Life Sciences Commons^™

Migratory Material: Epigenetics & Weaving At The Us-Mexico Border, Valerie Navarrete

Masters Theses

Discourse often sutures the body shut, disallowing representations of identity to outgrow sociopolitical interests. This issue may originate from borders, but also from the unnamable pathology that generational colonial trauma transmits to the mind, body, and environment. Without a direct form of translatability, this thesis proposes a new materialism that deviates from any object-oriented ontology. Untethered and intra-active, epigenetics and weaving represent objects that transform typical ways of knowing and seeing. Their sensitivity to the environment, in addition to their mobility across generations of time, broaden the spatiotemporal loci of the body and its embodiment. Proposing new materials that expand …

The Opioid Epidemic: How Genetics Play A Role In Addiction And Treatment, Kirsten Houston

Honors College Theses

The opioid epidemic is an issue within the pharmaceutical industry in the United States of America due to prescription and non-prescription substances being made available to the population. Opioids include chemical substances that affect the body and brain through opioid receptors, including the mu, kappa, and delta receptors. These substances are derived and synthesized from the poppy plant. Multiple causes have been linked to opioid abuse disorder, including but not limited to employment, income, housing, nutrition, mental health disorders, and genetics. By gathering information from previous literature, genetics may be the main cause of narcotic analgesic tolerance and abuse. Specific …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Understanding The Expression And Role Of Pros-1 In The Male Gonad Of C. Elegans, Jack Bozik

Undergraduate Theses

The gene pros-1 is a transcription factor that is highly expressed within neuronal sheath cells, glial cells, and excretory canal cells. pros-1 plays a role in cell determination of those cell types in the nematode C. elegans, which promotes organismal development. But the degree to which pros-1 presence is important is still not fully understood, because there are many genes involved in development that when mutated or damaged can result in unexpected phenotypes or even total loss of function to a certain developmental mechanism. What makes pros-1 valuable to research is that it is a functional homologue to a …

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …

A Survey Of Speech-Language Pathologists' Academic Preparation In Craniofacial Anomalies, Francesca Myerski

Honors Theses

Craniofacial anomalies occur in 1 of 750 newborns a year with the three main types being cleft lip, cleft palate, and cleft lip and/or cleft palate. There are six main factors that affect craniofacial anomalies that are focused on in this research, including genetics, environmental factors, medications, diet, health risks, and surgical procedures/surgeons. The research found that there is a lot of information on craniofacial anomalies and speech-language pathologists need to learn about as much as possible. The lack of knowledge and academic preparations speech-language pathologists have in craniofacial anomalies has decreased their awareness in the birth defect and has …

The Effects Of Physical Function And Genetics On Cognition And Blood Biomarkers In Individuals At-Risk For Alzheimer’S Disease And Related Dementias, Joshua Louis Gills

Graduate Theses and Dissertations

Alzheimer’s disease and related dementia (ADRD) rates are expected to triple by the year 2050. Early detection and specific mitigation efforts are warranted to blunt the alarming rate. Physical function (PF) declines with age, but higher physical function is associated with better cognitive functioning in middle-to- older age individuals. Moreover, greater physical activity (PA) is associated with better global cognition; however, Apoliporotein e4 carriers may not gain the same benefits with exercise. Additionally, plasma phosphorylated tau 217 (p-tau217) has been identified as a novel diagnostic ADRD biomarker which needs further research to examine associations with risk factors. Therefore, the aims …

Genetics And Genomics Education Among Physician Assistants, Wesley Patterson

All Dissertations

This dissertation comprises five chapters to describe genetics and genomics education among physician assistant/associate (PA) students and practicing PAs. Chapter I introduces the gap in supply and demand of genetic services, the need for non-genetics healthcare providers to fill the gap, and the PA profession as a solution.

