Genetics and Genomics Commons^™

Recent Genetic Connectivity And Clinal Variation In Chimpanzees, Jack D. Lester, Linda Vigilant, Paolo Gratton, Maureen S. Mccarthy, Christopher D. Barratt, Paula Dieguez, Anthony Agbor, Paula Alvarez-Varona, Samuel Angedakin, Emmanuel Ayuk Ayimisin, Emma Bailey, Mattia Bessone, Gregory Brazzola, Rebecca Chancellor, Heather Cohen, Emmanuel Danquah, Tobias Deschner, Villard Ebot Egbe, Manasseh Eno-Nku, Annemarie Goedmakers, Anne-Celine Granjon, Josephine Head, Daniela Hedwig, R. Adriana Hernandez-Aguilar, Kathryn J. Jeffery, Sorrel Jones, Jessica Junker, Parag Kadam, Michael Kaiser, Ammie K. Kalan, Laura Kehoe, Ivonne Kienast, Kevin E. Langergraber, Juan Lapuente, Anne Laudisoit, Kevin Lee, Sergio Marrocoli, Vianet Mihindou, David Morgan, Geoffrey Muhanguzi, Emily Neil, Sonia Nicholl, Christopher Orbell, Lucy Jayne Ormsby, Liliana Pacheco, Alex Piel, Martha M. Robbins, Aaron S. Rundus, Crickette Sanz, Lilah Sciaky, Alhaji M. Siaka, Veronika Staedele, Fiona Stewart, Nikki Tagg, Els Ton, Joost Van Schijndel, Magloire Kambale Vyalengerera, Erin G. Wessling, Jacob Willie, Roman M. Wittig, Yisa Ginath Yuh, Kyle Yurkiw, Klaus Zuberbuehler, Christophe Boesch, Hjalmar S. Kuehl, Mimi Arandjelovic

Psychology Faculty Publications

Much like humans, chimpanzees occupy diverse habitats and exhibit extensive behavioural variability. However, chimpanzees are recognized as a discontinuous species, with four subspecies separated by historical geographic barriers. Nevertheless, their range-wide degree of genetic connectivity remains poorly resolved, mainly due to sampling limitations. By analyzing a geographically comprehensive sample set amplified at microsatellite markers that inform recent population history, we found that isolation by distance explains most of the range-wide genetic structure of chimpanzees. Furthermore, we did not identify spatial discontinuities corresponding with the recognized subspecies, suggesting that some of the subspecies-delineating geographic barriers were recently permeable to gene flow. …

Stategra: Multi-Omics Data Integration - A Conceptual Scheme With A Bioinformatics Pipeline, Nuria Planell, Vincenzo Lagani, Patricia Sebastian-Leon, Frans Van Der Kloet, Ewoud Ewing, Nestoras Karathanasis, Arantxa Urdangarin, Imanol Arozarena, Maja Jagodic, Ioannis Tsamardinos, Sonia Tarazona, Ana Conesa, Jesper Tegner, David Gomez-Cabrero

Computational Medicine Center Faculty Papers

Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decision over which tools to use and how to combine them. Therefore, it is an unmet need to conceptualize how to integrate such data and implement and validate pipelines in different cases. We have designed a conceptual framework (STATegra), aiming it to be as generic as possible for multi-omics analysis, combining …

Presence Of Antibody-Dependent Cellular Cytotoxicity (Adcc) Against Sars-Cov-2 In Covid-19 Plasma, For Yue Tso, Salum J. Lidenge, Lisa K. Poppe, Phoebe B. Pena, Sara R. Privatt, Sydney J. Bennett, John R. Ngowi, Julius Mwaiselage, Michael Belshan, Jacob A. Siedlik, Morgan A. Raine, Juan B. Ochoa, Julia Garcia-Diaz, Bobby Nossaman, Lyndsey Buckner, W Mark Roberts, Matthew J. Dean, Augusto C. Ochoa, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. Methods Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific …

