Genomics Commons^™

Adapting Population Genetics, Practice, And Policy For Plant Conservation In A Changing World, Cooper M. Kimball-Rhines

Graduate Doctoral Dissertations

Biodiversity conservation is an inherently interdisciplinary goal that requires effective collaboration among academics, ecosystem managers, policymakers, and other stakeholders. Codesigning research with these groups ensures experiments are useful and improves adoption of policy and practice recommendations while advancing our understanding of basic science. This dissertation explores the power of codesigned research in shaping plant conservation strategies using stakeholder engagement, causal inference, demographic modeling, and multi-omic sequencing techniques. In chapter 1 I discuss the history of New England ecosystems and the need for research-driven changes to plant conservation policy and practice in the face of global change. In chapter 2, I …

Investigating Cryptic Diversity In The Hawaiian Endemic Plant, Psychotria Mariniana (Rubiaceae), Uyen Thi Hoang Nguyen

Master's Theses

Islands, with their isolation and steep environmental gradients, serve as natural laboratories for studying speciation. Molecular phylogenetic and population genetic methods utilizing Next-Generation Sequencing (NGS) have revolutionized our ability to document patterns of genetic divergence and diversity. Cryptic diversity, genetically distinct populations that were previously unrecognized as unique, and cryptic speciation, where divergent genetic populations may be deserving of status as unique species, have been observed in many taxa. The Hawaiian Islands provide an ideal setting for studying divergence and speciation due to their extreme isolation, known ages, and volcanic origin. Previous work has investigated the evolutionary relationships of the …

Denisovan Introgression And Selection At Cntnap2 In Ancient And Modern American Populations, Matthew Barker

All Theses

The peopling of the Americas created new opportunities for genetic adaptation as ancient populations encountered novel environments across North and South America. Previous research has shown that segments of Indigenous American ancestry contain elevated proportions of Denisovan alleles. The gene CNTNAP2, which is involved in brain development and neuronal function, contains a Denisovan-derived haplotype that represents a candidate locus for adaptive introgression in admixed American populations. A Denisovan-derived core haplotype approximately 55 kb in length was identified within intron 13 of CNTNAP2. This haplotype is primarily found in admixed American populations and occurs rarely outside the Americas, and …

Investigating The Taxonomic Uncertainties Of Potentilla Rupincola, Natalie Elizabeth Hieber

Master's Theses

Landscape stewardship is an integral role for land managers that becomes more important when rare or endangered species occur within managed areas. Conservation across the landscape is a primary concern for land managers, but resources allocated for conservation can be limited due to many competing goals. Taxonomic uncertainty surrounding rare and endangered taxa, particularly plant taxa, that have historically been classified solely using morphological features further complicates conservation planning. One such taxon is Potentilla rupincola, a rare plant endemic to the eastern Rocky Mountains in Colorado. For over a century, botanists have debated whether P. rupincola is a distinct species …

Sorghum Grain Secondary Metabolites And Underlying Genetics To Reduce Foodborne Pathogens In Poultry, Maria A. Conti

All Dissertations

The rise in antibiotic-resistant pathogens poses a threat to the poultry industry's ability to maintain animal health, prompting growing interest in alternatives to synthetic antibiotics. The use of non-tannin sorghum [Sorghum bicolor (L.) Moench] in poultry rations offers a valuable alternative, as this cereal grain has a high bioactive profile that can provide health benefits, including antimicrobial (AM) activity. The scope of this study was to examine the AM potential of non-tannin sorghum grain against Clostridium perfringens, a major foodborne pathogen that negatively impacts poultry health and production. To that end, the inhibitory effects of a non-tannin sorghum …

The Genetic Basis Of High Transformation Efficiency In The Model Yeast Saccharomyces Cerevisiae, Mary Kathryn E. Cheek

Biological Sciences Undergraduate Honors Theses

Transformation, a type of horizontal gene transfer, describes the uptake, maintenance, and integration of environmental DNA by cells. Despite the known effects of transformation on evolutionary processes, little is known about the genetic basis of this phenomenon. Saccharomyces cerevisiae is a eukaryote able to transform at quantifiable rates when made chemically competent and treated with a heat shock. S. cerevisiae also has variation in transformation efficiencies between various strains, and high recombination rates allow for sufficient allele “shuffling” in intercross populations. This project utilizes a bulk segregant analysis approach to compare sequencing data between transformant pools and non-transformant pools of …

