Genetics Commons^™

Late Diagnosis Of Klinefelter Syndrome: Overcoming Phenotypic Variability And Diagnostic Oversights, Amna Kamran, Chinelo Okigbo

Department of Medicine Faculty Publications

We report a case of Klinefelter syndrome (KS) diagnosed in adulthood, emphasizing the impact of phenotypic variability and the declining reliance on physical examination in delayed recognition. A 27-year-old male with obesity, low libido, and biochemical and clinical primary hypogonadism was found to have 47, XXY karyotype, consistent with KS. His hypogonadism was initially attributed to obesity and overlooked, despite classic signs of a micropenis and small testes. The case highlights the importance of physical examination, comprehensive history, and clinician awareness in diagnosing KS, particularly in atypical presentations. KS is associated with increased risks of osteoporosis, cardiovascular disease, and psychosocial …

Copula-Based Bayesian Model For Detecting Differential Gene Expression, Prasansha Liyanaarachchi, N. Rao Chaganty

Mathematics & Statistics Faculty Publications

Deoxyribonucleic acid, more commonly known as DNA, is a fundamental genetic material in all living organisms, containing thousands of genes, but only a subset exhibit differential expression and play a crucial role in diseases. Microarray technology has revolutionized the study of gene expression, with two primary types available for expression analysis: spotted cDNA arrays and oligonucleotide arrays. This research focuses on the statistical analysis of data from spotted cDNA microarrays. Numerous models have been developed to identify differentially expressed genes based on the red and green fluorescence intensities measured using these arrays. We propose a novel approach using a Gaussian …

Cath-Ddg: Towards Robust Mutation Effect Prediction On Protein-Protein Interactions Out Of Cath Homologous Superfamily, Guanglei Yu, Xuehua Bi, Teng Ma, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Protein-protein interactions (PPIs) are fundamental aspects in understanding biological processes. Accurately predicting the effects of mutations on PPIs remains a critical requirement for drug design and disease mechanistic studies. Recently, deep learning models using protein 3D structures have become predominant for predicting mutation effects. However, significant challenges remain in practical applications, in part due to the considerable disparity in generalization capabilities between easy and hard mutations. Specifically, a hard mutation is defined as one with its maximum TM-score < 0.6 when compared to the training set. Additionally, compared to physics-based approaches, deep learning models may overestimate performance due to potential data leakage.

Results: We propose new training/test splits that mitigate data leakage according to the CATH homologous superfamily. Under the constraints of physical …

An Edna Assessment Of The Diamond Darter (Crystallaria Cincotta) In Its Current And Historic Distribution Range, Cameron Moore Layne

Graduate Theses, Dissertations, and Problem Reports (ETD)

Environmental DNA (eDNA) can serve as a useful monitoring tool for cryptic and imperiled freshwater stream fishes. eDNA can fill knowledge gaps regarding species’ distribution, site abundance, and habitat usage. The last known stronghold of the Diamond Darter (Crystallaria cincotta) in the Elk River of West Virginia provides an excellent test case to examine the utility of this non-invasive method of surveying rare species. Diamond Darters are one of the most newly recognized freshwater fishes in North America and are among the most imperiled U.S. fishes, having been federally listed as endangered in 2013. The cryptic behavior and limitations of …

Tricolored Bat (Perimyotis Subflavus) Population Genetic Structure In The Southeastern United States, Laura Henderson

Master's Theses

Tricolored bats (Perimyotis subflavus) have experienced substantial population losses from white-nose syndrome (WNS), a disease caused by the pathogenic fungus Pseudogymnoascus destructans (Pd) which infects hibernating bats. Determining population genetic structure helps assess genetic diversity and the impacts of wildlife threats to populations. Pre-WNS data shows weak-to-negligible structure and panmictic P. subflavus populations at core portions of their range. However, current genetic data from their southeastern U.S. range is lacking. I sought to determine whether recent genetic data help resolve genetic structure among southeastern populations and assess genetic differences at two stages of impact: post-WNS and …

