Genetics and Genomics Commons^™

Reconstruction Of Fox Transcription Factor-Regulated Subnetworks Mediating Cardiac Progenitor Cell Divisions, Md Rezaul Hasan

All-Inclusive List of Electronic Theses and Dissertations

Congenital heart disease (CHD) is the most common congenital anomaly worldwide, affecting approximately 1% of live births, corresponding to 1.35 million infants born with CHD each year, and remains a leading cause of infant mortality; therefore, it is urgent to understand the genetic and molecular mechanisms underlying CHD for advancing early diagnosis and treatment. Because many aspects of the Drosophila heart formation are highly reminiscent of vertebrate heart development, Drosophila melanogaster serves as a simple yet powerful model system for studying cardiac development and CHD. While at least eight Forkhead box (Fox) transcription factors (TFs) are required for proper cardiac …

Analysis Of Developmental Cardiogenic Processes Mediated By Fox And Zinc-Finger Transcription Factors, Rajnandani Katariya

All-Inclusive List of Electronic Theses and Dissertations

Cardiogenesis is a highly choreographed biological process requiring the precise integration of gene regulatory networks to govern cell division, fate determination, and spatial positioning. Disruptions in these mechanisms lead to congenital heart defects (CHDs), which affect approximately 1% of live births globally. Due to the evolutionary conservation of cardiac signaling pathways and the structural homologies between the Drosophila dorsal vessel and the early vertebrate heart tube, Drosophila melanogaster serves as a powerful model for dissecting the fundamental mechanisms of heart development. This dissertation investigates the molecular orchestration of cardiac development, specifically focusing on the roles of the transcription factors Jumu …

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 …

Population Structure And Connectivity Of Atlantic Nurse Sharks (Ginglymostoma Cirratum) In The Bahamas And Outlying Areas, Baylie A. Fadool

School of Natural Resources: Dissertations, Theses, and Student Research

Understanding animal ecosystem dynamics and behavior at the individual and population levels is essential for identifying life-history patterns and important areas for management and conservation. Marine fish species often face minimal geographic barriers to movement, but environmental (temperature, salinity, current) or intrinsic barriers (philopatry, site fidelity) can dictate gene flow. Atlantic nurse sharks (Ginglymostoma cirratum) are an International Union for Conservation of Nature (IUCN) listed ‘vulnerable’ species and present a unique opportunity to investigate patterns of population structure and connectivity in large-bodied sharks. They are benthic and display reproductive philopatry, with recent work suggesting they have the capacity …

Validation Of A Real-Time Pcr Laboratory Developed Test For The Detection Of Pneumocystis Jirovecii In Bronchoalveolar Lavage Samples, Caitlyn Moon

Honors Scholar Theses

Pneumocystis jirovecii is an opportunistic, host-obligate fungal pathogen responsible for causing P. jirovecii pneumonia (PJP) in humans. PJP is treated with trimethoprim-sulfamethoxazole (TMP-SMX), a strong broad-spectrum antibiotic that carries risk of renal and hepatotoxicity. Therefore, rapid diagnosis or exclusion of PJP is crucial to ensure PJP-positive patients receive effective treatment and PJP-negative patients avoid unnecessary antibiotics. Unlike most microorganisms, P. jirovecii cannot be cultured, presenting complications for the typical methods of diagnosing fungal pathogens. Historically, the gold standard for diagnosis was direct microscopic examination with stains such as methenamine silver and calcofluor white, but this diagnostic technique requires highly skilled …

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 …

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

All Dissertations

Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Men’S Preconception Diet Quality Patterns Predict Supportive Food Parenting Practices: Evidence From A Longitudinal Cohort Study, Mariane H. De Oliveira, Brian K. Lo, Matthew M. Lee, Stephanie Armbruster, Natalie Grafft, In Young Park, Alejandra Cantu-Aldana, Katherine W. Bauer, Rebekah Levine Coley, Sebastien Haneuse, Kirsten Davison, Jess Haines

Human Genetics Publications

Background: Food parenting practices play a vital role in shaping children's food intake, yet evidence linking fathers' earlier diet patterns to later parenting is limited. This study examined the association between fathers' diet quality patterns during their adolescence and food parenting practices during fatherhood.

Methods: Data were drawn from Fathers & Families (F&F), a father-based cohort that recruited participants from an ongoing cohort in the United States that has followed participants since adolescence. Participants (n = 584) reported their dietary intake during adolescence (ages 10-18) using a Youth/Adolescent Food Frequency Questionnaire across multiple survey waves (1996-2011), and reported their food …

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 …

Modeling Repeated Evolution Of Polygenic Traits, Marshall N. Hoskins

All Theses

Understanding the genetic composition of adaptive evolution is a longstanding and primary goal of evolutionary genetics. Despite many advances in our knowledge of trait adaptation, it remains unclear how demographic changes and repeated selection might alter the expected genetic architecture of adaptation. We used forward-in-time genetic simulations to test and observe the effects of opposing, repeated selection regimes on a polygenic trait in populations with and without changes in demography to better understand the genetic alleles that underlie polygenic adaptation. To further illuminate how natural populations might evolve, we investigated the impact of mutation effect size, the role of dominant/recessive …

Characterizing The Molecular Response Of Embryonic Zebra Finch To Acute Sound Playback, Saidat O. Adeniran-Obey Miss

