Genetics and Genomics Commons^™

Functional Characteristics And Genomic Sequencing Of Antarctic Environmental Isolates, Amanda Kemper, Christina Aigner, Michelle Tigges, Sara Anderson

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Adaptive Variation In Tiger Salamander Populations, Meghan Parsley

Masters Theses & Specialist Projects

Amphibians face an unknown future in a time of rapid environmental change due to global climate perturbations. Since amphibians are perceived to be indicators of ecosystem health, understanding the causes of their declines can improve our perception of threats to other species. Molecular techniques have allowed us to explore how environmental change affects genetic variation and to predict evolutionary adaptive potential of amphibian populations. The identification of populations with the greatest potential to respond to changing environmental variables may be an important conservation strategy to aid in future management efforts. I utilized targeted exon capture sequencing to identify adaptive variation …

Key Challenges In Bringing Crispr-Mediated Somatic Cell Therapy Into The Clinic, Dianne Nicol, Lisa Eckstein, Michael Morrison, Jacob S. Sherkow, Margaret Otlowski, Tess Whitton, Tania M. Bubela, Kathryn P. Burdon, Don Chalmers, Sarah Chan

Office of the Provost

Genome editing using clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated proteins offers the potential to facilitate safe and effective treatment of genetic diseases refractory to other types of intervention. Here, we identify some of the major challenges for clinicians, regulators, and human research ethics committees in the clinical translation of CRISPR-mediated somatic cell therapy.

Creating A Data Resource: What Will It Take To Build A Medical Information Commons?, Patricia A. Deverka, Mary A. Majumder, Angela G. Villanueva, Margaret Anderson, Annette C. Bakker, Jessica Bardill, Eric Boerwinkle, Tania M. Bubela, Barbara J. Evans, Nanibaa' A. Garrison

Office of the Provost

National and international public-private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is widely available for both research and clinical uses. Stakeholder participation is essential in clarifying goals, deepening understanding of areas of complexity, and addressing long-standing policy concerns such as privacy and security and data ownership. This article describes eight core principles proposed by a diverse group of expert stakeholders to guide the formation of a successful, sustainable …

Infectious Disease And The Diversification Of The Human Genome, Jessica F. Brinkworth

Human Biology Open Access Pre-Prints

The human immune system is under great pathogen-mediated selective pressure. A combination of divergent infectious disease pathogenesis across human populations, and the overrepresentation of “immune genes” in genomic regions with signatures of positive selection suggests that pathogens have significantly altered the human genome. However, important features of the human immune system can confound searches for and interpretations of signatures of pathogen-mediated evolution. Immune system redundancy, immune gene pleiotropy, host ability to acquire immunity and alter the immune repertoire of their offspring through “priming”, and host microbiome complicate evolutionary interpretations of host- pathogen interactions. The overall promiscuity and sensitivity of the …

Comparative Phylogeographic, Population Genomic, And Selection Inference With Development Of Hierarchical Co-Demographic Models, Alexander Xue

Dissertations, Theses, and Capstone Projects

Comparing demographic histories across assemblages of populations, species, and sister pairs has been a focus in phylogeography since its inception. Initial approaches utilized organelle genetic data and involved qualitative comparisons of genetic patterns for evaluating hypotheses of shared evolutionary responses to past environmental changes. This endeavor has progressed with coalescent model-based statistical techniques and advances in next-generation sequencing, yet there remains a need for methods that can analyze aggregated genomic-scale data from non-model organisms within a unified framework that considers individual taxon uncertainty and variance. To this end, the aggregate site frequency spectrum (aSFS), an expansion of the site frequency …

A Comparative Genome Analysis Of Cercospora Sojina With Other Members Of The Pathogen Genus Mycosphaerella On Different Plant Hosts, Fanchang Zeng, Xin Lian, Guirong Zhang, Xiaoman Yu, Carl A. Bradley, Ray Ming

