Genetics and Genomics Commons^™

Multi-Ancestry Genome-Wide Association Study Of Cannabis Use Disorder Yields Insight Into Disease Biology And Public Health Implications, Daniel F Levey, Marco Galimberti, Joseph D Deak, Frank R Wendt, Arjun Bhattacharya, Dora Koller, Kelly M Harrington, Rachel Quaden, Emma C Johnson, Priya Gupta, Mahantesh Biradar, Max Lam, Megan Cooke, Veera M Rajagopal, Stefany L L Empke, Hang Zhou, Yaira Z Nunez, Henry R Kranzler, Howard J Edenberg, Arpana Agrawal, Jordan W Smoller, Todd Lencz, David M Hougaard, Anders D Børglum, Ditte Demontis, Veterans Affairs Million Veteran Program, J Michael Gaziano, Michael J Gandal, Renato Polimanti, Murray B Stein, Joel Gelernter

Faculty, Staff and Student Publications

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within …

Design And Characterization Of A Novel Eef2k Degrader With Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer, Changxin Zhong, Rongfeng Zhu, Ting Jiang, Sheng Tian, Xiaobao Zhao, Xiaoya Wan, Shilong Jiang, Zonglin Chen, Rong Gong, Linhao He, Jin-Ming Yang, Na Ye, Yan Cheng

Markey Cancer Center Faculty Publications

Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the …

A Study Of The Snd1/Prmt5 Axis In Liver Cancer By Genetic Mouse Models, Tanner Wright, Tanner Wright

Dissertations and Theses (Open Access)

Arginine methylation is an essential post-translational modification (PTM) in cells. Protein arginine methyltransferase 5 (PRMT5) is the primary enzyme that catalyzes symmetric dimethyl arginine (SDMA) and requires methylosome protein 50 (MEP50) for stability and enzymatic activity which are necessary for life and development. Effector proteins bind different types of PTM’s to facilitate signaling. Staphylococcal nuclease Tudor domain containing 1 (SND1) is an effector that specifically binds SDMA via its single C-terminal Tudor domain. Both SND1 and PRMT5 have been implicated in hepatocellular carcinoma (HCC). SND1 has been confirmed as a driver of HCC using genetically engineered mouse models (GEMMs), though, …

A Double-Robust Test For High-Dimensional Gene Coexpression Networks Conditioning On Clinical Information, Maomao Ding, Ruosha Li, Jin Qin, Jing Ning

Faculty, Staff and Student Publications

It has been increasingly appealing to evaluate whether expression levels of two genes in a gene coexpression network are still dependent given samples' clinical information, in which the conditional independence test plays an essential role. For enhanced robustness regarding model assumptions, we propose a class of double-robust tests for evaluating the dependence of bivariate outcomes after controlling for known clinical information. Although the proposed test relies on the marginal density functions of bivariate outcomes given clinical information, the test remains valid as long as one of the density functions is correctly specified. Because of the closed-form variance formula, the proposed …

Analyzing Extracellular Vesicles For Disease Monitoring In Metastatic Colorectal Cancer Patients, Vahid Bahrambeigi

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Metastases are the main cause of cancer-related death, and the most frequent metastatic sites in patients with CRCs are liver and lung. To confirm the diagnosis of metastatic CRC (mCRCs) and to classify mCRCs, tumor biopsy of a suspected metastasis is often required. The consensus molecular subtype (CMS) classification which is based on gene expression profiles of CRC tumor specimens, is a predictive factor for treatment outcomes of standard chemotherapies for mCRCs. The practicality of repeated tumor biopsies for disease monitoring in mCRC patients is …

Genomic Characterization Of Adolescent And Young Adult Cancers: Investigation Of Ewing Sarcoma Susceptibility And Chornobyl Thyroid Tumors, Olivia Lee

Dissertations and Theses (Open Access)

Adolescent and young adult (AYA) cancers, diagnosed between the ages of 15 and 39, can exhibit distinctive genetic and molecular characteristics. Reported epidemiologic findings and treatment outcomes based on pediatric and adult cancer studies are often not suitable for application to the AYA population, underscoring the need for more thorough genomic research. Advances in sequencing technologies have enabled comprehensive analyses of complex genomic characteristics of AYA cancers, crucial for understanding the underlying biology of these malignancies. Here, I have utilized advanced sequencing techniques and integrated analytic approaches to describe important genomic features in two different AYA cancer types: Ewing Sarcoma …