All Theses

Auditory stimuli are important cues that influence developmental plasticity in animals and are important for development and adaptation to an ever-changing environment. In the zebra finch (Taeniopygia guttata), there is evidence of adaptive developmental reprogramming in response to a prenatal ‘heat call’. Embryos exposed to this heat call exhibit changes in growth rate post-hatch, increased heat resistance, and enhanced reproductive success at maturity. However, it has long been assumed that embryonic zebra finches cannot respond to sound due to the immaturity of their auditory system. These findings raise the critical question of whether late-stage zebra finch embryos can, …

An Investigation Of Entamoeba Histolytica Chitin Synthases And Other Encystation Factors In Early Encystation, John N. Talledo

All Theses

Entamoeba histolytica is a food-and-water-borne human protozoan pathogen that relies on a two-stage life cycle for successful proliferation outside of the host. E. histolytica exists in its dormant cyst form while outside of its host and converts to the motile trophozoite (amoeba) form in the small intestine. The trophozoites colonize the large intestine to cause symptomatic disease in ~10% of infections, resulting in ~100 million cases of amoebic dysentery each year. Trophozoites can convert back to the cyst form, which is shed in feces to continue the infection cycle.

Currently, there is a lack of understanding of the exact molecular …

Dissecting The Complex Genomic Landscape Underlying Oxidative Stress Resistance Using Natural Variation In Yeast, Sonali Lakshika Anne Lenaduwe

Graduate Theses and Dissertations

Stress is experienced across the tree of life. Survival in fluctuating environments depends on a robust genetic architecture. This dissertation examines the genetic and metabolic determinants underlying one such adaptive response: cross-protection. Leveraging natural variation in the stress responses of budding yeast, Saccharomyces cerevisiae, I examine the genetic variation contributing to ethanol-induced cross-protection against oxidative stress. Acquired stress resistance, in which mild pre-exposure improves survival to subsequent stresses, is prevalent across diverse organisms and can involve both same-stress and cross-protection. Using high-throughput bulk segregant analysis (BSA-seq) and advanced intercross mapping populations derived from natural yeast isolates, I identify quantitative trait …

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 …

Using The Flexon Approach To Rnai To Identify Essential Genes That Affect Gonadal Development In C. Elegans, Joyce S. Lefevers

Undergraduate Theses

To elucidate the molecular role of essential genes in the gonadal development of Caenorhabditis elegans (C. elegans) it is necessary to utilize specialized molecular techniques such that the phenotypic effects of gene knockdown can be studied while the viability of the organism is preserved. Shaffer and Greenwald (2022) developed the floxed exon (flexon), a tool that improves upon previous approaches to spatiotemporal control of gene expression. The flexon subunit is made up of an artificial exon with a stop cassette flanked by artificial introns which, when inserted into a gene of interest, prevents the expression of that gene. …

Cross-Sectional Associations Of Metabolically Healthy Obesity, Lifestyle Factors, And Steatotic Liver Disease In Adults From The Fels Longitudinal Study, Ariana L. Garza, Audrey C. Choh, John Blangero, Cici X. Bauer, Stefan A. Czerwinski, Miryoung Lee

School of Medicine Publications

Objective: To examine the associations of metabolic health and obesity phenotypes with liver fat accumulation and hepatic steatosis in adults. Methods: We analyzed 676 non-Hispanic white adults (18–95 years; 55.8% female) from the Fels Longitudinal Study using a cross-sectional design. Participants were classified into metabolically healthy normal weight (MHNW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO) phenotypes. Metabolically unhealthy status was defined as the presence of ≥1 metabolic dysfunction, consistent with prior epidemiological definitions; secondary analyses using ≥2 were also performed. Obesity was defined using DXA-derived body fat percentage. Liver fat (%) was …

From Bench To Bedside: Unraveling The Role Of Sarm1 In Chronic Human Neurodegenerative Disease, Caitlin Dingwall

Arts & Sciences Graduate Student Theses and Dissertations

Axon degeneration (AxD) is an early and often causative event in many neurodegenerative diseases, yet no treatments exist to halt the breakdown of axons. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. NMNAT2 is a highly labile protein produced in the soma and trafficked into the axon. Nerve injury blocks axonal transport and leads to rapid depletion of axonal NMNAT2, causing NMN buildup and NAD+ loss. Recent breakthroughs led to the discovery that SARM1 is activated by an increase in the NMN to NAD+ ratio. While the SARM1 axon degeneration pathway …

Identification Of Lipid Quantitative Trait Loci Linked With Cardiometabolic Disease In Asian Indians And Europeans: A Genome-Wide Association Study And Mendelian Randomization, Madhusmita Rout, Christopher E. Aston, Ravindranath Duggirala, Harald H. H. Goring, Oliver Fiehn, Dharambir K. Sanghera

School of Medicine Publications

Background: Genetic mechanisms that predispose people to type 2 diabetes (T2D) and cardiovascular disease (CVD) remain poorly understood, partly because of a lack of sufficient data on non-European ethnic groups. Extending these evaluations to diverse cohorts is essential for gaining insights into the molecular pathways involved in disease development among human populations. In this study, we aimed to evaluate the genetic connection between the human lipidome and cardiometabolic disorders. We conducted a metabolite genome-wide association study (mGWAS) in a Punjabi population from India, along with multi-layer replication studies using the UK Biobank and other independent European and non-European cohorts.

Methods …