The Hitchhiker's Guide To The Host: Fleas And The History Of Pikas In North America, Josh Pletcher

All NMU Master's Theses

Parasite phylogenetics can offer windows into the cryptic evolutionary history of hosts, often highlighting events that are not recorded by the phylogenetics of the host. Pikas (small lagomorphs) host a diverse parasite community comprising endoparasites (e.g., coccidians, nematodes, and cestodes) and ectoparasites (e.g., fleas and mites). Phylogenetic analysis of pika endoparasites has revealed pikas evolved in Asia and colonized North America in two waves, and that contact between these two pika lineages allowed parasites to be transferred from one lineage to another and to survive the extinction of their original host. To uncover these cryptic histories, understanding the biogeography of …

Effects Of M6a Dna Methylation By Bacterial Methyltransferase In Colorectal Cancer, Fabian Alejandro Mendoza Galvan

Dissertations and Theses (Open Access)

Effects of m6A DNA methylation by bacterial methyltransferase in colorectal cancer Fabian Alejandro Mendoza Galvan Advisory Professor: Angela H. Ting, Ph.D. Fusobacterium nucleatum animalis (Fna) is found in the human oral cavity and gut. A distinct clade of Fna is primarily enriched in the tumor microenvironment (TME) and within colorectal cancer (CRC) cells. This clade DNA methylation pattern is primarily catalyzed by a cell-cycle regulated methyltransferase (CcrM) ortholog, M.FnI, that targets the GANTC sequence motif through methyl-6-Adenine (m6A) DNA methylation. We hypothesized that M.FnI enzyme can induce m6A methylation abnormalities in CRC cells to promote cancer progression. Evidence for endogenous …

Understanding Epigenomic Landscapes In Cancer Progression And Immunotherapy Response, Jonathan Schulz

Dissertations and Theses (Open Access)

Nonmutational epigenomic reprogramming has emerged as a key hallmark of cancer that plays crucial roles in tumor evolution during its progression and response to therapy. However, the extent and nature of epigenomic reprogramming remains poorly understood. This dissertation examines how epigenetic regulation shapes cancer progression and response to immunotherapy. Working at the intersection of cancer biology and computational genomics, it develops analytical frameworks for characterizing chromatin structure and DNA methylation across diverse tumor contexts and uses these frameworks to address two complementary biological questions: how promoter-associated chromatin organization varies across cancer types, and how epigenetic perturbation modulates tumor immunogenicity in …

Discovering The Genetics Underlying Speciation Traits In Heuchera (Coral Bells), Tajinder Singh

Honors Theses

Hybridization is a key evolutionary mechanism for generating biological diversity, ultimately shaping diversification and adaptation of plant lineages in natural and agroecosystems.  Our understanding of the frequency, distribution, and significance of hybridization is rapidly increasing, but the external driving forces that dictate why certain species hybridize, and others do not remain obscure. The physical traits that shape gene flow and trait sharing among species are likely to be among the key factors that directly control hybridization. Gene flow in most plants is mediated by pollinating insects and thus by pollination syndromes, which are suites of floral traits that have evolved …

Cleft Palate And The Coordination Of Wnt Signaling And Pax9 In Murine Palatogenesis, Landon Wyatt

Honors Theses

Cleft palate is a common craniofacial birth defect that arises when the molecular and morphogenetic events guiding secondary palate formation lose coordination during a narrow developmental window. In mice, successful palatogenesis requires the paired palatal shelves to grow vertically, elevate above the tongue, and fuse at the midline; disruption of any of these steps can result in clefting. Two important regulators of this process are canonical Wnt signaling and the transcription factor Pax9, both of which contribute to normal palatal mesenchymal growth and patterning during early development. This paper first examines whether altered Dkk1/Wnt signaling contributes to the Pax9-null palate …

Metagenomic Profiling Of Gut Microbiome Signatures Across Liver Disease Stages And Hcv-Related Hepatocellular Carcinoma In Egyptian Patients, Marwa A. Zahra

Theses and Dissertations

Dysbiosis in the gut microbiome, particularly concerning the synchronous crosstalk between the gut and the liver, has been associated with various diseases. This study profiles the gut microbiome in liver diseases among Egyptian patients, with a focus on the hepatitis C virus (HCV) and hepatocellular carcinoma (HCC), both of which are highly prevalent in Egypt. Utilizing shotgun metagenomic sequencing, we analyzed microbial gene catalogs and taxonomic profiles from 46 Egyptian patients categorized into five groups: healthy individuals, liver disease patients of different etiologies, post-HCV, treated HCV, and HCV-HCC patients. Healthy and treated HCV patients exhibited distinct microbial profiles characterized by …

