Genetics and Genomics Commons^™

Performance Analysis Of Computational Methods For Predicting Protein Function In Rare Diseases, Aichetou Mohamed Sidiya, Hanin Alzaher, Razan Almahdi, Tayeb Brahimi

Effat Undergraduate Research Journal

Protein function prediction is crucial for understanding the underlying mechanisms of rare diseases. With the increasing availability of computational methods including machine learning-based approaches, network-based methods, and sequence-based methods, predicting protein functions has become more accessible. However, it is not clear which of these methods performs better or how they compare to each other in terms of accuracy, efficiency, and scalability. In this study, we evaluate several computational methods for predicting protein functions in rare diseases using key performance indicators (KPIs). We analyze the strengths and weaknesses of each method and provide recommendations for researchers and clinicians interested in using …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Implementation Of A Forensic Ancestry Inference Indel Panel, Jacqueline Molina

Student Theses

Ancestry-informative markers (AIMs) are genetic variants that exhibit significant frequency differences between populations, making them valuable tools for inferring biogeographical ancestry in forensic investigations. Insertion/deletion polymorphisms (INDELs) offer particular advantages for degraded forensic samples due to their short amplicon sizes and binary allelic nature. As forensic laboratories adopt newer instrumentation, validation of established assays becomes critical to ensure analytical continuity and reliability. This study evaluated the comparative performance of the SeqStudio™ Genetic Analyzer in detecting a 46 AIMs INDEL multiplex panel, previously established with the ABI 3130 Genetic Analyzer. Four commercial blood samples were analyzed using both platforms to assess …

Development Of Emerin Mrna Lipid Nanoparticles To Rescue Myogenic Differentiation., Nicholas Marano, Liza Elif Guner, Rachel S Riley, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Emery-Dreifuss muscular dystrophy 1 (EDMD1) arises from mutations in EMD. Most EDMD1 patients lack detectable emerin expression. They experience symptoms such as skeletal muscle wasting, joint contractures, and cardiac conduction defects. Currently, physicians rely on treating patient symptoms without addressing the underlying cause-lack of functional emerin protein. Thus, there is a need for therapeutic approaches that restore emerin protein expression to improve patient outcomes. One way would be to deliver emerin mRNA or protein directly to affected tissues to restore tissue homeostasis. Here, we evaluated the utility of lipid nanoparticles (LNPs) to deliver emerin mRNA to diseased cells. LNPs …

The Swib Domain-Containing Dna Topoisomerase I Of Chlamydia Trachomatis Mediates Dna Relaxation, Li Shen, Abigail R. Swoboda, Caitlynn Diggs, Shomita Ferdous, Andrew Terrebonne, Amanda Santos, Noel Wolf, Luis Lorenzo Carvajal, Guangming Zhong, Scot P. Ouellette, Yuk Ching Tse-Dinh

School of Graduate Studies Faculty Publications

Chlamydia trachomatis has a DNA topoisomerase I with a unique C-terminal domain (CTD) homologous to eukaryotic SWIB domains. This study focused on determining the function of the SWIB domain-containing TopA from C. trachomatis (CtTopA). We demonstrated that, despite the lack of sequence similarity at the CTDs between CtTopA and TopA from Escherichia coli (EcTopA), full-length CtTopA removed negative DNA supercoils in vitro and complemented the growth defect of a topA mutant of E. coli. CtTopA is less processive in DNA relaxation than EcTopA in dose-response and time course studies. An antibody generated against the SWIB domain of CtTopA specifically recognized …

Non-Isolated Tetralogy Of Fallot (Tof+): Exome Sequencing Efficacy And Phenotypic Expansions, Julia Volpi, Xiaonan Zhao, Nichole Owen, Tia Evans, Muriel Holder-Espinasse, Nayana Lahiri, Eleanor Sherlock, Gemma Poke, Jeroen Breckpot, Koen Devriendt, Bjorn Cools, Alfredo Brusco, Giovanni Battista Ferrero, Enrico Grosso, Pradeep Vasudevan, Sara Loddo, Antonio Novelli, Maria Cristina Digilio, Aafke Engwerda, Marrit Hitzert, Alison Male, Lucy Bownass, Ruth Newbury-Ecob, Zosia Miedzybrodzka, Ruth Armstrong, Sally Ann Lynch, Gunnar Houge, Shiyi Xiong, Seema R Lalani, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Daryl A Scott