Effect Of Plant Genotype On Plant-Microbe Interactions And Multi-Generation Ecosystem Selection Of Microbial Communities Associated With Plant Biomass In Arabidopsis Thaliana, Nachiket Shankar

Graduate Doctoral Dissertations

The microbiome's role in shaping host phenotypes is a critical area of investigation, with implications for ecology, evolution, and host health. Dynamic plant-microbe interactions are influenced by factors like soil type, environment, and genotype. Understanding their impact on microbial communities is key for tailored plant benefits. An artificial ecosystem selection experiment was done for eight generations with Arabidopsis thaliana Ler and Cvi. This revealed distinct microbial communities shaped by genotypes and biomass treatments. Initially, environment dominated, but over time, genotype and biomass gained influence, explaining ~40% of the variation. Moreover, genotype-specific rhizobacterial associations were observed, enhancing understanding of community dynamics …

The Application Of Simultaneous Mainstem Bronchus Dilation With Pulmonary Artery Stenting In The Context Of Hypoplastic Left Heart Syndrome, Sylwia Hasterok, Thomas G Scott, Devin G Roller, Adam Spencer, Arun B Dutta, Kizhakke M Sathyan, Daniel E Frigo, Michael J Guertin, Daniel Gioeli

Faculty, Staff and Student Publications

The clinical success of combined androgen deprivation therapy (ADT) and radiotherapy (RT) in prostate cancer created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at a steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes …

Type 2 Diabetes Modifies The Association Of Cad Genomic Risk Variants With Subclinical Atherosclerosis, Natalie R Hasbani, Kenneth E Westerman, Soo Heon Kwak, Han Chen, Xihao Li, Daniel Di Corpo, Jennifer Wessel, Joshua C Bis, Chloè Sarnowski, Peitao Wu, Lawrence F Bielak, Xiuqing Guo, Nancy Heard-Costa, Gregory L Kinney, Michael C Mahaney, May E Montasser, Nicholette D Palmer, Laura M Raffield, James G Terry, Lisa R Yanek, Jessica Bon, Donald W Bowden, Jennifer A Brody, Ravindranath Duggirala, David R Jacobs, Rita R Kalyani, Leslie A Lange, Braxton D Mitchell, Jennifer A Smith, Kent D Taylor, April P Carson, Joanne E Curran, Myriam Fornage, Barry I Freedman, Stacey Gabriel, Richard A Gibbs, Namrata Gupta, Sharon L R Kardia, Brian G Kral, Zeineen Momin, Anne B Newman, Wendy S Post, Karine A Viaud-Martinez, Kendra A Young, Lewis C Becker, Alain G Bertoni, John Blangero, John J Carr, Katherine Pratte, Bruce M Psaty, Stephen S Rich, Joseph C Wu, Rajeev Malhotra, Patricia A Peyser, Alanna C Morrison, Ramachandran S Vasan, Xihong Lin, Jerome I Rotter, James B Meigs, Alisa K Manning, Paul S De Vries

Faculty, Staff and Student Publications

BACKGROUND: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.

METHODS: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 …

Clinical Exome Sequencing Efficacy And Phenotypic Expansions Involving Anomalous Pulmonary Venous Return, Emily A Huth, Xiaonan Zhao, Nichole Owen, Pamela N Luna, Ida Vogel, Inger L H Dorf, Shelagh Joss, Jill Clayton-Smith, Michael J Parker, Jacoba J Louw, Marc Gewillig, Jeroen Breckpot, Alison Kraus, Erina Sasaki, Usha Kini, Trent Burgess, Tiong Y Tan, Ruth Armstrong, Katherine Neas, Giovanni B Ferrero, Alfredo Brusco, Wihelmina S Kerstjens-Frederikse, Julia Rankin, Lindsey R Helvaty, Benjamin J Landis, Gabrielle C Geddes, Kim L Mcbride, Stephanie M Ware, Chad A Shaw, Seema R Lalani, Jill A Rosenfeld, Daryl A Scott