Characterization And Advancement Of Molluscan Venom Gland Cell Model Systems, James V. Parziale

Dissertations, Theses, and Capstone Projects

Venomous mollusks, including cone snails and coleoid cephalopods, produce rich repertoires of bioactive peptides with profound effects on cellular physiology, yet there are few tractable experimental systems that exist to study their development, maintenance, and venom secretion. Although therapeutics such as the cone snail peptide Ziconotide demonstrate the biomedical potential of molluscan venoms, progress in understanding how venom glands form, function, and evolve has been hindered by the lack of reliable husbandry and the complete absence of in vitro cell models. Modern comparative genomics has revealed widespread convergent evolution across venomous lineages, but molluscan datasets remain underrepresented, limiting insights into …

Varying Dna Methylation Patterns In The Florida Sand Skink (Plestiodon Reynoldsi) In Relation To Fire Histories, Victoire Hj Litre

College of Graduate Studies: Theses & Dissertations

Epigenetics is the study of changes in phenotype not caused by changes in DNA sequence. DNA methylation is the most well-studied epigenetic mechanism in an ecological context. Reptiles use DNA methylation to respond to environmental stressors and differences among habitats. The Florida Sand Skink (Plastidome reynoldsi) is federally listed as a threatened species. They are endemic to the threatened, fire-dependent Florida scrub habitat. As they persist in burned habitats, the Florida Sand Skink must be able to rapidly respond to wildfires. To better understand how the Florida Sand Skink adjusts to fire-driven habitat changes, it is important to …

Nutrient-Driven Transcription Factor-Dna Interactions And Their Signaling Mechanisms In Metabolic Disease, Evelyn A. Bates

Theses and Dissertations--Nutritional Sciences

Metabolic homeostasis is maintained through tightly coordinated signaling networks that integrate diverse physiological inputs. Central to this regulation are transcription factors, which sense nutrient, hormonal, and vitamin-derived signals and translate them into coordinated gene expression programs. Transcription factor activity is governed by DNA binding, recruitment of coregulatory proteins, and interactions with specific response elements in gene promoters, which allows them to selectively modulate diverse metabolic pathways. Owing to their multifactorial and tunable nature, transcription factors have emerged as promising targets for the treatment and diagnosis of metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). This dissertation explores the molecular …

Toward Interpretable Multi-Omics Multimodal Biomedical Artificial Intelligence, Yanjun Lyu

Computer Science and Engineering Dissertations

The complexity of human disease arises from biological processes that unfold across multiple scales, from molecular variation through cellular function, tissue organisation, brain phenotypes, each of which is associated with distinct measurement modalities, regularities, and characteristic. Contemporary biomedical artificial intelligence has brought the opportunity to reveal the complexity with in; however, its methodological default, in which models are trained on most readily available modality, does not adequately engage with the multi-scale connected structure by which biological meaning is constituted. The research area of multi-omics and multi-modal AI for biomedicine remains at an early exploratory stage, and the work presented in …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Equid Major Histocompatibility Complex (Mhc) Evolution & Genome Organization, Lauren C. Johnson

Theses and Dissertations--Veterinary Science

The evolution of modern horses has a well-documented fossil record and has long been of interest to the genetics community. Although non-caballine equids (e.g. zebras, donkeys, and asses) can hybridize with horses, the resulting offspring are typically infertile. Despite these reproductive barriers, genomic analyses reveal regions of high sequence similarity among equid species. This dissertation investigates the role of historical introgression in the evolution of modern Equus species. The first chapter re-evaluates earlier findings derived from a limited horse population and a single reference genome. The variants of the identified regions were pushed through Ensembl’s Variant Effect Predictor to assess …

Microbial Community Structure In Global Soils, Matthew Jabro

CMC Senior Theses

Soil harbors the most diverse microbial communities on Earth, yet whether predictable community types exist across biomes and whether taxonomic composition encodes habitat of origin remain open questions at global scale. This thesis addresses both questions by applying unsupervised clustering and supervised classification to transformed 16S ribosomal RNA (rRNA) amplicon profiles from two independent datasets: the global topsoil survey of Bahram et al. (193 samples) and the Earth Microbiome Project (EMP) soil subset of Thompson et al. (2,209 samples). Application of a sample clustering method based on a mixture of Gaussian Graphical Models (MixGGM) identified 19 clusters in the topsoil …

Phylogeography, Fungal Host Specificity, And Fitness In The Corallorhiza Maculata Species Complex, Hana Thixton-Nolan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mycoheterotrophic plants exploit fungi for most or all nutritional needs, providing a compelling system to address the evolutionary consequences of genome reduction, population-level variation, and germination requirements. I am using the widespread Corallorhiza maculata species complex to address questions of genomic variation, fungal host specificity, morphological variation, and germination requirements across the broad geographic range from Mexico to northern North America. This complex contains C. bulbosa, C. macrantha, and C. mertensiana, the latter with three varieties (maculata, occidentalis, and mexicana). These taxa vary in flowering time, floral morphology, and fungal associations. However, the degree …

Dosage Sensitivity And The Evolution Of Dosage Compensation: Tests Of The Insensitive Sex Chromosome Hypothesis In Flour Beetles, Shana Pau

Biology Dissertations

Sex chromosome evolution generates imbalances in gene dosage that can disrupt gene expression and organismal function. These imbalances are often resolved through dosage compensation mechanisms, yet the factors that drive the emergence and diversity of these systems remain poorly understood. This dissertation addresses a central question in evolutionary genomics: what governs the evolution of dosage compensation?

Focusing on dosage sensitivity as a potential driver, I evaluate the Insensitive Sex Chromosome Hypothesis (ISCH), which predicts that chromosome-wide compensation is more likely to evolve in genomic contexts that are not depleted of dosage-sensitive genes. Using flour beetles (Tribolium spp.) as a …

Genomic Determinants Of Appetite Regulation And Their Role In Obesity Risk, Timothy J. Renier

Dartmouth College Ph.D Dissertations

Over 40% of US adults and 20% of children live with obesity. It is related to increased risks of diseases including type II diabetes and cancer, is a source of harmful stigma, and impairs child development. Appetitive traits describing patterns of food approach and avoidance behaviors may serve as windows into the underlying pathophysiology of obesity. As both obesity and appetitive traits are heritable, common genetic drivers of obesity may lead to phenotypic obesity through appetitive traits as a disease mechanism. Additionally, GLP-1 receptor agonists (GLP-1RAs) have been shown to exert their profound clinical effects in part by modulating appetite. …

Characterization Of Microrna Expression In Neuron-Enriched Extracellular Vesicles During Early Life, Allison Molen

Theses and Dissertations

Extracellular vesicles (EVs) are membrane-bound sacs released by cells that carry molecular cargo reflective of their cell of origin. EVs enriched using L1 cell adhesion molecule (L1CAM) as a marker of putative neuronal origin can cross the blood–brain barrier and provide a minimally invasive window into brain-related processes. Exosomal microRNA (miRNA) regulate gene expression and have been implicated in psychiatric disorders, including major depressive disorder (MDD). However, measuring and analyzing miRNA from L1CAM-positive EVs presents substantial analytical challenges due to low abundance and sparse detection across samples.

Plasma samples from participants recruited through the Mid-Atlantic Twin Registry (MATR) were used …

A Fine-Scale Genomic Study Of Cheat Mountain Salamanders (Plethodon Nettingi) On Managed Public Land, Amylynn Nicole Ephraim

Graduate Theses, Dissertations, and Problem Reports (ETD)

Habitat fragmentation has the potential to isolate localized populations, particularly those which are understood to have limited dispersal capabilities. This isolation can reduce genetic diversity through the effects of inbreeding depression, and small populations are more susceptible to the impacts of genetic drift. In this study, I aim to understand the level of genetic connectivity between known occupied patches of Cheat Mountain salamanders (Plethodon nettingi; CMS) on managed public land. CMS are a federally threatened, high-elevation, West Virginia endemic species associated with red spruce (Picea rubens) forests. I used double-digest restriction site associated DNA (ddRAD) sequencing …

Genomic Signatures Of Decline And Recovery In An Endangered Bat, Myotis Grisescens, Marxe Altman-Orbach

Graduate Theses/Dissertations

Tremendous population declines may result in the loss of genetic diversity, which can, in turn, lead to reduced adaptive potential, overexpression of deleterious phenotypes, and further population declines. In this way, genetic drift from a severe demographic decline may ultimately lead to an extinction vortex. However, populations that avoid the loss of genetic diversity may remain viable, despite demographic crashes. Therefore, understanding genetic diversity is vital for assessing the conservation status of species that have undergone declines, and can even reflect the effectiveness of management actions. I investigated signatures of genetic bottlenecks in the gray bat (Myotis grisescens), …

Epigenetic Modifications In Dedifferentiated Liver Cells To Restore Lost Liver Function, Shreya Sharma

Masters Theses

The goal of the study is to investigate whether the epigenetic modifications can enhance the restoration of liver gene expression in dedifferentiated hepatoma cells or not. For the study, we used dedifferentiated H11 hepatoma cell lines which overexpress one of a panel of introduced candidate liver-enriched transcription factors H11-HNF1a, H11-CREB3L3, H11-CREG1, H11- HHEX, H11-HNF6, and H11-IGFBP1. The cells were treated with the DNA methyltransferase inhibitor 5-azacytidine and the histone deacetylase inhibitor sodium butyrate, both individually and in combination. Gene expression analysis was determined by RT-qPCR, which revealed that while transcription factor overexpression alone produced limited activation, epigenetic modulation, particularly Histone …

Regulation Of Chromatin Remodeling By The Post-Hsa Domain Of Brg1, A Subunit The Baf Atp-Dependent Chromatin Remodeling Complex, Min Sze Ewe

Theses & Dissertations

The ATP-dependent chromatin remodeler BAF complex regulates nucleosome positioning, chromatin accessibility, and tissue specific gene expression. Its catalytic subunit, BRG1, contains several regulatory domains including the post-HSA region, proposed to modulate ATPase activity. Multiple cancer-associated mutations map to these regulatory regions underscoring their importance, yet the precise role of the post-HSA region in chromatin remodeling remains poorly understood.

To investigate the function of the post-HSA domain, we ectopically expressed FLAG-tagged BRG1 with post-HSA deletion (Δpost-HSA BRG1) in mouse embryonic stem cells. Western blot analysis confirmed expression of the mutant protein. To determine the effects of mutant protein expression on chromatin …

Context Dependent Regulation Of Dicer Function During Oocyte-To-Embryo Transition, Nick A. Newkirk

Dissertations and Theses (Open Access)

Over two decades ago, Dicer was discovered as the primary enzyme responsible for the generation of small RNAs known as the microRNAs (miRNAs) and short interfering RNAs (siRNAs). Spatiotemporal regulation of Dicer-dependent small-RNA biogenesis affects many aspects of biology, including aging, disease progression, fertility, and cancer. Interestingly, a distinct population of Dicer-dependent small RNAs, known as the endogenous siRNAs (endo-siRNAs), are uniquely abundant in the germ cells and gametes, and are critical for normal fertility. Despite their function regulating new life, the mechanisms controlling their biogenesis and subsequent germ cell functions remain poorly defined. Work to parse these mechanisms in …

Population Structure Analysis Of Four Basal Higher-Attines Using Bioinformatic Approaches, Gabriel Mcdanield

Biology Theses

Metapopulations within the family Formicidae are unique among other animals due to the large colonies they build, and the mating strategies required to fertilize a specialized reproductive caste that will often produce young for the life of the colony. One group of ants, the fungus-gardeners (tribe Attini). The population structure of North American non-leafcutting, fungus-gardening ants has been understudied, especially in the southwest of the United States. Additionally, not much is known about their dispersal biology, so the dynamics of dispersal of these species and how they affect population structure is likewise not well known. To shed light on the …

Genetic Characterization And High-Resolution Total Mrna Sequencing Of The Millipede Cherokia Georgiana Bollman, 1889, Elena Cruz

Biology Theses

There are approximately 12,000 described species within the class Diplopoda. Only six species, falling within four of sixteen orders, have fully sequenced genomes. No whole genomes are available for incredibly diverse families like Xystodesmidae. Many interesting characteristics in this group are poorly defined at the genetic level, such as the production of a defensive hydrogen cyanide secretion and UV fluorescence in the order Polydesmida. Here, we present a genetic characterization of the polydesmid millipede Cherokia georgiana Bollman, 1889. We include tissue-specific sequencing metrics, alignment and assembly of mitochondrial DNA consensus sequence according to tissue type, and phylogenetic tree construction using …