Attainment And Maintenance Of Pubertal Cyclicity May Predict Reproductive Longevity In Beef Heifers, Sarah R. Nafziger, Sarah C. Tenley, Adam F. Summers, Mohamed A. Abedal-Majed, Mariah Hart, Jeffrey W. Bergman, Scott G. Kurz, John S. Davis, Jennifer R. Wood, Andrea S. Cupp

Department of Animal Science: Faculty Publications

We hypothesized the manner that heifers achieve puberty may indicate their future reproductive longevity. Heifers with discontinued or delayed cyclicity during puberty attainment may have irregular reproductive cycles, anovulation, and infertility in their first breeding season contributing to a shorter reproductive lifespan. Therefore, plasma progesterone (P4) was measured from weaning to breeding on 611 heifers born 2012–2017 and four pubertal classifications were identified: (1) Early; P4 ≥ 1 ng/ml < March 12 with continued cyclicity, (2) Typical; P4 ≥ 1 ng/ml ≥ March 12 with continued cyclicity, (3) Start-Stop; P4 ≥ 1 ng/ml but discontinued cyclicity, and (4) Non-Cycling; no P4 ≥ 1 ng/ml. Historical herd records indicated that 25% of heifers achieved puberty prior to March 12th in the 10 years prior to the study. Start-Stop and Non-Cycling yearling heifers were lighter indicating reduced growth and reproductive maturity traits compared with Early/Typical heifers. In addition, Non-Cycling/Start-Stop heifers were less responsive to prostaglandin F2 alpha (PGF2α) to initiate estrous behavior and ovulation to be artificially inseminated. Non-Cycling heifers had fewer reproductive tract score-5 and reduced numbers of calves born in the first 21-days-ofcalving during their first breeding season. Within the Start-Stop classification, 50% of heifers reinitiated cyclicity with growth traits and reproductive parameters that were similar to heifers in the Early/Typical classification while those that remained non-cyclic were more similar to heifers in the Non-Cycling group. Thus, heifers with discontinued cyclicity or no cyclicity during puberty attainment had delayed reproductive maturity resulting in subfertility and potentially a shorter reproductive lifespan.

Spatio-Temporal Selection Of Reference Genes In The Two Congeneric Species Of Glycyrrhiza, Yuping Li, Xiaoju Liang, Xuguo Zhou, Yu An, Ming Li, Ling Yuan, Yongqing Li, Ying Wang

Entomology Faculty Publications

Glycyrrhiza, a genus of perennial medicinal herbs, has been traditionally used to treat human diseases, including respiratory disorders. Functional analysis of genes involved in the synthesis, accumulation, and degradation of bioactive compounds in these medicinal plants requires accurate measurement of their expression profiles. Reverse transcription quantitative real-time PCR (RT-qPCR) is a primary tool, which requires stably expressed reference genes to serve as the internal references to normalize the target gene expression. In this study, the stability of 14 candidate reference genes from the two congeneric species G. uralensis and G. inflata, including ACT, CAC, CYP, …

“Adopt-A-Tissue” Initiative Advances Efforts To Identify Tissue-Specific Histone Marks In The Mare, N B. Kingsley, Natasha A. Hamilton, Gabriella Lindgren, Ludovic Orlando, Ernie Bailey, Samantha Brooks, Molly Mccue, T S. Kalbfleisch, James N. Macleod, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone

Department of Animal Science: Faculty Publications

No abstract provided.

Ectopic Expression Of Pericentric Hsatii Rna Results In Nuclear Rna Accumulation, Mecp2 Recruitment, And Cell Division Defects, C. C. Landers, Christina Rabeler, E. K. Ferrari, Lia R. D'Alessandro , '21, D. D. Kang, J. Malisa, Safia M. Bashir , '20, Dawn M. Carone

