Genetics and Genomics Commons^™

Understanding Genetic Disorders: A Case Of 17-Hydroxylase Deficiency, Hannah Peterson, Neikelyn Burgos- Tirado, Jiayan Liu, Richard Auchus

Summer Research

The adrenal glands contain a complex enzyme system that modifies cholesterol into glucocorticoids, mineralocorticoids, and sex steroids. Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive diseases that occur when the genes that encode for the enzymes of cortisol biosynthesis are mutated. One example of CAH is 17- hydroxylase deficiency, (17OHD). In 17OHD, Cytochrome P450 17A1 (CYP17A1) is dysfunctional. CYP17A1 is essential for cortisol and sex steroid production; when CYP17A1 is mutated, its reagents divert into mineralocorticoid production. Some classic symptoms of 17OHD include hypertension, hypokalemia, low cortisol levels, and sexual infantilism. The purpose of this study was …

Tissue Expression Patterns Identify Mouse Cilia Genes, Timothy S. Mcclintock

Physiology Research Data

A summary of 2,127 mouse genes linked to cilia by previous high-throughput approaches (reviewed in Inglis et al., 2006), published studies of individual gene products, or by McClintock et al. 2008. Each gene was viewed at Entrez Gene to verify and update the Gene ID and Gene Symbol. Each was also searched against PubMed (Gene Symbol AND (cili* OR flagel*)) for published evidence linking the mouse gene or putative orthologs to cilia or flagella. This searchable file lists identifying information about each gene, functional information about the encoded protein, the number of high-throughput studies linking the gene to cilia, and …

Mitochondrial Dna Analysis Of Mazahua And Otomi Indigenous Populations From Estado De Mexico Suggests A Distant Common Ancestry, Angelica GonzáLez-Oliver, Ernesto Garfias-Morales, D G. Smith, Mirsha Quinto-Sánchez

Human Biology Open Access Pre-Prints

The indigenous Mazahua and Otomi have inhabited the same localities in Estado de Mexico since pre-Columbian times. Their languages, Mazahua and Otomi, belong to the Otomanguean linguistic family, and, while they share cultural traditions and a regional history that suggest close genetic relationships and common ancestry, the historical records concerning their origin are confusing. To understand the biological relationships between Mazahua and Otomi we analyzed the mitochondrial DNA (mtDNA) genetic variation. We identified the mtDNA haplogroups by restriction fragment length polymorphism typing and sequenced the hypervariable region I of the mtDNA control region in 141 Mazahua and 100 Otomi. These …

Comparison Of Three Assembly Strategies For A Heterozygous Seedless Grapevine Genome Assembly, Sagar Patal, Zhixiu Lu, Xiaozhu Jin, Padmapriya Swaminathan, Erliang Zeng, Anne Y. Fennell Dr

Agronomy, Horticulture and Plant Science Faculty Publications

Background
De novo heterozygous assembly is an ongoing challenge requiring improved assembly approaches. In this study, three strategies were used to develop de novo Vitis vinifera ‘Sultanina’ genome assemblies for comparison with the inbred V. vinifera (PN40024 12X.v2) reference genome and a published Sultanina ALLPATHS-LG assembly (AP). The strategies were: 1) a default PLATANUS assembly (PLAT_d) for direct comparison with AP assembly, 2) an iterative merging strategy using METASSEMBLER to combine PLAT_d and AP assemblies (MERGE) and 3) PLATANUS parameter modifications plus GapCloser (PLAT*_GC).
Results
The three new assemblies were greater in size than the AP assembly. PLAT*_GC had the …

Recurrent Neural Networks And Their Applications To Rna Secondary Structure Inference, Devin Willmott

Theses and Dissertations--Mathematics

Recurrent neural networks (RNNs) are state of the art sequential machine learning tools, but have difficulty learning sequences with long-range dependencies due to the exponential growth or decay of gradients backpropagated through the RNN. Some methods overcome this problem by modifying the standard RNN architecure to force the recurrent weight matrix W to remain orthogonal throughout training. The first half of this thesis presents a novel orthogonal RNN architecture that enforces orthogonality of W by parametrizing with a skew-symmetric matrix via the Cayley transform. We present rules for backpropagation through the Cayley transform, show how to deal with the Cayley …