Faculty, Staff and Students Publications

Anomalous pulmonary venous return (APVR) frequently occurs with other congenital heart defects (CHDs) or extra-cardiac anomalies. While some genetic causes have been identified, the optimal approach to genetic testing in individuals with APVR remains uncertain, and the etiology of most cases of APVR is unclear. Here, we analyzed molecular data from 49 individuals to determine the diagnostic yield of clinical exome sequencing (ES) for non-isolated APVR. A definitive or probable diagnosis was made for 8 of those individuals yielding a diagnostic efficacy rate of 16.3%. We then analyzed molecular data from 62 individuals with APVR accrued from three databases to …

Complex Evolutionary History With Extensive Ancestral Gene Flow In An African Primate Radiation, Axel Jensen, Frances Swift, Dorien De Vries, Robin M D Beck, Lukas F K Kuderna, Sascha Knauf, Idrissa S Chuma, Julius D Keyyu, Andrew C Kitchener, Kyle Farh, Jeffrey Rogers, Tomas Marques-Bonet, Kate M Detwiler, Christian Roos, Katerina Guschanski

Faculty, Staff and Students Publications

Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented …

Biallelic Med27 Variants Lead To Variable Ponto-Cerebello-Lental Degeneration With Movement Disorders, Reza Maroofian, Rauan Kaiyrzhanov, Elisa Cali, Mina Zamani, Maha S Zaki, Matteo Ferla, Domenico Tortora, Saeid Sadeghian, Saadia Maryam Saadi, Uzma Abdullah, Ehsan Ghayoor Karimiani, Stephanie Efthymiou, Gözde Yeşil, Shahryar Alavi, Aisha M Al Shamsi, Homa Tajsharghi, Mohamed S Abdel-Hamid, Nebal Waill Saadi, Fuad Al Mutairi, Lama Alabdi, Christian Beetz, Zafar Ali, Mehran Beiraghi Toosi, Sabine Rudnik-Schöneborn, Meisam Babaei, Pirjo Isohanni, Jameel Muhammad, Sheraz Khan, Maha Al Shalan, Scott E Hickey, Daphna Marom, Emil Elhanan, Manju A Kurian, Dana Marafi, Alihossein Saberi, Mohammad Hamid, Robert Spaull, Linyan Meng, Seema Lalani, Shazia Maqbool, Fatima Rahman, Jürgen Seeger, Timothy Blake Palculict, Tracy Lau, David Murphy, Niccolo Emanuele Mencacci, Katharina Steindl, Anais Begemann, Anita Rauch, Sinan Akbas, Ayça Dilruba Aslanger, Vincenzo Salpietro, Hammad Yousaf, Shay Ben-Shachar, Katarina Ejeskär, Aida I Al Aqeel, Frances A High, Amy E Armstrong-Javors, Seyed Mohammadsaleh Zahraei, Tahereh Seifi, Jawaher Zeighami, Gholamreza Shariati, Alireza Sedaghat, Samaneh Noroozi Asl, Mohmmad Shahrooei, Giovanni Zifarelli, Lydie Burglen, Claudia Ravelli, Johannes Zschocke, Ulrich A Schatz, Maryam Ghavideldarestani, Walaa A Kamel, Hilde Van Esch, Annette Hackenberg, Jenny C Taylor, Lihadh Al-Gazali, Peter Bauer, Joseph J Gleeson, Fowzan Sami Alkuraya, James R Lupski, Hamid Galehdari, Reza Azizimalamiri, Wendy K Chung, Shahid Mahmood Baig, Henry Houlden, Mariasavina Severino

Faculty, Staff and Students Publications

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± …

Birth Defects In Offspring Of Adolescent And Young Adults With A History Of Cancer: A Population-Based Study Of 27,000 Women, Caitlin C Murphy, Andrea C Betts, Sandi L Pruitt, Barbara A Cohn, L Aubree Shay, Marlyn A Allicock, Jennifer S Wang, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: We examined birth defects in offspring of adolescent and young adult (AYA) women with a history of cancer (age 15-39 years at diagnosis).

