Genetics and Genomics Commons^™

Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Zhonggang Li, James A Votava, Gregory J M Zajac, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks

Faculty, Staff and Students Publications

Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as …

Principles Of Rna Processing From Analysis Of Enhanced Clip Maps For 150 Rna Binding Proteins, Eric L Van Nostrand, Gabriel A Pratt, Brian A Yee, Emily C Wheeler, Steven M Blue, Jasmine Mueller, Samuel S Park, Keri E Garcia, Chelsea Gelboin-Burkhart, Thai B Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R Graveley, Gene W Yeo

Faculty, Staff and Students Publications

BACKGROUND: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types.

RESULTS: Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA …

De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton

Faculty, Staff and Students Publications

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 …

Assessing Seed Handling Processes To Facilitate A Community-Engaged Approach To Regional Forest Restoration, Meredith Cobb, Michaela J. Woods, Ryan Mcewan

Biology Faculty Publications

In the Midwestern United States, there is a strong management impetus toward reforestation to replace trees lost to due to tree mortality and to establish forests on previously cleared properties. Here, we describe a public outreach and volunteer effort that aimed to generate positive, community-engaged restoration outcomes and report on a practical experiment involving seed handling. We obtained tree seeds that were donated by members of the community to local land managers. We evaluated the size of the seeds collected and tested the influence of common stratification media (none, sand and vermiculite) and seed size on germination success of three …

Assessing Social Media For Themes Of Trisomy 18 And 13, Falecia Metcalf

Theses and Dissertations

Themes within virtual communities have been explored examining topics such as prenatal diagnosis and termination for fetal anomalies, and it is known that when receiving a diagnosis of trisomy 18 or 13 parents may turn to online resources for information and emotional support. Knowledge of what content patients may encounter on various social media platforms about prenatal testing for trisomy 18 and 13 at large has not yet been established. However, this information would aid healthcare professionals in providing anticipatory guidance for patients using social media.

This study is a preliminary scan of social media to identify content areas and …

De Novo Sequencing And Analysis Of Salvia Hispanica Tissue-Specific Transcriptome And Identification Of Genes Involved In Terpenoid Biosynthesis, James Wimberley, Joseph Cahill, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Salvia hispanica (commonly known as chia) is gaining popularity worldwide as a healthy food supplement due to its low saturated fatty acid and high polyunsaturated fatty acid content, in addition to being rich in protein, fiber, and antioxidants. Chia leaves contain plethora of secondary metabolites with medicinal properties. In this study, we sequenced chia leaf and root transcriptomes using the Illumina platform. The short reads were assembled into contigs using the Trinity software and annotated against the Uniprot database. The reads were de novo assembled into 103,367 contigs, which represented 92.8% transcriptome completeness and a diverse set of Gene Ontology …

Liver Ubd Is Upregulated In The Lew.1wr1 Rat, Helen Gibson, Amelia Clopp, Genoah Collins

Research Horizons Day Posters

No abstract provided.

Care: Collecting And Assessing Cancer Family History To Identify At Risk Individuals Educational Intervention For Community Health Workers, Laura Moreno

USF Tampa Graduate Theses and Dissertations

Background: Collection of family health history (FHH) can identify individuals at increased risk and guide disease-specific recommendations for management, early detection, and prevention. Yet, collection of FHH is often low or infrequent despite national initiatives. In the Hispanic/Latino population, community outreach and education professionals (CORE-Ps) have effectively increased cancer prevention and control behaviors; but, limited research has been conducted to assess genetic and family health history knowledge among CORE-Ps. We sought to evaluate an educational program designed to improve cancer FHH and cancer genetics knowledge, self-efficacy and attitudes. Methods: The ARBOLES Program educates bilingual (Spanish-English) CORE-P to increase knowledge about …

The Sineb1 Element In The Long Non-Coding Rna Malat1 Is Necessary For Tdp-43 Proteostasis, Tuan M Nguyen, Elena B Kabotyanski, Lucas C Reineke, Jiaofang Shao, Feng Xiong, Joo-Hyung Lee, Julien Dubrulle, Hannah Johnson, Fabio Stossi, Phoebe S Tsoi, Kyoung-Jae Choi, Alexander G Ellis, Na Zhao, Jin Cao, Oluwatoyosi Adewunmi, Josephine C Ferreon, Allan Chris M Ferreon, Joel R Neilson, Michael A Mancini, Xi Chen, Jongchan Kim, Li Ma, Wenbo Li, Jeffrey M Rosen