Plant Pathology Faculty Publications

Fungi are the causal agents of many of the world's most serious plant diseases causing disastrous consequences for large-scale agricultural production. Pathogenicity genomic basis is complex in fungi as multicellular eukaryotic pathogens. Here, we report the genome sequence of C. sojina, and comparative genome analysis with plant pathogen members of the genus Mycosphaerella (Zymoseptoria. tritici (synonyms M. graminicola), M. pini, M. populorum and M. fijiensis - pathogens of wheat, pine, poplar and banana, respectively). Synteny or collinearity was limited between genomes of major Mycosphaerella pathogens. Comparative analysis with these related pathogen genomes indicated distinct genome-wide repeat …

Comprehensive Genomic Profiling In Routine Clinical Practice Leads To A Low Rate Of Benefit From Genotype-Directed Therapy, Talal Hilal, Mary Nakazawa, Jacob Hodskins, John L. Villano, Aju Mathew, Gaurav Goel, Lars M. Wagner, Susanne M. Arnold, Philip Desimone, Lowell B. Anthony, Peter J. Hosein

Markey Cancer Center Faculty Publications

Background: Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options.

Methods: Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT.

Results: A total of 125 pediatric …

Itraq-Based Proteomics Analysis And Network Integration For Kernel Tissue Development In Maize, Long Zhang, Yongbin Dong, Qilei Wang, Chunguang Du, Wenwei Xiong, Xinyu Li, Sailan Zhu, Yuling Li

Department of Biology Faculty Scholarship and Creative Works

Grain weight is one of the most important yield components and a developmentally complex structure comprised of two major compartments (endosperm and pericarp) in maize (Zea mays L.), however, very little is known concerning the coordinated accumulation of the numerous proteins involved. Herein, we used isobaric tags for relative and absolute quantitation (iTRAQ)-based comparative proteomic method to analyze the characteristics of dynamic proteomics for endosperm and pericarp during grain development. Totally, 9539 proteins were identified for both components at four development stages, among which 1401 proteins were non-redundant, 232 proteins were specific in pericarp and 153 proteins were specific in …

Transcriptional Analysis Of Abdominal Fat In Chickens Divergently Selected On Bodyweight At Two Ages Reveals Novel Mechanisms Controlling Adiposity: Validating Visceral Adipose Tissue As A Dynamic Endocrine And Metabolic Organ, Christopher W. Resnyk, Wilfrid Carré, Xiaofei Wang, Tom E. Porter, J. Simon, Elisabeth Le Bihan-Duval, Michel J. Duclos, Sammy E. Aggrey, Larry A. Cogburn

Biology Faculty Research

Background

Decades of intensive genetic selection in the domestic chicken (Gallus gallus domesticus) have enabled the remarkable rapid growth of today’s broiler (meat-type) chickens. However, this enhanced growth rate was accompanied by several unfavorable traits (i.e., increased visceral fatness, leg weakness, and disorders of metabolism and reproduction). The present descriptive analysis of the abdominal fat transcriptome aimed to identify functional genes and biological pathways that likely contribute to an extreme difference in visceral fatness of divergently selected broiler chickens.

Methods

We used the Del-Mar 14 K Chicken Integrated Systems microarray to take time-course snapshots of global gene transcription …

More Haste, Less Speed: Could Public-Private Partnerships Advance Cellular Immunotherapies?, Tania M. Bubela, Katherine Bonter, Silvy Lachance, Jean-Sébastien Delisle, E Richard Gol

Office of the Provost

Cellular immunotherapies promise to transform cancer care. However, they must overcome serious challenges, including: (1) the need to identify and characterize novel cancer antigens to expand the range of therapeutic targets; (2) the need to develop strategies to minimize serious adverse events, such as cytokine release syndrome and treatment-related toxicities; and (3) the need to develop efficient production/manufacturing processes to reduce costs. Here, we discuss whether these challenges might better be addressed through forms of public-private research collaborations, including public-private partnerships (PPPs), or whether these challenges are best addressed by way of standard market transactions. We reviewed 14 public-private relationships …