A Moving Landscape For Comparative Genomics In Mammals, Stephen James O'Brien, Gaik Tamazian, Aleksey Komissarov, Pavel Dobrynin, Ksenia Krasheninnikova, Sergey Kliver, Nikolay Cherkasov, Klaus-Peter Koepfli

Biology Faculty Proceedings, Presentations, Speeches, Lectures

Today we count some 62,000 species of vertebrates (half are fishes) including some 550 species of mammals on earth. The genome sequencing of non-laboratory species in recent years is expanding our breadth and understanding of genetic bases of adaptation and evolution in varied and amazing ways.

Recent completion and inspection of whole genome sequence and assembly for over 200 species of mammals, from platypus to panda to human, offer the prospect of a better view of the patterns of changes within genome organization across the mammalian radiations. In 2009 my colleagues and I have created Genome-10K, an international consortium of …

X Chromosome Evolution In Cetartiodactyla, Anastasiya A. Proskuryakova, Anastasia I. Kulemzina, Polina L. Perelman, Alexey I. Makunin, Natalya A. Lemskaya, Violetta R. Beklemisheva, Denis M. Larkin, Marta Farre, Anna V. Kukekova, Oliver A. Ryder, Stephen James O'Brien, Alexander S. Graphodatsky

Biology Faculty Proceedings, Presentations, Speeches, Lectures

The mammalian X chromosome is characterized by high level of conservation. On the contrary the Cetartiodactyl X chromosome displays variation in morphology and G-banding pattern. It is hypothesized that X chromosome has undergone multiple rearrangements during Cetartiodactyla speciation. To investigate the evolution of this sex chromosome we have selected 26 BAC clones from cattle CHORI-240 library evenly distributed along the cattle X chromosome. High-resolution maps were obtained by fluorescence in situ hybridisation in a representative range of cetartiodactyl species from different families: pig (Suidae), gray whale (Eschrichtiidae), pilot whale (Delphinidae), hippopotamus (Hippopotamidae), Java mouse deer (Tragulidae), pronghorn (Antilocapridae), Siberian musk …

Pinniped Karyotype Evolution Substantiated By Comparative Chromosome Painting Of 10 Pinniped Species (Pinnipedia, Carnivora), Violetta R. Beklemisheva, Polina L. Perelman, Natalya A. Lemskaya, Anastasia I. Kulemzina, Anastasiya A. Proskuryakova, Vladimir N. Burkanov, Stephen James O'Brien, Alexander S. Graphodatsky

Biology Faculty Proceedings, Presentations, Speeches, Lectures

Numerous Carnivora karyotype evolution investigations have been performed by classical and molecular cytogenetics and were supplemented by reconstructions of the Ancestral Carnivora Karyotype (ACK). However, the group of Pinnipedia was not studied in detail. Here we reconstruct pinniped karyotype evolution and refine ACK using published and our new painting data for 10 pinniped species. The combination of human (HSA) and domestic dog (CFA) whole-chromosome painting probes was used for the construction of the comparative chromosome maps for species from all three pinniped families: Odobenidae– Odobenus rosmarus Linnaeus, 1758, Phocidae – Phoca vitulina Linnaeus, 1758, Pusa sibirica Gmelin, 1788, Erignathus barbatus …

Altered Ratio Of T Follicular Helper Cells To T Follicular Regulatory Cells Correlates With Autoreactive Antibody Response In Simian Immunodeficiency Virus–Infected Rhesus Macaques, Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (T_FH) cells, and T follicular regulatory (T_FR) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses. We hypothesized that an altered ratio of T_FH/T_FR cells in the GC contributes to the …

Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo

Nebraska Center for Virology: Faculty Publications

HIV mutates rapidly and infects CD4⁺ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4⁺ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV …

Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive glial tumor that occurs in children. The extremely poor median and 5-year survival in children afflicted with DIPG highlights the need for novel biology-driven therapeutics. Here, we have implicated the chromatin remodeler and regulator of brain development called RE1 Silencing Transcription Factor (REST), in DIPG pathology. We show that REST protein is aberrantly elevated in at least 21% of DIPG tumors compared to normal controls. Its knockdown in DIPG cell lines diminished cell growth and decreased their tumorigenicity in mouse intracranial models. DIPGs are vascularized tumors and interestingly, REST loss in …

