Genetics and Genomics Commons^™

Factors Influencing Adherence To Surveillance Guidelines In Individuals With Tuberous Sclerosis Complex, Kashish Khanna

Theses and Dissertations

Tuberous Sclerosis Complex (TSC) is a genetic condition that is caused by pathogenic changes in either the TSC1 or TSC2 gene and is characterized by multiple benign tumors, otherwise known as hamartomas, in various organs such as the brain, skin, lungs, and kidneys. Because of the many different clinical manifestations of TSC, extensive surveillance guidelines are recommended for individuals with TSC. Past studies have shown that there has been a gap in knowledge of these surveillance guidelines. These studies also suggest projects that measure adherence to surveillance guidelines and address specific challenges hindering surveillance guideline adherence. This study aims to …

Utilizing Evisits To Increase Access To Genetic Services For The Hearing Loss Population: A Tailored Service Delivery Model, Ansley Roberts

Theses and Dissertations

Purpose: Patients referred for genetics services have specific barriers decreasing accessibility, such as communication difficulties, long wait times, and misconceptions about the utility of genetic testing. We assessed a new tailored service delivery model used by the Greenwood Genetic Center to evaluate patients referred for hearing loss to determine if this model increases access to genetics services for individuals with hearing loss. Methods: Data points such as wait times, testing plan, and diagnostic yield were compiled from patient medical records. Comparison and analysis of data was completed by visit type, in-person, virtual, and electronic visits (eVisits), between October 2023 – …

Next Generation Sequencing Based Profiling Of Genes In Patients With Syndromic Forms Of Retinitis Pigmentosa, Harshavardhini G

Theses and Dissertations

India is one of the largest populations in the world and is estimated to have a high prevalence of Retinitis Pigmentosa (RP). RP is clinically and genetically heterogenous, characterized initially as night blindness, leading to complete vision loss due to retinal degeneration. RP can occur in non-syndromic or syndromic forms, affecting other organs as observed in Bardet Biedl Syndrome (BBS) and Usher syndrome (USH).

BBS is characterized by RP, polydactyly, obesity, renal anomalies and learning difficulties. USH is characterized by RP and sensorineural hearing loss (SNHL), with variable presence of vestibular dysfunction. Nextgeneration sequencing (NGS) has become a cost-effective technology …

Deciphering Evolutionary Co-Option By Studying The Origin Of Self-Fertility In Caenorhabditis Nematodes, Jonathan P. Harbin

Theses and Dissertations

In my research, I examined the characteristics of male and female sex-determination mutants in C. nigoni and investigated the regulatory pathway they define. This work tested whether flexibility in the sex-determination pathway was a preexisting condition that favored the origin of self-fertility in Caenorhabditis. Furthermore, I developed an approach for using interspecies hybrid mutants to assess the robustness of the C. nigoni pathway. My findings showed that the C. nigoni pathway is highly robust and canalized, suggesting that changes leading to self-fertility must have involved the impairment of this canalization in the germ line, to allow eventual alteration of germ …

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.

Perspectives On Transition To Adult Healthcare For Adults With Williams Syndrome And Their Caregivers, Andrea Johnson

Theses and Dissertations

Transitioning to adult care services is a crucial time for young adults with a genetic condition. Many of these conditions are diagnosed early in childhood, with follow-up care fragmented and dependent on the specific needs of the individual. Williams syndrome (WS) is a complex genetic condition characterized by multisystemic features. The variation in the clinical presentation of adults with WS can influence the individual’s ability to transition from pediatric care because of its medical complications, variable and poorly characterized psychiatric needs, and intellectual disability that causes difficulty communicating health-related needs to providers. This study focused on understanding the needs of …

Patients’ Experience Of Care Following Perinatal Case Conference, Mary Elise Nolen

Theses and Dissertations

The Perinatal Case Conference (PCC) at Prisma Health-Midlands Maternal-Fetal Medicine (MFM) is a biweekly multidisciplinary meeting to discuss pregnancies with prenatally identified congenital anomalies. Patients are primarily cared for by MFM and may have appointments with various subspecialists during their pregnancy. The goals of the PCC are multidisciplinary collaboration in planning for the management of each pregnancy and familiarizing each practitioner with the pending cases, so if or when intervention is needed, the clinicians are familiar with the case.