Draft Nuclear Genome, Complete Chloroplast Genome, And Complete Mitochondrial Genome For The Biofuel/ Bioproduct Feedstock Species Scenedesmus Obliquus Strain Doe0152z, S. R. Starkenburg, Juergen Polle, B. Hovde, H. E. Daligault, K. W. Davenport, A. Huang, P. Neofotis, Zaid Mckie-Krisberg

Publications and Research

The green alga Scenedesmus obliquus is an emerging platform species for the industrial production of biofuels. Here, we report the draft assembly and annotation for the nuclear, plastid, and mitochondrial genomes of S. obliquus strain DOE0152z.

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O⁶-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O⁶-alkylguanine and O⁴-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ω_ave. We found …

An Approach To Identify Mycobacteriophage Diversity Prior To Dna Sequencing, Charles Gregory

Mahurin Honors College Capstone Experience/Thesis Projects

Over 6,869 Mycobacteriophages have been isolated and purified. Of these, 1,367 genomes have been sequenced at the DNA level and more are added each year through the SEA-PHAGES program. Sequenced mycobacteriophages are grouped into clusters based on a 50% or greater nucleotide identity. The number and breadth of these clusters represents the diversity present in the environment. Each year, as new phages are discovered by students in the SEA-PHAGES program, the question arises, “Which isolates should we sequence?” In order to sequence phages that represent the greatest possible diversity, and thus broaden under-represented clusters and identify new singletons, we need …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Sivasai Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Selected Works Temporary Series

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Departmental Papers (Biology)

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Lichen Conservation In Eastern North America: Population Genomics, Climate Change, And Translocations, Jessica Allen

Dissertations, Theses, and Capstone Projects

Conservation biology is a scientific discipline that draws on methods from diverse fields to address specific conservation concerns and inform conservation actions. This field is overwhelmingly focused on charismatic animals and vascular plants, often ignoring other diverse and ecologically important groups. This trend is slowly changing in some ways; for example, increasing number of fungal species are being added to the IUCN Red-List. However, a strong taxonomic bias still exists. Here I contribute four research chapters to further the conservation of lichens, one group of frequently overlooked organisms. I address specific conservation concerns in eastern North America using modern methods. …

Body Size Regulation Via Bmp Signaling In Caenorhabditis Elegans, Uday Madaan

Dissertations, Theses, and Capstone Projects

The body size of an organism can be a crucial determinant of access to nutrition, reproductive success and overall survival in the wild. However, how body size of an individual is determined is incompletely understood. Body size is a complex trait determined by multiple pathways and genes, making it difficult to understand the role of individual genes and pathways in determining overall size. In Caenorhabditis elegans, a homolog of Bone Morphogenetic Proteins (BMP) is a major regulator of body size; functional loss of DBL-1 leads to a small body size. Due to a drastic change in body size in dbl-1 …

Isolation And Comparative Genomic Analysis Of Final Third Of Satis Genome, Kelly Hartigan, Nicole Curnutt, Matthew Mcdermut

Undergraduate Research Symposium Posters

A highly novel Streptomyces phage, Satis, was isolated from a direct environmental sample collected from outside Danforth House on the Washington University campus. Satis infects bacterial species Streptomyces lividans producing pinpoint, cloudy plaques less than 1mm in diameter. Electron microscope data shows rare atypical physical features. Rather than the common octahedral capsid shape, Satis has a prolate head with visible cross-linked hexagonal protein structure and average measurements of 285 nm by 47 nm with a long, flexible tail measuring 268 nm. Upon sequencing, it was found that Satis contains the longest phage genome discovered to date through the SEA-PHAGE program …

Using Mathematical Models Of Biological Processes In Genome-Wide Association Studies Of Psychiatric Disorders, Amy Cochran

Biology and Medicine Through Mathematics Conference

No abstract provided.

