Genetics and Genomics Commons^™

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Characterization Of Pathological Tau Mutants, Charles J. Mcdonald

Dissertations, Theses, and Capstone Projects

Tau is a protein expressed exclusively in glia and neurons in the central nervous system and implicated in several neurogenerative diseases called “tauopathies”. Among all the tauopathies, one third is characterized by the presence of genetic mutations leading to the synthesis of tau proteins with single amino acid substitutions at specific locations and affecting protein function. While most of the initial studies have emphasize the functional role of tau as modulator of the axonal cytoskeleton, it has recently been well accepted that tau is also an intrinsically disordered protein that tends to form membraneless organelles called coacervates, due to a …

Population Genomics, Ecology And Conservation Of Asterias Sea Stars In The North Atlantic, Melenia I. Giakoumis

Dissertations, Theses, and Capstone Projects

Uncovering how species respond to environmental change is a central question in biology (Ehrlén & Morris 2015; Habibullah et al. 2022). It is the key to elucidating the past, understanding the present and predicting the future of species’ population dynamics. This dissertation investigates the influence of environmental change on intertidal species’ distributions and genomics at several timescales, with implications for conservation.

Environmental changes have occurred throughout history, on a geological scale, and have shaped the global patterns of species’ distributions and population sizes. Biologists have long studied how geological history has shaped species distributions (Sanmartín 2012) in both terrestrial (Liu …

Illuminating The Drivers Of Genomic Diversification In Lamprologine Cichlids Of The Lower Congo River, Naoko P. Kurata

Dissertations, Theses, and Capstone Projects

Freshwater fishes are extraordinarily diverse, considering their available habitats represent a tiny proportion of the earth’s surface. Rivers connect heterogeneous habitats in a linear form and provide excellent simplified models to understand how aquatic biodiversity evolves. In particular, the lower Congo River (LCR) in west Central Africa consists of a dynamic hydroscape exhibiting extraordinary aquatic biodiversity, endemicity, and morphological and ecological specialization. This system is thus an excellent natural laboratory for understanding complex speciation and population diversification processes. In my research, I explore various drivers of diversification, and adaptive evolution in rheophilic lamprologine cichlids endemic to the LCR, including Lamprologus …

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

American Eel (Anguilla Rostrata) And Other Fishes As Surveyed By Environmental Dna In The Bronx River And Hudson River Watershed, Sam C. Chin

Dissertations, Theses, and Capstone Projects

Mounting an effective response to the threats faced by freshwater fish may require expansions to aquatic biomonitoring in excess of what is feasible using the capture-based survey techniques currently relied upon by natural resource managers. Methods for analyzing environmental DNA (eDNA) are emerging as a minimally invasive and cost-effective approach for surveying fish and other organisms. By detecting taxon-specific DNA sequences recovered from environmental samples (e.g. water, sediment), eDNA methods are able to infer species presence from samples that can be collected rapidly with simple equipment. In many cases, eDNA detection rates of fish species have been shown to meet …

Effects Of The Otx2ecr2 Enhancer & Prox1 Overexpression In Murine Retina Development, Erick J. Subillaga

Dissertations and Theses

There is a large subset of retinal progenitor cells that upregulate the OTX2 gene in the developing retina of the mouse. OTX2 is a homeobox transcription factor important for the development of photoreceptors and bipolar cells. If OTX2 is knocked out, photoreceptors and bipolar cells fail to differentiate. In order for OTX2 to be activated in certain retinal populations, it requires the activity of an enhancer called OTX2ECR2. Past studies demonstrated that retinal progenitor cells that had activity of OTX2ECR2 turned into horizontal cells, which require OTX2 for cell genesis and survival, and photoreceptors which require OTX2 for cell …

Rescue Of Deficits By Brwd1 Copy Number Restoration In The Ts65dn Mouse Model Of Down Syndrome, Sasha L. Fulton, Wendy Wenderski, Ashley E. Lepack, Andrew L. Eagle, Tomas Fanutza, Ryan M. Bastle, Aarthi Ramakrishnan, Emma C. Hays, Arianna Neal, Jaroslav Bendl, Lorna A. Farrelly, Amni Al-Kachak, Yang Lyu, Bulent Cetin, Jennifer C. Chan, Tina N. Tran, Rachael L. Neve, Randall J. Roper, Kristen J. Brennand, Panos Roussos, John C. Schimenti, Allyson K. Friedman, Li Shen, Robert D. Blitzer, Alfred J. Robison, Gerald R. Crabtree, Ian Maze

