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2023

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Full-Text Articles in Genetics and Genomics

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari Jan 2023

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari

Biotechnology Theses

The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …


[Research Note] The Random Somatic Mutation Is Not Quite Random, Florentin Smarandache Jan 2023

[Research Note] The Random Somatic Mutation Is Not Quite Random, Florentin Smarandache

Branch Mathematics and Statistics Faculty and Staff Publications

This research note challenges the idea that Random Somatic Mutations are entirely random, highlighting their non-equiprobable nature and their influence on evolution, involution, or indeterminacy. It recalls the Neutrosophic Theory of Evolution, extending Darwin’s theory, and emphasizes the importance of distinguishing between different senses of “random mutation” in evolutionary theory.


Unusual Chromosome Configurations: Evaluation Of Sex Univalent And Trivalent Chromosome Models, Ashley B. Borseth Jan 2023

Unusual Chromosome Configurations: Evaluation Of Sex Univalent And Trivalent Chromosome Models, Ashley B. Borseth

Master’s Theses

Aneuploidy, or abnormal number of chromosomes in a haploid set, in XY/XX organisms has consequences that can impede physical and cognitive development. To prevent aneuploidy, cellular division relies on the correct position of paired chromosomes and subsequent segregation in the meiotic program. If connections between paired chromosomes sever or errors in chromosome contraction towards spindle poles arise, aneuploidy occurs. Many arthropod species have chromosomes that naturally do not pair, or that pair differently than typical autosomes. Through the evaluation of such systems, novel insights into chromosomal coordination and positioning may be revealed. The objective of this study is twofold: (1) …


Multi-Omic Analysis Of Vegetative Propagation Induced Plant Rejuvenation In Grapevines: Implications For The Generation Of Locally Adapted Cultivars Using Epigenetics, Tajbir Raihan Jan 2023

Multi-Omic Analysis Of Vegetative Propagation Induced Plant Rejuvenation In Grapevines: Implications For The Generation Of Locally Adapted Cultivars Using Epigenetics, Tajbir Raihan

Theses and Dissertations--Plant and Soil Sciences

Epigenetic memory of the growing environment is a process capable of increasing plants’ resilience to abiotic stimuli. The cultivated grapevine is a long-living perennial species with a large corpus of research suggesting that plant adaptation to the environment has implications for the selection of genetic material in a changing climate. Moreover, vine age has been traditionally correlated with enhanced fruit quality. Recent studies have shown that environment/age-acquired traits in grapevine (e.g., adaptation to the growing environment and fruit/wine quality, respectively) are associated with epigenetic mechanisms. These studies also indicate that of propagation type affects the maintenance/erasure of the acquired traits …


Species-Specific Microsymbiont Discrimination Mediated By A Medicago Receptor Kinase, Xiaocheng Yu Jan 2023

Species-Specific Microsymbiont Discrimination Mediated By A Medicago Receptor Kinase, Xiaocheng Yu

Theses and Dissertations--Plant and Soil Sciences

Legumes form a mutualistic partnership with nitrogen-fixing bacteria to meet their nitrogen requirements. This collaboration leads to the development of root nodules, offering an ideal environment for the bacteria to convert atmospheric nitrogen into ammonia. A salient aspect of this symbiotic relationship is host range specificity, such that nodulation capacity and nitrogen fixation efficiency differ significantly between different host-bacterial combinations. Understanding the genetic basis of this specificity could pave the way for strategies to overcome the host range barrier. Sinorhizobium meliloti and Sinorhizobium medicae are two closely related species that display differential symbiotic behaviors with legume plants of the Medicago …


Prediction Of Kinase-Substrate Associations Using The Functional Landscape Of Kinases And Phosphorylation Sites, Serhan Yilmaz, Filipa Blasco Tavares Pereira Lopes, Mark R. Chance, Mehmet Koyutürk Jan 2023

