Cunnea, Hani Gabra, Elena I Braicu, Jalid Sehouli, Silvia Darb-Esfahani, Adriaan Vanderstichele, Ignace Vergote, Caroline Kreuzinger, Dan Cacsire Castillo-Tong, Gijsbertha Ba Wisman, Els M J J Berns, Nadeem Siddiqui, James Paul, Robert Brown
PURPOSE: DNA damage repair can lead to epigenetic changes. DNA mismatch repair proteins bind to platinum DNA adducts and at sites of DNA damage can recruit the DNA methylating enzyme DNMT1, resulting in aberrant methylation. We hypothesised that DNA damage repair during platinum-based chemotherapy may cause aberrant DNA methylation in normal tissues of patients such as blood. EXPERIMENTAL DESIGN: We used Illumina 450k methylation arrays and bisulphite pyrosequencing to investigate methylation at presentation and relapse in blood DNA from ovarian cancer patients enrolled in the SCOTROC1 trial (n=247) and in a cohort of ovarian tumour DNA samples collected at first relapse (n=46)...
September 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Roby Joehanes, Allan C Just, Riccardo E Marioni, Luke C Pilling, Lindsay M Reynolds, Pooja R Mandaviya, Weihua Guan, Tao Xu, Cathy E Elks, Stella Aslibekyan, Hortensia Moreno-Macias, Jennifer A Smith, Jennifer A Brody, Radhika Dhingra, Paul Yousefi, James S Pankow, Sonja Kunze, Sonia Shah, Allan F McRae, Kurt Lohman, Jin Sha, Devin M Absher, Luigi Ferrucci, Wei Zhao, Ellen W Demerath, Jan Bressler, Megan L Grove, Tianxiao Huan, Chunyu Liu, Michael M Mendelson, Chen Yao, Douglas P Kiel, Annette Peters, Rui Wang-Sattler, Peter M Visscher, Naomi R Wray, John M Starr, Jingzhong Ding, Carlos J Rodriguez, Nicholas J Wareham, Marguerite R Irvin, Degui Zhi, Myrto Barrdahl, Paolo Vineis, Srikant Ambatipudi, André G Uitterlinden, Albert Hofman, Joel Schwartz, Elena Colicino, Lifang Hou, Pantel S Vokonas, Dena G Hernandez, Andrew B Singleton, Stefania Bandinelli, Stephen T Turner, Erin B Ware, Alicia K Smith, Torsten Klengel, Elisabeth B Binder, Bruce M Psaty, Kent D Taylor, Sina A Gharib, Brenton R Swenson, Liming Liang, Dawn L DeMeo, George T O'Connor, Zdenko Herceg, Kerry J Ressler, Karen N Conneely, Nona Sotoodehnia, Sharon L R Kardia, David Melzer, Andrea A Baccarelli, Joyce B J van Meurs, Isabelle Romieu, Donna K Arnett, Ken K Ong, Yongmei Liu, Melanie Waldenberger, Ian J Deary, Myriam Fornage, Daniel Levy, Stephanie J London
BACKGROUND: -DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. METHODS AND RESULTS: -To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15,907 blood derived DNA samples from participants in 16 cohorts (including 2,433 current, 6,518 former, and 6,956 never smokers)...
September 20, 2016: Circulation. Cardiovascular Genetics
Thanh Nha Uyen, Kazuo Sakashita, Lika'a Fasih Y Al-Kzayer, Yozo Nakazawa, Takashi Kurata, Kenichi Koike
BACKGROUND: The outcome of approximately 20% of patients with acute lymphoblastic leukemia (ALL) remains poor because of disease recurrence. We examined whether DNA methylation of cadherin superfamily genes is a useful biomarker for ALL relapse. PROCEDURE: We used Infinium Methylation 450K Arrays to assess genome-wide DNA methylation status. The methylation status of each individual gene was then determined by a combination of bisulfite restriction analysis and genome bisulfite sequencing...
September 19, 2016: Pediatric Blood & Cancer
Xianan Zhang, Xiaowei Jia, Liangying Mei, Min Zheng, Chen Yu, Meng Ye
BACKGROUND: Silicosis is a respiratory disease caused by long-term silica dust exposure. Our previous study has demonstrated that silica mediates the activation of phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/serine or threonine kinase (AKT)/mitogen-activated protein kinases (MAPK)/AP-1 pathway in human embryo lung fibroblasts (HELFs). The purpose of this study is to identify genome-wide aberrant DNA methylation profiling in lung tissues from silicosis patients...
August 2016: Journal of Thoracic Disease
Zongying Liu, Haixiu Yan, Jinshu Zhang
To determine whether blood DNA methylation is associated with hepatocellular carcinoma (HCC) for Chinese patients, we used genome-wide DNA methylation detection to access the blood samples of Chinese patients by Illumina Human methylation 450K arrays. Sixty potentially gene locis which had different methylated levels significantly among tumor and adjacent normal tissues would be tested in this study. A previous study was conducted in China communities and followed with 7 years. The DNA from white blood cells (WBC) from 192 patients with HCC and 215 matched controls were assayed in this study...
July 2016: Pakistan Journal of Pharmaceutical Sciences
Shicheng Guo, Qi Zhu, Ting Jiang, Rongsheng Wang, Yi Shen, Xiao Zhu, Yan Wang, Fengmin Bai, Qin Ding, Xiaodong Zhou, Guangjie Chen, Dong Yi He
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA. METHOD: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray...
