Genetics and Genomics Commons^™

Modelling Climate Effects On Site Productivity And Developing Site Index Conversion Equations For Jack Pine And Trembling Aspen Mixed Stands, Mahadev Sharma

Aspen Bibliography

Forest site productivity estimates are crucial for making informed forest resource management decisions.These estimates are valuable both for the tree species currently growing in the stands and for those being considered for future stands. Current models are generally designed for pure stands and do not account for the influence of climate on tree growth. Consequently, site index (SI) conversion equations were developed specifically for jack pine (Pinus banksiana Lamb.) and trembling aspen (Populus tremuloides Michx.) trees grown in naturally originated mixed stands. This work involved sampling 186 trees (93 of each species) from 31 even-aged mixed stands (3 …

Advancement In In-Silico Drug Discovery From Virtual Screening Molecular Dockings To De-Novo Drug Design Transformer-Based Generative Ai And Reinforcement Learning, Dony Ang

Computational and Data Sciences (PhD) Dissertations

The field of drug discovery has seen remarkable advancements over the past few decades, transitioning from traditional experimental methods to highly sophisticated computational approaches. One of the pivotal techniques in this evolution is virtual screening, which utilizes molecular docking to predict the interaction between small molecules and target proteins. This method has significantly accelerated the initial stages of drug discovery by enabling the high-throughput screening of large chemical libraries. By simulating the binding affinity and stability of potential drug candidates, virtual screening has become a cornerstone in identifying promising compounds for further development.

A notable application of virtual screening was …

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 …

Industrial Applications Of Molecular Techniques., Jesse Lee Rozsa

Electronic Theses and Dissertations

Multidisciplinary research is vital in modern science. Combining molecular genetics with engineering disciplines such as material science, robotics, or 3D printing is not a new concept but one that can continue to lead to breakthroughs that will benefit society. Science does not and should not occur in a vacuum, and, in early 2020, the world saw the emergence of a pandemic that shifted the focus of scientific research for a time. This manuscript describes aspects of this journey and the fruit that was born from this historic event. In this dissertation, we used plants and bacteria to produce compounds that …

The Role Of Elevation In The Migration, Physiology, And Genomic Diversification Of Birds, Jessie L. Williamson

Biology ETDs

Elevational gradients cause profound eco-climatic variation across short distances. Partial pressure of oxygen (PO₂) is a severe challenge that organisms face at high elevations; due partly to specialization on PO₂, most Neotropical bird species have narrow elevational ranges. However, a small fraction are elevational generalists that span sea level to high elevations, and a subset undertake extreme migratory journeys from low to high elevations biannually. My dissertation combines diverse approaches across levels of biological organization to understand how elevation impacts the ecology, evolution, physiology, and migration of montane birds. I examined ‘extreme’ elevational …

Regulation Of Serpina1 Mrna Expression By Environmental Conditions In Hepatocyte Cells, Fnu Jiamutai

All Theses

The SERPINA1 gene encodes the critical protease inhibitor α-1-antitrypsin (A1AT). A1AT represses neutrophil elastase activity to protect lung tissue from inflammatory damage. A deficiency in α-1-antitrypsin can lead to chronic obstructive pulmonary disease (COPD). Pathogenic genetic variants in SERPINA1 are also associated with A1AT protein misfolding and liver cirrhosis. The regulatory mechanisms of SERPINA1 expression are not well understood, but previous studies suggest that alternative polyadenylation in the 3' untranslated region (3'UTR) affects A1AT protein expression. In this study, we used the liver cancer cell line HepG2 to determine how environmental conditions influence SERPINA1 mRNA expression and post-transcriptional regulation. We …

Identifying Genes Linked To Variation In Metabolic And Whole Plant Phenotypes Using Data From Genome Resequencing, Transcriptomics, And Metabolic Profiling Of A Field-Grown Maize Diversity Panel, Ramesh Kanna Mathivanan