Hidden Markov Model For Identifying Local Variants In Human Genomes Using Simulated Data, Scott Mccallum

Electronic Theses and Dissertations

Identifying adaptive mutations in genetic data is challenging due to the low frequency of occurrence of such events, and because signatures of selection are intertwined with the footprints of various other evolutionary forces that shape our genomes. Even when a larger region appears to be under selection, genomic sites that are linked to adaptive mutations have similar statistical signals, and thus can obfuscate the identification of the actual adaptive mutation. The new method described here uses a Hidden Markov Model that allows for classification of neutral, linked, and sweep (adaptive mutation) genomic sites. This model is general and can be …

Morphological And Molecular Identification Of Saurida Spp. (Teleostei: Synodontidae) From Saudi Arabia And Indonesia, Muhammad Browijoyo Santanumurti, Suciyono Suciyono, Mohamed Ahmed Abu El-Regal

Makara Journal of Science

Saurida is a unique fishery commodity because it is difficult to differentiate visually. They can be only effectively con-served once accurately identified. This study aimed to determine the morphology and molecular characteristics of Sau-rida spp. from Banyuwangi (Indonesia) and Jizan (Saudi Arabia). Meristic and morphometric analysis was performed for morphological identification, whereas COI gene analysis was performed for molecular identification. Morphological analysis was performed to identify Saurida in this study, such as S. tumbil (Jizan, Saudi Arabia) and S. micropectoralis (Banyuwangi, Indonesia). S. tumbil did not have dark brown spots on the lateral line and upper caudal fin, whereas S. …

Gonadal Absence Of Pig-1: Exploration Of Pig-1 In The Gonad Of Caenorhabditis Elegans, Winston S. Bennah

Undergraduate Theses

Caenorhabditis elegans are model organisms frequently studied to better understand biological processes. They have short life spans and produce a large number of progeny. Additionally, many of their molecular development processes can be found in human, providing insight into cell death and cell fate. In this project, our research aims to create a triple mutant strain to test the importance of the pig-1 gene in the gonad of C. elegans. This strain carries the following alleles: ckb-3::degron; him-8; gfp::pig-1. The pig-1 gene has been previously studied in neuroblast cells in C. elegans and is required for …

The Effects Of Ewing Sarcoma Through The Overexpression And Knockdown Of Transcription Factors Sox18 And Stat1, Victoria Castillo, Melany Cervantes, Nicole Robles, Terry Jo Shackleford

Cell and Molecular Methods

SOX18, a transcription factor with a DNA-binding HMG domain, plays a critical role in regulatory processes linked to cancer progression. Exhibiting oncogenic properties, SOX18 has been linked to various cancers, where it promotes tumor growth by enhancing cell invasion, uncontrolled proliferation, and resistance to apoptosis through dysregulated signaling pathways. STAT1, a protein crucial for immune system regulation, is prominently expressed in immune-associated tissues like the lymph nodes, and bone marrow, suggesting it could play a role in tumor growth. Ewing Sarcoma (EWS), an aggressive cancer that targets bone and soft tissue, carries a high mortality rate of 90% without treatment …

Unilateral Tongue Atrophy In Smad3: A Case Report, Gloria Galloway

Nursing & Health Sciences Research Journal

Background: Mothers Against Decapentaplegic Homolog 3 (SMAD3) is a disorder of the protein encoded at locus 15q22.33 and involved in the transcription of growth factor-beta (TGF) signalling. In this disorder, SMAD3 encoding is impaired, resulting in a connective tissue disorder with multisystem involvement (Bertoli-Avella et al., 2015; Dulac et al., 2019). This case is the first to describe unilateral tongue atrophy as an initial presentation of SMAD3, thereby providing an important contribution to the literature. Clinical History and Exam: A 43-year-old patient described a 1–2-week history in which he noted that half of his tongue had wasted away, and he …

Bap1: Genotype-Phenotype Correlation, Variant Classification, And Treatment Efficacy, Elizabeth Hobbs

