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 …

Effects Of A Vitamin And Mineral Bolus On Beef Heifer Feedlot Performance, Feeding Behavior, Carcass Characteristics, And Liver Mineral Concentrations, Kacie L. Mccarthy, Sarah R. Underdahl, Carl R. Dahlen

Department of Animal Science: Faculty Publications

Crossbred beef heifers (n = 23; initial body weight [BW] = 370 ± 12 kg) housed at the North Dakota State University Beef Cattle Research Complex in Fargo, North Dakota, were used to evaluate the effects of a 250-d slow-release vitamin and mineral bolus on feedlot performance, feeding behavior, carcass characteristics, and liver mineral concentrations. Heifers were assigned to one of two treatments: 1) received no supplemental mineral or vitamin (CON, n = 12 or 2) received two boluses on day 0 (minimum of 3,740 mg Ca, 16,456 mg Mg, 112 mg Na, 11,220 mg Cu, 2,995 mg I, …

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 …

Environmental Dna Metabarcoding Detects Mammal Use Of Stock Tanks And Natural Springs On The Prescott National Forest, K. A. Smith, Berenice Carreras Mendiolea, C. E. Benson, F. B. Anaya

Discovery Day - Prescott

Recent research has shown the viability of environmental DNA (eDNA) analysis as a tool for identifying species presence in aquatic ecosystems. However, there is limited research indicating the feasibility of eDNA as a survey tool in water sources such as springs and stock tanks. Because of the scarcity of water in the high desert landscape of Arizona, natural springs and stock tanks are an important water resource. In this study, we examined whether 16S rRNA metabarcoding could detect mammal eDNA in springs and stock tanks in the Prescott National Forest. During summer 2019, we collected and analyzed water samples at …

Relative Model Fit Does Not Predict Topological Accuracy In Single-Gene Protein Phylogenetics, Stephanie J. Spielman

College of Science & Mathematics Departmental Research

It is regarded as best practice in phylogenetic reconstruction to perform relative model selection to determine an appropriate evolutionary model for the data. This procedure ranks a set of candidate models according to their goodness of fit to the data, commonly using an information theoretic criterion. Users then specify the best-ranking model for inference. Although it is often assumed that better-fitting models translate to increase accuracy, recent studies have shown that the specific model employed may not substantially affect inferences. We examine whether there is a systematic relationship between relative model fit and topological inference accuracy in protein phylogenetics, using …

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 …

Diversity, Function And Regulation Of Cell Surface And Intracellular Immune Receptors In Solanaceae, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

The first layer of the plant immune system comprises plasma membrane-localized receptor proteins and intracellular receptors of the nucleotide-binding leucine-rich repeat protein superfamily. Together, these immune receptors act as a network of surveillance machines in recognizing extracellular and intracellular pathogen invasion-derived molecules, ranging from conserved structural epitopes to virulence-promoting effectors. Successful pathogen recognition leads to physiological and molecular changes in the host plants, which are critical for counteracting and defending against biotic attack. A breadth of significant insights and conceptual advances have been derived from decades of research in various model plant species regarding the structural complexity, functional diversity and …

Npgreat: Hybrid Assembly Of Human Subtelomeres With The Use Of Nanopore And Linked-Read Datasets, Eleni Adam, Desh Ranjan, Harold Riethman

College of Sciences Posters

The telomeres are vitally important regions that are located at the tips of the chromosomes. Their dysfunction, caused by length shortening can lead to senescent cells, which in turn cause age-related diseases, including cancer. The subtelomeres, located next to the telomeres, possess the critical role of regulating the adjacent telomere lengths. Even after many years of research, human subtelomeres have proven to be very hard to assemble due to their morphology. In order to overcome these problems, the hybrid assembly method we develop utilizes two of the latest available types of data, which complement each other: Linked-Reads and ultralong Nanopore …