48839 (Gmr19b04), Neha Gogia, Ankita Sarkar, Amit Singh

Dpp Enhancer Sequences Utilized in GMR Line

dpp enhancer - 48839

• Id - GMR19B04,
• Location - 2L:2432214,2435785
• Base pairs – 3571 bp

47472 (Gmr16g02), Neha Gogia, Ankita Sarkar, Amit Singh

Dpp Enhancer Sequences Utilized in GMR Line

dpp enhancer - 47472

• Id - GMR16G02
• Location 2L:2425041, 2428154
• Base pairs – 3113 bp

48770 (Gmr17e04), Neha Gogia, Ankita Sarkar, Amit Singh

Dpp Enhancer Sequences Utilized in GMR Line

dpp enhancer - 48770

• Id - GMR17E04
• Location 2L: 2428913..2432834
• Base pairs – 3921 bp

Methylation-Based Enrichment Facilitates Low-Cost, Noninvasive Genomic Scale Sequencing Of Populations From Feces, Kenneth L. Chiou, Christina M. Bergey

United States Public Health Resources

Obtaining high-quality samples from wild animals is a major obstacle for genomic studies of many taxa, particularly at the population level, as collection methods for such samples are typically invasive. DNA from feces is easy to obtain noninvasively, but is dominated by bacterial and other non-host DNA. The high proportion of non-host DNA drastically reduces the efficiency of high-throughput sequencing for host animal genomics. To address this issue, we developed an inexpensive capture method for enriching host DNA from noninvasive fecal samples. Our method exploits natural differences in CpG-methylation density between vertebrate and bacterial genomes to preferentially bind and isolate …

Triennial Reproduction Symposium: Looking Back And Moving Forward—How Reproductive Physiology Has Evolved, Deb L. Hamernik, Andrea S. Cupp, John S. Davis

Department of Animal Science: Faculty Publications

In honor of the 50th anniversary of the Society for the Study of Reproduction (SSR), a Triennial Reproduction Symposium was cosponsored by SSR and the American Society of Animal Science (ASAS). The Society for the Study of Reproduction was formed in 1967 when a group of reproductive biologists that were members of ASAS met with physician scientists and decided to organize a new scientific society. The goal of SSR was to promote the study of reproduction by fostering interdisciplinary communication among scientists, holding conferences, and publishing meritorious studies. Today after its 50th anniversary, the mission for SSR is to harness …

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …

National Beef Quality Audit–2016: Assessment Of Cattle Hide Characteristics, Offal Condemnations, And Carcass Traits To Determine The Quality Status Of The Market Cow And Bull Beef Industry, Mckensie K. Harris, L. Clay Eastwood, Courtney A. Boykin, Ashley N. Arnold, Kerri B. Gehring, Daniel S. Hale, Christopher R. Kerth, Davey B. Griffin, J.W. Savell, Keith E. Belk, Dale R. Woerner, Josh D. Hasty, Jennifer N. Martin, Ty E. Lawrence, Trenton J. Mcevers, Deborah L. Vanoverbeke, Gretchen G. Mafi, Morgan M. Pfeiffer, Ty B. Schmidt, Robert J. Maddock, D. Dwain Johnson, Chad C. Carr, Jason M. Scheffler, T. Dean Pringle, Alexander M. Stelzleni, Robert J. Delmore Jr.

Department of Animal Science: Faculty Publications

To continue the series that began in 1994, the National Beef Quality Audit (NBQA) – 2016 was conducted to quantify the quality status of the market cow and bull beef sector, as well as determine improvements made in the beef and dairy industry since 2007. The NBQA-2016 was conducted from March through December of 2016, and assessed hide-on carcasses (n = 5,278), chilled carcasses (n = 4,285), heads (n = 5,720), and offal items (n = 4,800) in 18 commercial processing facilities throughout the United States. Beef cattle were predominantly black-hided; 68.0% of beef cows and 67.2% of beef bulls …