Faculty, Staff and Students Publications

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD). TOF may present in isolation or in conjunction with one or more non-cardiac congenital anomalies or neurodevelopmental disorders (TOF+). Uncertainty regarding the efficacy of various genetic testing strategies, and an incomplete understanding of the genetic causes of TOF+, may lead to hesitancy in recommending genetic testing, particularly, clinical exome sequencing (cES). Here, we analyzed cES data from 131 individuals with TOF+. A definitive or probable diagnosis was made for 31 individuals, yielding a diagnostic rate of 23.6% (31/131). One individual received three diagnoses. Commercially available CHD panels …

Northern Arizona Ecological Conservation: Assessing Quaking Aspen Health In Northern Arizona Using Earth Observations, Ikram Morso, Luke Collins, Margaret Cox, Melissa Schwan

Aspen Bibliography

Quaking aspen (Populus tremuloides) forests in Northern Arizona provide critical habitat for endangered bird species and support regional tourism and recreation. However, aspen populations are declining due to a combination of abiotic and biotic stressors. In response, land managers implemented strategies, such as ungulate exclusion fencing, prescribed burns, and stand thinning, but efforts are constrained by limited data on where and when to intervene. This project worked in collaboration with the U.S. Forest Service, the National Park Service, the Arizona Department of Forestry and Fire Management, and Northern Arizona University School of Forestry. The team utilized Earth observations …

Global Erk/Mapk Activation Determines Oncogenic Fitness In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Rachel A. Burge

MUSC Theses and Dissertations

In pancreatic ductal adenocarcinoma (PDAC), ~95% of cases harbor an activating KRAS mutation. The most common KRAS mutations in PDAC are KRAS^G12D (42%), KRAS^G12V (31%), and KRAS^G12R (15%). Patients harboring KRAS^G12R mutations have increased overall survival compared to those with KRAS^G12D/V-mutations. While KRAS^G12D/Vare common in all KRAS-mutant cancers, KRAS^G12Ris only common in PDAC.

KRAS^G12R is unable to activate the lipid kinase PIK3CA, a KRAS effector that is important for tumorigenesis in murine models. To investigate the tumorigenic potential of KRAS^G12R and the mechanisms that enable this mutation …

From Gametes To Genes: Genetic Quality Assessment Of Anuran Cryopreserved Spermatozoa And Derived Embryos, Trinity Isabella Kassuhn

Theses and Dissertations

Sperm cryopreservation is an important tool within the suite of assisted reproductive technologies (ART) as it enables long-term storage of genetically valuable gametes. However, knowledge of the diagnostic criteria for assessing sperm quality and the genetic consequences of using cryopreserved sperm in amphibians is limited. This gap has raised concerns in captive breeding and reintroduction programs regarding the potential impact that cryopreserved sperm and the derived embryos may have on a population. The thesis aims to investigate how sperm cryopreservation affects the genetic material in both sperm and resulting embryos, with implications for in situ and ex situ amphibian populations. …

Profiling Brain Morphology For Autism Spectrum Disorder With Two Cross-Culture Large-Scale Consortia, Xue-Ru Fan, Ye He, Yin-Shan Wang, Lei Li, Lifespan Brain Chart Consortium (Lbcc), China Autism Brain Imaging Consortium (Cabic), Xujun Duan, Xi-Nian Zuo, John Blangero

Human Genetics Publications

We explore neurodevelopmental heterogeneity in Autism Spectrum Disorder (ASD) through normative modeling of cross-cultural cohorts. By leveraging large-scale datasets from Autism Brain Imaging Data Exchange (ABIDE) and China Autism Brain Imaging Consortium (CABIC), our model identifies two ASD subgroups with distinct brain morphological abnormalities: subgroup “L” is characterized by generally smaller brain region volumes and higher rates of abnormality, while subgroup “H” exhibits larger volumes with less pronounced deviations in specific areas. Key areas, such as the isthmus cingulate and transverse temporal gyrus, were identified as critical for subgroup differentiation and ASD trait correlations. In subgroup H, the regional volume …

Quantile Index Predictors Using R Package Hyper.Gam, Tingting Zhan, Misung Yi, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

MOTIVATION: Evaluation of single-cell protein expression from immunohistochemistry images is used increasingly in biomedical research. Many proteins are used solely for phenotyping cells in the tumor microenvironment. Other proteins with meaningfully quantitative expression levels provide so-called functional protein biomarkers. There is still a limited number of methods and software tools available for utilizing the entire distributions of single-cell expression levels.