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Maize metabolism is highly complex and influenced by genetic variation, yet the specific genes contributing to this variation and their links to non-metabolic traits remain less understood. To address this knowledge gap, we identified genes involved in maize metabolic variation and linked them to non-metabolic traits. We utilized a quadruplicate dataset of whole genome resequencing, transcriptomic, metabolic, and whole plant phenotype data from a single common field experiment of 660 diverse maize inbred lines. Leaf samples were collected shortly before flowering and analyzed using GC-MS for 26 metabolites. A Resampling Model Inclusion Probability Genome-Wide Association Study (RMIPGWAS) of approximately 2.6 …

De Novo Variants In The Rnu4-2 Snrna Cause A Frequent Neurodevelopmental Syndrome, Yuyang Chen, Ruebena Dawes, Hyung Chul Kim, Alicia Ljungdahl, Sarah L Stenton, Susan Walker, Jenny Lord, Gabrielle Lemire, Alexandra C Martin-Geary, Vijay S Ganesh, Jialan Ma, Jamie M Ellingford, Erwan Delage, Elston N D'Souza, Shan Dong, David R Adams, Kirsten Allan, Madhura Bakshi, Erin E Baldwin, Seth I Berger, Jonathan A Bernstein, Ishita Bhatnagar, Ed Blair, Natasha J Brown, Lindsay C Burrage, Kimberly Chapman, David J Coman, Alison G Compton, Chloe A Cunningham, Precilla D'Souza, Petr Danecek, Emmanuèle C Délot, Kerith-Rae Dias, Ellen R Elias, Frances Elmslie, Care-Anne Evans, Lisa Ewans, Kimberly Ezell, Jamie L Fraser, Lyndon Gallacher, Casie A Genetti, Anne Goriely, Christina L Grant, Tobias Haack, Jenny E Higgs, Anjali G Hinch, Matthew E Hurles, Alma Kuechler, Katherine L Lachlan, Seema R Lalani, François Lecoquierre, Elsa Leitão, Anna Le Fevre, Richard J Leventer, Jan E Liebelt, Sarah Lindsay, Paul J Lockhart, Alan S Ma, Ellen F Macnamara, Sahar Mansour, Taylor M Maurer, Hector R Mendez, Kay Metcalfe, Stephen B Montgomery, Mariya Moosajee, Marie-Cécile Nassogne, Serena Neumann, Michael O'Donoghue, Melanie O'Leary, Elizabeth E Palmer, Nikhil Pattani, John Phillips, Georgia Pitsava, Ryan Pysar, Heidi L Rehm, Chloe M Reuter, Nicole Revencu, Angelika Riess, Rocio Rius, Lance Rodan, Tony Roscioli, Jill A Rosenfeld, Rani Sachdev, Charles J Shaw-Smith, Cas Simons, Sanjay M Sisodiya, Penny Snell, Laura St Clair, Zornitza Stark, Helen S Stewart, Tiong Yang Tan, Natalie B Tan, Suzanna E L Temple, David R Thorburn, Cynthia J Tifft, Eloise Uebergang, Grace E Vannoy, Pradeep Vasudevan, Eric Vilain, David H Viskochil, Laura Wedd, Matthew T Wheeler, Susan M White, Monica Wojcik, Lynne A Wolfe, Zoe Wolfenson, Caroline F Wright, Changrui Xiao, David Zocche, John L Rubenstein, Eirene Markenscoff-Papadimitriou, Sebastian M Fica, Diana Baralle, Christel Depienne, Daniel G Macarthur, Joanna M M Howson, Stephan J Sanders, Anne O'Donnell-Luria, Nicola Whiffin

Faculty, Staff and Students Publications

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of …

Cardiomyopathy, An Uncommon Phenotype Of Congenital Disorders Of Glycosylation: Recommendations For Baseline Screening And Follow-Up Evaluation, Roni Zemet, Kyle D Hope, Andrew C Edmondson, Rameen Shah, Maria Patino, Abigail M Yesso, Justin H Berger, Kyriakie Sarafoglou, Austin Larson, Christina Lam, Eva Morava, Fernando Scaglia