Researchers performed a chart review and surveyed patients whose pregnancies were discussed in the PCC to learn the patient’s perspective of …

Perception Of Alzheimer’S Actionability Among End Users Of Direct-To-Consumer Genetic Tests, Emily Mason

Theses and Dissertations

The APOE ε4 allele is the best-known genetic risk factor for developing late-onset Alzheimer’s disease. Although new evidence is emerging, the extent to which lifestyle improvements can reduce Alzheimer’s risk needs further investigation. Research suggests that individuals with a higher genetic risk may be more likely to engage in risk-reducing health behavior changes following results disclosure. This study aimed to better understand these findings by assessing the health behavior and perceptions of Alzheimer’s actionability among consumers of DTC genetic tests. Our study revealed that individuals with 2 copies of the APOE ε4 allele were less likely to make lifestyle modifications …

Assessing Obgyn Residents’ Knowledge, Attitudes, And Current Practices For Carrier Screening, Aubrey Morgan Surian

Theses and Dissertations

Obstetricians and gynecologists (OBGYNs) are the main providers that order carrier screening on a regular basis, so it is important to understand their knowledge, attitudes, and current practices regarding this screening. There are two primary professional organizations that have established practice guidelines for carrier screening, the American College of Obstetrics and Gynecology (ACOG) and American College of Medical Genetics (ACMG). With the growth of pan-ethnic carrier screening, these guidelines have become remarkably different. This study aimed to assess resident OBGYN’s utilization of pan-ethnic carrier screening, discern any discrepancies between knowledge, attitudes, and current practices, identify possible practice resources that may …

Cancer Screening For Patients With Intellectual Disability: Exploring Parent And Caregiver Perspectives, Jennifer Ryan

Theses and Dissertations

Intellectual disability (ID) is defined as a combination of deficits in cognitive and adaptive function, both of which must be present early in life. Adults with ID frequently have unique healthcare needs; however, they also require care that is routine for all adults. This includes cancer screening. The goal of this study was to evaluate whether or not adults with ID are undergoing cancer screening, understand the barriers they have faced in obtaining screening, and collect recommendations from parents and caregivers on ways to improve access to and facilitate screening for this population. We surveyed parents and caregivers of adults …

The Autistic Adult's Perspective On Genetic Testing In The Prenatal And Cancer Settings, Robin Lisa Urban

Theses and Dissertations

Prenatal and cancer genetic tests are recommended by many professional medical organizations. Previous studies have shown that autistic adults have a negative opinion towards genetic testing for autism but have not explored if this sentiment is shared for other types of genetic testing. We used a descriptive, web-based survey of autistic adults to assess their attitudes towards prenatal and cancer genetic testing (n=36). Our data showed that overall attitudes towards prenatal and cancer genetic testing are positive. Notably, participants had slightly more positive attitudes towards prenatal genetic testing related to neurodevelopmental disorders when compared to testing for disorders primarily affecting …

Perspectives From Caregivers For Children With Retinoblastoma: Psychosocial Concerns And Genetic Counseling, Kayla Marie Lashinger

Theses and Dissertations

Caregivers play a vital role in the care of children affected with retinoblastoma as most cases are diagnosed before the age of five years old. While previous studies have explored the psychosocial needs of caregivers of children with pediatric cancer, these have not specifically focused on retinoblastoma in the United States (US). Prior research identified the profound emotional burden in terms of depression, anxiety, guilt, isolation, and loneliness experienced by caregivers. Given previous findings and the National Cancer Institute’s recommendation for genetic counseling and testing for all individuals affected with retinoblastoma, this study aimed to assess psychosocial concerns in relation …