RESULTS: We present the R package hyper.gam, providing a supervised learning framework for deriving biomarkers based on single-cell distribution quantiles. The single-cell data are first converted into sample quantile functions, which are then used as predictors in scalar-on-function regression models …

Dermatoglyphic Fluctuating Asymmetry In Schizotypy, Marcus R. Thomas

All-Inclusive List of Electronic Theses and Dissertations

Schizotypy has been linked with many of the proposed endophenotypes of schizophrenia, but research is limited on the relationship between schizotypy and dermatoglyphic fluctuating asymmetry. The present study sought to examine relationships between schizotypy, dermatoglyphic fluctuating asymmetry, handedness, and season of birth. 146 undergraduate students were identified as schizotypes (n = 52) or controls (n = 94) based on the Multidimensional Schizotypy Scale and had their finger and palm prints collected along with completing additional measures of schizotypy and handedness. Schizotypes did not exhibit a greater degree of dermatoglyphic fluctuating asymmetry, negative schizotypy was associated with increased absolute finger ridge …

A Toi Rna Editing In Three Members Of The Microbotryum Violaceum Fungal Complext And Characterization Of Adar Genes Of Microbotryum Superbum., Shikhi Baruri

Electronic Theses and Dissertations

A-to-I RNA editing is a process that occurs post-transcriptionally. Through this process, adenosine (A) is replaced by inosine (I) in RNAs by adenosine deaminase enzymes that act on the single-stranded RNA. These enzymes, also known as ADARs, act on RNA. The translation and splicing mechanisms subsequently interpret inosine as guanosine (G), which effectively alters genetic information. This kind of RNA alteration can cause both nonsynonymous and synonymous changes in codon, which may have an impact on protein function. A group of over 89 basidiomycete fungal species known as the Microbotryum violaceum complex infects a similarly large group of plant host …

Genes That Matter: Survival Modeling In Tcga-Brca With Treatment Interactions., David Pratt

Electronic Theses and Dissertations

High-dimensional genomic data offer both promise and challenges for identifying clinically relevant biomarkers. This study developed a parallelized survival modeling pipeline to identify genes associated with overall survival in breast cancer, with a focus on gene-by-treatment interactions and patient heterogeneity. RNA-Seq data from female patients in the TCGA-BRCA cohort were analyzed. Univariate Cox proportional hazards models were used to screen genes, adjusting for age, race/ethnicity, treatment status, and cancer stage. A LASSO-penalized Cox regression was fit across 2000 random seeds to assess feature stability. Genes were filtered by expression level, statistical significance, and hazard ratios (effect sizes) in either direction, …

Breeding Biofortified Protein Rich Organic Pulses For Better Human Health, Sonia Salaria

All Dissertations

Pulse crops are dry grains of legumes, the second most consumed plant crops in the world after cereals. These crops are one of the primary sources of plant-based protein and contain high concentrations of pre-biotic carbohydrates, minerals and vitamins. Recognizing the health benefits of pulses intake, their demands as sustainable food and changes in people’s diet preferences for plant-based protein have increased awareness for pulses consumption. With this scenario, improving the nutritional profile of pulse crops for rich nutrition has been an opportunity for breeders to explore and tailor the available germplasm to develop nutrient dense pulses. Furthermore, the genomic …

Alternative Therapeutics For Human Breast Cancer: Nutraceutical Underpinnings, In Vitro Metabolomic Profiling, Treatment Efficacy, And Contextual Ethical Implications, Aubrey A. Mattingly

All Dissertations

Breast cancer remains one of the most prevalent diseases worldwide, yet therapeutic equity is still lacking. Standard treatments including surgery, radiotherapy, chemotherapy, and long-term hormone therapy. These approaches are often accompanied by significant side effects. While newer methods such as immunotherapy and targeted therapies have emerged, chemotherapy protocols and incorporation have remained largely unchanged in the past decades. In this context, nutraceuticals represent an alternative or adjuvant to therapy worthy of exploration. The reviewed literature highlights the anti-carcinogenic activity in selected nutraceuticals, marjoram, thyme and persimmon, considering their phytochemical constituents and secondary metabolites. Metabolomic profiling using the Biolog Phenotype Mammalian …

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

Electronic Theses and Dissertations

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

The Role Of Cleavage And Polyadenylation Spcific Factor 6 (Cpsf6) In Hematopoiesis, Fengxi Ye

Dissertations and Theses (Open Access)

Cleavage and polyadenylation specific factor 6 (Cpsf6) translocation is frequently reported in APLL, which is Acute Promyelocytic Leukemia (APL)-like acute myeloid leukemia (AML) and other types of blood diseases associated with abnormal hematopoiesis. CPSF6 is a subunit of the Cleavage Factor I mammalian (CFIm) complex, which regulates post-transcriptional alternative polyadenylation (APA) of pre-mRNAs. Previous research indicated that Cpsf6 plays an essential role in alternative polyadenylation, development, and tumorigenesis. However, the role of Cpsf6 in hematopoiesis is unknown. Given its roles in APA, development and cancer, we hypothesize that Cpsf6 plays a critical role in hematopoiesis and that its …