Faculty, Staff and Students Publications

Introduction:

Congenital disorders of glycosylation (CDG) are a continuously expanding group of monogenic disorders that disrupt glycoprotein and glycolipid biosynthesis, leading to multi-systemic manifestations. These disorders are categorized into various groups depending on which part of the glycosylation process is impaired. The cardiac manifestations in CDG can significantly differ, not only across different types but also among individuals with the same genetic cause of CDG. Cardiomyopathy is an important phenotype in CDG. The clinical manifestations and progression of cardiomyopathy in CDG patients have not been well characterized. This study aims to delineate common patterns of cardiomyopathy across a range of …

Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera

All Dissertations

Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …

Atypical Brain Aging And Its Association With Working Memory Performance In Major Depressive Disorder, Natalie C.W. Ho, Richard A.I. Bethlehem, Jakob Seidlitz, Nikita Nogovitsyn, Paul Metzak, Pedro L. Ballester, Stefanie Hassel, Susan Rotzinger, Jordan Poppenk, John Blangero

Human Genetics Publications

Background: Patients with major depressive disorder (MDD) can present with altered brain structure and deficits in cognitive function similar to those seen in aging. However, the interaction between age-related brain changes and brain development in MDD remains understudied. In a cohort of adolescents and adults with and without MDD, we assessed brain aging differences and associations through a newly developed tool that quantifies normative neurodevelopmental trajectories. Methods: A total of 304 participants with MDD and 236 control participants without depression were recruited and scanned from 3 studies under the Canadian Biomarker Integration Network for Depression. Volumetric data were used to …

Investigating Associations Between Activity And Performance Traits Across Three Breeds Of Swine Using NuTrack, Dalton R. Obermier

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Feed costs are the largest contributor towards the variable costs of pork production. To decrease feed cost while not sacrificing output requires an improvement in feed efficiency (FE). A potential approach to expand available phenotypes associated with FE is with activity tracking, yet the relationship between activity and performance is not well defined in swine. Therefore, the objective of this study was to quantify associations between activity and feed intake traits. Average daily feed intake (ADFI) was collected on 1,766 purebred boars of three genetic lines (Duroc, Landrace, and Yorkshire) using FIRE (Osborne Industries, Inc., Osborne, Kansas) at a testing …

Transcriptomics Analysis Reveals Potential Regulatory Role Of Nsmase2 (Smpd3) In Nervous System Development And Function Of Middle-Aged Mouse Brains, Zhihui Zhu, Timothy S. Mcclintock, Erhard Bieberich

Markey Cancer Center Faculty Publications

Neutral sphingomyelinase-2 (nSMase2), gene name sphingomyelin phosphodiesterase-3 (Smpd3), is a key regulatory enzyme responsible for generating the sphingolipid cer- amide. The function of nSMase2 in the brain is still controversial. To better under- stand the functional roles of nSMase2 in the aging mouse brain, we applied RNA-seq analysis, which identified a total of 1462 differentially abundant mRNAs between +/fro and fro/fro, of which 891 were increased and 571 were decreased in nSMase2-deficient mouse brains. The most strongly enriched GO and KEGG annota- tion terms among transcripts increased in fro/fro mice included synaptogenesis, syn- apse development, synaptic signaling, axon development, and …

Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition: Insights Into Cellular Mechanisms And Signaling Pathways, Sarah Mohammed Alqithami, Amrita Machwe, David K. Orren

Markey Cancer Center Faculty Publications

This review delves into the molecular complexities underpinning the epithelial-to-mesenchymal transition (EMT) induced by cigarette smoke (CS) in human bronchial epithelial cells (HBECs). The complex interplay of pathways, including those related to WNT//β-catenin, TGF-β/SMAD, hypoxia, oxidative stress, PI3K/Akt, and NF-κB, plays a central role in mediating this transition. While these findings significantly broaden our understanding of CS-induced EMT, the research reviewed herein leans heavily on 2D cell cultures, highlighting a research gap. Furthermore, the review identifies a stark omission of genetic and epigenetic factors in recent studies. Despite these shortcomings, the findings furnish a consolidated foundation not only for the …