Preimplantation Genetic Testing For Sickle Cell Disease; Exploring The Effect Health Disparities Have On Parental Awareness And Interest, Justine Frances Manigault

Theses and Dissertations

Sickle cell disease (SCD) is a group of disorders of the hemoglobin resulting in episodes of chronic pain, pulmonary hypertension, progressive multiorgan damage, risk for stroke, and increased mortality. It is caused by biallelic pathogenic variants in the HBB gene and 1 in 12 African Americans, 1 in 100 Hispanic individuals, and 1 in 30-50 Mediterranean people are reported to be carriers of the disease and have sickle cell trait (SCT). SCD is typically diagnosed through newborn screening; however, when prospective parents are aware of their carrier status, they can conceive via in vitro fertilization (IVF) and have genetic testing …

The Utility Of Referrals From A State Early Intervention System To A Pediatric Genetics Clinic To Increase Access To Genetic Services, Mikayla Jennings

Theses and Dissertations

Infants or toddlers enrolled in state early intervention programs have developmental delays or are diagnosed with conditions that may result in developmental delays. These infants receive a wide range of services from early intervention. In the state of South Carolina, children in the early intervention program are offered genetic evaluations at no cost to the family. Exploring the relationship between state early intervention systems and genetic clinics and the impact on this particular patient population can provide support for new and continued use of this service delivery model.

The purpose of this study was to evaluate the service delivery model …

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …

Investigation Of Brain Function And Structural Development As Risk Factors Of Suicidal Thoughts And Behaviors, Yi Zhou

Theses and Dissertations

Background: Identifying risk factors for suicidal thoughts and behaviors, especially causal ones, will be imperative to improving screening and treatment interventions. To identify replicable brain-based risk factors, there is increasing evidence indicating the need for large sample sizes, in the hundreds to thousands, in order to achieve a sufficient level of statistical power to detect them. Furthermore, longitudinal studies of brain and behavioral factors will be essential to understanding how suicide develops, especially the transition from suicide ideation to attempt. While experimental studies may not be feasible or ethical, genetically informed methods for testing evidence for causation are an alternative …

Plk1 Overexpression Drives Tumorigenesis In A Prostate Cancer Mouse Model, Emile Kachouh

Theses and Dissertations

Prostate cancer is the leading cause of cancer-related deaths among men worldwide, and the development of resistance to existing treatments necessitates the exploration of new therapeutic strategies, including combination therapies. This study investigates the role of Polo-like kinase 1 (PLK1), located on chromosome 16p12.2, as an oncogene in prostate cancer. We generated a transgenic mouse model with prostate-specific overexpression of PLK1 to closely mimic human prostate cancer progression. Quantitative PCR (qPCR) analysis was employed to characterize the molecular profile of PLK1, revealing its implication in multiple pathways. To further elucidate the functional consequences of PLK1 overexpression, we confirmed phenotypic progression …

The Splice Index As A Prognostic Biomarker Of Strength And Function In Myotonic Dystrophy Type 1, Marina Provenzano

Theses and Dissertations

Myotonic dystrophy type 1 (DM1) is a slowly progressive, multisystem disorder caused by a CTG repeat expansion in the DMPK 3’UTR that leads to global dysregulation of alternative splicing. The resulting decline in physical function is slow, and no reliable biomarkers exist for predicting disease progression; however, an RNA mis-splicing biomarker associated with weakness may have utility in predicting functional outcomes. Here we validate the Splice Index (SI) as a potential biomarker of DM1-associated strength and function. Muscle biopsies of the tibialis anterior were collected from DM1-affected individuals at baseline (n = 46) and 3-months (n = 34), along with …

Re-Programming Transcription Factor Function For Neuroscience Research Of Addiction: Investigating The Role Of Zinc Finger Proteins In Driving Cocaine Reinforcement In Mice, Joseph A. Picone