Faculty, Staff and Students Publications

Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the …

Journey Mapping The Minority Student’S Path Toward Genetic Counseling: A Holistic Picture, Tatiana E. Alvarado-Wing

USF Tampa Graduate Theses and Dissertations

Reasons for limited ethnic and racial diversity among genetic counselors in the United States may be elucidated through better understanding the experiences of minority students who are attending genetic counseling graduate programs as well as recent graduates. Semi-structured interviews were conducted with minority participants using Journey Mapping to elicit touchpoints that positively or negatively impact success at varying points on the path to becoming a genetic counselor. Touchpoints with negative impacts include; late awareness of the profession, observing the lack of diversity in the field, the financial burden of the application process, and microaggressions from peers, program leadership, and clinical …

Terms Of Service: The Use And Protection Of Genomic Information By Companies, Databases, And Law Enforcement, Sophia Kallas

Honors Program: Senior Projects (Public)

Private genomic companies have become a popular trend in the last two decades by providing customers with information regarding their ancestry and health risks. However, the profiles received from these companies can also be uploaded to public databases for various purposes, including locating other family members. Both testing companies and public databases have private interests, and both are at risk of law enforcement intervention for the purpose of forensic familial searching. There is little federal legislation protecting the privacy of an individual’s genetic profile. Consequently, it has been up to federal agencies, state laws, and judicial precedents to prevent the …

Evaluating Effects Of Cancer Genetic Counseling On Several Brief Patient Impact Measures, Alyson Kneusel

USF Tampa Graduate Theses and Dissertations

Many outcomes for assessing cancer genetic counseling (GC) utility have been proposed, with few studies evaluating multiple, theory-based, brief patient-reported experience and outcome measures simultaneously as part of a single study. We conducted a pilot study in which patients seen for pre-test cancer GC took a survey before and after their GC session to evaluate the session’s impact on multiple patient impact measures and assess the relationship between these measures. Measures based on the self-determination theory (SDT) assessed three basic needs including: 1) perceived autonomy support, 2) relatedness to the provider, and 3) competence to make a decision. SDT posits …

Molecular Differentiation Of Astragalus Species And Varieties From The Western United States: The Chloroplast Dna Bridge Between Evolution And Molecular Systematics, Marwa Neyaz, Daniel Cook, Rebecca Creamer

Poisonous Plant Research (PPR)

Locoweeds are the most widespread poisonous plant problem in the world and have been reported in the Western United States since the 1800s, causing tremendous losses in livestock. Consumption of locoweeds by grazing animals stimulates the neurological disease, locoism, characterized by weight loss, ataxia, and lack of muscular coordination. The name locoweed is used for Astragalus and Oxytropis species known to contain swainsonine, the toxic principle produced by the plant endophytic fungus Undifilum. Astragalus includes 2,500-3,000 species and many varieties that have almost identical morphological characteristics that overlap among species, leading to improper identification. Therefore, the aim of this study …

Dibutyltin Alters Immune Cell Production Of The Pro-Inflammatory Cytokines Interleukin (Il) 1Β And Il-6: Role Of Mitogen-Activated Protein Kinases And Changes In Mrna, Linda B Sushak, Sahra Gabure, Jaquel Maise, Jessica Arnett, Margaret Whalen

Chemistry Faculty Research

Dibutyltin (DBT) is used to stabilize plastics and as a deworming agent in some poultry. It is found in human blood (levels as high as 0.3 μM). Interleukin (IL) 1β (IL-1β) and IL-6 are pro-inflammatory cytokines produced by lymphocytes, monocytes, and other cells. Elevated levels of IL-1β and IL-6 have been associated with pathologies including rheumatoid arthritis and cancers. DBT was shown to decrease IL-1β and IL-6 secretion from immune cells at higher concentrations while causing increases at lower concentrations. However, it was not clear if these changes were due to DBT's alteration of the secretory process or due its …