Biology Faculty Works

Within the pericentric regions of human chromosomes reside large arrays of tandemly repeated satellite sequences. Expression of the human pericentric satellite HSATII is prevented by extensive heterochromatin silencing in normal cells, yet in many cancer cells, HSATII RNA is aberrantly expressed and accumulates in large nuclear foci in cis. Expression and aggregation of HSATII RNA in cancer cells is concomitant with recruitment of key chromatin regulatory proteins including methyl-CpG binding protein 2 (MeCP2). While HSATII expression has been observed in a wide variety of cancer cell lines and tissues, the effect of its expression is unknown. We tested the effect …

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Indian Institute Of Technology Indore, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canonical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for antiviral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Biophysical and biochemical analysis of the RNA sequences containing these potential GQ sequences suggested the existence of …

De Novo Whole Genome Assembly Of The Swede Midge (Contarinia Nasturtii), A Specialist Of Brassicaceae, Using Linked-Read Sequencing, Boyd A. Mori, Cathy Coutu, Yolanda H. Chen, Erin O. Campbell, Julian R. Dupuis, Martin A. Erlandson, Dwayne D. Hegedus

Entomology Faculty Publications

The swede midge, Contarinia nasturtii, is a cecidomyiid fly that feeds specifically on plants within the Brassicaceae. Plants in this family employ a glucosinolate-myrosinase defense system, which can be highly toxic to non-specialist feeders. Feeding by C. nasturtii larvae induces gall formation, which can cause substantial yield losses thus making it a significant agricultural pest. A lack of genomic resources, in particular a reference genome, has limited deciphering the mechanisms underlying glucosinolate tolerance in C. nasturtii, which is of particular importance for managing this species. Here, we present an annotated, scaffolded reference genome of C. nasturtii using linked-read …

Improved Boreal Forest Wildfire Fuel Type Mapping In Interior Alaska Using Aviris-Ng Hyperspectral Data, Christopher William Smith, Santosh K. Panda, Uma Suren Bhatt, Franz J. Meyer

Aspen Bibliography

In Alaska the current wildfire fuel map products were generated from low spatial (30 m) and spectral resolution (11 bands) Landsat 8 satellite imagery which resulted in map products that not only lack the granularity but also have insufficient accuracy to be effective in fire and fuel management at a local scale. In this study we used higher spatial and spectral resolution AVIRIS-NG hyperspectral data (acquired as part of the NASA ABoVE project campaign) to generate boreal forest vegetation and fire fuel maps. Based on our field plot data, random forest classified images derived from 304 AVIRIS-NG bands at Viereck …

Effects Of Structural Isomers Of Spermine On The Higher-Order Structure Of Dna And Gene Expression, Tomoki Kitagawa, Takashi Nishio, Yuko Yoshikawa, Naoki Umezawa, Tsunehiko Higuchi, Chwen-Yang Shew, Takahiro Kenmotsu, Kenichi Yoshikawa

Publications and Research

Polyamines are involved in various biological functions, including cell proliferation, differentiation, gene regulation, etc. Recently, it was found that polyamines exhibit biphasic effects on gene expression: promotion and inhibition at low and high concentrations, respectively. Here, we compared the effects of three naturally occurring tetravalent polyamines, spermine (SPM), thermospermine (TSPM), and N4-aminopropylspermidine (BSPD). Based on the single DNA observation with fluorescence microscopy together with measurements by atomic force microscopy revealed that these polyamines induce shrinkage and then compaction of DNA molecules, at low and high concentrations, respectively. We also performed the observation to evaluate the effects of these polyamine isomers …

Multimodal Single-Cell/Nucleus Rna Sequencing Data Analysis Uncovers Molecular Networks Between Disease-Associated Microglia And Astrocytes With Implications For Drug Repurposing In Alzheimer’S Disease, Jielin Xu, Pengyue Zhang, Yin Huang, Yadi Zhou, Yuan Hou, Lynn M. Bekris, Justin Lathia, Chien-Wei Chiang, Lang Li, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng

School of Medicine Faculty Research

Because disease-associated microglia (DAM) and disease-associated astrocytes (DAA) are involved in the pathophysiology of Alzheimer's disease (AD), we systematically identified molecular networks between DAM and DAA to uncover novel therapeutic targets for AD. Specifically, we develop a network-based methodology that leverages single-cell/nucleus RNA sequencing data from both transgenic mouse models and AD patient brains, as well as drug-target network, metaboliteenzyme associations, the human protein-protein interactome, and large-scale longitudinal patient data. Through this approach, we find both common and unique gene network regulators between DAM (i.e., PAK1, MAPK14, and CSF1R) and DAA (i.e., NFKB1, FOS, and JUN) that are significantly enriched …

Machine Learning Approaches For The Prediction Of Bone Mineral Density By Using Genomic And Phenotypic Data Of 5130 Older Men, Qing Wu, Fatma Nasoz, Jongyun Jung, Bibek Bhattarai, Mira V. Han, Robert A. Greenes, Kenneth G. Saag

School of Medicine Faculty Research

The study aimed to utilize machine learning (ML) approaches and genomic data to develop a prediction model for bone mineral density (BMD) and identify the best modeling approach for BMD prediction. The genomic and phenotypic data of Osteoporotic Fractures in Men Study (n = 5130) was analyzed. Genetic risk score (GRS) was calculated from 1103 associated SNPs for each participant after a comprehensive genotype imputation. Data were normalized and divided into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and linear regression were used to develop BMD prediction models separately. Ten-fold …

Recent Advances In The Application Of Crispr/Cas9 Gene Editing System In Poultry Species, Collins N. Khwatenge, Samuel N. Nahashon

Agricultural and Environmental Sciences Faculty Research

CRISPR/Cas9 system genome editing is revolutionizing genetics research in a wide spectrum of animal models in the genetic era. Among these animals, is the poultry species. CRISPR technology is the newest and most advanced gene-editing tool that allows researchers to modify and alter gene functions for transcriptional regulation, gene targeting, epigenetic modification, gene therapy, and drug delivery in the animal genome. The applicability of the CRISPR/Cas9 system in gene editing and modification of genomes in the avian species is still emerging. Up to date, substantial progress in using CRISPR/Cas9 technology has been made in only two poultry species (chicken and …

Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R. Irvin, Praful Aggarwal, Steven A. Claas, Lisa De Las Fuentes, Anh N. Do, C. Charles Gu, Andrea Matter, Benjamin S. Olson, Amit Patki, Karen Schwander, Joshua D. Smith, Vinodh Srinivasasainagendra, Hemant K. Tiwari, Amy J. Turner, Deborah A. Nickerson, Dabeeru C. Rao, Ulrich Broeckel, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Indices of left ventricular (LV) structure and geometry represent useful intermediate phenotypes related to LV hypertrophy (LVH), a predictor of cardiovascular (CV) disease (CVD) outcomes.

Methods and Results: We conducted an exome-wide association study of LV mass (LVM) adjusted to height^2.7, LV internal diastolic dimension (LVIDD), and relative wall thickness (RWT) among 1,364 participants of African ancestry (AAs) in the Hypertension Genetic Epidemiology Network (HyperGEN). Both single-variant and gene-based sequence kernel association tests were performed to examine whether common and rare coding variants contribute to variation in echocardiographic traits in AAs. We then used a data-driven …

Neoadjuvant Anti-Ox40 (Medi6469) Therapy In Patients With Head And Neck Squamous Cell Carcinoma Activates And Expands Antigen-Specific Tumor-Infiltrating T Cells., Rebekka Duhen, Carmen Ballesteros-Merino, Alexandra K Frye, Eric Tran, Venkatesh Rajamanickam, Shu-Ching Chang, Yoshinobu Koguchi, Carlo Bifulco, Brady Bernard, Rom Leidner, Brendan Curti, Bernard A Fox, Walter Urba, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of …