Chapter II is a rapid literature review that summarizes the available literature regarding genetics and genomics education for PAs. A paucity of literature exists to describe the current state of PA genetics-genomics education. The few studies retrieved describe content being taught in PA programs, the number of genetics-genomics contact hours PA students …

Strategic Plan For Genomic Competencies Into Undergraduate Nursing Curriculum, Myerann Royce M. Mangalino

UNLV Theses, Dissertations, Professional Papers, and Capstones

Problem: As genomics research continues to grow in medicine and in popular culture, an educational gap in nursing is inevitable. Nurses must have a strong understanding of genetics and genomics to effectively integrate them into current practice.Objectives: The objective is to identify gaps in the current undergraduate curriculum and build threads that may be incorporated into the current curriculum to fill the identified gaps. Methods: The foundation of this project was the Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines, and Outcome Indicators, 2nd Edition (Consensus Panel on Genetic/Genomic Nursing Competencies, 2008). A strategic plan was created to increase …

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 …

The Genetics Of Pain: An Exploration Of Gene-By-Environment Interactions And Their Effects On Pain, Mohamad F. Fakhereddin

Electronic Thesis and Dissertation Repository

The findings presented in this dissertation are part of the bigger SYMBIOME project which aims to use the biopsychosocial model of pain to develop a prognostic clinical phenotype for people that experience musculoskeletal (MSK) trauma. Chapter 2 presents an exploratory analysis to assess the relationships between genetic polymorphisms and pain severity and interference. Early childhood trauma was also explored as a moderator between genetic polymorphisms and pain outcomes. For pain severity, major allele carriers (A/A and G/A) of FKBP5 rs9394314 reported significantly higher scores than minor allele carriers (G/G). Further, major allele carriers who had at least one adverse childhood …

Examination Of Common And Rare Variant Genetic Architecture Of Psychiatric Disorders, Mohammad Ahangari

Theses and Dissertations

Psychiatric disorders are often heterogenous in their manifestation and genome-wide association studies have identified many common risk variants involved in their polygenic architectures with varying degrees of pleiotropy. In recent years, large-scale biobanks have also begun sequencing the genome of their participants to elucidate the role of rare risk variation in the genetic architecture of complex phenotypes, including psychiatric traits. This dissertation sought to better understand the role of both common and rare risk variation in the genetic architecture of psychiatric disorders with a particular focus on schizophrenia and alcohol problems. In the first three analyses, we focused on characterizing …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Genetic Approaches For The Study Of Complex Human Diseases, Julieta Lazarte

Electronic Thesis and Dissertation Repository

The field of human genetics has evolved from its initial narrow focus on single-gene Mendelian disorders, which largely affect children, to our current understanding that for most diseases there is continuum of rare to common variants which can exert a range of phenotypic effects. Despite advances in sequencing capabilities and our overall understanding of diseases, there remains a large proportion of heritability unexplained. Through the use of next-generation sequencing technologies and DNA microarray, I have explored a spectrum of genetic variations from rare, single and structural variants to common variants in individuals with i) “lone” atrial fibrillation; ii) familial hypercholesterolemia; …

Molecular And Genetic Studies Of Robo2 Transcriptional Regulation In The Central Nervous System Of Drosophila Melanogaster, Muna Abdal Rahim Abdal Rhida

Graduate Theses and Dissertations

Drosophila Robo2 axon guidance receptor is a member of the evolutionarily conserved Roundabout (Robo) protein family that is involved in directing axons that cross the midline to the other side of the animal body. Robo2 roles mainly depend on two factors: The functional domains of the Robo2 protein, which is extensively studied, and the dynamic transcription of robo2 in various subsets of cells throughout embryogenesis which is not fully understood. Thus, knowing robo2 enhancers that transcriptionally regulate robo2 during embryogenesis is significant. To investigate robo2 potential enhancers, we screened 17 transgenic lines of Drosophila that were generated by Janelia Research …

Evaluating Insurance Approval Rates Of Exome Sequencing And Its Effect On Minority Patients' Access To Genetic Care, Katlyn Frane

Dissertations & Theses (Open Access)