Synthesis And Molecular Mechanics Study Of Platinum Triamine Complex With N-Acetyl-L-Methionine And Guanosine 5’Monophosphate, Nitin Tanajirao Katare

Masters Theses & Specialist Projects

Cisplatin and its analogues have been used and tested over decades for cancer treatment, but because of the serious side effects, it is important to find ways to overcome those side effect by synthesizing a novel platinum molecule. We have synthesized triamine complex and conducted its reaction with biomolecules such as 5’GMP and Methionine in the lab as well as conducted molecular mechanics (MM). MM methods are used for predicting and designing new structures and properties, and to model geometries of small molecules. MM and dynamics calculations have been used to study the 9 Ethylguanine and N-Ac-Lmethionine complexes with platinum …

Delineation Of Undescribed, Morphologically Cryptic Cave Beetles Of The Pseudanophthalmus Pubescens Species-Group (Coleoptera: Carabidae: Trechinae), Jedidiah John Nixon

Masters Theses & Specialist Projects

The genus Pseudanophthalmus Jeannel is a widespread and extremely diverse taxon of troglobiont beetle endemic to the karst of eastern North America, with its distribution centered in Tennessee and Kentucky. Despite lying near the heart of this region, the pubescens species-group was thought to contain many undescribed species. In this study, the validities of several of the late Dr. Thomas Barr’s unpublished putative new species in the pubescens-group were tested both morphologically and molecularly. Body measurements (length and width for head, thorax, and abdomen), as well as male genital morphology were compared to see if they reflected theorized species limits.. …

An Intergrative Ecological And Taxonomic Assessment Of The Stoneflies (Insecta, Plecoptera) Of The Black Mountains, North Carolina, Usa, Madeline Lake Metzger

Masters Theses & Specialist Projects

The Black Mountains are a part of the Blue Ridge region of the Appalachian Mountains and include Mount Mitchell, the highest peak east of the Mississippi River at 2,037 m (= 6,684 ft). A comprehensive inventory of the stonefly fauna was conducted between 2014-2019 within Mt. Mitchell State Park and adjacent Pisgah National Forest. Collections occurred seasonally from 44 unique locations, covering a broad range of stream sizes and elevations in the region. Sequencing of the mitochondrial cytochrome c oxidase subunit I (mtCOI) gene was completed to assist with making positive determinations to species for females of taxonomically challenging genera …

Publisher Correction: Memote For Standardized Genome-Scale Metabolic Model Testing., Christian Lieven, Moritz E Beber, Brett G Olivier, Frank T Bergmann, Meric Ataman, Parizad Babaei, Jennifer A Bartell, Lars M Blank, Siddharth Chauhan, Kevin Correia, Christian Diener, Andreas Dräger, Birgitta E Ebert, Janaka N Edirisinghe, José P Faria, Adam M Feist, Georgios Fengos, Ronan M T Fleming, Beatriz García-Jiménez, Vassily Hatzimanikatis, Wout Van Helvoirt, Christopher S Henry, Henning Hermjakob, Markus J Herrgård, Ali Kaafarani, Hyun Uk Kim, Zachary King, Steffen Klamt, Edda Klipp, Jasper J Koehorst, Matthias König, Meiyappan Lakshmanan, Dong-Yup Lee, Sang Yup Lee, Sunjae Lee, Nathan E Lewis, Filipe Liu, Hongwu Ma, Daniel Machado, Radhakrishnan Mahadevan, Paulo Maia, Adil Mardinoglu, Gregory L Medlock, Jonathan M Monk, Jens Nielsen, Lars Keld Nielsen, Juan Nogales, Intawat Nookaew, Bernhard O Palsson, Jason A Papin, Kiran R Patil, Mark Poolman, Nathan D Price, Osbaldo Resendis-Antonio, Anne Richelle, Isabel Rocha, Benjamín J Sánchez, Peter J Schaap, Rahuman S Malik Sheriff, Saeed Shoaie, Nikolaus Sonnenschein, Bas Teusink, Paulo Vilaça, Jon Olav Vik, Judith A H Wodke, Joana C Xavier, Qianqian Yuan, Maksim Zakhartsev, Cheng Zhang