Movement In Cats, Valerie N. Plummer

College of Graduate Studies: Theses & Dissertations

Feral cats (Felis catus) are listed as one of the '100 world's worst invasive alien species'. There are as many as 70-100 million feral cats in the United States as well as an estimated 117-157 million domestic indoor and outdoor cats. Management efforts include a nonlethal feeding and sterilization program known as "trap-neuter-release" (TNR) where cats are surgically sterilized and returned to the environment. Population size and structure, immigration rates, spay/neuter rates, and data on spatial use all play a role in whether TNR is a viable management option. This study focuses on population structure and spatial use. …

Floral Symmetry Genes Elucidate The Development And Evolution Of Oil-Bee Pollinated Flowers Of Malpighiaceae And Krameriaceae, Farahnoz N. Khojayori

Theses and Dissertations

Specialization on insect and animal pollinators is thought to be the driving force for the evolution of floral traits. Specifically in the New World (NW), the oil-bee pollination syndrome has led to the convergence of floral characters in two distantly related families of core eudicots, Malpighiaceae and Krameriaceae. Both families display a flag-like structure that establishes a zygomorphic flower and floral oil rewards in epithelial elaiophores. These traits work concomitantly to attract and reward female oil-bees that help fertilize these flowers and in return receive oils. The underlying genetics of floral zygomorphy were studied in several clades of core eudicots, …

Analysis Of The Transcription Factors Expressed In The Mature Seed Embryos Of Moringa Oleifera Lam. Using Rna-Sequencing And De Novo Transcriptome Assembly, Vivian A. Panes, R.D Baoas

Biology Faculty Publications

Moringa oleifera Lam. is well known for its numerous documented properties, particularly its significant applications in nutrition, therapeutics, biocontrol, energy, and bioremediation. These properties are the consequences of the vibrant physiological processes of the plant in the context of the ever-changing biotic and abiotic factors, in which transcription factors play substantial roles. Transcription factors (TFs) are the regulators of gene expression. Transcription factors enable the activation or repression of transcription. Along with the advent of ultrahighthroughput sequencing technologies such as RNA sequencing (RNA-Seq), in combination with bioinformatics techniques, the investigation of the TFs of M. oleifera was made possible. This …

Interitance Pattern Of Vestigial Mutation In Drosophila Melanogaster, Tori R. Witruck, Adam Padron

A with Honors Projects

The purpose of this experiment was to determine the inheritance pattern of the vestigial mutation in Drosophila melanogaster. The experiment was to include two crosses with wild type and vestigial mutation, but the second cross experienced environmental setbacks potentially affecting the results, the experiment could lead to future testing on environmental effects on mutation.

Role Of Glycerol-3-Phosphate Permeases In Plant Defense, Juliana Moreira Soares

Theses and Dissertations--Plant Pathology

Systemic acquired resistance (SAR) is a type of plant defense mechanism that is induced after a localized infection and confers broad-spectrum immunity against related or unrelated pathogens. During SAR, a number of chemical signals and proteins generated at the site of primary infection travel to the uninfected tissues and are thought to alert the distal sites against secondary infections. Glycerol-3-phosphate (G3P) is one of the chemical signals that play an important role in SAR. G3P is synthesized in the cytosol and chloroplasts via the enzymatic activities of G3P Dehydrogenase (G3Pdh) or Glycerol Kinase (GK). Interestingly, a mutation in three of …

Validating Functional Mechanisms For Non-Coding Genetic Variants Associated With Complex Traits, Cynthia Ann Kalita

Wayne State University Dissertations

Genome-wide association studies (GWAS) have identified a large number of genetic variants associated with disease as well as normal phenotypic variation for complex traits. However challenges remain in determining the functional relevance of human DNA sequence variants. Even after fine mapping, most variants are located in non-coding regions making it difficult to infer mechanisms linking individual genetic variants with the disease trait. In addition, we do not know under which environmental conditions the sequence variants have a functional impact, and whether they become one of many factors involved in complex phenotypes at the organismal level.