METHODS: We identified AYA women diagnosed with cancer between January 1, 1999, and December 31, 2015 using population-based data from the Texas Cancer Registry; data were linked with live birth and fetal death certificates through December 31, 2016 to identify singleton births to AYA women after diagnosis. Birth defects in offspring through age 12 months were ascertained from the Texas Birth Defects Registry. We estimated risk of birth defects in offspring of AYA women and women …

Assessment Of Immune Responses To A Trivalent Pichinde Virus-Vectored Vaccine Expressing Hemagglutinin Genes From Three Co-Circulating Influenza A Virus Subtypes In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Hinh Ly, Yuying Liang, Hiep Vu

Department of Animal Science: Faculty Publications

Pichinde virus (PICV) can infect several animal species and has been developed as a safe and effective vaccine vector. Our previous study showed that pigs vaccinated with a recombinant PICV-vectored vaccine expressing the hemagglutinin (HA) gene of an H3N2 influenza A virus of swine (IAV-S) developed virus-neutralizing antibodies and were protected against infection by the homologous H3N2 strain. The objective of the current study was to evaluate the immunogenicity and protective efficacy of a trivalent PICV-vectored vaccine expressing HA antigens from the three co-circulating IAV-S subtypes: H1N1, H1N2, and H3N2. Pigs immunized with the trivalent PICV vaccine developed virus-neutralizing (VN) …

Potential Hybridization Among Two Species Of California Salvia, Ellie Morrison, Bryan Drew

Transactions of the Nebraska Academy of Sciences and Affiliated Societies

Hybridization among plants is fairly common, particularly in instances where closely related species are sympatric. One example of a group in which hybridization has been detected is the genus Salvia (Lamiaceae; mint family). Salvia is a diverse genus consisting of about 1,000 species and is defined primarily by having only two stamens, each with their anther sacs separated by elongated connective tissue. The genus has diversity centers around the world, including Southwest Asia and the Mediterranean region, Mexico/Central America, northern and central South America, and temperate East Asia. The genus also has a smaller species radiation of 19 species in …

Functional And Evolutionary Analysis Of Host Synaptogyrin-2 In Porcine Circovirus Type 2 Susceptibility, Lianna R. Walker, Hiep L. Vu, Kristi Montooth, Daniel C. Ciobanu

Department of Animal Science: Faculty Publications

Mammalian evolution has been influenced by viruses for millions of years, leaving signatures of adaptive evolution within genes encoding for viral interacting proteins. Synaptogyrin- 2 (SYNGR2) is a transmembrane protein implicated in promoting bacterial and viral infections. A genome-wide association study of pigs experimentally infected with porcine circovirus type 2b (PCV2b) uncovered a missense mutation (SYNGR2 p.Arg63Cys) associated with viral load. In this study, CRISPR/Cas9-mediated gene editing of the porcine kidney 15 (PK15, wtSYNGR2^+p.63Arg) cell line generated clones homozygous for the favorable SYNGR2 p.63Cys allele (emSYNGR2^+p.63Cys). Infection of edited clones resulted …

Single-Cell Multiomics Of The Human Retina Reveals Hierarchical Transcription Factor Collaboration In Mediating Cell Type-Specific Effects Of Genetic Variants On Gene Regulation, Jun Wang, Xuesen Cheng, Qingnan Liang, Leah A Owen, Jiaxiong Lu, Yiqiao Zheng, Meng Wang, Shiming Chen, Margaret M Deangelis, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

BACKGROUND: Systematic characterization of how genetic variation modulates gene regulation in a cell type-specific context is essential for understanding complex traits. To address this question, we profile gene expression and chromatin accessibility in cells from healthy retinae of 20 human donors through single-cell multiomics and genomic sequencing.

RESULTS: We map eQTL, caQTL, allelic-specific expression, and allelic-specific chromatin accessibility in major retinal cell types. By integrating these results, we identify and characterize regulatory elements and genetic variants effective on gene regulation in individual cell types. The majority of identified sc-eQTLs and sc-caQTLs display cell type-specific effects, while the cis-elements containing genetic …

Lactic Acid Bacterial Surface Display Of Scytovirin Inhibitors For Anti-Ebolavirus Infection, Joshua Wiggins, Ngan Nguyen, Wenzhong Wei, Leah Liu Wang, Haley Hollingsead Olson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, …

Clinical, Genetic And Structural Delineation Of Rpl13-Related Spondyloepimetaphyseal Dysplasia Suggest Extra-Ribosomal Functions Of El13, Prince Jacob, Hillevi Lindelöf, Cecilie F Rustad, Vernon Reid Sutton, Shahida Moosa, Prajna Udupa, Anna Hammarsjö, Gandham Srilakshmi Bhavani, Dominyka Batkovskyte, Kristian Tveten, Ashwin Dalal, Eva Horemuzova, Ann Nordgren, Emma Tham, Hitesh Shah, Else Merckoll, Laura Orellana, Gen Nishimura, Katta M Girisha, Giedre Grigelioniene

