Life Sciences Commons^™

The Stability Of Epigenetic Variants That Can Act As Loci Causing Phenotypic Change, Raul Faburrieta

Biology Theses

Epigenetic variations are a possible source of heritable phenotypic variation. In this study I focus on phenotypic alterations seen in epigenetic Recombinant Inbred Lines (epiRILs) of Arabidopsis thaliana. These epiRILs allow me to study the effects differentially methylated regions (DMRs) have on phenotypic variance. In a study performed in 2014 by Cortijo et al., they found that DMR’s affect flowering time and root length when grown under greenhouse conditions. In this study, I replicated the Cortijo et al. (2014) study, with some changes, to see whether the same significant eQTL regions are found. I found that, some of the eQTLs …

Unravelling The Genetic Basis Of Schizophrenia, Clara Casey, John F. Fullard, Roy D. Sleator

Department of Biological Sciences Publications

Neuronal development is a highly regulated mechanism that is central to organismal function in animals. In humans, disruptions to this process can lead to a range of neurodevelopmental phenotypes, including Schizophrenia (SCZ). SCZ has a significant genetic component, whereby an individual with an SCZ affected family member is eight times more likely to develop the disease than someone with no family history of SCZ. By examining a combination of genomic, transcriptomic and epigenomic datasets, large-scale ‘omics’ studies aim to delineate the relationship between genetic variation and abnormal cellular activity in the SCZ brain. Herein, we provide a brief overview of …

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

A Study Of The Snd1/Prmt5 Axis In Liver Cancer By Genetic Mouse Models, Tanner Wright, Tanner Wright

Dissertations & Theses (Open Access)

Arginine methylation is an essential post-translational modification (PTM) in cells. Protein arginine methyltransferase 5 (PRMT5) is the primary enzyme that catalyzes symmetric dimethyl arginine (SDMA) and requires methylosome protein 50 (MEP50) for stability and enzymatic activity which are necessary for life and development. Effector proteins bind different types of PTM’s to facilitate signaling. Staphylococcal nuclease Tudor domain containing 1 (SND1) is an effector that specifically binds SDMA via its single C-terminal Tudor domain. Both SND1 and PRMT5 have been implicated in hepatocellular carcinoma (HCC). SND1 has been confirmed as a driver of HCC using genetically engineered mouse models (GEMMs), though, …

Epigenetics In Forensic Science, Reagan Faunce

Honors Projects

DNA methylation can be useful for forensic scientists because it can be used to differentiate between the DNA of identical twins, determine the age of a contributor of a DNA sample, and help us understand the actions and tendencies of violent criminals. Research shows that DNA methylation changes over time and can be caused by traumatic events, suggesting that methylation increases with age. Prior studies of DNA methylation at the promoters of the EDARADD, TOM1L1, and NPTX2 genes have been able to predict age within 5.2 years and a study of the ASPA, EDARADD, PDE4C, and ELOVL2 genes predicted age …

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

Electronic Theses and Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

Methylation Patterns Across Tissue Type And Time In Peromyscus Leucopus: A Targeted Museum Study, Loryn Smith

Master's Theses

Museum specimens are a vital data source for many types of studies. One relatively new use includes studying methylation patterns. Methylation patterns are a form of epigenetics or how gene expression changes without alteration of the genetic code. These patterns have been examined in many mammals. However, the focus has previously been on overall epigenetic patterns. Few studies have investigated whether methylation patterns differ across tissue types, time, or preservation method. In this study, I compared methylation patterns in muscle, liver, toe pads, and nasal bones from Peromyscus leucopus (white-footed mouse) museum specimens collected in 2022, 2018, 2014, and 2008 …

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations & Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Increased Risk Of Mental Illness Due To Epigenetic Alteration Of The Nr3c1 Gene After Early Life Adversity., Erin Mccue

Thinking Matters Symposium

Early life adversity (ELA), such as malnutrition, abuse, and economic disparity, is an issue commonly seen in adolescents, a group already facing increased risk for stress-related disorders. This review of current literature reveals that gestational stress exposure, as well as variations in maternal care during postnatal development, cause latent effects on the epigenome, specifically impacting the glucocorticoid receptors (GRs) encoded by the NR3C1 gene. GRs bind to glucocorticoids to regulate the body’s neuroendocrine stress response. However, in those with a history of ELA, the number of GRs is reduced, generating dysregulation within the hypothalamic-pituitary-adrenal (HPA) axis. Rodent studies are utilized …

