Genetics and Genomics Commons^™

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 …

The Influence Of Environmental Change On Genetic Diversity Across Spatial And Taxonomic Scales, Connor M. French

Dissertations, Theses, and Capstone Projects

The spatial distribution of genetic diversity is of interest to biodiversity scientists and conservationists and is a fundamental metric of biodiversity. Genetic diversity patterns across spatial and taxonomic scales contain information about population and assemblage dynamics that can convey their resilience to environmental change. Ectotherms are especially linked to their environments and may be especially sensitive to fluctuations in the environment over time. Herein, I investigate global and regional patterns of genetic diversity in two groups of ectotherms, insects and lizards, to understand the relationship between environmental change and genetic diversity, from populations to assemblages. Overall, my research aims to …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

The Correspondence Between Genotype At Bacterial And Viral-Facing Toll-Like Receptors And Preen Oil Chemical Composition In Song Sparrows, Justin To

Electronic Thesis and Dissertation Repository

Mate choice can optimize immune genotypes of offspring and thus reinforce parasite-mediated selection on immune genes. Information about genotype at class II major histocompatibility complex (MHC) is conveyed through body odour, possibly mediated by symbiotic odour-producing bacteria. This can influence mate choice: many jawed vertebrates prefer mates dissimilar to themselves (‘compatible’) at MHC. However, whether odour conveys information about genotype at other immune loci remains unknown. I assessed whether preen oil chemical composition (a proxy for body odour in birds) varies with genotype at viral-facing (TLR3) and bacterial-facing (TLR4) Toll-like receptors in song sparrows (Melospiza melodia). Pairwise distance …

Regulation Of Serpina1 Mrna Expression By Environmental Conditions In Hepatocyte Cells, Fnu Jiamutai

All Theses

The SERPINA1 gene encodes the critical protease inhibitor α-1-antitrypsin (A1AT). A1AT represses neutrophil elastase activity to protect lung tissue from inflammatory damage. A deficiency in α-1-antitrypsin can lead to chronic obstructive pulmonary disease (COPD). Pathogenic genetic variants in SERPINA1 are also associated with A1AT protein misfolding and liver cirrhosis. The regulatory mechanisms of SERPINA1 expression are not well understood, but previous studies suggest that alternative polyadenylation in the 3' untranslated region (3'UTR) affects A1AT protein expression. In this study, we used the liver cancer cell line HepG2 to determine how environmental conditions influence SERPINA1 mRNA expression and post-transcriptional regulation. We …

Advancement In In-Silico Drug Discovery From Virtual Screening Molecular Dockings To De-Novo Drug Design Transformer-Based Generative Ai And Reinforcement Learning, Dony Ang

Computational and Data Sciences (PhD) Dissertations

The field of drug discovery has seen remarkable advancements over the past few decades, transitioning from traditional experimental methods to highly sophisticated computational approaches. One of the pivotal techniques in this evolution is virtual screening, which utilizes molecular docking to predict the interaction between small molecules and target proteins. This method has significantly accelerated the initial stages of drug discovery by enabling the high-throughput screening of large chemical libraries. By simulating the binding affinity and stability of potential drug candidates, virtual screening has become a cornerstone in identifying promising compounds for further development.

A notable application of virtual screening was …

The Role Of Elevation In The Migration, Physiology, And Genomic Diversification Of Birds, Jessie L. Williamson

Biology ETDs

Elevational gradients cause profound eco-climatic variation across short distances. Partial pressure of oxygen (PO₂) is a severe challenge that organisms face at high elevations; due partly to specialization on PO₂, most Neotropical bird species have narrow elevational ranges. However, a small fraction are elevational generalists that span sea level to high elevations, and a subset undertake extreme migratory journeys from low to high elevations biannually. My dissertation combines diverse approaches across levels of biological organization to understand how elevation impacts the ecology, evolution, physiology, and migration of montane birds. I examined ‘extreme’ elevational …

Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera

All Dissertations

Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …

Resistance To Double-Stranded Rna (Dsrna) In Colorado Potato Beetle (Leptinotarsa Decemlineata Say): Genetic And Molecular Insights, Swati Mishra

Doctoral Dissertations

Double-stranded RNA (dsRNA) insecticides delivered through transgenic and non-transgenic means have been approved for commercialization in the US. As with other insecticides development of insect resistance is expected, necessitating the implementation of an Insecticide Resistance Management (IRM) framework for their long-term use. Laboratory-selected insect resistance strains can provide useful insights for an effective IRM plan. The Colorado potato beetle (CPB) is the target pest for the first commercial dsRNA foliar spray, making it an ideal model to study dsRNA resistance. In this dissertation, we studied the previously described CEAS 300 strain of CPB that exhibits >11,100-fold resistance against V-ATPase subunit …