All Dissertations

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene located on chromosome 3p21.3 and encodes a deubiquitinase enzyme (DUB) involved in DNA repair, cell cycle and metabolism, and apoptosis. BAP1 pathogenic germline variants are primarily associated with a familial cancer syndrome, Tumor Predisposition Syndrome 1 (TPDS1), but new missense variants have been linked to a neurodevelopmental disorder known as Kury-Isidor Syndrome (KURIS). Patients with TPDS1 variants have an increased risk for developing cancers, such as uveal and cutaneous melanomas, mesothelioma, and renal cell carcinoma, at an earlier age with lower thresholds for environmental exposures, mainly UV rays and asbestos, compared …

Behavior In Phelan-Mcdermid Syndrome: Clinical Characteristics, Genetic And Metabolic Contributions, And Evaluation Of Behavioral Assessment Tools, Emily Payne

All Dissertations

Phelan-McDermid syndrome (PMS) is characterized by genetic and phenotypic variability with varying levels of developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), speech delay, minor dysmorphic features, and behavioral issues. Genetic causes of PMS involve deletions in the 22q13.3 region or pathogenic/likely pathogenic variants in SHANK3. Due to the significant heterogeneity and complexities seen in individuals with PMS, there are numerous challenges surrounding research, accurate diagnoses, assessments, and the creation of treatments. Behavioral issues are present in the majority of individuals with PMS, including lower levels of adaptive behavioral skills needed for daily functioning, disruptive behaviors, restricted and …

Drosophila Model Of Cocaine Use Disorder, Jeffrey Hatfield

All Dissertations

Cocaine use disorder (CUD) is a major public health challenge. While the primary mechanism of action of cocaine has been well characterized, and family studies have identified a strong genetic component, the specific genetic factors that influence susceptibility to development of CUD remain poorly understood. Genetic studies of cocaine use disorder are difficult in humans, but can be readily performed in Drosophila, where environment, genetic background, and cocaine exposure can be controlled. Drosophila exhibit behavioral and transcriptomic responses to cocaine, which binds to the dopamine transporter in fruit flies as it does in humans. Here, we use Drosophila to …

Genome-Wide Expression Profiling And Phenotypic Analysis Of Downstream Targets Identify The Fox Transcription Factor Jumeau As A Master Regulator Of Cardiac Progenitor Cell Division, M. Rezaul Hasan

Bakerman Student Research Awards

Forkhead box (Fox) transcription factors (TFs) mediate multiple conserved cardiogenic processes in both mammals and Drosophila. Our prior work identified the roles of two Drosophila Fox genes, jumeau (jumu) and Checkpoint suppressor 1-like (CHES-1-like), in cardiac progenitor cell specification and division, and in the proper positioning of cardiac cell subtypes. Fox TF binding sites are also significantly enriched in the enhancers of genes expressed in the heart, suggesting that these genes may play a core regulatory role in one or more of these cardiogenic processes. We identified downstream targets of Jumu by comparing transcriptional expression profiles of flow cytometry-sorted mesodermal …

Production Objectives And Trait Preferences Of Smallholder Farmers In The Philippines: Implications For Designing Breeding Schemes Utilizing Indigenous Swine Genetics, Joy Banayo, Kathlyn Louise Manese, Kaito Furusho, Madeline Kingan, Justine Ayomen, Marcelino Saliw-An, Karina Marie Nicolas, Kayvin Joel Petipit, Dorothy Pagbilao, Vea Roven Arellano, Rene Santiago, Flomella Caguicla, Arnolfo Monleon, Giselle Perlas, Giselle Perlas, Rea Palma Ortego, Sharon Singzon, Agapita Salces, Takahiro Yamagata

The Philippine Agricultural Scientist

Profit maximization is not the only production objective in farming. For smallholder farms worldwide, family sustenance often takes priority, with production being viewed more as savings-oriented than market-oriented. Furthermore, market pressures can lead to the mismanagement of indigenous livestock resources, increasing their risk of genetic erosion. To ensure the long-term conservation of the Philippine native pig, this study aimed to determine the various types of native pig farmers and define the intervention strategies for each type. A total of 432 native pig farmers representing seven provinces in the Philippines (Benguet, Kalinga, Isabela, Nueva Vizcaya, Quezon, Marinduque, and Eastern Samar; n …