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Liquid Biopsies For Type 2 Diabetes Mellitus: Biomarkers For Disease Risk And Diagnosis, Stephanie Chidester

Dissertations

Background: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the United States. There is a critical need for earlier and more effective screening and diagnostic tools. Innovative liquid biopsy technologies may play a key role in meeting this need. Liquid biopsies are a non-invasive, adjunctive tool for determining diagnosis, prognosis, and therapeutic response. This dissertation focuses on two potential applications of liquid biopsy technologies to T2DM: (1) epigenome-wide association studies to identify epigenetic markers of risk for T2DM, and (2) extracellular vesicle (EV)-based biomarker studies to identify and detect markers associated with T2DM development and progression. Dissertation studies: …

Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.

Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV₁, FVC, and FEV₁/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.

Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery …

Opioid Medication Use And Blood Dna Methylation: Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Roby Joehanes, Daniel L. Mccartney, Minjung Kho, Anke Hüls, Annah B. Wyss, Chunyu Liu, Rosie M. Walker, Sharon L.R. Kardia, Thomas S. Wingo, Adam Burkholder, Jiantao Ma, Archie Campbell, Aliza P. Wingo, Tianxiao Huan, Sinjini Sikdar, Amena Keshawarz, David A. Bennett, Jennifer A. Smith, Kathryn L. Evans, Daniel Levy, Stephanie J. London

Mathematics & Statistics Faculty Publications

Aim: To identify differential methylation related to prescribed opioid use. Methods: This study examined whether blood DNA methylation, measured using Illumina arrays, differs by recent opioid medication use in four population-based cohorts. We meta-analyzed results (282 users; 10,560 nonusers) using inverse-variance weighting. Results: Differential methylation (false discovery rate <0.05) was observed at six CpGs annotated to the following genes: KIAA0226, CPLX2, TDRP, RNF38, TTC23 and GPR179. Integrative epigenomic analyses linked implicated loci to regulatory elements in blood and/or brain. Additionally, 74 CpGs were differentially methylated in males or females. Methylation at significant CpGs correlated with gene expression in blood and/or brain. Conclusion: This study identified DNA …

Decoding The Equine Genome: Lessons From Encode, Sichong Peng, Jessica L. Petersen, Rebecca R. Bellone, Ted Kalbfleisch, N. B. Kingsley, Alexa Barber, Eleonora Cappelletti, Elena Giulotto, Carrie J. Finno

Department of Animal Science: Faculty Publications

The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data …

Decoding The Equine Genome: Lessons From Encode, Sichong Peng, Jessica L. Petersen, Rebecca R. Bellone, Theodore S. Kalbfleisch, N. B. Kingsley, Alexa M. Barber, Eleonora Cappelletti, Elena Giulotto, Carrie J. Finno

Veterinary Science Faculty Publications

The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data …

Exploring Epigenetics As A Tool For Population Assessment And Conservation In Large Marine Predators, Andria Paige Beal

FIU Electronic Theses and Dissertations

Worldwide, many large marine predator populations are in decline. These populations can be difficult to study due to the extensive home ranges and migration patterns often exhibited by these species. Molecular tools are therefore necessary to measure specific parameters on these populations that would otherwise be nearly impossible to obtain. This dissertation pioneers the use of environmental epigenetic approaches for that purpose, and specifically the epigenetic modification known as DNA methylation, using sharks and small cetaceans as model organisms. This work is organized into five chapters. Chapter I is an introductory chapter that lays out the fundamentals of environmental epigenetics …

Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula

Dissertations & Theses (Open Access)

G-quadruplexes are non-B DNA structures formed by four or more runs of repeated guanines that confer unique features to living organism’s genomes. These sequences are enriched in regulatory regions, such as promoters and 5’ UTRs, and have distinct regulatory roles in both health and disease states. Even though previous studies showed the impact of G4 in gene expression, none of them summarized the location-specific effect of G4. Also, there is no broad understanding about the most common G4 repeat in the human genome, named here as G4-22, and how it links to the evolution of mammals and their biology. In …

Successful Atac-Seq From Snap-Frozen Equine Tissues, Sichong Peng, Rebecca Bellone, Jessica L. Petersen, Theodore S. Kalbfleisch, Carrie J. Finno