Exome sequencing (ES) is often a standard step in the genetic testing process for patients with rare or complex disease. Despite clinical implementation of ES, insurance companies (payers) continue to deny this test. We investigated if the payer barrier is influenced by payer type, and if other demographic or clinical information correlated to ES approval and obtainment. To do this, a retrospective chart and clinical database review was completed on patients seen at a tertiary care center and community-based clinic. Patient demographics, clinical indications, and testing recommendations and outcomes were used to assess ES approval and obtainment. We found that …

Awareness Of Genetic Predispositions That Increase The Risk Of Breast Cancer, Carly Huber

Honors Undergraduate Theses

Breast cancer is the most commonly diagnosed cancer in women in the United States and is the leading cause of cancer-related death among women worldwide. Certain demographics, such as racial/ethnic, age, and gender groups, are underrepresented in breast cancer studies. This lack of representation results in issues with creating genetic tests, as variants associated with those groups are not being detected. Furthermore, these underrepresented demographics are receiving a worse prognosis than those that are overrepresented in research. This study aimed to understand how informed the understudied racial/ethnic, gender, and age populations are regarding breast cancer and genetic testing compared to …

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

A Strategic Plan To Thread Genomics Competencies Into Undergraduate Curriculum, Holly Mathis

Dissertations

Problem: Genomics in undergraduate nursing education has experienced slow adoption in the United States. Various approaches have been proposed but do not address barriers to successful implementation.

Methods: A strategic plan was developed to increase the amount of genetics and genomic content in the curriculum of an undergraduate nursing program. A gap analysis was performed on the curriculum revealing a paucity of content. A SWOT analysis informed the strategic plan, which included a faculty education program using the ANA/ISONG’s Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines and Outcome Indicators (2^nd ed.) (2009) as a foundation.

Results: Faculty …

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 …

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …

Associations Among Beef Cattle Genotypes, Neospora Caninum Infection, And Reproductive Performance, Ryan James Page

Graduate Theses and Dissertations

Reproductive performance is crucial for sustained financial success in the beef cattle industry. This dissertation includes a population study that quantified the incidence of Neospora caninum infections in the central region of the United States and tested its relationship with reproductive performance in beef cattle. Trial one of that study concluded that 6.9% of open, replacement heifers (n = 1306) tested seropositive. The second trial in that project found that 9.6% of the breeding age females (n = 500) tested were seropositive for Neospora caninum; and that state in which the cattle lived and age impacted (P < 0.05) infection rate. Breed composition, number of farm dogs on the ranch, and use of total mixed rations were not associated (P > 0.1) with seropositive …

Advanced Phenotyping Of Otosclerosis In An Ontario Population And Two Large Newfoundland Families, Matthew B. Lucas

Electronic Thesis and Dissertation Repository

Otosclerosis is a relatively common hearing loss disorder characterized by abnormal bone growth in the otic capsule leading to stapes fixation. In approximately half of cases, otosclerosis is inherited as an autosomal dominant trait. Typically, gene discovery efforts rely on surgical confirmation, audiometry and occasionally acoustic reflexes to identify affected cases of otosclerosis within families, requiring that the otosclerosis was at an advanced stage to be detected. This makes it difficult to identify individuals with early otosclerosis. The use of advanced phenotyping to identify cases of otosclerosis was tested in an Ontario otosclerotic population as well as in two large …

The Now Trial: A Pragmatic Randomized Controlled Trial Of Personalized, Genetic-Based Lifestyle Advice, Justine Rochelle Horne

Electronic Thesis and Dissertation Repository

Background: The impact of nutrigenomics and lifestyle genomics interventions on health outcomes and behaviours remains controversial and under-explored.

Objectives: To determine the short-term (3-month), moderate-term (6-month) and long-term (12-month) impact of providing personalized, genetic-based lifestyle information and advice on anthropometric measures, as well as dietary intake and adherence.