September 1, 2016: Modern Rheumatology
Liang-Liang Cai, Guo-Yan Liu, Chi-Meng Tzeng
BACKGROUND: During development, methylation permanently changes gene activity, while aberrant gene methylation is key to human tumorigenesis. Gene methylation is an epigenetic event leading to gene silencing and some tumor suppressor genes that are aberrantly methylated in both thyroid cancer and benign thyroid tumor, suggesting a role for methylation in early thyroid tumorigenesis. Specific gene methylation occurs in certain types of thyroid cancer and depends on particular signaling pathways...
August 2016: Medicine (Baltimore)
Per Wahlberg, Anders Lundmark, Jessica Nordlund, Stephan Busche, Amanda Raine, Karolina Tandre, Lars Rönnblom, Daniel Sinnett, Erik Forestier, Tomi Pastinen, Gudmar Lönnerholm, Ann-Christine Syvänen
AIM: To identify regions of aberrant DNA methylation in acute lymphoblastic leukemia (ALL) cells of different subtypes on a genome-wide scale. MATERIALS & METHODS: Whole-genome bisulfite sequencing (WGBS) was used to determine the DNA methylation levels in cells from four pediatric ALL patients of different subtypes. The findings were confirmed by 450k DNA methylation arrays in a large patient set. RESULTS: Compared with mature B or T cells WGBS detected on average 82,000 differentially methylated regions per patient...
October 2016: Epigenomics
Kyle J Burghardt, Jacyln M Goodrich, Dana C Dolinoy, Vicki L Ellingrod
OBJECTIVES: Atypical antipsychotics (AAPs) carry a significant risk of cardiometabolic side effects, including insulin resistance. It is thought that the insulin resistance resulting from the use of AAPs may be associated with changes in DNA methylation. We aimed to identify and validate a candidate gene associated with AAP-induced insulin resistance by using a multi-step approach that included an epigenome-wide association study (EWAS) and validation with site-specific methylation and metabolomics data...
August 2016: Bipolar Disorders
Sean Whittaker
van Doorn et al. have defined the DNA methylomes of Sézary cells based on a genome-wide methylation analysis using the Illumina 450K array platform (Illumina, San Diego, CA). Their results show aberrant DNA methylation patterns in CD4-enriched T cells from peripheral blood samples, patterns that are distinct from those of patients with inflammatory erythroderma and from healthy volunteers. Whereas 7.8% of 473,921 5'-cytosine-phosphate-guanine-3' (CpG) sites were hypomethylated, 3.2% showed marked enrichment and selection for hypermethylated CpG sites within the proximal region of gene promoters, including some genes that have previously been shown to be hypermethylated in cutaneous T-cell lymphomas (CTCLs), using standard bisulfite modification techniques...
September 2016: Journal of Investigative Dermatology
T G Jenkins, K I Aston, J M Hotaling, M B Shamsi, L Simon, D T Carrell
Semen analysis is commonly used as a tool to assess the fertility potential of a male, despite its relatively low predictive power. In this study, we have assessed associations between semen analysis findings (low count, low motility, low viability, poor sperm penetration assay results, poor morphology, and increased DNA damage) and DNA methylation patterns in mature spermatozoa. DNA methylation patterns in the mature spermatozoa are thought to be indicative of patterns in the adult germline stem cells and may offer insight into potential perturbations to cellular pathways involved in spermatogenesis...
September 2016: Andrology
Stephanie Kim, Melissa Eliot, Devin C Koestler, Eugene A Houseman, James G Wetmur, John K Wiencke, Karl T Kelsey
AIM: We examined whether variation in blood-based epigenome-wide association studies could be more completely explained by augmenting existing reference DNA methylation libraries. MATERIALS & METHODS: We compared existing and enhanced libraries in predicting variability in three publicly available 450K methylation datasets that collected whole-blood samples. Models were fit separately to each CpG site and used to estimate the additional variability when adjustments for cell composition were made with each library...
September 2016: Epigenomics
Adam R Smith, Rebecca G Smith, Daniel Condliffe, Eilis Hannon, Leonard Schalkwyk, Jonathan Mill, Katie Lunnon
Although mutations within the TREM2 gene have been robustly associated with Alzheimer's disease, it is not known whether alterations in the regulation of this gene are also involved in pathogenesis. Here, we present data demonstrating increased DNA methylation in the superior temporal gyrus in Alzheimer's disease brain at a CpG site located 289 bp upstream of the transcription start site of the TREM2 gene in 3 independent study cohorts using 2 different technologies (Illumina Infinium 450K methylation beadchip and pyrosequencing)...
July 16, 2016: Neurobiology of Aging
Kristina Gervin, Christian Magnus Page, Hans Christian D Aass, Michelle A Jansen, Heidi Elisabeth Fjeldstad, Bettina Kulle Andreassen, Liesbeth Duijts, Joyce B van Meurs, Menno C van Zelm, Vincent W Jaddoe, Hedvig Nordeng, Gunn Peggy Knudsen, Per Magnus, Wenche Nystad, Anne Cathrine Staff, Janine F Felix, Robert Lyle
Epigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused by cellular heterogeneity is a major concern. This can be adjusted for using reference data consisting of DNA methylation signatures in cell types isolated from blood. However, the most commonly used reference data set is based on blood samples from adult males and is not representative of the cell type composition in neonatal cord blood...
September 2016: Epigenetics: Official Journal of the DNA Methylation Society
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