Faculty, Staff and Students Publications

Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, …

Clinical, Genetic And Structural Delineation Of Rpl13-Related Spondyloepimetaphyseal Dysplasia Suggest Extra-Ribosomal Functions Of El1, Prince Jacob, Hillevi Lindelöf, Cecilie F Rustad, Vernon Reid Sutton, Shahida Moosa, Prajna Udupa, Anna Hammarsjö, Gandham Srilakshmi Bhavani, Dominyka Batkovskyte, Kristian Tveten, Ashwin Dalal, Eva Horemuzova, Ann Nordgren, Emma Tham, Hitesh Shah, Else Merckoll, Laura Orellana, Gen Nishimura, Katta M Girisha, Giedre Grigelioniene

Faculty, Staff and Students Publications

Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, …

Announcing The Adsa Loyalty Program And Other Developments, Paul J. Kononoff, Jessica A.A. Mcart

Department of Animal Science: Faculty Publications

At the core of scientific peer review is “sharing insights and information among peers so that researchers can learn from each other and move science forward” (Schultz, 2020). This year will mark the 107th year of existence for the Journal of Dairy Science. Over this time, the journal has been a stable pillar of ADSA, the dairy sector, and the scientific community. Several years ago, Kent Anderson published an article (Anderson, 2016) in the Scholarly Kitchen, an online blog of the Society for Scholarly Publishing, and discussed the vibrant community that makes up virtually all successful scholarly publications. Anderson wrote …

Multi-Omics Reveals Largely Distinct Transcript- And Protein-Level Responses To The Environment In An Intertidal Mussel, Lani U. Gleason, Florian J. Fekete, Richelle L. Tanner, W. Wesley Dowd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Organismal responses to stressful environments are influenced by numerous transcript- and protein-level mechanisms, and the relationships between expression changes at these levels are not always straightforward. Here, we used paired transcriptomic and proteomic datasets from two previous studies from gill of the California mussel, Mytilus californianus, to explore how simultaneous transcript and protein abundance patterns may diverge under different environmental scenarios. Field-acclimatized mussels were sampled from two disparate intertidal sites; individuals from one site were subjected to three further treatments (common garden, low-intertidal or high-intertidal outplant) that vary in temperature and feeding time. Assessing 1519 genes shared between …

Association Of The Abcb1 Gene Polymorphism And Infertility In Azoospermia Males In Iraqi Kurdish Population, Muhsin Jamil Abdulwahid

Polytechnic Journal

The P-glycoprotein (P-gp), a product of the ABCB1 gene (ATP binding cassette subfamily B member 1) or MDR: multiple drug resistance 1 gene is expressed in various parts of the human body, like testis. The ABCB1 gene has several single nucleotide polymorphisms in its exons and introns that have been discovered. This study used DNA sequencing and polymerase chain reaction (PCR) to discover and characterize nucleotide variations in exons 27 of the ABCB1 gene in seven infertile and three normally fertile individuals. In this study, a set of primers were designed using the NCBI primer designing tool to amplify 394bp …

A Novel Subcluster Of Closely Related Bacillus Phages With Distinct Tail Fiber/Lysin Gene Combinations, Rachel E. Loney, Veronique A. Delesalle, Brianne E. Chaudhry, Megan Czerpak, Alexandra A. Guffey, Leo Goubet-Mccall, Michael Mccarty, Madison S. Strine, Natalie T. Tanke, Albert C. Vill, Gregory P. Krukonis

Biology Faculty Publications

Bacteriophages (phages) are the most numerous entities on Earth, but we have only scratched the surface of describing phage diversity. We isolated seven Bacillus subtilis phages from desert soil in the southwest United States and then sequenced and characterized their genomes. Comparative analyses revealed high nucleotide and amino acid similarity between these seven phages, which constitute a novel subcluster. Interestingly, the tail fiber and lysin genes of these phages seem to come from different origins and carry out slightly different functions. These genes were likely acquired by this subcluster of phages via horizontal gene transfer. In conjunction with host range …

Engaging Students In A Genetics Course-Based Undergraduate Research Experience Utilizing Caenorhabditis Elegans In Hybrid Learning To Explore Human Disease Gene Variants, Natalie Forte, Virginia Veasey, Bethany Christie, Amira Carter, Marli Hanks, Alan Holderfield, Taylor Houston, Anil Challa, Ashley Turner