Theses and Dissertations

Administration of addictive drugs like cocaine or morphine initiates aberrant gene transcription within brain reward circuitry neurons, which contributes to the lasting behavioral maladaptations that define addiction. The drug-induced expression and function of key brain transcription factors (TFs) is one major mechanism through which these drugs are able to regulate transcription, and as a consequence, lasting damaging drug-related behaviors including compulsive drug use. The goal of this dissertation is to more fully understand the molecular mechanistic drug-specific actions of TFs within the rodent nucleus accumbens (NAc). The findings from these studies could serve as the basis to identify novel candidate …

Role Of Human Intermediate Form Prl Receptor I-Tail In The Pathogenesis Of Breast Cancer, Shanwei Shen

Theses and Dissertations

Breast cancer continues to be the second most common cancer in women in the United States. The neuroendocrine hormone human prolactin (hPRL) plays an important role in normal mammary gland development and growth, stimulating normal breast tissue proliferation and differentiation. Considerable evidence has shown that hPRL is involved in the malignant transformation of human breast tissue. hPRL enhances viability, invasiveness, and proliferation of breast cancer cells in vitro. Evidence from epidemiologic and genetic studies also implicates role of hPRL in the pathogenesis of breast cancer. Its cognate receptor the human prolactin receptor (hPRLr) is required for the action of hPRL. …

Range-Wide Analysis Of The Genetic Diversity And Genetic Structure Of The Spotted Turtle (Clemmys Guttata), Madison S. Whitehurst

Theses and Dissertations

Understanding the spatial distribution of genetic diversity and structure in endangered species is vital for effective conservation management. This research discusses the results of an initial analysis of the genetic structure and variation of the spotted turtle (Clemmys guttata), a species of conservation interest. The study sampled 913 individuals from 78 unique locales across 16 states in the eastern portion of the species' range. Utilizing ddRADSeq, a de novo genome assembly was developed to identify nearly 20,000 potential loci. A total of 926 were selected for this analysis. Results revealed no spatial clustering of genetic diversity or structure, …

Genetic And Transcriptomic Investigations Of Progressive Ethanol Consumption In The Diversity Outbred Mouse, Zachary Tatom

Theses and Dissertations

As a complex genetic disorder, alcohol use disorder (AUD) is thought to be influenced by many genes each contributing only a small effect to the overall disease liability. Dozens of genes have been implicated as potentially affecting risk for AUD and alcohol consumption. However, understanding the full genetic architecture of AUD – what genes are involved, to what extent, and how these genes are regulated – remains a challenging step in identifying novel treatments. Gene expression studies in humans have attempted to augment GWAS of alcohol consumption but are often confounded by environmental factors; the difficulty of collecting tissue from …

Redesign, Evaluation, And Validation Of A Commercially Viable High-Resolution Melt Based Mixture Screening Tool, Chastyn Smith

Theses and Dissertations

Analysis of evidentiary samples containing DNA from multiple contributors (“mixtures”) is a time intensive process for a forensic analyst and one where the contributor nature of a sample is not revealed until the end of the traditional forensic workflow. Often, at this stage, retesting or additional testing of mixture samples may not be possible, particularly if the DNA collection device did not preserve the DNA well enough; consequently leaving only trace amounts of a contributor’s DNA present. Thus, a new collection device that would allow for the increased preservation/integrity of evidentiary samples as well as a method that would allow …

The Genetic Architecture Of Cervical Change During Pregnancy: From Modeling To Mechanism — Does The Cervix Mediate Maternal Risk For Spontaneous Preterm Birth?, Hope M. Wolf