Publications and Research

With an incidence of ~1 in 800 births, Down syndrome (DS) is the most com- mon chromosomal condition linked to intellectual disability worldwide. While the genetic basis of DS has been identified as a triplication of chromosome 21 (HSA21), the genes encoded from HSA 21 that directly contribute to cognitive de fi cits remain incompletely understood. Here, we found that the HSA21- encoded chromatin effector, BRWD1, was upregulated in neurons derived from iPS cells from an individual with Down syndrome and brain of trisomic mice. We showed that selective copy number restoration of Brwd1 in trisomic animals rescued de fi …

Novel Therapeutic Strategies For Alzheimer’S Disease: Prostaglandin D2 Signaling And Its Human Polymorphisms As Well As A Polypharmacological Approach, Charles H. Wallace

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is an age related neurodegenerative disease with pathology that includes amyloid plaques, neurofibrillary tangles and non-resolving neuroinflammation. Non-resolving neuroinflammation lasts the entire course of the disease and has deleterious effects and is often thought to accelerate AD pathology. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) have commonly been used as therapeutics to treat pain, inflammation and vascular. NSAIDs work by altering the cyclooxygenase (COX) mediated biosynthesis of prostaglandins which are lipid mediators that have many physiological functions, for example nociception, inflammation and vasodilation. Epidemiological studies support the notion that NSAIDs could be used to treat AD. Yet, clinical trials using …

Using Direct Pcr For Disaster Victim Identification Reference Samples, Mary Habib

Student Theses

Forensic genetic testing is an important tool for the identification of victims after a mass fatality event but degradation of remains, presence of PCR inhibitors, and limited amounts of sample can make testing difficult. Standard protocols typically include extraction of genetic material from recovered post-mortem samples, and from ante-mortem reference samples or families of a missing person. This is a time-consuming and laborious process and may result in the loss of trace amounts of DNA available for amplification. Incorporating workflows that bypass the extraction step and directly amplify recovered DNA for short tandem repeat (STR) profile generation has the potential …

Symmetry-Inspired Analysis Of Biological Networks, Ian Leifer

Dissertations, Theses, and Capstone Projects

The description of a complex system like gene regulation of a cell or a brain of an animal in terms of the dynamics of each individual element is an insurmountable task due to the complexity of interactions and the scores of associated parameters. Recent decades brought about the description of these systems that employs network models. In such models the entire system is represented by a graph encapsulating a set of independently functioning objects and their interactions. This creates a level of abstraction that makes the analysis of such large scale system possible. Common practice is to draw conclusions about …

Genomic Insights Into Mechanisms Of Microbial Evolution And Evolution-Inspired Strategies To Combat Pathogen Diversity, Saymon Akther

Dissertations, Theses, and Capstone Projects

We live in an era of emerging infectious diseases that are increasingly common, rapidly spreading, and gravely devastating. Lyme disease, caused by bacteria belonging to the genus Borreliella, is rapidly rising in the Northern Hemisphere because of geographic range expansion of both the tick vectors and the pathogens. Evolutionary comparative analysis of Borreliella genomes is a key to understanding the phylogeographic history and mechanisms of their global diversification. Moreover, genomic variations in Borreliella associated with human pathogenicity, e.g., at loci encoding cell-surface antigens interacting with the vertebrate hosts, have not been fully identified. Similarly, the ongoing COVID-19 pandemic, caused …

Genetic Impacts Of Deforestation On Mouse Lemurs, Darice Westphal

Dissertations, Theses, and Capstone Projects

The impact of deforestation on the genetic structure of mouse lemurs is poorly understood. In this project, I assess deforestation of Madagascar’s terrestrial protected regions, quantify genomic wide genetic variation in two sympatric mouse lemurs, and evaluate the role of landscape structure in genetic relatedness patterns within two sympatric mouse lemur species. Overall deforestation rates across the 98 terrestrial protected areas in Madagascar are increasing, resulting in an average annual deforestation rate of 0.68% per year, with approximately 10,600 km² lost between 2000 and 2019. In a comparison of relatedness patterns between the sympatric gray mouse lemur (Microcebus …

Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip

Dissertations, Theses, and Capstone Projects

Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at …

Assessing The Utility Of The Pmm And Mmc Indices Among Extant Hominoid Genera, Julie A. Strain

Theses and Dissertations

This thesis set out to incorporate extant hominoid genera into an analysis of PMM and MMC to assess utility in phylogeny and predicting known taxonomic groups. Based on previous claims, we expect PMM/pmm and MMC/mmc to perform better than M1/m1 shape and size, our baseline for success, but they do not.

The Central Dogma: Gene Expression, Ayisha Sookdeo

Open Educational Resources

In this lesson plan, students will learn the basic structure and function of DNA and RNA. They will also learn the process of gene expression. Finally, students will learn about the scientific contributor, Ernest Everest Just, and his contributions to the field of Biology.