The Genomics Of Ecological Flexibility, Large Brains, And Long Lives In Capuchin Monkeys Revealed With Fecalfacs., Joseph D Orkin, Michael J Montague, Daniela Tejada-Martinez, Marc De Manuel, Javier Del Campo, Saul Cheves Hernandez, Anthony Di Fiore, Claudia Fontsere, Jason A Hodgson, Mareike C Janiak, Lukas F K Kuderna, Esther Lizano, Maria Pia Martin, Yoshihito Niimura, George H Perry, Carmen Soto Valverde, Jia Tang, Wesley C Warren, João Pedro De Magalhães, Shoji Kawamura, Tomàs Marquès-Bonet, Roman Krawetz, Amanda D Melin

Department of Biochemistry and Molecular Biology Faculty Papers

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to …

Generation Of A Biobank From Two Adult Thoroughbred Stallions For The Functional Annotation Of Animal Genomes Initiative, Callum G. Donnelly, Rebecca R. Bellone, Erin N. Hales, Annee Nguyen, Scott A. Katzman, Ghislaine A. Dujovne, Kelly E. Knickelbein, Felipe Avila, Ted S. Kalbfleisch, Elena Giulotto, Nicole B. Kingsley, Jocelyn Tanaka, Elizabeth Esdaile, Sichong Peng, Anna Dahlgren, Anna Fuller, Michael J. Mienaltowski, Terje Raudsepp, Verena K. Affolter, Jessica L. Petersen, Carrie J. Finno

Department of Animal Science: Faculty Publications

Following the successful creation of a biobank from two adult Thoroughbred mares, this study aimed to recapitulate sample collection in two adult Thoroughbred stallions as part of the Functional Annotation of the Animal Genome (FAANG) initiative. Both stallions underwent thorough physical, lameness, neurologic, and ophthalmic (including electroretinography) examinations prior to humane euthanasia. Epididymal sperm was recovered from both stallions immediately postmortem and cryopreserved. Aseptically collected full thickness skin biopsies were used to isolate, culture and cryopreserve dermal fibroblasts. Serum, plasma, cerebrospinal fluid, urine, and gastrointestinal content from various locations were collected and cryopreserved. Under guidance of a board-certified veterinary anatomic …

Physical Mapping Of The Anopheles (Nyssorhynchus) Darlingi Genomic Scaffolds, Míriam Silva Rafael, Leticia Cegatti Bridi, Igor V. Sharakhov, Osvaldo Marinotti, Maria V. Sharakhova, Vladimir A. Timoshevskiy, Giselle Moura Guimarães-Marques, Valéria Silva Santos, Carlos Gustavo Nunes Da Silva, Spartaco Astolfi-Filho, Wanderli Pedro Tadei

Biology Faculty Publications

The genome assembly of Anopheles darlingi consists of 2221 scaffolds (N50 = 115,072 bp) and has a size spanning 136.94 Mbp. This assembly represents one of the smallest genomes among Anopheles species. Anopheles darlingi genomic DNA fragments of ~37 Kb were cloned, end-sequenced, and used as probes for fluorescence in situ hybridization (FISH) with salivary gland polytene chromosomes. In total, we mapped nine DNA probes to scaffolds and autosomal arms. Comparative analysis of the An. darlingi scaffolds with homologous sequences of the Anopheles albimanus and Anopheles gambiae genomes identified chromosomal rearrangements among these species. Our results confirmed that physical mapping …

European Aspen With High Compared To Low Constitutive Tannin Defenses Grow Taller In Response To Anthropogenic Nitrogen Enrichment, Franziska Bandau, Benedicte Riber Albrectsen, Kathryn M. Robinson, Michael J. Gundale

Aspen Bibliography

Boreal forests receive nitrogen-(N)-enrichment via atmospheric deposition and industrial fertilization. While it is known that N-enrichment can intensify interactions with natural antagonists, it remains poorly understood how genetic variability in plant defense chemistry can affect biotic interactions and height growth in N-enriched environments. We grew replicates of five low- and high-tannin Populus tremula genotypes, respectively, under three N-treatments (ambient, 15, and 150 kg N ha−1 yr−1). We assessed shoot blight occurrence (i.e. symptoms caused by Venturia fungi) during four growing seasons, and tree height growth during the same period. Damage by Venturia spp. increased with N-addition during all years, likely …