Expression Level Of Sh2 And Bt2 Genes In Some Advanced Corn Lines Under Tropical Environment, Fatemeh Abna, Farhat A. Avin, Noorma Wati Haron

Agricultural and Environmental Sciences Faculty Research

The rate-limiting step in starch synthesis entails the synthesis of ADP-Glc from Glc-1-P and ATP by AGPase. AGPase is a heterotetramer composed of two large subunits encoded by Sh2 and two small subunits encoded by Bt2. We examined the transcript level of each gene that encodes AGPase through quantitative real-time PCR (qRT_PCR) within endosperm and leaf tissues from 6 newer composite corn lines. The Sh2 and Bt2 genes presented upregulated expression levels in leaf and endosperm tissue. The highest expression level of these two genes in leaf tissues was observed in UM 1 with 6.96 fold and in UM 11 …

A Positive Feedback Loop Of Hippo- And C-Jun-Amino-Terminal Kinase Signaling Pathways Regulates Amyloid-Beta-Mediated Neurodegeneration, Madison Irwin, Meghana Tare, Aditi Singh, Oorvashi Roy Puli, Neha Gogia, Matthew Riccetti, Prajakta Deshpande, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Alzheimer's disease (AD, OMIM: 104300) is an age-related disorder that affects millions of people. One of the underlying causes of AD is generation of hydrophobic amyloid-beta 42 (Aβ42) peptides that accumulate to form amyloid plaques. These plaques induce oxidative stress and aberrant signaling, which result in the death of neurons and other pathologies linked to neurodegeneration. We have developed a Drosophila eye model of AD by targeted misexpression of human Aβ42 in the differentiating retinal neurons, where an accumulation of Aβ42 triggers a characteristic neurodegenerative phenotype. In a forward deficiency screen to look for genetic modifiers, we identified a molecularly …

Probing The Function Of Long Noncoding Rnas In The Nucleus, Sajal Medha K. Akkipeddi , '20, A. J. Velleca, Dawn M. Carone

Biology Faculty Works

The nucleus is a highly organized and dynamic environment where regulation and coordination of processes such as gene expression and DNA replication are paramount. In recent years, noncoding RNAs have emerged as key participants in the regulation of nuclear processes. There are a multitude of functional roles for long noncoding RNA (lncRNA), mediated through their ability to act as molecular scaffolds bridging interactions with proteins, chromatin, and other RNA molecules within the nuclear environment. In this review, we discuss the diversity of techniques that have been developed to probe the function of nuclear lncRNAs, along with the ways in which …

Mitochondrial Dna Diversity And Evolutionary History Of Native Human Populations Of Northwest Patagonia (Argentina), María Bárbara Postillone, Virginia Agustina Cobos, Celmira Urrutia, Cristina Beatriz Dejean, Paula N. Gonzalez, Sergio Ivan Perez, Valeria Bernal

Human Biology Open Access Pre-Prints

The genetic composition of Amerindian descendants from Patagonia has long been a focus of interest, although the information available is still scarce for many geographic areas. Here, we report the first analysis of the variation in the mtDNA control region for an area of northwestern Patagonia, the North of Neuquén, with the aim of studying the processes and historical events that modeled the evolutionary history of these human groups. We analyzed 113 individuals from two localities of northern Neuquén, along with 6 from southern Neuquén and 223 mtDNA sequences previously published from neighboring areas from Argentina and Chile. We estimated …

The Bacillus Subtilis K-State Promotes Stationary-Phase Mutagenesis Via Oxidative Damage, Holly A. Martin, Amanda A. Kidman, Jillian Socea, Carmen Vallin, Mario Pedraza-Reyes, Eduardo A. Robleto

Life Sciences Faculty Research

Bacterial cells develop mutations in the absence of cellular division through a process known as stationary-phase or stress-induced mutagenesis. This phenomenon has been studied in a few bacterial models, including Escherichia coli and Bacillus subtilis; however, the underlying mechanisms between these systems differ. For instance, RecA is not required for stationary-phase mutagenesis in B. subtilis like it is in E. coli. In B. subtilis, RecA is essential to the process of genetic transformation in the subpopulation of cells that become naturally competent in conditions of stress. Interestingly, the transcriptional regulator ComK, which controls the development of competence, does influence the …