Functional Genomics Of Phosphatidylcholine Biosynthesis In Saccharomyces Cerevisiae, Amanda Marie Maliva

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

Phosphatidylcholine (PtdCho) is a prominent structural building block of cell and organelle membranes in animal, plant, and fungal cells and some bacteria. Due to its abundant nature in the plasma membrane and intracellular organelle membranes in eukaryotes, the biosynthesis of PtdCho must remain regulated to preserve the correct membrane lipid composition. Dysregulations in PtdCho metabolism can lead to mitochondrial dysfunction, cell death, and the development of diseases including cancer, atherosclerosis, and hepatic diseases. Knowledge of PtdCho has remained limited to the genes involved in its three biosynthetic pathways (Kennedy (K), methylation (M), and acyltransferase (A)), despite the growing realization of …

Exploring Variability Of The Cg18562578 Methylquant Assay For The Forensic Discrimination Of Monozygotic Twins, Sydney E. Arnold

Student Theses

Monozygotic (MZ) twins possess identical DNA sequences, posing a problem for forensic scientists, as they are incapable of distinguishing MZ twins from each other using traditional DNA identification methods. However, the epigenomes of MZ twins will differ and might be used for their forensic discrimination. Here, we explored the variability of an assay previously developed by our laboratory that showed high discrimination potential for MZ twins using buccal swab DNA, cg18562578 MethylQuant. We measured precision at each step: bisulfite conversion, nested PCR, and qPCR, reproducibility, and repeatability. DNA methylation ratios were compared between two analysts carrying each step using the …

Exploring Transcriptional Stress Responses In Sorghum And Evolutionary Insights Into Yth Domain Proteins Across Plants, Shikha Bharti

Theses and Dissertations

Understanding how plants respond to abiotic stress is crucial for enhancing crop resilience in the face of climate change. This thesis explores plant stress adaptation mechanisms through two interlinked studies that address different aspects of gene regulation. The first study investigates the transcriptional dynamics of Sorghum bicolor under drought and heat stress at 1-hour and 6-hour time points. By employing 3'-end RNA sequencing, this study provides a comprehensive temporal view of gene expression changes, revealing stress-responsive transcription factors, hormone-associated pathways, and chromatin regulators. The comparative analysis highlights both common and distinct molecular responses between drought and heat stress, providing insights …

Predicting Genetic Interactions Using Functional Interaction Networks, Iulia Veronica Gheorghe

Dissertations and Theses (Open Access)

Mapping genetic interactions is central to understanding cellular systems and identifying therapeutic vulnerabilities, particularly in the context of cancer. Among these interactions, synthetic lethality, where simultaneous loss of two genes is lethal but loss of either alone is tolerated, offers a powerful framework for selectively targeting tumor-specific dependencies. In model organisms like S. cerevisiae, comprehensive double-knockout screens have revealed detailed genetic interaction maps, enabling systems-level insights into pathway structure, gene function, and cellular organization. Replicating this achievement in human cells, however, is complicated by the scale and complexity of the human genome. Recent advances in genome-wide CRISPR knockout screening have …

Investigating The Role Of The Lysine-Specific Demethylase 4c In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen

Dissertations and Theses (Open Access)

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell-like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared to non-neoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomics analyses revealed that loss of KDM4C in both human …

Associations Of Variation In Mtdna With Feed Efficiency In Beef Cattle And The Evaluation Of Transcriptomic Changes In Fetal Kidney Due To Hydrallantois, Lauren Elizabeth Seier

Department of Animal Science: Dissertations, Theses, and Student Research

Project 1 focused on the central role that mitochondria play in ATP production, highlighting that variation within the mtDNA may influence feed efficiency. Variation in the mitochondrial genome was uncovered, and associations with feed efficiency in beef cattle were identified. Growth and feed intake phenotypes, as well as low-pass sequencing, were collected on beef steers across two populations. Protein coding variants were identified and used to classify animals into mitochondrial haplotypes. A linear mixed model was employed, which detected a significant association between mitochondrial haplotype and DMI. A significant haplotype with a variant in Complex I was associated with reduced …

Identification Of Crustose Coralline Algae Species In Florida And Their Ability To Induce Larval Settlement Of Caribbean Corals, Danielle Macias