Utilizing The In4mer Crispr/Cas12a Multiplex Knockout Platform To Investigate Synthetic Lethality In The Human Genome, Xingdi Ma

Dissertations & Theses (Open Access)

The emergence of high-throughput sequencing technologies and the development of targeted cancer therapies have significantly advanced our understanding of cancer genomics and prolonged patient survival. Despite these advances, durable response remains difficult to achieve in the clinic. The concept of synthetic lethality has gained traction as a promising opportunity to discover novel cancer-specific vulnerabilities and therapeutic targets. Unfortunately, initial technologies for combinatorial genetic perturbation in mammalian cells suffer from inefficiency and are challenging to scale. In this dissertation, I report: 1) paralog selection method to select candidate synthetic lethal paralogs; 2) our Cas12a multiplex platform “IN4MER” that provides superior sensitivity …

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations & Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

Assessment Of Enzyme Stability In Subsurface Sediments By Computational Methods, Kambiz Kalhor

Masters Theses

The microorganisms found in marine subseafloor sediment play a vital role in global carbon and nitrogen cycles, with an estimated 2.9×10²⁹ cells, accounting for about 0.6% of Earth’s total living biomass. These microbes grow at a very slow rate, with carbon turnover occurring over the course of years to thousands of years, about six orders of magnitude slower than sulfate reducing bacteria in pure culture. These slow metabolic rates suggest that the enzymes they produce must also have extended lifespans in order to be effective over such long periods of time. As a result, these enzymes are likely to …

Assessment Of Genetic Diversity Of The Invasive Callery Pear, Pyrus Calleryana Decne. Using Mitochondrial Microsatellites And Its Molecular Detection Using Lamp, Alina Pokhrel

Masters Theses

Pyrus calleryana Decne. (Callery pear; [PC]) is a popular ornamental tree in the urbanized areas of the United States of America (US), owing to its aesthetical value, with showy white blossoms in early spring and vibrant fall foliage. The tree native to Asia is now becoming one of the most problematic invasive tree species in the eastern US. From its introduction in the early 20^th century, PC has been commercially used as rootstocks for propagating fruiting pears, alongside other closely related pear species. Several states are restricting the sale of rootstocks to limit the ongoing spread of PC. As …

Computational Drug Repositioning And 3d Skin-Like Tissues Identify Anti-Fibrotic Targets For Systemic Sclerosis (Ssc), Dillon Popovich

Dartmouth College Ph.D Dissertations

Systemic Sclerosis (SSc) is a rare autoimmune disease characterized by dermal and internal organ fibrosis, including heart, lungs, and gastrointestinal tract, and autoantibody formation. Although disease etiology is currently unknown, like other autoimmune diseases, SSc likely develops due to environmental factor exposure in genetically susceptible individuals. Fibrotic diseases are notoriously difficult to treat. Coupled with the autoimmune aspect, SSc is difficult to study scientifically due to the lack of complex disease models that can recapitulate the immune-fibrotic axis of the disease. Due to this, there are only two FDA approved medical treatments for SSc approved for symptomatic treatment of SSc …

Cherokia Georgiana Mitogenome Sequencing And Analysis, William Wittstock

Biology Theses

Despite the vast diversity of millipedes, complete genomic and mitogenomic data available in public databases is limited, hindering comprehensive studies on their classification, evolution, and genetics. Among the underrepresented taxa are the Xystodesmidae, a family comprising approximately 500 species with minimal mitogenomic data, and no complete genomes sequenced. Our research involves sequencing the mitochondrial genome of Cherokia georgiana, a representative of this diverse family with interesting traits that are not clearly defined at a genetic level. This research also serves as a pilot study to develop DNA extraction methods and protocols for whole genome sequencing. Multiple DNA extraction kits …

Exploring The Functional Significance Of A Yap1 Missense Variant Of Uncertain Significance In Caenorhabditis Elegans, Nathan Jones

Theses

Polycystic ovary syndrome (PCOS) is a complex disorder with various implications, such as polycystic ovaries, visceral obesity, and increased risk of cancer. YAP1 was recently identified as a gene of interest in the development of PCOS. Researchers have established that single nucleotide variants in YAP1 are likely to play a role in PCOS development. This project aims to provide insight into the potential impact of a YAP1 variant of uncertain significance (VUS). Studies in C. elegans have established yap-1 as a nematode ortholog for human YAP1. A YAP1 VUS was identified through ClinVar, YAP1 c.1015A>G (p.Asn339Asp). Evolutionary conservation …