Chapter 1 describes computational methods …

The Cytoscape Automation App Article Collection., Barry Demchak, David Otasek, Alexander R Pico, Gary D Bader, Keiichiro Ono, Brett Settle, Eric Sage, John H Morris, William Longabaugh, Christian Lopes, Michael Kucera, Adam Treister, Benno Schwikowski, Piet Molenaar, Trey Ideker

Articles, Abstracts, and Reports

Cytoscape is the premiere platform for interactive analysis, integration and visualization of network data. While Cytoscape itself delivers much basic functionality, it relies on community-written apps to deliver specialized functions and analyses. To date, Cytoscape's CyREST feature has allowed researchers to write workflows that call basic Cytoscape functions, but provides no access to its high value app-based functions. With Cytoscape Automation, workflows can now call apps that have been upgraded to expose their functionality. This article collection is a resource to assist readers in quickly and economically leveraging such apps in reproducible workflows that scale independently to large data sets …

The Microbiome Stress Project: Toward A Global Meta-Analysis Of Environmental Stressors And Their Effects On Microbial Communities., Jennifer D Rocca, Marie Simonin, Joanna R Blaszczak, Jessica G Ernakovich, Sean M Gibbons, Firas S Midani, Alex D Washburne

Articles, Abstracts, and Reports

Microbial community structure is highly sensitive to natural (e.g., drought, temperature, fire) and anthropogenic (e.g., heavy metal exposure, land-use change) stressors. However, despite an immense amount of data generated, systematic, cross-environment analyses of microbiome responses to multiple disturbances are lacking. Here, we present the Microbiome Stress Project, an open-access database of environmental and host-associated 16S rRNA amplicon sequencing studies collected to facilitate cross-study analyses of microbiome responses to stressors. This database will comprise published and unpublished datasets re-processed from the raw sequences into exact sequence variants using our standardized computational pipeline. Our database will provide insight into general response patterns …

Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The HIV-1 pandemic is a consequence of the cross-species transmission of simian immunodeficiency virus in wild chimpanzees (SIVcpz) to humans. Our previous study demonstrated SIVcpz strains that are closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) and two SIVcpz lineages that are not associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), all can readily infect and robustly replicate in the humanized-BLT mouse model of humans. However, the comparative pathogenicity of different SIVcpz strains remains unknown. Herein, we compared the pathogenicity of the above four SIVcpz strains with HIV-1 using humanized-BLT mice. …

Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu

Nebraska Center for Virology: Faculty Publications

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission.We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 10⁴ TCID₅₀) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses …

Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Daniela Gonzalez, John T. West, Charles Wood, Joel Palefsky, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

We have tested a multiplex polymerase chain reaction (PCR) human papillomavirus (HPV) genotyping assay to fill the need for rapid and low‐cost HPV detection in Sub‐ Saharan Africa. This method allows high throughput genotyping and simultaneous detection of 14 high‐risk and two low‐risk HPV types, by PCR amplification of HPV DNAs in a single reaction tube. In this study, we describe stepwise experiments to validate the multiplex HPV PCR assay for determination of HPV genotypes from 104 cervical brush samples from Tanzanian women. Assay performance was evaluated by determination of intra‐laboratory reproducibility, sensitivity, and specificity. Further performance was assessed by …

Discovery Of A Non-Nucleoside Rna Polymerase Inhibitor For Blocking Zika Virus Replication Through In Silico Screening, Aryamav Pattnaik, Nicholas Palermo, Bikash R. Sahoo, Zhe Yuan, Duoyi Hu, Arun S. Annamalai, Hiep L. X. Vu, Ignacio Correas, Pavan Kumar Prathipati, Christopher J. Destache, Qingsheng Li, Fernando A. Osorio, Asit K. Pattnaik, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), an emerging arbovirus, has become a major human health concern globally due to its association with congenital abnormalities and neurological diseases. Licensed vaccines or antivirals against ZIKV are currently unavailable. Here, by employing a structure-based approach targeting the ZIKV RNA-dependent RNA polymerase (RdRp), we conducted in silico screening of a library of 100,000 small molecules and tested the top ten lead compounds for their ability to inhibit the virus replication in cell-based in vitro assays. One compound, 3-chloro-N-[({4-[4-(2-thienylcarbonyl)-1-piperazinyl]phenyl}amino)carbonothioyl]-1-benzothiophene-2-carboxamide (TPB), potently inhibited ZIKV replication at submicromolar concentrations. Molecular docking analysis suggests that …