Root Plasticity Of Selected Corn (Zea Mays L.) Varieties Grown For Food And Forage In Response To Fertigroe®-N And Urea, Vanica Apostol, Edna Aguilar, Lilia Fernando, Lourdes Edano Ma., Tonette Laude, Eureka Teresa Ocampo

The Philippine Agricultural Scientist

Root plasticity, the capacity of a corn root system to modify its growth and development in response to varying environmental conditions, is a crucial adaptability trait for optimizing water and nutrient uptake, especially in a challenging environments. Understanding root plasticity provides insights into the pattern basis of crop adaptation, contributing to the development of improved corn varieties and agricultural practices that optimize the production of both ear shoots and forage. This study assessed root traits and other morphological-physiological responses of three corn varieties (NK8840, IPB Var 6, and Pearl Sweet) grown for food (ear shoots) and forage (baby corn fodder) …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Lam-Ha T. Dang, Alice Lee, Sharon Krinsky-Mchale, Deborah Pang, Lisa Melilli, Sid E. O’Bryant, Rachel L. Henson, Charles Laymon, Florence Lai, H. Diana Rosas, Beau Ances, Ira Lott, Christy Hom, Bradley Christian, Sigan Hartley, Shahid Zaman, Elizabeth Head, Mark Mapstone, Zhezhen Jin, Wayne Silverman, Nicole Schupf, Benjamin Handen, Joseph H. Lee, Alzheimer’S Biomarker Consortium – Down Syndrome (Abc-Ds)

Neurology Faculty Publications

Background Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer’s disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

Methods We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium–Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

The Role Of Wt1 In Müllerian Duct Development, Jace Aloway

Dissertations and Theses (Open Access)

WT1 is a zinc finger transcription factor widely expressed in the urogenital system. Human mutations of WT1 lead to pediatric nephroblastoma as well as frequent differences of sex development (DSDs). Previous studies have suggested that WT1 acts as an activator for Amhr2, a necessary component of typical male differentiation. We used the mouse as a model to investigate the role of WT1 in sex development, where we deleted Wt1 in the Müllerian duct (MD) mesenchyme using a novel conditional null reporter allele, Wt1 flox-RFP. This allele utilizes the Cre-lox system to delete exons 8 and 9 of Wt1 …

Independent Evolution Of Oleate Hydratase Clades In Bacillales Reflects Molecular Convergence, Robert J. Neff, Priscilla C. Lages, Shannon K. Donworth, James D. Brien, Christopher D. Radka

Markey Cancer Center Faculty Publications

Oleate hydratase (OhyA), a flavoenzyme that catalyzes the hydration of unsaturated fatty acids, has been identified in various Bacillales organisms, including those in the Listeria, Lysinibacillus, Paenibacillus, and Staphylococcus genera. In this study, we combine structural biology with molecular and phylogenetic analyses to investigate the evolutionary dynamics of the OhyA protein family within the Bacillales order. Our evolutionary analysis reveals two distinct OhyA clades (clade I and clade II) within Bacillales that, while sharing catalytic function, exhibit significant genomic and structural differences. Our findings suggest that these OhyA clades originated from independent evolutionary processes through convergent evolution rather than gene …

Assessing The Temporal Role Of Mir-200 Loss In Murine Models Of Nsclc, Jared Fradette

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer related deaths in the United States, with non-small cell lung cancer (NSCLC) making up a majority of new diagnoses. Metastasis is the big killer in NSCLC and is driven by epithelial-mesenchymal transition (EMT) and immune evasion. The microRNA 200 family is a master regulator of EMT and is implicated in immune regulation. In this study we have developed a novel genetically engineered mouse model (GEMM) and derived primary cell lines from them to explore the role of microRNA-200 in early EMT and immune changes. Our model combines conditional activation of Kras^{G12D …}