Prediction Of Kinase-Substrate Associations Using The Functional Landscape Of Kinases And Phosphorylation Sites, Serhan Yilmaz, Filipa Blasco Tavares Pereira Lopes, Mark R. Chance, Mehmet Koyutürk

Faculty Scholarship

Protein phosphorylation is a key post-translational modification that plays a central role in many cellular processes. With recent advances in biotechnology, thousands of phosphorylated sites can be identified and quantified in a given sample, enabling proteome-wide screening of cellular signaling. However, for most (> 90%) of the phosphorylation sites that are identified in these experiments, the kinase(s) that target these sites are unknown. To broadly utilize available structural, functional, evolutionary, and contextual information in predicting kinase-substrate associations (KSAs), we develop a network-based machine learning framework. Our framework integrates a multitude of data sources to characterize the landscape of functional relationships …


Knockout Of Endospanin 1 Via Crispr In Zebrafish, Danio Rerio, Jared Kittinger Jan 2023

Knockout Of Endospanin 1 Via Crispr In Zebrafish, Danio Rerio, Jared Kittinger

Williams Honors College, Honors Research Projects

I made endospanin 1 knockout (KO) zebrafish to examine its effects on lipid and bone metabolism. Endospanin 1, or leptin receptor overlapping transcript (leprot), is a cytosolic protein linked to the protein hormone leptin that influences the trafficking of leptin receptors to the plasma membrane of cells. Genes for endospanin and tyrosinase (a pigmentation enzyme) were targeted via a microinjection of guide RNAs and CRISPR Cas9 into zebrafish embryos at 2-4 cell stages. I was able to disrupt the endospanin 1 gene (based upon the disruption of tyrosinase), but very few mutant zebrafish fully developed into adults. Only low KO …


Advancing Methods Of Diet Analysis: A Case Study Using Degraded Merlin (Falco Columbarius) Prey Remains, Taylor A. Coon Jan 2023

Advancing Methods Of Diet Analysis: A Case Study Using Degraded Merlin (Falco Columbarius) Prey Remains, Taylor A. Coon

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Prey remains have long been used as a mechanism to approach diet analyses. As understanding diet is key to comprehending ecosystem dynamics, prey remains identification requires a unique methodological approach to determine diversity within a sample. With the advancement of technology, molecular protocols designed for species-specific identification have improved to incredible accuracy and precision. Yet, the visual identification method has remained a predominant technique within diet studies. With entry-level observers, we matched visual identifications with molecular-based methods to quantify the accuracy of the visual identification method. This study determined what fraction of visually identified prey remains could be correctly identified …


Expanding Our Grasp Of Two-Component Signaling In Clostridioides Difficile, Orlando Berumen Alvarez, Erin B. Purcell Jan 2023

Expanding Our Grasp Of Two-Component Signaling In Clostridioides Difficile, Orlando Berumen Alvarez, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The intestinal pathogen Clostridioides difficile encodes roughly 50 TCS, but very few have been characterized in terms of their activating signals or their regulatory roles. A. G. Pannullo, B. R. Zbylicki, and C. D. Ellermeier (J Bacteriol 205:e00164-23, 2023, https://doi.org/10.1128/jb.00164-23) have identified both for the novel C. difficile TCD DraRS. DraRS responds to antibiotics that target lipid-II molecules in the bacterial cell envelope, and regulates the production of a novel glycolipid necessary for bacitracin and daptomycin resistance in C. difficile.


Incorporating A Developmental Perspective Into Gene Identification Models For Alcohol Use Behaviors, Nathaniel S. Thomas Jan 2023

Incorporating A Developmental Perspective Into Gene Identification Models For Alcohol Use Behaviors, Nathaniel S. Thomas

Theses and Dissertations

Frequent alcohol use can lead to alcohol use disorder, which accounts for three million deaths and over 133 million life years lost to disability and death worldwide per year. Alcohol use behaviors unfold across development, beginning with initiation of drinking and progressing through various escalating stages of use. Alcohol use behaviors are also under genetic influence. Genome-wide association represents the state-of-the-science statistical methodology for identifying genes associated with alcohol use outcomes. However, contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. In this project, I applied novel multivariate genomic methods to combine …