Articles, Abstracts, and Reports

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Novel Landscape Of Nuclear Human Cdk2 Substrates Revealed By In Situ Phosphorylation., Yong Chi, John H Carter, Jherek Swanger, Alexander V Mazin, Robert L Moritz, Bruce E Clurman

Articles, Abstracts, and Reports

Cyclin-dependent kinase 2 (CDK2) controls cell division and is central to oncogenic signaling. We used an "in situ" approach to identify CDK2 substrates within nuclei isolated from cells expressing CDK2 engineered to use adenosine 5'-triphosphate analogs. We identified 117 candidate substrates, ~40% of which are known CDK substrates. Previously unknown candidates were validated to be CDK2 substrates, including LSD1, DOT1L, and Rad54. The identification of many chromatin-associated proteins may have been facilitated by labeling conditions that preserved nuclear architecture and physiologic CDK2 regulation by endogenous cyclins. Candidate substrates include proteins that regulate histone modifications, chromatin, transcription, and RNA/DNA metabolism. Many …

Assay Development For Isolation And Characterization Of Anticancer Properties Of Marine Fungi, Kyra Ricci

Honors Theses

Metabolites from fungi have potential use in the drug discovery process and have been used in the past to develop therapeutic agents for human use. Initial characterization of potential therapeutic properties of fungi is thus an important first step in identifying novel therapeutic compounds. In the present study, marine fungi were isolated from Myrtle Beach and assayed for anticancer properties using the soft agar colony formation assay in a 3D in vitro cellular environment. Many species were isolated from environmental samples, displaying unique morphologies and growth patterns. To optimize the soft agar assay in a six-well cell culture plate for …

Diversity Of The Major Histocompatibility Complex In African Penguins (Spheniscus Demersus) In Situ, Athena Schalk

Undergraduate Honors Thesis Projects

The Major Histocompatibility Complex (MHC) is responsible for the immune response in all jawed vertebrates and protects individuals against a variety of pathogens and diseases. Maintaining genetic diversity within the MHC exons is critical to protecting endangered species. African penguins (Spheniscus demersus) are in danger of losing their MHC diversity in isolated populations due to reductions in population size associated with environmental changes and human activity. This study analyzes the diversity within the exons in the DNA encoding the MHC by amplifying the exons through polymerase chain reaction and identifying alleles through denaturing gradient gel electrophoresis. Wild populations of …

The Era Of Commercialized Genetics: Examining The Intersection Of Dna, Identity, And Personal Origin, Joanna Hutchins 20

Honor Scholar Theses

No abstract provided.

Conservation Of Bta-Mir-29b And Its Effect On Human Gene Expression, Anna Barent, Katie Meinders, Daniel Gutzmann, Audrey L. Atkin

UCARE: Research Products

The purposeof this work was to examine conservation of miR-29b and its binding sites in target mRNAs as well as co-expression of bta-miR-29b in bovine milk exosomes and its target mRNAs in HEK293 cells

•miRNAs are often highly conserved across species and bind to target mRNAs resulting in decreased gene expression. •Bovine milk exosomes contain miRNAs and most of these miRNAs are identical to human miRNAs. •Because these miRNAs are so conserved, it is hypothesized that bovine miRNAs can regulate gene expression and be linked to disease risk.