Veterinary Science Faculty Publications

An assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) has become an increasingly popular method to assess genome-wide chromatin accessibility in isolated nuclei from fresh tissues. However, many biobanks contain only snap-frozen tissue samples. While ATAC-seq has been applied to frozen brain tissues in human, its applicability in a wide variety of tissues in horse remains unclear. The Functional Annotation of Animal Genome (FAANG) project is an international collaboration aimed to provide high quality functional annotation of animal genomes. The equine FAANG initiative has generated a biobank of over 80 tissues from two reference female animals and experiments to begin …

Epigenetic Mechanisms As Drivers Of Environmental Responses In Stony Corals, Javier A. Rodriguez Casariego

FIU Electronic Theses and Dissertations

The current pace of anthropogenic global change is imposing unprecedented conditions to biological systems. Coral reef ecosystems are particularly sensitive to the rapid increase in thermal anomalies and the changes in water chemistry caused by global change. However, although their decline has been documented worldwide, there are signs suggesting that stony corals harbor greater phenotypic plasticity than previously expected, sparking the interest in the study acquired non-genetic modifications (e.g., epigenome, microbiome) potentially increasing their resilience to global change, and constituting one of the main targets for intervention.

Epigenetics constitutes an exciting frontier to understand how the environment influences the regulation …

Discovery Of Novel Ubiquitin- And Methylation-Dependent Interactions Using Protein Domain Microarrays, Jianji Chen

Dissertations & Theses (Open Access)

Post-translational modifications (PTMs) drive signal transduction by interacting with "reader" proteins. Protein domain microarray is a high throughput platform to identify novel readers for PTMs. In this dissertation, I applied two protein domain microarrays identifying novel readers for histone H2Aub1 and H2Bub1, and H3TM K4me3. Ubiquitinations of histone H2A at K119 (H2Aub1) and histone H2B at K120 (H2Bub1) function in distinct transcription regulation and DNA damage repair pathways, likely mediated by specific "reader" proteins. There are only two H2Aub1-specific readers identified and no known H2Bub1-specific readers. Using a ubiquitin-binding domain microarray, I discovered the phospholipase A2-activating protein (PLAA) PFU domain …

“Adopt-A-Tissue” Initiative Advances Efforts To Identify Tissue-Specific Histone Marks In The Mare, N. B. Kingsley, Natasha A. Hamilton, Gabriella Lindgren, Ludovic Orlando, Ernest Bailey, Samantha Brooks, Molly Mccue, Theodore S. Kalbfleisch, James N. Macleod, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

“Adopt-A-Tissue” Initiative Advances Efforts To Identify Tissue-Specific Histone Marks In The Mare, N B. Kingsley, Natasha A. Hamilton, Gabriella Lindgren, Ludovic Orlando, Ernie Bailey, Samantha Brooks, Molly Mccue, T S. Kalbfleisch, James N. Macleod, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone

Department of Animal Science: Faculty Publications

No abstract provided.

Initial And Advanced Stages Of Microbiota Establishment Within The Tsetse Fly, Miguel Eduardo Medina Munoz

Graduate Theses, Dissertations, and Problem Reports

Symbiosis is a long-term physical association between two or more species, although little is known regarding its evolutionary origins, particularly at the genetic level. Tsetse flies are the vector of African trypanosomes, causative agents of Human and Animal African Trypanosomiases. Tsetse provide an ideal model for studying initial and advanced stages of symbiosis. Tsetse have a simple digestive tract microbiota primarily consisting of two bacteria; the ancient mutualist Wigglesworthia glossinidia and the recently acquired Sodalis glossinidius. This work presents a chronological study in evolutionary terms of the history of a microbial-insect association. First, I present concepts on symbiosis and …

Characterization Of Higher Order Chromatin Structures And Chromatin States In Cell Models Of Human Herpesvirus Infection, Michael Mariani

Graduate College Dissertations and Theses

Human herpesviruses are ubiquitous pathogens worldwide with 90% of the global population infected with one or more Human herpesviruses (HHV’s) by adulthood. All herpesviruses have three unique life cycle stages. Upon resolution of a primary acute stage infection, they can establish a latent stage infection within the host cell nucleus. This stage is characterized primarily by transcriptional quiescence of the viral genome. Specific physiological conditions (e.g., cell stress) can cause the latent virus to enter the reactivation stage, often many years after resolution of the acute infection, in which the virus becomes replicationally active again. HHV’s are known to cause …