All HCAS Student Capstones, Theses, and Dissertations

Crustose coralline algae (CCA) are a diverse, globally spread and yet poorly studied group of benthic organisms. They act as settlement cues for coral larvae, but this interaction is often species-specific, as CCA species can be either inducers or inhibitors to larval settlement and metamorphosis. Despite this importance, information on Caribbean CCA distribution, diversity, and impact on coral species is limited due to the difficulty in identifying them. In the present study, CCA samples were collected from seven different reef sites in the southeastern region of Florida’s Coral Reef and genetically identified using molecular analyses. Some of the samples collected …

Health Patterns Of Dementia Caregivers With Chronic Pain: Latent Profile Analysis Of The Promis-29 Measure, Shelbie G. Turner, Dakota D. Witzel, Shana Garza, Karl Pillemer, M Carrington Reid

Human Genetics Publications

We identified patterns of health and functioning in a national sample of dementia family caregivers experiencing chronic pain (N = 273). Utilizing latent profile analysis of the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29), we identified three discrete groups: an average group (48%), a low health challenges group (30%), and a high health challenges group (22%). Women were more likely to be in the high (vs. low) health challenges group. There are discrete health patterns of caregivers with chronic pain, with over 20% reporting comorbid poor health and functioning that may negatively affect caregiving quality. Screening caregivers for high …

The Island Biogeography Of Mangrove-Dwelling Vertebrates: Isolation, Specialisation, And Extinction, Jian Xiong David Tan

Biology ETDs

Mangroves are highly dynamic ecosystems that are widely distributed across the coastlines of the tropics and subtropics. Despite their low plant diversity, mangroves host a disproportionately high number of terrestrial vertebrate taxa. However, mangrove specialists — taxa that only occur in mangrove habitats — exhibit a global distribution that is incongruous with the broader background distribution patterns of mangrove-associated fauna, exhibiting higher diversity in Australia and Southeast Asia. This dissertation therefore aims to assess how the diversity and distribution of mangrove specialist fauna may have been shaped by the historical biogeography of mangroves, and the effects of mangrove specialisation on …

Transformation With Genes To Improve Lipid Production And Barcoding To Identify Unknown Algal Species, Michelle T. Rada

Theses and Dissertations

With the rising demand for alternative fuels, algal-based biofuels are a promising, sustainable source that meets commercial interest while producing lower greenhouse gas emissions compared to fossil fuels. This thesis explored two studies, evaluating microalgae for their future potential in lipid yield for biofuel production.

The first study involved developing a cost-efficient electroporation protocol that allowed for the genetic transformation of Chlamydomonas reinhardtii using the pChlamy_4 vector, which supports future cloning of genes to enhance lipid production. Parameters affecting DNA uptake and integration into algal genomes were studied: the effect of cell density, the settings of the electroporation device, and …

Perception Of Quality Of Life, Brain Regions, And Cognitive Performance In Hispanic Adults: A Canonical Correlation Approach, Juan C. Lopez-Alvarenga, Jesus D. Melgarejo, Jesus Rivera-Sanchez, Lorena Velazquez-Alvarez, Rosa V. Pirela, John Blangero, Jose E. Cavazos, Michael C. Mahaney, Joseph D. Terwilliger, Gladys E. Maestre

School of Medicine Publications

The quality of life (QoL) perception has been studied in neurological diseases; however, there is limited information linking brain morphological characteristics, QoL, and cognition. Human behavior and perception are associated with specific brain areas that interact through diffuse electrochemical networking. We used magnetic resonance imaging (MRI) to analyze the brain region volume (BRV) correlation with the scores of Rand’s 36-item Short Form Survey (SF-36) and cognitive domains (memory and dementia status). We analyzed data from 420 adult participants in the Maracaibo Aging Study (MAS). Principal component analysis with oblimin axis rotation was used to gather redundant information from brain parcels …

Autism Spectrum Disorder: A Review Of Genomic Risk Factors, Diagnostic And Pharmacotherapeutic Strategies, Zohor Azher

Saudi Toxicology Journal

Autism Spectrum Disorder (ASD) is a multifactorial neurodevelopmental condition characterized by impairments in social communication and delayed language development, repetitive behaviors, and sensory processing abnormalities. The genetic background of ASD remains incompletely understood due to significant genetic heterogeneity and complexity. This review aims to present current insights into the genetic landscape of ASD, focusing on both common and rare genomic variations. We describe candidate genes associated with ASD, as they are involved in synaptic function and neuronal signaling, making these findings potential therapeutic targets. This review emphasizes the importance of integrating comprehensive clinical assessments with advanced genetic investigations to enhance …