•miR-29b is highly conserved. •Identified 17 experimentally validated miR-29b target mRNAs. •The …

Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

About 5.4 million basal and squamous cell skin cancers are diagnosed every year in the US. ΔNp63a, a member of the p53 transcription factor family, is overexpressed in non-melanoma skin cancer and regulates cell survival, migration and invasion. TIP60 is histone acetyltransferase (HAT) which mediates cellular processes such as transcription and the DNA damage response (DDR). Previous studies in our lab have shown that overexpression of TIP60 induces ΔNp63a protein stabilization in a catalytic-dependent manner. Since ΔNp63a is known to transcriptionally regulate several DDR genes and promote cisplatin resistance, its stabilization by TIP60 may contribute to the failure of platinum-based …

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 …

Checkmate: Exploring Father-Son Communication Regarding Reproduction And Sexual Health In Males With Cystic Fibrosis, Dianna C. Sanderson

Theses and Dissertations

Cystic fibrosis (CF) is a heritable monogenic condition with allelic heterogeneity. A variety of sequence alterations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene results clinically in multisystem disease including a reduced reproductive capacity in affected males. Knowledge of reproductive capacity is often disclosed to parents by medical providers and to affected male children by medical providers and their parents. Despite advanced technology and therapeutics yielding the benefits of increased life expectancy and quality of life, males affected with CF largely remain uninformed in broader areas of sexual health and particularly in how their concept of masculine …

Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan

Nebraska Center for Virology: Faculty Publications

Intracellular iron concentration is tightly regulated to maintain cell viability. Iron plays important roles in electron transport, nucleic acid synthesis, and oxidative stress. A Mycobacterium avium subsp. paratuberculosis (MAP)-specific genomic island carries a putative metal transport operon that includes MAP3773c, which encodes a Fur-like protein. Although well characterized as a global regulator of iron homeostasis in multiple bacteria, the function of Fur (ferric uptake regulator) in MAP is unknown as this organism also carries IdeR (iron dependent regulator), a native iron regulatory protein specific to mycobacteria. Computational analysis using PRODORIC identified 23 different pathways involved in respiration, metabolism, and virulence …

Distortion Of The Local Magnetic Field Appears To Neither Disrupt Nocturnal Navigation Nor Cue Shelter Recognition In The Amblypygid Paraphrynus Laevifrons, Daniel D. Wiegmann, Patrick Casto, Eileen Hebets, Verner P. Bingman

Eileen Hebets Publications

Many arthropods are known to be sensitive to the geomagnetic field and exploit the field to solve spatial problems. The polarity of the geomagnetic field is used, for instance, as an orientation cue by leafcutter ants as they travel on engineered trails in a rainforest and by Drosophila larvae as they move short distances in search of food. A ubiquitous orientation cue like the geomagnetic field may be especially useful in complex, cluttered environments like rainforests, where the reliability of celestial cues used to navigate in more open environments may be poor. The neotropical amblypygid Paraphrynus laevifrons is a nocturnal …

Evaluating Pregnancy Outcomes Of Abnormal Non-Invasive Prenatal Screening Results In A High Risk Obstetrics Practice, Olivia Kesler

Theses and Dissertations

Non-invasive prenatal screening (NIPS) has rapidly grown in uptake since its introduction to clinical practice in 2011. In contrast to more traditional methods of screening, NIPS is the first to utilize cell-free fetal DNA for risk assessment of chromosomal aneuploidy and other conditions. Clinical validity has been established for the most common autosomal aneuploidies (Trisomy 21, Trisomy 18, and Trisomy 13) and sex chromosome aneuploidies, though some laboratories screen for conditions beyond these. A screen positive does not always indicate a true positive, therefore professional guidelines recommend diagnostic testing for confirmation and informed decision making on pregnancy management. Furthermore, the …

Experiences With And Knowledge Of Genetics In Families Affected By Congenital Adrenal Hyperplasia: The Parent Perspective, Christine Maccia

Theses and Dissertations

Purpose: This project was conducted in order to assess how parents of a child affected by CYP21A2-related classic CAH experienced receiving genetic information, The goal was to determine their knowledge of the genetics of the condition and how that knowledge has affected different aspects of their lives such as emotional well-being. Methods: Parents of a child with classic CAH diagnosed in the past 10 years were invited to participate in an online survey via an advertisement posted in the support group, Major Aspects of Growth in Children. Survey questions consisted of demographic information, experience with the diagnostic process, knowledge of …