Epigenetic Regulation Of Prostate Cancer, Ruixin Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer is (PCa) the second leading cause of cancer death in males in the United State, with 174,650 new cases and 31,620 deaths estimated in 2019. It has been documented that epigenetic deregulation such as histone modification and DNA methylation contributes to PCa initiation and progression. EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the Polycomb Repressive Complex (PRC2) responsible for H3K27me3 and gene repression, has been identified as a promising target in PCa. In addition, overexpression of other epigenetic regulators such as DNA methyltransferases (DNMT) is also observed in PCa. These epigenetic regulators undergo extensive post-translational …

The Genome-Wide Roles Of The Lung Lineage Transcription Factor Nkx2-1 In The Regulation Of Opposing Cell Fates In Vivo, Danielle Renae Little

Dissertations & Theses (Open Access)

Lineage transcription factors mark, promote, and maintain multiple distinct cell types originating from a common progenitor. Despite their essential role, how such factors function and bind genome wide to orchestrate the epigenetic changes necessary to form and maintain these identities in vivo is unclear. One lineage transcription factor NK Homeobox 2-1 (NKX2-1) is expressed throughout the lung epithelium during development and was thought to be lost in the extraordinarily thin cell type required for gas exchange– the alveolar type 1 (AT1) cell. Complementing precise genetic knockouts with cell type-specific ChIP-seq, ATAC-seq, and scRNA-seq, our study shows that AT1 and AT2 …

Epigenetics A Decolonizing Science, Wade Paul

Electronic Thesis and Dissertation Repository

Epigenetics is the study of gene expression that does not entail alterations to the actual DNA. Decolonization is a theoretical and political movement that seeks to deconstruct colonial institutions and ideologies and reconstruct new and balanced approaches that accept and respect Indigenous worldviews. This project studies the decolonizing potential of epigenetics. Using genealogy as the method, the study establishes a long history of reductionist and deterministic thought that shaped the study of genetic science. Particular instances like thrift gene theory are explored to highlight how genetic explanations have been detrimental to the health and wellbeing of Indigenous people and illustrate …

Transcription Factor-Mediated Epigenetic Regulation In The Healthy Brain And Neurological Disease, Alexander J. Cammack

Arts & Sciences Electronic Theses and Dissertations

Proper cellular development and function is a complex process established by elaborate gene expression networks. These networks are regulated by epigenetic processes, which alter chromatin states and coordinate the binding of transcription factors (TFs) to regulatory elements (REs), such as enhancers, across the genome to facilitate gene expression. It follows then that a major experimental effort is to profile and understand the binding patterns of TFs to REs in various cellular types and contexts. Critically however, current TF profiling techniques are limited in their abilities to profile TF occupancy in targeted cellular populations and temporal windows, hindering investigations into epigenetic …

Developing Tools For Identifying Tissue-Specific Epigenetic Marks And Predicting Dna Hydroxy/Methylation, Yu He

Arts & Sciences Electronic Theses and Dissertations

A single genome can derive phenotypically unique cell types through various epigenetic modifications that instruct specific gene expression patterns. Histone modifications, DNA methylation, and DNA hydroxymetylation are the most common epigenetic modifications. To understand the mechanisms how these epigenetic modifications regulate gene expression, one often needs to map these marks genome-wide through profiling methods. Firstly, for histone modifications, Roadmap Epigenomics Consortium generated The Human Reference Epigenome Map, containing thousands of genome-wide histone modification datasets that describe epigenomes of a variety of different human tissue and cell types. This map has allowed investigators to obtain a much deeper and more comprehensive …

Discrimination Of Monozygotic Twins Using Dna Methylation Levels Of One Cpg Site At Chromosome 3, Dino O. Robinson

Student Theses

Conventional STR typing, commonly used in forensics for human identification, poses a problem in criminal cases and paternity disputes involving monozygotic (MZ) twins because they share identical DNA sequences. To date, no routine method is available in forensics to differentiate between individuals of MZ pairs. Recently, epigenetic methods measuring differential DNA methylation patterns have been applied to MZ twin differentiation. In this study, we investigated the potential to identify MZ twins using a previously identified DNA methylation site in chromosome 3, cg18562578, in a sample of 129 MZ and 37 dizygotic (DZ) twin pairs. We used bisulfite converted saliva DNA …