Methods: The nutrigenomics, overweight/obesity and weight management trial (NOW Trial) is a pragmatic randomized controlled trial that was incorporated into the Group Lifestyle Balance™ (GLB) program (N=140). Inclusion criteria: overweight or obesity (BMI ≥ 25 kg/m²), ≥ 18 years of age, English-speaking, having access to internet at least …

Genetic And Functional Approaches To Understanding Autoimmune And Inflammatory Pathologies, Abbas Raza

Graduate College Dissertations and Theses

Our understanding of genetic predisposition to inflammatory and autoimmune diseases has been enhanced by large scale quantitative trait loci (QTL) linkage mapping and genome-wide association studies (GWAS). However, the resolution and interpretation of QTL linkage mapping or GWAS findings are limited. In this work, we complement genetic predictions for several human diseases including multiple sclerosis (MS) and systemic capillary leakage syndrome (SCLS) with genetic and functional data in model organisms to associate genes with phenotypes and diseases.

Focusing on MS, an autoimmune inflammatory disease of the central nervous system (CNS), we experimentally tested the effect of three of the GWAS …

Identifying Pathogenic Variants In Hereditary Cancer Syndrome Genes Via Tumor Molecular Profiling, Carol Nowlen

Dissertations & Theses (Open Access)

Tumor molecular profiling is often performed in order to direct cancer treatment options. However, because many of the genes analyzed on tumor molecular profiling overlap with genes known to be associated in the germline with hereditary cancer predisposition syndromes, tumor molecular profiling can unknowingly uncover germline predisposition to cancer development. In this study, we determined the number of patients with pathogenic variants (PVs) identified in BRCA1 and BRCA2 (BRCA1/2) via tumor molecular profiling at The University of Texas MD Anderson Cancer Center, then performed a retrospective chart review to determine the proportion of such patients that received germline …

Using Genetic Diversity To Understand Susceptibility To Cognitive Decline In Aging And Alzheimer’S Disease, Sarah M. Neuner

Theses and Dissertations (ETD)

An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging and transition to dementia such as Alzheimer's disease (AD). Identifying the specific genetic variants that contribute to cognitive aging and AD may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we turned to genetically diverse mice from the BXD genetic reference panel (GRP) to overcome some of the …

The Influence Of Stressful Life Events On The Development Of Type 2 Diabetes, Joshua Minks

Dissertations

This study examined the relationship between distress and the development of Type 2 diabetes mellitus (T2DM) in the presence of established risk factors. Distress secondary to mental health disparities, stressful life events, and work conditions has been shown to promote insulin resistance and the development of T2DM.

Subjects (N=79) diagnosed with T2DM within the previous six months were recruited from SSM Health Centers and VA Medical Centers in the greater St. Louis area. They completed the Recent Life Changes Questionnaire, ENRICHD Social Support Instrument, and a demographic survey and analyses were conducted to determine differences between the veteran …

Associations Between Income, Acculturation, Country Of Origin, And Type Ii Diabetes Among African Immigrants To Ontario, Canada, Girma Aman Goshe

Walden Dissertations and Doctoral Studies

Diabetes has become a longstanding public health challenge around the world. Over the last 3 decades, the number of people with Type II diabetes (T2DM) has grown to an epidemic level in Canada. Prior research indicated African immigrants residing in Ontario, Canada experienced a 2-4 times higher prevalence of T2DM than Canadian-born individuals. The social determinants of health theoretical framework guided this study assessing the relationship of the risk factors with T2DM. A quantitative, cross-sectional design was employed using the 2007-2014 Canadian Community Health Survey data. The random sample included 1,526 African immigrants residing in Ontario, Canada. Descriptive, bivariate, and …

Evidence-Based Practice Self-Study Education Program For Staff Nurses On Genomics, Nancy L. Norman-Marzella

Walden Dissertations and Doctoral Studies

Nurses routinely obtain genomic data when collecting family health histories. However, they report low confidence in their knowledge and understanding of genomics and the genetically engineered medications prescribed for their patients. The purpose of this project was the development and implementation of an evidence-based online education program about genetics and genomics to increase the nurses' understanding and ability to provide competent care for their patients receiving treatments based on the science of genomics. Knowles's principles of adult learning theory guided the development and delivery of the online education project to 12 medical-surgical registered nurses employed in a hospital in the …