Conservation, Comparative Genomics And Species Delimitation Of The Reindeer Lichens (Cladonia), Jordan R. Hoffman

Dissertations, Theses, and Capstone Projects

The genus Cladonia represents one of the most speciose genera of lichenized fungi, with more than 500 known species encompassing a diverse array of morphologies and habits. These lichens form keystone species in many habitats, serving a variety of ecological roles. However, despite being among of the more well studied lichens, there is much still unknown or under-studied about them. As is the case with most lichen study systems, phylogenetic study has been limited to a small number of partial loci, while adoption of next-generation sequence methods has been slow. As a consequence, there are still knowledge gaps in Cladonia …

Novel Strategies For Glutamate Clearance In The Glia-Deprived Synaptic Hub Of C. Elegans, Joyce Chan

Dissertations, Theses, and Capstone Projects

As the major excitatory neurotransmitter in the mammalian brain, Glutamate (Glu) is critical for normal neuronal physiology. Disruption in Glu clearance results in hyper-stimulation of glutamatergic circuits, potentially leading to excitotoxic neurodegeneration. The canonical model of brain connectivity describes glutamatergic synapses as well insulated and enveloped by glia. These glia express Glu Transporters (GluTs) which work to clear Glu following synaptic activity. However, critical areas of the brain such as the mammalian hippocampus display poor synaptic isolation, which may result in Glu spillover between adjacent synapses and subsequent loss of circuit specificity. How accurate signal transmission is achieved in these …

Population Structure Of The Lizard Ecpleopus Gaudichaudii Coincides With A Biogeographic Barrier - The Doce River, Alexander J. Garretson

Dissertations and Theses

Intraspecific genetic variation is an integral component of diversification and the accumulation of biodiversity. The degree to which isolated populations of the same species are genetically structured in geographical space is impacted by a variety of mechanisms. In this study, I document patterns and discuss possible drivers of genetic structure within Ecpleopus gaudichaudii, a lizard species endemic to the Atlantic Forest of Brazil. For that, I assembled ddRadseq sequences from 48 individuals across much of the range of the E. gaudichaudii and analyzed its population structure. I created an intraspecific phylogeny for this group utilizing RAxML and conducted a …

Evaluating A Test For Shedding Propensity Using Tape Lifts From Different Skin Locations, Xiao M. Chen

Student Theses

The shedding propensity of a person can assist data interpretation in casework when assessing the possibility of passive transfer for DNA analysis. Past studies on shedding propensity evaluated palmar skin (washed and unwashed) deposits. This study compared different skin locations with respect to shedding propensity, and explored the potential of tape-lifts as a skin surface collection method. Eight different skin types and samples were collected with adhesive tape disks from 28 participants over three non-consecutive days; the washed and unwashed fingers from both hands, toe, and arm, neck below ear, and nape. Samples were extracted, quantified, amplified, genotyped, and evaluated …

Genomic Epidemiology Of Clostridium Difficile Colonization And Transmission In An Intensive Care Unit Cohort, Brianne Ciferri

Dissertations and Theses

Abstract

Genomic epidemiology of Clostridium difficile colonization and transmission in an intensive care unit cohort

by Brianne Ciferri, MPH

Advisor: C. Mary Schooling, PhD

Introduction: Clostridiodes difficile (C. difficile) is a leading cause of healthcare associated infections (HAI) in the United States and responsible for an estimated incidence of 223,900 cases and 12,800 deaths per year^1,2. C. difficile can cause gastrointestinal illness with symptoms ranging from mild diarrheal illness to a life-threatening condition. C. difficile is an opportunistic pathogen in which spores can live in an undisturbed dormant state within the intestinal tract and become …

Genome-Scale Data Reveal Deep Lineage Divergence And A Complex Demographic History In The Texas Horned Lizard (Phrynosoma Cornutum) Throughout The Southwestern And Central Us, Nicholas Finger, Keaka Farleigh, Jason T. Bracken, Adam D. Leaché, Olivier François, Ziheng Yang, Tomas Flouri, Tristan Charran, Tereza Jezkova, Dean A. Williams, Christopher Blair

Publications and Research

The southwestern and central US serve as an ideal region to test alternative hypotheses regarding biotic diversification. Genomic data can now be combined with sophisticated computational models to quantify the impacts of paleoclimate change, geographic features, and habitat heterogeneity on spatial patterns of genetic diversity. In this study we combine thousands of genotyping-by-sequencing (GBS) loci with mtDNA sequences (ND1) from the Texas Horned Lizard (Phrynosoma cornutum) to quantify relative support for different catalysts of diversification. Phylogenetic and clustering analyses of the GBS data indicate support for at least three primary populations. The spatial distribution of populations appears concordant …