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 …

The Utility Of Whole Exome Sequencing In Patients With Intellectual Disability And Developmental Delay As A First-Tier Diagnostic Testing Strategy, Ellen Richardson

Theses and Dissertations

The purpose of this study is to evaluate the diagnostic utility of whole exome sequencing (WES) in patients with intellectual disability (ID) or developmental delay (DD), and to determine which patients may be the best candidates for WES as a first-tier diagnostic test. The diagnostic and clinical utility of WES has emerged to be greater than that of karyotype and chromosomal microarray for patients with ID or DD of unknown etiology, which are currently recommended as first-tier diagnostic tests for these patients. The emergence of next generation sequencing has led to more rapid identification of rare and novel genetic disorders. …

Revisiting The Essential Informational Needs Of Parents Receiving A Diagnosis Of Down Syndrome, Margaret Jean Wilkes

Theses and Dissertations

Down syndrome is a condition characterized by varying degrees of intellectual disability (ID), distinctive facial appearance, and congenital anomalies that results from the presence of a third 21st chromosome. Down syndrome is the most common chromosomal condition, affecting approximately 12.6 per 10,000 live births in the United States, making it imperative that we determine which information is most essential to impart to parents when first presenting the diagnosis. The aim of the present study is to reassess the informational needs of parents during the presentation of a Down syndrome diagnosis. In 2009, data were collected to define the essential information …

Association Of Interleukin 17f With Arthritis In Punjabi Families Of Pakistan, Asia Parveen, Andleeb Batool, Maryam Mukhtar, Abdul Wajid, Naila Malkani

Journal of Bioresource Management

Arthritis is a chronic inflammatory disease that causes severe joint pain. Interleukin 17F (IL17F) is considered as a candidate gene functionally; it mediates pro-inflammatory responses, depending on the type and site of inflammation. The present study examined the polymorphism of IL17F (rs763780 and rs2397084) among the families affected by arthritis. Demographic data and blood samples were collected from the families with at least one affected offspring with arthritis. Analysis of the IL17F gene polymorphism was performed by the digestion of DNA with NlaIII and AvaII. The results showed that IL17F rs763780 (AA, AG and GG genotypes) and rs2397084 (AA, AG …

Accumulation Of Unacetylatable Snf2p At The Ino1 Promoter Is Detrimental To Remodeler Recycling Supply For Cup1 Induction, Michelle Esposito, Goldie Libby Sherr, Anthony Esposito, George Kaluski, Farris Ellington, Chang-Hui Shen

Publications and Research

Chromatin structure plays a decisive role in gene regulation through the actions of transcriptional activators, coactivators, and epigenetic machinery. These trans-acting factors contribute to gene expression through their interactions with chromatin structure. In yeast INO1 activation, transcriptional activators and coactivators have been defined through intense study but the mechanistic links within these trans-acting factors and their functional implications are not yet fully understood. In this study, we examined the crosstalk within transcriptional coactivators with regard to the implications of Snf2p acetylation during INO1 activation. Through various biochemical analysis, we demonstrated that both Snf2p and Ino80p chromatin remodelers accumulate …

Generating High Quality Libraries For Dia Ms With Empirically Corrected Peptide Predictions., Brian C Searle, Kristian E Swearingen, Christopher A Barnes, Tobias Schmidt, Siegfried Gessulat, Bernhard Küster, Mathias Wilhelm

Articles, Abstracts, and Reports

Data-independent acquisition approaches typically rely on experiment-specific spectrum libraries, requiring offline fractionation and tens to hundreds of injections. We demonstrate a library generation workflow that leverages fragmentation and retention time prediction to build libraries containing every peptide in a proteome, and then refines those libraries with empirical data. Our method specifically enables rapid, experiment-specific library generation for non-model organisms, which we demonstrate using the malaria parasite Plasmodium falciparum, and non-canonical databases, which we show by detecting missense variants in HeLa.