Accucalc: A Python Package For Accuracy Calculation In Gwas, Jana Biová, Nicholas Dietz, Yen On Chan, Trupti Joshi, Kristin Bilyeu, Mária Škrabišová Jan 2023

Accucalc: A Python Package For Accuracy Calculation In Gwas, Jana Biová, Nicholas Dietz, Yen On Chan, Trupti Joshi, Kristin Bilyeu, Mária Škrabišová

Biomedical Sciences

The genome-wide association study (GWAS) is a popular genomic approach that identifies genomic regions associated with a phenotype and, thus, aims to discover causative mutations (CM) in the genes underlying the phenotype. However, GWAS discoveries are limited by many factors and typically identify associated genomic regions without the further ability to compare the viability of candidate genes and actual CMs. Therefore, the current methodology is limited to CM identification. In our recent work, we presented a novel approach to an empowered “GWAS to Genes” strategy that we named Synthetic phenotype to causative mutation (SP2CM). We established this strategy to identify …


Placing The Evolutionary History Of Desmognathus Salamanders In Context: A Phylogeographic Approach, Kara Jones Jan 2023

Placing The Evolutionary History Of Desmognathus Salamanders In Context: A Phylogeographic Approach, Kara Jones

Theses and Dissertations--Biology

Patterns of genetic variation do not arise in a vacuum but are instead shaped by the interplay between evolutionary forces and ecological constraints. Here, I use a phylogeographic approach to examine the role that ecology played in lineage divergence in the Desmognathus quadramaculatus species complex (Family: Plethodontidae), which consists of three nominal species: D. quadramaculatus, D. marmoratus, and D. folkertsi. Previous phylogenetic studies have shown that individuals from these species do not form clades based on phenotype. My approach to reconciling phylogenetic discordance was two-fold, using (1) genome-wide markers to provide insight into the …


A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer Jan 2023

A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer

Markey Cancer Center Faculty Publications

Ruthenium complexes are often investigated as potential replacements for platinum-based chemotherapeutics in hopes of identifying systems with improved tolerability in vivo and reduced susceptibility to cellular resistance mechanisms. Inspired by phenanthriplatin, a non-traditional platinum agent that contains only one labile ligand, monofunctional ruthenium polypyridyl agents have been developed, but until now, few demonstrated promising anticancer activity. Here we introduce a potent new scaffold, based on [Ru(tpy)(dip)Cl]Cl (tpy = 2,20:60,200-terpyridine and dip = 4,7-diphenyl-1,10-phenanthroline) in pursuit of effective Ru(II )-based monofunctional agents. Notably, the extension of the terpyridine at the 40 position with an aromatic ring resulted in a molecule that …


Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson Jan 2023

Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self- renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 …


Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson Jan 2023

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …


Early-Phase Drive To The Precursor Pool: Chloroviruses Dive Into The Deep End Of Nucleotide Metabolism, David Dunigan, Irina Agarkova, Ahmed Esmael, Sophie Alvarez, James L. Van Etten Jan 2023

Early-Phase Drive To The Precursor Pool: Chloroviruses Dive Into The Deep End Of Nucleotide Metabolism, David Dunigan, Irina Agarkova, Ahmed Esmael, Sophie Alvarez, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Viruses face many challenges on their road to successful replication, and they meet those challenges by reprogramming the intracellular environment. Two major issues challenging Paramecium bursaria chlorella virus 1 (PBCV-1, genus Chlorovirus, family Phycodnaviridae) at the level of DNA replication are (i) the host cell has a DNA G+C content of 66%, while the virus is 40%; and (ii) the initial quantity of DNA in the haploid host cell is approximately 50 fg, yet the virus will make approximately 350 fg of DNA within hours of infection to produce approximately 1000 virions per cell. Thus, the quality and quantity of …