Phylogenomics Of Alligator Lizards Elucidate Diversification Patterns Across The Mexican Transition Zone And Support The Recognition Of A New Genus, Christopher Blair, Robert W. Bryson Jr, Uri O. García-Vázquez, Adrián Nieto-Montes De Oca, David Lazcano, John E. Mccormack, John Klicka

Publications and Research

Genomic data continue to advance our understanding of species limits and biogeographic patterns. However, there is still no consensus regarding appropriate methods of phylogenomic analysis that make the best use of these heterogeneous data sets. In this study, we used thousands of ultraconserved element (UCE) loci from alligator lizards in the genus Gerrhonotus to compare and contrast species trees inferred using multiple contemporary methods and provide a time frame for biological diversification across the Mexican Transition Zone (MTZ). Concatenated maximum likelihood (ML) and Bayesian analyses provided highly congruent results, with differences limited to poorly supported nodes. Similar topologies were inferred …

Regulatory Non-Coding Rnas Modulate Transcriptional Activation During B Cell Development, Mary Attaway, Tzippora Chwat-Edelstein, Bao Q. Vuong

Publications and Research

B cells play a significant role in the adaptive immune response by secreting immunoglobulins that can recognize and neutralize foreign antigens. They develop from hematopoietic stem cells, which also give rise to other types of blood cells, such as monocytes, neutrophils, and T cells, wherein specific transcriptional programs define the commitment and subsequent development of these different cell lineages. A number of transcription factors, such as PU.1, E2A, Pax5, and FOXO1, drive B cell development. Mounting evidence demonstrates that non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), modulate the expression of these transcription factors directly by binding …

Informed Consent: Foundations And Applications, Joanna Smolenski

Dissertations, Theses, and Capstone Projects

Since its advent in the 20th century, informed consent has become a cornerstone of ethical healthcare, and obtaining it a core obligation in medical contexts. In my dissertation, I aim to examine the theoretical underpinnings of informed consent and identify what values it is taken to protect. I will suggest that the fundamental motivation behind informed consent rests in something I’ll call bodily self-sovereignty, which I argue involves a coupling of two groups of values: autonomy and non-domination on the one hand, and self-ownership and personal integrity on the other. I will then go on to consider two 'case …

Investigation Of Notch Signaling In Cone Fate Specification In Vertebrate Retina, Xueqing Chen

Dissertations, Theses, and Capstone Projects

In the vertebrate retina, cone photoreceptors are crucial for high acuity color vision. Several retinal diseases lead to loss of cones and there is a need to identify the normal developmental genesis of these cells to inform the development of stem cell-based therapies. Cone genesis has previously been shown to be repressed by Notch signaling, however, the mechanism by which Notch signaling controls cone fate determination is still unclear. It has been identified that cone photoreceptors are formed from multipotent retinal progenitor cells (RPCs) that first generate genetically-defined, restricted RPCs with limited mitotic and fate potential to preferentially form cones …

You Are What You Eat — Exploring The Microbiome Through Inquiry-Based Labs. Microbiome Lesson Plans, Karla S. Fuller

Open Educational Resources

If these commonly used spices have the ability to inhibit pathogenic bacterial growth, could they also potentially inhibit the growth of normal, harmless bacteria that live in your body? In this lab, we will test common bacteria for resistance to food additives.

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

The Effects Of Climate And Demographic History In Shaping Genomic Variation Across Populations Of The Desert Horned Lizard (Phrynosoma Platyrhinos), Keaka Farleigh, Sarah A. Vladimirova, Christopher Blair, Jason T. Bracken, Nazila Koochekian, Drew R. Schield, Daren C. Card, Nicholas Finger, Jonathan Henault, Adam D. Leaché, Todd A. Castoe, Tereza Jezkova

Publications and Research

Species often experience spatial environmental heterogeneity across their range, and populations may exhibit signatures of adaptation to local environmental characteristics. Other population genetic processes, such as migration and genetic drift, can impede the effects of local adaptation. Genetic drift in particular can have a pronounced effect on population genetic structure during large-scale geographic expansions, where a series of founder effects leads to decreases in genetic variation in the direction of the expansion. Here, we explore the genetic diversity of a desert lizard that occupies a wide range of environmental conditions and that has experienced post-glacial expansion northwards along two colonization …

Predicting Synchronized Gene Coexpression Patterns From Fibration Symmetries In Gene Regulatory Networks In Bacteria, Ian Leifer, Mishael Sánchez‑Pérez, Cecilia Ishida, Hernán A. Makse

Publications and Research

Background: Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the question whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression can be predicted from symmetries in the gene regulatory networks described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their ’input trees’, the set of paths in the network through which …