Theses and Dissertations

This project leverages clinical data and biospecimens from a prospective longitudinal cohort of pregnant women to study the genetic and phenotypic relationships between cervical shortening and the duration of pregnancy. Sonographic cervical length (CL) was measured throughout pregnancy in a cohort of 5,160 Black/African American women in Detroit, Michigan. Maternal DNA samples were sequenced with a next-generation low-pass whole genome platform. The heritability of cervical change during pregnancy and its genetic correlation with gestational age at delivery (GAD) were estimated using Genome-Wide Complex Trait Analysis. These estimates suggest that cervical change is heritable (h²CL = 51%) and highly polygenic trait. …

Investigating The Impact Of Transcription On Mutation Rates, Sarah Patterson

Theses and Dissertations

tRNA genes are highly transcribed and perform one of the most fundamental cellular functions. Although a universal pattern observed across all three domains of life is that highly transcribed genes tend to evolve slowly, tRNA genes have been shown previously to evolve rapidly. This rapid sequence evolution could result from relaxed selection, increased mutation rate, or a combination of both. Here, we use mutation-accumulation line sequencing data to show that tRNA genes accumulate more mutations than other gene types. Our results indicate that this elevated mutation rate is a consequence of both elevated transcription-associated mutagenesis and a lack of transcription-coupled …

Towards Understanding The Interactions Between Ospreys And Human-Made Structures In The Tennessee River Valley, Natasha Karina Murphy

Theses and Dissertations

Raptor nests on human-built structures represent a significant source of conflict as they can result in bird mortality, fires, structure damage, service distribution, or power outages when falling nest materials or animals connect with energized conductors. Power companies, such as the Tennessee Valley Authority (TVA), wish to mitigate these conflicts to avoid service disruptions. In this dissertation, I present my work towards understanding and mitigating the interactions between Ospreys (Pandion haliaetus) and human-made structures. To achieve this, I explored multiple elements of conflict identification, monitoring, and basic ecology of the target species to better inform conflict mitigation. In Chapter I, …

Increased Coding Potential Of Bovine Herpesvirus 1, Victoria Jefferson

Theses and Dissertations

Bovine respiratory disease (BRD) costs the cattle industry millions of dollars in costs in treatment and loss every year in the United States. A significant pathogen often contributes to BRD is Bovine Herpesvirus 1 (BoHV-1), a double stranded DNA virus with the ability to establish latency in the trigeminal ganglia and neurons. Primary infection with BoHV-1 results in immunosuppression that increases the risk of secondary bacterial infection and pneumonia. Because herpesviruses infect their hosts for life and can be reactivated in times of stress, BoHV-1 can present a recurring risk of BRD. The following research aims to expand the knowledge …

Gene Expression Effects On Productivity And Stress Tolerance In Polyclonal Plantings Of Populus Deltoides, Macy Gosselaar

Theses and Dissertations

Polyclonal plantings of Populus deltoides are expected to display increased site resource use, productivity, and tolerance to stress through plasticity changes leading to niche differentiation (i.e changes to crown/canopy structures). In the present study, P. deltoides Clones S7C8, 110412, and polyclonal plots were tested for differentially expressed genes and enriched biological pathways between planting schemes. Transcriptomic analysis of leaves revealed upregulation of an active growth gene and gene family members that play important roles in plant stress and stress tolerance in polyclonal plantings. A gene associated with oxidative stress was upregulated in polyclonal plantings across all treatments. Secondary metabolic pathways …

Upland Cotton And Nematodes: An Analysis Of Historical Resistance, Upcoming Threats, And Co-Inoculation Effects, Amanda Gaudin

Theses and Dissertations

Upland cotton (Gossypium hirsutum ) is an important fiber crop grown throughout the southern United States. Plant-pathogenic nematodes are worm-like animals that feed on the roots of most agronomic crops, including cotton. The southern root-knot nematode (Meloidogyne incognita, RKN) and the reniform nematode (Rotylenchulus reniformis, RN) cause significant yield losses in cotton every year. Current sources of resistance are effective but limited, therefore historical screenings of cotton accessions were revisited in search for novel resistance sources. None were identified but many of the screened accessions possessed markers of known root-knot nematode and reniform nematode resistance. …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …