Genetics Commons^™

Analysis Of An Ethanol Sensitive Bmp-Nkx2.3-Fgf Signaling Pathway In Pouch Morphogenesis., Hieu Dai Le Vo

Electronic Theses and Dissertations

Craniofacial malformations lie at the heart of Fetal Alcohol Spectrum Disorders (FASD). While there is growing evidence for a genetic component to FASD, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. Bone Morphogenetic Protein (Bmp) signaling pathway dependent pouch formation is a key mechanism in facial development. We have previously shown that multiple Bmp mutants are sensitized to ethanol-induced facial defects. However, ethanol does not directly impact Bmp signaling. This suggests that downstream effectors, like nkx2.3 and Fibroblast Growth Factor (Fgf) signaling, may mediate the impact of ethanol on Bmp mutants. Here, I …

Life History Inhibits Deleterious Effects Of Dams On Genetic Health And Structure Of A Headwater Stream Fish, Riley Phelps

Electronic Theses and Dissertations

Habitat loss, fragmentation, and land use changes in river networks are common globally. The resulting fragmentation of landscapes and riverscapes threatens biodiversity and can affect dispersal and subsequently, gene flow and genetic health of species. Headwater streams are an integral part of river networks and contribute to biodiversity by providing habitat for temporary and permanent residents, yet they are easily altered and fragmented. The sandhills chub (Semotilus lumbee) is an endemic headwater leuciscid that lives in highly fragmented streams of the sandhills ecoregion in North and South Carolina, USA. New knowledge on the population genetics of the sandhills chub is …

Investigation Into Mycorrhizae Associated With Native Venus' Flytrap Root Tissue, Anna Carnaggio

Electronic Theses and Dissertations

Dionaea muscipula, a plant commonly known as the Venus' flytrap, is found native to the southeast corner of North Carolina and the northeast corner of South Carolina. Several populations of native Venus' flytraps are known to exist in the nutrient-poor peat bog conditions in and around Lewis Ocean Bay Heritage Preserve (LOBHP) in Northeastern South Carolina. Anthropogenic pressures in Horry County, specifically surrounding LOBHP, have resulted in a loss of habitat for several native and endangered species. As a result, conservation efforts are focused on relocating native Venus' flytraps into adjacent habitats to ensure survival. This is only a temporary …

Hidden Markov Model For Identifying Local Variants In Human Genomes Using Simulated Data, Scott Mccallum

Electronic Theses and Dissertations

Identifying adaptive mutations in genetic data is challenging due to the low frequency of occurrence of such events, and because signatures of selection are intertwined with the footprints of various other evolutionary forces that shape our genomes. Even when a larger region appears to be under selection, genomic sites that are linked to adaptive mutations have similar statistical signals, and thus can obfuscate the identification of the actual adaptive mutation. The new method described here uses a Hidden Markov Model that allows for classification of neutral, linked, and sweep (adaptive mutation) genomic sites. This model is general and can be …

Population Genetic Diversity In Two Biological Systems, Alyson Emery

Electronic Theses and Dissertations

Population genetic analysis can be used to answer questions about population structure and composition in many biological systems. Recent improvements to sequencing technologies have made population genetic studies more accessible than ever before. Many of the same techniques can be applied to different biological systems, but some analyses may differ depending on how genetically divergent the populations in question are. Here, we describe two unique projects using next-generation genome sequencing, each looking at population structure at different levels of genetic divergence: the first involved determining interspecific population structure between two species of hybridizing field cricket using a novel sequencing method, …

Akt Disruption Leads To Non-Canonical Apical Constriction In Drosophila Embryos, Vincent Brown

Electronic Theses and Dissertations

The Akt/mTOR pathway (Akt pathway) has largely been examined in terms of its role as the primary nutrient sensing pathway due to its ability to recognize nutrient availability within a cell, particularly amino acids and glucose. Among its nutrient sensing characteristics, this pathway also contributes to a large variety of other cell functions such as cell growth, proliferation, protein synthesis, and cell survival via anti-apoptotic signaling. Although many aspects of this pathway have been carefully studied, the extent to which it regulates embryonic development remains unclear. Here, I examine Akt function in the early Drosophila embryo and demonstrate that Akt …

Uncovering The Hidden Diversity Of Antibody Heavy Chains And Their Implications For Autoantibody Mediated Disease., Easton Earl Ford

Electronic Theses and Dissertations

Understanding the diversity of antibody (IG) molecules at the DNA and RNA level is imperative for understanding immunological processes and disease. Much of the work to uncover IG diversity has been focused on diversity in the variable region of the IG molecule which is crucial for antigen binding. However, the diversity of the constant region responsible for the functions of IG has largely been ignored in the field of immunogenetics. The work presented in this thesis challenges the dogma that the constant region is invariant in terms of genetic diversity. In this thesis we present the development of a long-read …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Spatial Structure Formation By The Post-Transcriptional Gene Regulator Rsme In Pseudomonas Fluorescens Pf0-1, Anton Evans

Electronic Theses and Dissertations

Microorganisms are often found in microbial communities we call biofilms. Organisms living in these crowded environments have significant evolutionary pressure to retain access to the resources necessary to sustain life. My research uses the bacterium Pseudomonas fluorescens Pf0-1 to study how organisms evolve strategies to solve this crowding problem as aging colonies repeatedly generate mutant patches. These mutants expand the reach of the colony resulting in decreased local density as they push themselves up to the resource rich surface. These spatial structures result from social interactions between the mutant and the parental cells mediated through extracellular secretions, resulting in the …

Characterization Of The Immunoglobulin Lambda Chain Across Diverse Human Populations., William Gibson

Electronic Theses and Dissertations

The adaptive immune system relies on a diverse set of over one hundred immunoglobulin (IG) genes across three genomic loci that are variably combined to form antibodies (Ab). The IG Lambda locus is one of two loci which encodes the IG light chain. The complexity of the IGL locus severely limits the effective use of standard short-read sequencing, limiting our knowledge of population diversity in these loci. We leveraged single molecule real-time (SMRT) long-read sequencing in conjunction with IGL-targeted DNA capture to develop the method IG-Cap for accurate and high-throughput sequencing of the IGL locus. We benchmarked this method using …

A Comparison Of Microsatellites And Single Nucleotide Polymorphisms For The Assessment Of Population Structure In The Amblyomma Maculatum Koch, 1844 Species Complex, Henrey A. Deese

Electronic Theses and Dissertations

The Gulf Coast tick, Amblyomma maculatum Koch, 1844 is widespread throughout North and Central America and is the primary vector for the emerging pathogen Rickettsia parkeri. In the U.S., the population in the Southwest (A. maculatum morphotype III) is morphologically different from the population east of the Rocky Mountains (A. maculatum morphotype II). This research tests the hypothesis that A. maculatum morphotype II and morphotype III represent distinct species through the analysis and comparison of 6 microsatellite loci and suite of 135,221 Single nucleotide polymorphisms (SNPs) generated from ddRADseq. Population genetic analysis of both microsatellites and SNPs …

The Evolutionary Causes And Consequences Of Mammalian Hybridization, Kelsie E. Hunnicutt

Electronic Theses and Dissertations

The natural recombination of divergent genomes within hybrid offspring provides windows through which we can study evolutionary processes and the dynamics of speciation. In this work, I use a combination of comparative and population genomics on both laboratory crosses of divergent rodent lineages and a hybrid zone of cottontail rabbits in the wild to study the causes and consequences of hybridization in mammals. Hybrid sterility is a common reproductive barrier between species that tends to preferentially manifest in the heterogametic sex and frequently genetically maps to the sex chromosomes. Thus, the sex chromosomes appear to play a special role in …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

A Review Of Current Methods In Avian Dietary Analysis And Their Integrated Application To Characterize The Trophic Niche Of Louisiana Waterthrush (Parkesia Motacilla)., Brandon Hoenig

Electronic Theses and Dissertations

Characterizing a species’ dietary composition presents an avenue to understand many facets of its ecological niche and can provide essential information for the species’ long-term conservation. To date, the vast majority of diet studies have relied on direct identification of prey during foraging observations or from diet samples to characterize the dietary habits of birds. However, advancements in laboratory-based approaches have revolutionized the field of trophic ecology by allowing researchers to indirectly infer dietary habits with higher resolution across greater time scales. Here, I apply two of these laboratory-based techniques, namely DNA metabarcoding and stable isotope analysis, to characterize the …

Analysis Of Water Quality And Fish Communities Of Crooked Creek, Tributary To The Allegheny River In Southwestern Pennsylvania, Katherine Stupar

Electronic Theses and Dissertations

Crooked Creek is a tributary of the Allegheny River with a drainage area of 292 square miles. It has been historically affected by mine drainage pollution. Extensive cleanup and monitoring efforts by the Commonwealth of Pennsylvania and the U.S. Army Corps of Engineers (USACE) have taken place over the last four decades. Unconventional oil extraction, or fracking, presents an emerging threat to the water quality of this stream and the health of its fish communities. Here we perform an analysis of the Crooked Creek watershed utilizing backpack electrofishing, eDNA metabarcoding, and various methods of water quality analysis. Seven sites on …

Functional Role Of Ppal And Potential For Moss In Industrial Applications., Susana Perez Martinez

Electronic Theses and Dissertations

This dissertation is an examination and characterization of the functional roles of PPAL. PROTEIN PRENYLTRANSFERASE ALPHA SUBUNIT-LIKE (PPAL) is a recently discovered gene. PPAL homologs are present in all plants and many animals, where its function is largely unknown. It is possible that PPAL could participate in prenylation processes since it shares similarity to the α subunits of known prenylation enzymes. Prenylation is a post-translational modification of proteins that involves the addition of a lipid moiety to proteins to facilitate membrane targeting and association and promote protein-protein interactions. Prenylation has important roles in plant growth and development, including …

Genomic Tools And Models For Investigating The Role Of Germline Diversity In Mouse Antibody Repertoire Development., Justin T. Kos

Electronic Theses and Dissertations

Given the diversity and complexity within immunoglobulin (IG) loci, effective mouse models first require characterization of intra-strain differences and construction of high-quality reference assemblies for IG loci in several representative strains. To understand light chain germline diversity across biomedically significant mouse strains, we profiled the expressed IGK and IGL repertoires of 18 commonly used laboratory mouse strains using AIRR-seq. Across strains, we observed germline IGKV sequences shared by three different IGK haplotypes and a more conserved IGLV germline repertoire among common laboratory strains. Pacific Biosciences (PacBio) Single-Molecule Real-Time (SMRT) sequencing was used to sequence and assemble bacterial artificial chromosomes (BAC) …

Characterization Of Hemocytes In Amblyomma Americanum And Investigation Of Traf6’S Role In Proliferation Of Hemocytes In Response To Infection, Jacquelyn T. May

Electronic Theses and Dissertations

Amblyomma americanum is a medically important vector in the southeast United States. Cellular and molecular aspects of the immune system of this species were examined. To investigate cellular processes, hemocytes produced in response to gram-negative infection were characterized according to their ultrastructure. Four hemocyte types were identified: prohemocytes, plasmatocytes, type-I granulocytes, and type-II granulocytes. To elucidate molecular processes, we investigated AamTRAF as an immune-related gene by silencing the gene using RNAi then quantifying the hemocytes after inoculation with gram-negative and positive bacteria. It was found that silencing AamTRAF caused a decrease in hemocyte proliferation in response to gram-positive but not …

Understanding Snow Leopard (Panthera Uncia) Population Structure, Diet, And Human-Wildlife Dimensions Using Noninvasive Genetic Approaches, Charlotte Hacker