On The Distribution Of Genetic Variation In Ecological Communities, Isaac Overcast

Dissertations, Theses, and Capstone Projects

Biodiversity in ecological communities is structured hierarchically across spatial and temporal scales. Many open questions remain as to how this structure accumulates. For example, what are the relative contributions of dispersal versus in situ speciation? Or, how important are stochastic drift versus deterministic processes? Up to this point, these questions have been investigated by isolated disciplines (e.g. macroecology, comparative phylogeography, macroevolution) using tools and data that tend to focus on only one axis of community scale data (e.g. phylogenies, relative abundances, and/or trait information). Yet we know that there are feedbacks among processes that respond on short, medium, and long …

Essential Role Of The Crk Family-Dosage In Digeorge-Like Anomaly And Metabolic Homeostasis, Akira Imamoto, Sewon Ki, Leiming Li, Kazunari Iwamoto, Venkat Maruthamuthu, John Devany, Ocean Lu, Suxiang Zhang, Takuji Yamada, Akiyoshi Hirayama, Shinji Fukuda, Yutaka Suzuki, Mariko Okada

Mechanical & Aerospace Engineering Faculty Publications

CRK and CRKL (CRK-like) encode adapter proteins with similar biochemical properties. Here, we show that a 50% reduction of the family-combined dosage generates developmental defects, including aspects of DiGeorge/del22q11 syndrome in mice. Like the mouse homologs of two 22q11.21 genes CRKL and TBX1, Crk and Tbx1 also genetically interact, thus suggesting that pathways shared by the three genes participate in organogenesis affected in the syndrome. We also show that Crk and Crkl are required during mesoderm development, and Crk/Crkl deficiency results in small cell size and abnormal mesenchyme behavior in primary embryonic fibroblasts. Our systems-wide analyses reveal impaired …

Using Genetics To Inform Restoration And Predict Resilience In Declining Populations Of A Keystone Marine Sponge, Sarah M. Griffiths, Evelyn D. Taylor-Cox, Donald C. Behringer, Mark J. Butler Iv, Richard F. Preziosi

Biological Sciences Faculty Publications

Genetic tools can have a key role in informing conservation management of declining populations. Genetic diversity is an important determinant of population fitness and resilience, and can require careful management to ensure sufficient variation is present. In addition, population genetics data reveal patterns of connectivity and gene flow between locations, enabling mangers to predict recovery and resilience, identify areas of local adaptation, and generate restoration plans. Here, we demonstrate a conservation genetics approach to inform restoration and management of the loggerhead sponge (Spheciospongia vesparium) in the Florida Keys, USA. This species is a dominant, habitat-forming component of marine ecosystems in …

Identification Of Uncommon Antibiotic-Producing Illinois Soil Isolates, Lesly Muniz, Dr. Lori Scott

Identifying and Characterizing Novel Antibiotic Producing Microbes From the Soil

This project is a collaboration with the Tiny Earth Project Initiative (TEPI), which is a global network of educators and students focused on student sourcing antibiotic discovery from the soil. We researched tester strains B. subtilis and E. coli from the soil isolates obtained. We further verified if the isolates were common antibiotic bacteria. Unfortunately, this project heavily relied on biochemical tests, colony morphology, and Gram stains to reject or fail to reject our hypothesis. Our goal was to discover new antibiotic-producing bacteria that could be beneficial in combating ESKAPE strains. A proper PCR and DNA extraction would be required …

Isolated Antibiotic Producing Bacteria In Local Soil Samples Determined To Be Bacillus, Cassidy Potter, Dr. Lori Scott

Identifying and Characterizing Novel Antibiotic Producing Microbes From the Soil

Nosocomial pathogens are multi-drug resistant to antibiotics that fight bacterial infections posing danger to the public health, the most dangerous of them being the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). This project is a collabortaion with the TIny Earth Project Initiative (TEPI), which is a global network of educators and students focused on studentsourcing antibiotic discovery from the soil. TEPI allows student-led research on local soil samples from Bettendorf, IA to discover potential novel antibiotic producing bacteria that could potentially treat ESKAPE pathogens and reduce public health risk. Two soil isolates …