The Persistence And Stabilization Of Auxiliary Genes In The Human Skin Virome, Ema H. Graham, Wesley A. Tom, Alison C. Neujahr, Michael Adamowicz, Jennifer Clarke, Joshua R. Herr, Samodha C. Fernando Jan 2023

The Persistence And Stabilization Of Auxiliary Genes In The Human Skin Virome, Ema H. Graham, Wesley A. Tom, Alison C. Neujahr, Michael Adamowicz, Jennifer Clarke, Joshua R. Herr, Samodha C. Fernando

Nebraska Center for Virology: Faculty Publications

Background The human skin contains a diverse microbiome that provides protective functions against environmental pathogens. Studies have demonstrated that bacteriophages modulate bacterial community composition and facilitate the transfer of host-specific genes, potentially influencing host cellular functions. However, little is known about the human skin virome and its role in human health. Especially, how viral-host relationships influence skin microbiome structure and function is poorly understood.

Results Population dynamics and genetic diversity of bacteriophage communities in viral metagenomic data collected from three anatomical skin locations from 60 subjects at five different time points revealed that cutaneous bacteriophage populations are mainly composed of …


Dna Transfer And Persistence On Non-Porous Surfaces Submerged In Spring Water [Preliminary Study], Morgan L.. Korzik, Josep De Alcaraz-Fossoul, Michael S. Adamowicz, David San Pietro Jan 2023

Dna Transfer And Persistence On Non-Porous Surfaces Submerged In Spring Water [Preliminary Study], Morgan L.. Korzik, Josep De Alcaraz-Fossoul, Michael S. Adamowicz, David San Pietro

Forensic Science: Faculty Publications

Submerged items are often thought to lack evidentiary value. However, previous studies have shown the ability to recover DNA from submerged porous items for upwards of six weeks. The crevices or interweaving fibers in porous items are thought to protect DNA from being washed away. It is hypothesized that, because non-porous surfaces do not have the same traits that might aid in DNA retention, then DNA quantities and the number of donor alleles recovered would decrease over longer submersion periods. Additionally, it is hypothesized that DNA quantity and the number of alleles would be negatively affected by flow conditions. Neat …


Molecular Analysis Of Epigenetic Memory Of Stress Establishment And Long-Term Maintenance In A Perennial Woody Plant, Jia Wen Tan Jan 2023

Molecular Analysis Of Epigenetic Memory Of Stress Establishment And Long-Term Maintenance In A Perennial Woody Plant, Jia Wen Tan

Theses and Dissertations--Plant and Soil Sciences

Plants adapt to extreme environmental conditions through physiological adaptations, which are usually transient. Recent research has suggested that environmental conditions can activate a memory of stress that can result in a primed response to subsequent stress events. While the effect of priming has been observed in many plants, the underlying mechanisms are puzzling and seldom studied. A large body of research has been developed in the last decade linking response to stress, stress priming, and memory of stress with epigenetic mechanisms. This understanding of plant epigenetics has opened the door to the application of epigenetics to crop improvement, such as …


Understanding The Basis For Increased 2,4-D Tolerance In Red Clover (Trifolium Pratense): Field Evaluations, Metabolism, And Gene Expression, Lucas Pinheiro De Araujo Jan 2023

Understanding The Basis For Increased 2,4-D Tolerance In Red Clover (Trifolium Pratense): Field Evaluations, Metabolism, And Gene Expression, Lucas Pinheiro De Araujo

Theses and Dissertations--Plant and Soil Sciences

Incorporation of red clover (Trifolium pratense L.) into grass pastures offers several benefits. However, red clover cultivars available for Kentucky producers are highly susceptible to synthetic auxin herbicides, such as 2,4-D (2,4-dichlorophenoxy acetic acid), used for pasture broadleaf weed control. To overcome this problem, UK2014 red clover was bred for increased tolerance to 2,4-D. We compared the field performance of UK2014 to Kenland, a standard cultivar grown in the transition zone of the United States. UK2014 and Kenland were seeded in the springs of 2017 and 2018. Single applications of 0, 1.12, or 2.24 kg ae ha-1 2,4-D …