Electronic Theses and Dissertations

Snow leopards (Panthera uncia) are a large cat endemic to the mountains of Central Asia. Despite their status as a flagship species, there are numerous knowledge gaps surrounding their population status, dietary ecology, and relationship with humans. Such knowledge gaps are prohibitive for effective conservation action for the species. Snow leopards are threatened by habitat loss, decreased prey availability, retaliatory killings, and large-scale negative impacts associated with climate change. In order to help bridge these gaps, noninvasive genetic methodologies were deployed in this work across several disciplines. Population genetic metrics were garnered at local, regional, and range-wide scales, …

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …

Efficient Conditional Inactivation Of Rdh10 Reveals Important Role Of Retinoic Acid During Lung Branching Morphogenesis., Nhut Quang Huy Tran

Electronic Theses and Dissertations

Birth defects are complicated pathological processes. Many birth defects can be traced back to disrupted regulation of molecular signaling pathways during embryogenesis. One of the most important gene regulatory factors during embryo development is retinoic acid (RA). However, studying the specific roles of RA in each organ during embryogenesis in vivo is challenging. The Sandell laboratory has a conditional mutant mouse model that can potentially be used for studying the role of RA during embryogenesis by inducing stage-specific RA deficiency. This model allows retinol dehydrogenase 10 (Rdh10), a gene required for RA production, to be inactivated at a …

Human Genetics, Psychotropic Drugs, And Acts Of Violence, Selma Jolanda Eikelenboom-Schieveld

Electronic Theses and Dissertations

From the start of the use of psychoactive prescription medications in the 1950s, physicians reported paradoxical adverse reactions, ranging from newly developing depressions to an increase in existing mood disorders, and extremely violent and bizarre acts of suicide and homicide. In this research, it is hypothesized that the pharmacological properties of the prescribed drugs or the interaction between the drugs and the enzymes that are primarily responsible for their metabolism (cytochrome P450s) could cause these reactions. Given that acts of violence could be medication-induced, the role of the rate of drug metabolism is discussed. Genetic testing of certain CYP450s could …

Functional Analysis Of Squamosa-Promoter Binding Protein Like 13 In Controlling Flowering Time, Plant Architecture, Grain Size, And Grain Number In Wheat, Ajay Gupta

Electronic Theses and Dissertations

Higher and stable yield is always a major objective of wheat genetic improvement programs. The SQUAMOSA-promoter binding protein-like (SPL) genes constitute a small family of plant-specific transcription factors with diverse functions in plant development and growth and have great potential in improving yield and other major agronomic traits. However, the functional characterization of the SPL gene family in wheat is far behind other cereal crops such as rice. Using phylogenetic analysis, we identified 56 wheat orthologues of rice SPL genes belonging to 19 homoeologous groups. Among these 19 orthologous TaSPL genes, nine harbor the micro RNA 156 recognition element (MRE) …

Genetic And Biochemical Analysis Of A Conserved, Multi-Gene System Regulation Spore-Associated Proteins In Streptomyces Coelicolor, Joseph Sallmen

Electronic Theses and Dissertations

Streptomyces coelicolor is a Gram positive, filamentous soil dwelling bacterium that exhibits a complex life cycle including the transition from a vegetative mycelium to a sporulating, aerial mycelium. Early genetic studies identified two classes of genes that resulted in developmental blocks, bald and white. The bald (bld) phenotype occurs when colonies cannot produce aerial hyphae. White (whi) colonies exhibit incomplete sporulation and/or loss of production of the concurrently produced grey pigment. While some of the original mutants have been explored, the developmental functions of many of the identified genes are not well understood. Of particular interest …

A Possible Luxr Solo Type Regulator Of An Antibiotic-Like Compound From The Soil Bacterium Rhodococcus, Katelyn Sellick

