Genetics and Genomics Commons^™

Mediation And Moderation Of Intergenerational Epigenetic Effects Of Trauma, Stefanie Renee Pilkay

Doctoral Dissertations

Trauma and early-life stress have been linked to poor mental and physical health outcomes. In fact, research has identified trauma and stress can influence epigenetic marks on genes that can alter gene activity. It is suspected that epigenetically altered gene activity is involved in behavior and mental health. This may help explain why some individuals don’t experience great benefit from treatment for the effects of stress, and severe mental health symptoms can be chronic for decades or a lifetime. Moreover, some trauma-related mental health symptoms have shown generational patterns that appear linked to epigenetic marks. Therefore, this study sought to …

Single-Base Resolution Mapping Of 5-Hydroxymethylcytosine Modifications In Hippocampus Of Alzheimer's Disease Subjects, Elizabeth M. Ellison, Melissa A. Bradley-Whitman, Mark A. Lovell

Chemistry Faculty Publications

Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects. Our …

Transient And Permanent Changes In Dna Methylation Patterns In Inorganic Arsenic-Mediated Epithelial-To-Mesenchymal Transition, Meredith Eckstein, Matthew Rea, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Chronic low dose inorganic arsenic exposure causes cells to take on an epithelial-to-mesenchymal phenotype, which is a crucial process in carcinogenesis. Inorganic arsenic is not a mutagen and thus epigenetic alterations have been implicated in this process. Indeed, during the epithelial-to-mesenchymal transition, morphologic changes to cells correlate with changes in chromatin structure and gene expression, ultimately driving this process. However, studies on the effects of inorganic arsenic exposure/withdrawal on the epithelial-to-mesenchymal transition and the impact of epigenetic alterations in this process are limited. In this study we used high-resolution microarray analysis to measure the changes in DNA methylation in cells …

Whole-Genome Dna Methylation Status Associated With Clinical Ptsd Measures Of Oif/Oef Veterans., R Hammamieh, N Chakraborty, A Gautam, S Muhie, R Yang, D Donohue, R Kumar, B J Daigle, Y Zhang, D A Amara, S-A Miller, S Srinivasan, J Flory, R Yehuda, L Petzold, O M Wolkowitz, S H Mellon, L Hood, F J Doyle, C Marmar, M Jett

Articles, Abstracts, and Reports

Emerging knowledge suggests that post-traumatic stress disorder (PTSD) pathophysiology is linked to the patients' epigenetic changes, but comprehensive studies examining genome-wide methylation have not been performed. In this study, we examined genome-wide DNA methylation in peripheral whole blood in combat veterans with and without PTSD to ascertain differentially methylated probes. Discovery was initially made in a training sample comprising 48 male Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans with PTSD and 51 age/ethnicity/gender-matched combat-exposed PTSD-negative controls. Agilent whole-genome array detected ~5600 differentially methylated CpG islands (CpGI) annotated to ~2800 differently methylated genes (DMGs). The majority (84.5%) of these CpGIs …

Transcriptomic And Epigenetic Responses To Environmental Stress In Marine Bivalves With A Focus On Harmful Algal Blooms, Maria Victoria Suarez Ulloa

FIU Electronic Theses and Dissertations

Global change poses new threats for life in the oceans forcing marine organisms to respond through molecular acclimatory and adaptive strategies. Although bivalve molluscs are particularly tolerant and resilient to environmental stress, they must now face the challenge of more frequent and severe Harmful Algal Blooms (HABs) episodes. These massive outbreaks of microalgae produce toxins that accumulate in the tissues of these filter-feeder organisms, causing changes in their gene expression profiles, which in turn modify their phenotype in order to maintain homeostasis. Such modifications in gene expression are modulated by epigenetic mechanisms elicited by specific environmental stimuli, laying the foundations …

Variation In Dna Methylation Is Not Consistently Reflected By Sociality In Hymenoptera, Karl M. Glastad, Samuel V. Arsenault, Kim L. Vertacnik, Scott M. Geib, Sasha Kay, Bryan N. Danforth, Sandra M. Rehan, Catherine R. Linnen, Sarah D. Kocher, Brendan G. Hunt

Biology Faculty Publications

Changes in gene regulation that underlie phenotypic evolution can be encoded directly in the DNA sequence or mediated by chromatin modifications such as DNA methylation. It has been hypothesized that the evolution of eusocial division of labor is associated with enhanced gene regulatory potential, which may include expansions in DNA methylation in the genomes of Hymenoptera (bees, ants, wasps, and sawflies). Recently, this hypothesis garnered support from analyses of a commonly used metric to estimate DNA methylation in silico, CpG content. Here, we test this hypothesis using direct, nucleotide-level measures of DNA methylation across nine species of Hymenoptera. In doing …

Cpt1a Methylation Is Associated With Plasma Adiponectin, S. Aslibekyan, A. N. Do, H. Xu, S. Li, M. R. Irvin, D Zhi, H. K. Tiwari, D. M. Absher, A. R. Shuldiner, T. Zhang, W. Chen, K. Tanner, C. Hong, B. D. Mitchell, G. Berenson, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background and Aims—Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood.

Methods and Results—We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n= 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression …

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

The Rs16906252:C>T Snp Is Not Associated With Increased Overall Survival Or Temozolomide Response In A Han-Chinese Glioma Cohort., Kuo-Chen Wei, Chia-Yuan Chen, Li-Ying Feng, Wei-Tzu Huang, Chia-Hua Chen, Peng-Wei Hsu, Kai Wang, Leroy Hood, Leslie Y Chen

Articles, Abstracts, and Reports

The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST) and the response to temozolomide (TMZ) treatment. However, these findings haven't been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients. The MGMT promoter methylation was measured by bisulfite conversion followed by pyro-sequencing, while rs16906252 was measured by restriction endonuclease …