Association Of The Bb Genotype Of The Abo Gene With The Risk Of Acute Myocardial Infarction In Hospital-Based Study, Farzana Abubakar Yousuf, Iqbal Azam Syed, Asal Khan Tareen, Khawar A. Kazmi, Jibran Sualeh Muhammad, Mohammad Perwaiz Iqbal Jan 2023

Association Of The Bb Genotype Of The Abo Gene With The Risk Of Acute Myocardial Infarction In Hospital-Based Study, Farzana Abubakar Yousuf, Iqbal Azam Syed, Asal Khan Tareen, Khawar A. Kazmi, Jibran Sualeh Muhammad, Mohammad Perwaiz Iqbal

Department of Biological & Biomedical Sciences

Objectives: The ABO gene locus has been identified to be associated with myocardial infarction in patients with coronary heart disease. The primary focus of this hospital-based study was to explore the relationship of ABO blood groups and ABO genotypes with acute myocardial infarction (AMI) in Karachi, Pakistan.
Methods: In a comparative cross-sectional study, an equal number of adult AMI patients and healthy controls (n=275 in each group; age range 30-70 years, both males and females) were recruited from the Aga Khan University and NICVD, Karachi, with informed consent. The blood samples were analyzed for ABO blood groups and other biomarkers. …


Effects Of The Otx2ecr2 Enhancer & Prox1 Overexpression In Murine Retina Development, Erick J. Subillaga Jan 2023

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 …


Genome-Wide Mendelian Randomization Identifies Putatively Causal Gut Microbiota For Multiple Peptic Ulcer Diseases, Jingwei Zhao, Yucheng Hou, Tianyi Xie, Yizhang Zhu, Xinyi Feng, Yong Zhang, Ziyi Yang, Wei Gong Jan 2023

Genome-Wide Mendelian Randomization Identifies Putatively Causal Gut Microbiota For Multiple Peptic Ulcer Diseases, Jingwei Zhao, Yucheng Hou, Tianyi Xie, Yizhang Zhu, Xinyi Feng, Yong Zhang, Ziyi Yang, Wei Gong

Faculty, Staff and Student Publications

OBJECTIVE: The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation.

DESIGN: The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting …


Whole Genome Sequence Analysis Of Apparent Treatment Resistant Hypertension Status In Participants From The Trans-Omics For Precision Medicine Program, Nicole D Armstrong, Vinodh Srinivasasainagendra, Farah Ammous, Themistocles L Assimes, Amber L Beitelshees, Jennifer Brody, Brian E Cade, Yii-Der Ida Chen, Han Chen, Paul S De Vries, James S Floyd, Nora Franceschini, Xiuqing Guo, Jacklyn N Hellwege, John S House, Chii-Min Hwu, Sharon L R Kardia, Ethan M Lange, Leslie A Lange, Caitrin W Mcdonough, May E Montasser, Jeffrey R O'Connell, Megan M Shuey, Xiao Sun, Rikki M Tanner, Zhe Wang, Wei Zhao, April P Carson, Todd L Edwards, Tanika N Kelly, Eimear E Kenny, Charles Kooperberg, Ruth J F Loos, Alanna C Morrison, Alison Motsinger-Reif, Bruce M Psaty, Dabeeru C Rao, Susan Redline, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Albert V Smith, Marguerite R Irvin, Donna K Arnett Jan 2023