New Insights On Hybridization In Potamogeton Floridanus (The Florida Pondweed)), Kaitlyn R. Sampson

<strong> Theses and Dissertations </strong>

Freshwater ecosystems are some of the most important and highest threatened habitats in the world, and aquatic plants play an important, but often-overlooked, role in maintaining them. Potamogeton is a diverse and ecologically important aquatic plant genus well known for taxonomic difficulty and rampant hybridization. lbis study aimed to 1) test the hypothesis that Potamogeton jloridanus (Florida pondweed) is a hybrid between P. oakesianus and P. pulcher, and 2) to investigate correlations in ecological conditions for the focal species. This study revealed the discovery of a new population of P. jloridanus in Big Coldwater Creek in Santa Rosa Co., FL, …

Evaluating Past Progress And Assessing Prediction Breeding Strategies For Sustained Genetic Gains In The Louisiana Sugarcane Variety Development Program, Brayden A. Blanchard

LSU Doctoral Dissertations

The aim of this dissertation is to outline important considerations for the Louisiana Sugarcane Variety Development Program (LSVDP) as it pertains to historical progress, impact, goal setting, and new strategies for continued genetic gains. Industry progress was evaluated with robust regression models to quantify rates of productivity gains. Over the last 50 years, statistically significant productivity gains were identified in sucrose content (45%), cane yield (32.2%), and sugar yield (93%) while pairwise comparisons of decades showed that progress was incremental rather than rapid and sustained once achieved. The decade from 1990-1999 was identified as the only decade with a significant …

Investigating The Role Of Ebf3a In Craniofacial Development, Shujan A. Sharafeldeen

Undergraduate Theses, Capstones, and Recitals

Proper craniofacial development requires many genes. Single-cell RNA sequencing (scRNA-seq) allows us to identify genes expressed in precursor cells for craniofacial structures, but the function of many of these genes in craniofacial development has yet to be characterized. In our scRNA-seq of cranial neural crest cells (NCCs), which are precursor cells for the craniofacial skeleton, we found a gene called early B-cell factor 3 (ebf3a) that may be involved in craniofacial development. In our scRNA-seq data, ebf3a expression is restricted to cranial NCCs of the dorsal and ventral domains of pharyngeal arches 1 and 2. In humans, damaging variants in …

Evolution And Adaptation To Temperature In Thermotogota, Anne Amelia Farrell

Dartmouth College Ph.D Dissertations

Life thrives across incredibly diverse environmental conditions, yet most organisms are restricted to growing within a narrow range around their optimum growth temperature (OGT). The evolutionary events leading to changes in OGT are poorly understood, and it is uncertain if specific genes are required to thrive at a particular temperature. The bacterial phylum Thermotogota is an excellent model for the evolution of OGT. It comprises mesophilic, thermophilic, and hyperthermophilic members that collectively grow between 20°C and 90°C.

In this work, I analyze the history of OGT in the Thermotogota phylum and show how horizontal gene transfer contributes to the evolution …

Reports Of Autosomal Recessive Disease And Consanguineous Mating Within The Human Population, Johnathon L. Schluter

Master's Theses

It is anecdotally evident when investigating published reports of autosomal recessive disease that a substantial number of cases are the result of related (consanguineous) mating. This research seeks to quantify the percent of manuscripts describing autosomal recessive diseases published between 2000 and 2020 in which consanguineous mating is indicated. We analyzed 602 peer-reviewed manuscripts to identify the percentage of cases presented in which consanguineous mating was indicated, the underlying genes (novel gene or new mutation) and geographical region. These papers were accessed through a specific set of parameters on the free access PubMed Central (PMC) database. A total of 552 …

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 …

Screen For Beneficial Genetic And Chemical Modifiers In Drosophila Models Of Als And Traumatic Brain Injury, Will Bonderer

Biological Sciences Theses and Dissertations

The underlying molecular processes of aberrant protein expression in neurodegeneration are intricate and multifaceted, with ribosome-associated quality control (RQC) emerging as a promising avenue of exploration. Ribosome-associated quality control is integral to cellular function. Its evolutionarily conserved pathway encompasses a network of mechanisms designed to ensure the fidelity of protein synthesis, folding, and degradation within the cells of all eukaryotes. The ribosome, central to protein synthesis, plays a pivotal role in this quality control network, and its malfunction can lead to the accumulation of misfolded or aberrant proteins. In the context of neurodegenerative disorders, this dysfunction can have dire consequences. …