Nsd3::Nutm1 Fusion Sarcoma Mimicking Malignant Peripheral Nerve Sheath Tumor With Prolonged Survival, Jing Di, Ali M. Alhaidary, Chi Wang, Jinge Liu, Sainan Wei, Joseph Valentino, Therese J. Bocklage

Markey Cancer Center Faculty Publications

Nuclear Protein in Testis (NUT)-rearranged tumors comprise predominantly NUT car- cinoma but also include certain lymphomas, leukemias, skin appendage tumors, and sarcomas. Although histologically diverse, all are genetically identified by oncogenic rearrangement in the NUTM1 gene. Many fusion partners occur, and NSD3 is NUT carcinoma’s third most common partner. Herein, we present a case of a 26-year-old man with an NSD3::NUTM1 fusion sarcoma. The patient presented at the age of 13 months with a scalp nodule. Over the next 24 years, he experienced five local recurrences and ultimately expired of a rapidly progressive recurrence. His treatment included surgical resections, radiation, …

Delineating Metastasis In Mss Colorectal Cancer By Single - Cell Rna Sequencing, Shuangjie You

Dissertations and Theses (Open Access)

Colorectal cancer Colorectal Cancer (CRC) is the leading cause of cancer-related deaths, with the majority of these deaths occurring after metastases. In this study, we used single-cell RNA transcriptome sequencing to characterize the cellular and molecular features of primary CRC and colorectal liver metastases (CRLM). Analysis of 130 samples revealed significant heterogeneity in the tumor microenvironment (TME) characterized by a diversity of cancer-associated fibroblasts, immune cells, and endothelial cell populations. Notably, we identified different CAF subtypes, including inflammatory (iCAFs), matrix(mCAFs), complement (cCAFs), and vascular (vCAFs). iCAFs were enriched in primary tumors expressing higher levels of inflammation-associated genes, whereas mCAFs were …

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

Exploring The Role Of The Arginine-Methylation Writer-Reader Pair Prmt5/Snd1 In Jak2-Mutant Myeloproliferative Neoplasms, Rocio Rubiano

Dissertations and Theses (Open Access)

Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible …

The Role Of An Ultraconserved Long Non-Coding Rna In B-Cell Lymphomagenesis, Swati Mohapatra

Dissertations and Theses (Open Access)

Ultraconserved regions (UCRs) are genomic segments with perfect (100%) conservation between the orthologous regions of human, rat, and mouse genomes. UCRs can be transcribed into mono-exonic long non-coding RNAs (lncRNAs) known as transcribed ultraconserved regions (T-UCRs). These regions, despite lacking protein-coding potential, are increasingly recognized for their regulatory roles in gene expression, including the modulation of non-coding RNA (ncRNA) transcripts. NcRNAs play crucial roles in cellular processes, including oncogenic transformation, with emerging evidence revealing their ability to encode small peptides known as ncRNA-encoded peptides (ncPEPs). These peptides, originating from small open reading frames (smORFs), contribute to diverse cellular functions and …

Utilizing The In4mer Crispr/Cas12a Multiplex Knockout Platform To Investigate Synthetic Lethality In The Human Genome, Xingdi Ma

Dissertations and Theses (Open Access)

The emergence of high-throughput sequencing technologies and the development of targeted cancer therapies have significantly advanced our understanding of cancer genomics and prolonged patient survival. Despite these advances, durable response remains difficult to achieve in the clinic. The concept of synthetic lethality has gained traction as a promising opportunity to discover novel cancer-specific vulnerabilities and therapeutic targets. Unfortunately, initial technologies for combinatorial genetic perturbation in mammalian cells suffer from inefficiency and are challenging to scale. In this dissertation, I report: 1) paralog selection method to select candidate synthetic lethal paralogs; 2) our Cas12a multiplex platform “IN4MER” that provides superior sensitivity …