Whole Genome Sequence Analysis Of Apparent Treatment Resistant Hypertension Status In Participants From The Trans-Omics For Precision Medicine Program, Nicole D Armstrong, Vinodh Srinivasasainagendra, Farah Ammous, Themistocles L Assimes, Amber L Beitelshees, Jennifer Brody, Brian E Cade, Yii-Der Ida Chen, Han Chen, Paul S De Vries, James S Floyd, Nora Franceschini, Xiuqing Guo, Jacklyn N Hellwege, John S House, Chii-Min Hwu, Sharon L R Kardia, Ethan M Lange, Leslie A Lange, Caitrin W Mcdonough, May E Montasser, Jeffrey R O'Connell, Megan M Shuey, Xiao Sun, Rikki M Tanner, Zhe Wang, Wei Zhao, April P Carson, Todd L Edwards, Tanika N Kelly, Eimear E Kenny, Charles Kooperberg, Ruth J F Loos, Alanna C Morrison, Alison Motsinger-Reif, Bruce M Psaty, Dabeeru C Rao, Susan Redline, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Albert V Smith, Marguerite R Irvin, Donna K Arnett

Faculty, Staff and Student Publications

Introduction: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive (AHT) classes to achieve blood pressure (BP) control. In the current study, we conducted single-variant and gene-based analyses of aTRH among individuals from 12 Trans-Omics for Precision Medicine cohorts with whole-genome sequencing data.

Methods: Cases were defined as individuals treated for hypertension (HTN) taking three different AHT classes, with average systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg, or four or more medications regardless of BP (n = 1,705). A normotensive control group was defined as individuals with BP < 140/90 mmHg (n = 22,079), not on AHT medication. A second control group comprised individuals who were treatment responsive on one AHT medication with BP < 140/ 90 mmHg (n = 5,424). Logistic regression with kinship adjustment using the Scalable and Accurate Implementation of Generalized mixed models (SAIGE) was performed, adjusting for age, sex, and genetic ancestry. We assessed variants using SKAT-O in rare-variant analyses. Single-variant and gene-based tests were conducted in a pooled multi-ethnicity stratum, as well as self-reported ethnic/racial strata (European and African American).

Results: One variant in …


Epithelial Membrane Protein 3 (Emp3b) Is A Novel Regulator Of Sympathetic Nervous System Development In Zebrafish., Jessica M. White Jan 2023

Epithelial Membrane Protein 3 (Emp3b) Is A Novel Regulator Of Sympathetic Nervous System Development In Zebrafish., Jessica M. White

Theses and Dissertations

Notable progress has been made in understanding the development of the neural crest (NC). Neural crest cells (NCCs) can be divided into 4-5 subpopulations. A major lineage among trunk NC derivatives are sympathoadrenal (SA) cells, which give rise to the sympathetic nervous system (SNS). Trunk NCCs follow a ventromedial migration pathway where signals derived from the dorsal aorta instruct migrating NCCs to a SA cell fate. Defects in NC development can result in syndromes known as neurocristopathies. Neuroblastoma is one of the most common forms of pediatric cancer affecting nearly 800 infants each year in the United States (Takita et …


Genomic Comparison Of Dba/2j And C57bl/6j Strains Of Mus Musculus And Best Practice Of Genome Alignment For Bioinformatics Analyses, Dustin J. Zeliff Jan 2023

Genomic Comparison Of Dba/2j And C57bl/6j Strains Of Mus Musculus And Best Practice Of Genome Alignment For Bioinformatics Analyses, Dustin J. Zeliff

Theses and Dissertations

Alcohol use disorder is known to have significant genetic components that contribute to an individual’s susceptibility to the disease. Mouse models are commonly used to study the mechanisms underlying alcohol use disorder, with C57BL/6J (B6) and DBA/2J (D2) being two of the more prominently used inbred strains. Research in the Miles Laboratory has used these two strains, and genetic panels of mice derived from them, to identify potential genes associated with variance in ethanol-related behaviors using quantitative trait loci (QTL) analysis. For example, Ninein (Nin) was identified as a potential candidate gene for the anxiolytic effects of ethanol, discovered because …


Examining Genetically-Informed Etiologic Models Of Co-Occurring Posttraumatic Stress Disorder And Recreational Cannabis Use Among College Students, Terrell A. Hicks Jan 2023