Electronic Theses and Dissertations

Rhodococcus, a species of bacteria commonly found in the soil, is an under-explored producer of small bioactive compounds including siderophores, pigments and antibiotics. MTM3W5.2 is a strain of Rhodococcus that was previously discovered to produce an antibiotic-like compound that has inhibitory effects on other Rhodococcus strains, including the veterinary pathogen, R. equi. The biosynthetic gene cluster responsible for production of the antibiotic has been identified, and a small gene, BTZ20_3964 at the start of the operon is believed to be a luxR solo regulator of the gene cluster. The goal of this project was to determine this gene’s …

Genetic Diversity Of White-Tailed Deer Populations In Southwestern Pennsylvania And The Development Of A Forensics Panel, Melanie Quain

Electronic Theses and Dissertations

During the 20^thcentury, white-tailed deer (Odocoileus virginianus) became scarce, prompting conservation efforts by hunters and wildlife managers with the goal to recover this species. Various strategies were implemented including reintroductions from areas that still had large deer populations, developing bag limits, seasonal restrictions, and habitat management. These efforts were highly successful across the United States.

Today, white-tailed deer are one of the most abundant and widely-distributed large-bodied mammals in North America. However, there are several important management concerns. In numerous states, including Pennsylvania, CWD negatively impacts deer populations and has become a major health concern. When …

Divergence Of Threespine Stickleback That Differ In Nuptial Coloration, Clara Sophie Jenck

Electronic Theses and Dissertations

Recent research has led to a much better understanding of the evolutionary processes that mold and structure variation within and among populations. How populations diverge at the genome-wide level and how polymorphism is maintained within a species, however, remains unclear. We address these questions with two freshwater color morphs, red and black, of the threespine stickleback fish (Gasterosteus aculeatus) from the northwest United States, in which a shift from red to black nuptial coloration occurred in several locations following glacial retreat. We measured phenotypic variation in a suite of traits and used next generation sequencing to characterize within-species and among-morph …

Proximate And Ultimate Consequences Of Stressed-Induced Maternal, Paternal, And Joint Parental Effects In A Changing World, Whitley Rayen Lehto

Electronic Theses and Dissertations

Parental experience can alter the developmental and rearing environments of offspring, resulting in parental effects on offspring traits. I addressed the consequences of stress-induced maternal, paternal, and joint parental effects from both ultimate (ecological/evolutionary) and proximate (physiological/epigenetic) perspectives. I used a full-factorial design in which threespine stickleback (Gasterosteus aculeatus) mothers, fathers, both, or neither were exposed to a model predator at developmentally appropriate times to test for predator-induced maternal, paternal, and joint parental effects on daughters’ mating behavior and egg glucocorticoids (stress hormones) and on offspring gene expression. Maternal and paternal predator exposure independently yielded daughters who preferred …

A Sustainable Future In The Implementation Of Clinical Pharmacogenomics, Nicholas Keeling

Electronic Theses and Dissertations

Purpose: The sustainability of clinical pharmacogenomics requires further study of clinical education on the topic, its effects on clinical workflow, and the responsibilities of different providers for its delivery. Tools from the discipline of implementation science were utilized herein to help achieve the purposes of the three studies. The broad purpose of this dissertation is to advance the work of clinical pharmacogenomic implementation through a more rigorous convergence with implementation science.

Methods: Three studies constitute the whole of this dissertation. The first is a scoping review that provides a broad characterization of the methods utilized in available peer-revieliterature focusing on …

Application And Refinement Of Molecular Ecology Techniques For Amphibian Conservation, Stephanie Marie Burgess

Electronic Theses and Dissertations

Wildlife conservation has become increasingly difficult due to habitat loss habitat fragmentation and land use change. Thus conservationists have embraced advances in molecular ecology such as landscape genetics and microbial bioinformatics that employ genetic techniques to further understand the relationship between individuals and their environment. In landscape genetics model inferences can be used to identify features that facilitate or resist gene flow providing a framework for anticipating the impacts of land use changes on a species’ ability to disperse. However the factors that affect the transferability of landscape genetics inferences are poorly understood and little is known about the effect …