Screening For Antibiotic-Producers In Soil From A Garden, Long Tran, Dr. Lori Scott

Identifying and Characterizing Novel Antibiotic Producing Microbes From the Soil

Multidrug-resistant pathogens are the leading cause of nosocomial infection, which killed more than 30,000 people in the United States every year. Among these, ESKAPE strains bugs, which comprise six highly drug-resistant bacteria, pose the greatest challenge to the healthcare system. In order to fight the antibiotic-resistant crises, novel antibiotic-producers must be discovered. This project is a collaboration with the Tiny Earth Project Initiative (TEPI), which is a global network of educators and students focused on student sourcing antibiotic discovery from the soil. Pseudomonas was revealed to produce a zone of inhibition against Bacillus subtilis on LB media. The next step …

Pseudomonas And Bacillus Soil Isolates Produce Antibiotics, Chelsea Brandt, Dr. Lori Scott

Identifying and Characterizing Novel Antibiotic Producing Microbes From the Soil

The recent emergence of antibiotic resistance bacterial strains presents a significant challenge and threat to human healthcare. While new methods of treatment such as bacteriophage therapy and combinations of existing antibiotics are being researched, the human population is in dire need of new antibiotics to replace those that are ineffective. This research addresses this need by identifying antibiotic producing bacteria in a soil sample from Davenport, IA. This project is a collaboration with the Tiny Earth Project Initiative (TEPI), which is a global network of educators and students focused on studentsourcing antibiotic discovery from soil. Microbiology lab techniques and 16S …

Identification Of Antibiotic Producing Soil Bacteria Against Bacillus Subtilis, Morgan Brockhouse, Dr. Lori Scott

Identifying and Characterizing Novel Antibiotic Producing Microbes From the Soil

This project is a collaboration with the Tiny Earth Project Initiative (TEPI), which is a global network of educators and students focused on student-sourcing antibiotic discovery from soil. Individual strains of soil bacteria were isolated and produced antibiotic against Bacillus subtilis. Two of these samples were sequenced using the 16S rRNA gene to reveal they are very closely related to the genus Pseudomonas.

"When The Enemy Drew Our Attention": Reconsidering Prior Restraint In The Context Of Dual Use Research Of Concern, Caine Caverly

William & Mary Bill of Rights Journal

Through 2016 and 2017, a team led by Canadian virologist David Evans, and funded by an American pharmaceutical company, attempted to synthesize the previously extinct horsepox virus. After just six months and an expenditure of $100,000, the research team was able to successfully construct the virus “using only commercially available information, technology and tools.” In January of 2018, the team went on to publish their information in an American-based journal, PLOS ONE.

The publication was controversial because it included a potential “blueprint” for the synthesis of a genetic strand in the same viral family as the highly lethal, albeit eradicated, …

Human Genetics, Psychotropic Drugs, And Acts Of Violence, Selma Jolanda Eikelenboom-Schieveld

Electronic Theses and Dissertations

From the start of the use of psychoactive prescription medications in the 1950s, physicians reported paradoxical adverse reactions, ranging from newly developing depressions to an increase in existing mood disorders, and extremely violent and bizarre acts of suicide and homicide. In this research, it is hypothesized that the pharmacological properties of the prescribed drugs or the interaction between the drugs and the enzymes that are primarily responsible for their metabolism (cytochrome P450s) could cause these reactions. Given that acts of violence could be medication-induced, the role of the rate of drug metabolism is discussed. Genetic testing of certain CYP450s could …

A Look At Gene Control: Tracking The Ccnd1 Gene, Bryan Anders

Mahurin Honors College Capstone Experience/Thesis Projects

Cancer occurs when the cell does not properly control its own cell cycle. It then replicates in an out of control fashion leading to the death of various organs and then the demise of the organism as a whole. As it seems to have always been a problem for cell-based life, certain safeguards against cancer have been evolved over time. One such method comes in the form of prevention via cyclin proteins, which are encoded from cyclin genes. The gene that is the focus of this research is the CCND1, or cyclin D1, gene that controls the progression through various …