Examining Genetically-Informed Etiologic Models Of Co-Occurring Posttraumatic Stress Disorder And Recreational Cannabis Use Among College Students, Terrell A. Hicks

Theses and Dissertations

The college years encompass a period of increased risk recreational cannabis use (RCU), as well as a time of increased risk for trauma exposure and developing posttraumatic stress disorder (PTSD). Given the high co-occurrence between RCU and PTSD, and the potentially negative consequences of the two (e.g., worse academic outcomes), there is a need to understand the etiologic mechanisms of these commonly co-occurring conditions. Two primary phenotypic models exist: self-medication model (i.e., PTSD to RCU) and the high-risk model (i.e., RCU to PTSD). To date, there are two existing studies longitudinally examining the etiologic models proposed to explain co-occurring RCU …


Integrative Post-Gwas Analyses Of Psychiatric Disorders: Identifying Putative Risk Genes And Gene Sets Using Transcriptome, Proteome And Methylome Information, Huseyin Gedik Jan 2023

Integrative Post-Gwas Analyses Of Psychiatric Disorders: Identifying Putative Risk Genes And Gene Sets Using Transcriptome, Proteome And Methylome Information, Huseyin Gedik

Theses and Dissertations

Genome-wide association studies (GWAS) of psychiatric disorders (PD) yield numerous loci with significant signals, but often they do not implicate specific protein coding genes. Because GWAS risk loci are enriched in expression/protein/methylation quantitative loci (e/p/mQTL, hereafter xQTL), transcriptome/proteome/methylome-wide association studies (T/P/MWAS, hereafter XWAS), which integrate information from GWAS and x-level (mRNA, protein or DNA methylation levels) coming from largest xQTL studies, can link GWAS signals to effects on specific genes. For gene level analyses, researchers use mendelian randomization (MR) methods to fine-map the association between x-levels and trait. However, none of the previous studies ever jointly analyzed XWAS of multiple …


Homeobox Transcription Factor Hbxa Influences Expression Of Over One Thousand Genes In The Model Fungus Aspergillus Nidulans, Sandesh Sharma Pandit Jan 2023

Homeobox Transcription Factor Hbxa Influences Expression Of Over One Thousand Genes In The Model Fungus Aspergillus Nidulans, Sandesh Sharma Pandit

Graduate Research Theses & Dissertations

In fungi, conserved homeobox-domain (HD) proteins are transcriptional regulators governing development. In Aspergillus species, several HD transcription factor genes have been identified, among them, hbxA/hbx1. For instance, in the opportunistic human pathogen Aspergillus fumigatus, hbxA is involved in conidial production and germination, as well as virulence and secondary metabolism (SM), including production of fumigaclavines, fumiquinazolines, and chaetominine. In the agriculturally important fungus Aspergillus flavus, disruption of hbx1 results in fluffy aconidial colonies unable to produce sclerotia. hbx1 also regulates production of aflatoxins, cyclopiazonic acid and aflatrem. Furthermore, transcriptome studies revealed that hbx1 has a broad effect on the A. flavus …


Genetic And Environmental Contributions To Wolbachia-Induced Cytoplasmic Incompatibility, Kelley Van Vaerenberghe Jan 2023

Genetic And Environmental Contributions To Wolbachia-Induced Cytoplasmic Incompatibility, Kelley Van Vaerenberghe

Graduate Student Theses, Dissertations, & Professional Papers

Maternally-transmitted Wolbachia infect the cells of most insect species, but their frequencies in host populations vary. While much of their success can be attributed to their ability to manipulate host reproduction, these manipulations are context-dependent, varying due to several biotic and abiotic factors. Wolbachia’s most common manipulation, cytoplasmic incompatibility (CI), is a conditional sterility phenotype where male-female host compatibility depends on their infection status. Specifically, CI occurs when infected males produce modified sperm that cause increased embryonic lethality unless the female carries a similar infection. Rescuing their eggs from CI increases the relative fitness of infected females, promoting Wolbachia spread …