Research, Publications & Creative Work

Genetic analysis in model systems using bioinformatic approaches provides a rich context for a concrete and conceptual understanding of gene structure and function. With the intent to engage students in research and explore disease biology utilizing the nematode Caenorhabditis elegans model, we developed a semester-long course-based undergraduate research experience (CURE) in a hybrid (online/in-person) learning environment—the gene-editing and evolutionary nematode exploration CURE (GENE-CURE). Using a combination of bioinformatic and molecular genetic tools, students performed structure-function analysis of disease-associated variants of uncertain significance (VUS) in human orthologs. With the aid of a series of workshop-style research sessions, students worked in teams …

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

Using Encrypted Genotypes And Phenotypes For Collaborative Genomic Analyses To Maintain Data Confidentiality, Tianjing Zhao, Fangyi Wang, Richard Mott, Jack Dekkers, Hao Cheng

Department of Animal Science: Faculty Publications

To adhere to and capitalize on the benefits of the FAIR (findable, accessible, interoperable, and reusable) principles in agricultural genome- to-phenome studies, it is crucial to address privacy and intellectual property issues that prevent sharing and reuse of data in research and industry. Direct sharing of genotype and phenotype data is often prohibited due to intellectual property and privacy concerns. Thus, there is a pressing need for encryption methods that obscure confidential aspects of the data, without affecting the outcomes of certain statistical analyses. A homomorphic encryption method for genotypes and phenotypes (HEGP) has been proposed for single-marker regression in …

Brown Anole (Anolis Sagrei) Hoxa5: Insights Into The Divergence Of Hoxa5 Gene Expression And Regulation Across Evolutionarily Divergent Gnathostome Vertebrates, Jennifer A. Lange, Amber L. Rittgers, Adam Davis

Georgia Journal of Science

Hox genes are evolutionarily conserved developmental regulatory genes that function, in part, to pattern the anterior-posterior (AP) axis of organs and organ systems during animal embryonic development. Hoxa5, specifically, is shown to be expressed in the spinal cord, somites, or transient compartments giving rise to the vertebrae and ribs, developing gut, lungs, and limbs of the mouse (Mus musculus). The cis-regulatory elements (CREs), or short DNA sequences, that direct Hoxa5 expression in these embryonic domains have been mapped and functionally tested in the mouse as well. Similar Hoxa5 expression patterns have been observed in chicken ( …

An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field …

Effect Of Ploidy On Salinity And Temperature Tolerance In Early Life Stages Of The Eastern Oyster (Crassostrea Virginica), Christian Boudreaux, Jessica Pruett, Alexz Carpenter, Kristie Willett, Deborah Gochfeld

Honors Theses

The U.S. Gulf of Mexico contains the largest remaining wild oyster fishery in the world, but populations have declined in recent decades. A growing interest in off-bottom aquaculture that relies on triploid eastern oysters (Crassostrea virginica) has emerged in the Gulf region, yet these faster growing oysters suffer high mortality as adults during low salinity events (< 5 ppt) in warmer summer months. The combined effects of salinity and temperature stressors on early life stages of triploid oysters are unknown. Early life stages are particularly crucial to understand because triploid oysters do not occur naturally and must be reared in hatchery settings, requiring appropriate water conditions to yield the greatest survival and growth. Thus, we tested the effects of different temperatures (28oC and 32oC) and salinities (5, 10, and 15 ppt) on diploid and triploid oysters at three critical production stages: veliger, pediveliger, and spat. Veliger survival was significantly lower for triploids relative to diploid oysters at all experimental conditions, but triploid veligers had faster growth than diploids at 32oC and 15 ppt. Pediveliger settlement was not affected by ploidy type and only reduced at high temperature (32oC) and the lowest salinity (5 ppt). Diploid spat showed highest survival at 28oC and 15 ppt, while triploids survived best at 32oC and 15 ppt. Triploid spat attained greater shell height compared to diploids in our 6-day exposures, but growth decreased for both ploidies at lower salinities. At the salinity and temperature levels examined, diploid early life stages performed best at 28oC and 15 ppt, whereas triploids were more successful at 32oC and 15 ppt. A broader understanding of the combined effects of environmental stressors will improve the success of hatchery production yields and the resulting economic and environmental benefits of the oyster industry.