Software Development For Genome Sequence Analysis, David Farr

Symposium Of University Research and Creative Expression (SOURCE)

The cost of genome sequencing has decreased rapidly, expanding availability for many biological applications (Muir 2016). For example, researchers can now obtain genome sequences from multiple populations under different types of selection. Comparison of these sequences allows for identification of chromosome regions and specific genes associated with adaptive evolution (Kelly 2013). As an increasing number of researchers engage in this type of inquiry, many have created in-house computer scripts to analyze the raw sequence data (e.g., Kelly 2013), creating a gap in both continuity and standardization.

Using a test dataset and preliminary results from an ongoing artificial selection experiment in …

Dna Sequences Of The Mitochondrial Cytochrome C Oxidase I (Coi) Genes From Deep Sea Fishes. Cruises Dp01 And Dp02 From May 2015 - August 2015, Andrea Bernard, Max Weber, Kimberly A. Finnegan, Mahmood S. Shivji, Ron Eytan

DEEPEND Datasets

The deep sea ecosystem is believed to contain the highest biomass of fish in the oceans. However, the taxonomic diversity in this ecosystem is incompletely described and likely to be vastly underestimated. DNA sequence data (barcodes) have become a key tool to discover hidden biodiversity. We generated mitochondrial DNA barcode datasets based on the Cytochrome c oxidase I (COI) gene from deep sea fishes. These data were analyzed using phylogenetic and statistical methods to reveal cryptic species and make taxonomic linkages between adult fishes and their early life stages. These datasets were generated from fishes collected in the Northern Gulf …

Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure

Theses & Dissertations

Preterm birth is a complex multifactorial process. Despite the well-known role of the placenta in supporting the fetal development and maternal-fetal tolerance, the placental epigenetic modifications and preterm birth (PTB) remains poorly understood and under investigated. Various maternal and environment factors can influence epigenetic programming during fetal development to affect the functioning and structures of organs, including the placenta, which can lead to adverse pregnancy outcomes, including PTB. The understanding of the placental epigenetic alterations and maternal determinants associated with PTB are apparently indispensable for the development of actual diagnosis and methods of prevention and treatment of premature labor. The …

Study Of Rickettsia Parkeri Colonization And Proliferation In The Tick Host Amblyomma Maculatum (Acari: Ixodidae), Khemraj Budachetri

Dissertations

Amblyomma maculatum (Gulf coast tick) ticks are prevalent across the Atlantic to Gulf Coast region of United States. These ticks are recognized vectors of Rickettsia parkeri, a spotted fever group of Rickettsia (SFGR) known to cause American boutonneuse fever associated with fever and eschar rashes localized to the site of bites. We hypothesized that Rickettsia parkeri colonization and proliferation in the tick vector involve pathogen-symbiont dynamics and tick-pathogen interactions, which influence rickettsial transmission to the victims after tick bites. The rickettsial infection is maintained across the tick life cycle for many generations due to transovarial and transstadial transmission of …

Denoising Tandem Mass Spectrometry Data, Felix Offei

Electronic Theses and Dissertations

Protein identification using tandem mass spectrometry (MS/MS) has proven to be an effective way to identify proteins in a biological sample. An observed spectrum is constructed from the data produced by the tandem mass spectrometer. A protein can be identified if the observed spectrum aligns with the theoretical spectrum. However, data generated by the tandem mass spectrometer are affected by errors thus making protein identification challenging in the field of proteomics. Some of these errors include wrong calibration of the instrument, instrument distortion and noise. In this thesis, we present a pre-processing method, which focuses on the removal of noisy …

Statistical Methods For Two Problems In Cancer Research: Analysis Of Rna-Seq Data From Archival Samples And Characterization Of Onset Of Multiple Primary Cancers, Jialu Li

Dissertations and Theses (Open Access)

My dissertation is focused on quantitative methodology development and application for two important topics in translational and clinical cancer research.

The first topic was motivated by the challenge of applying transcriptome sequencing (RNA-seq) to formalin-fixation and paraffin-embedding (FFPE) tumor samples for reliable diagnostic development. We designed a biospecimen study to directly compare gene expression results from different protocols to prepare libraries for RNA-seq from human breast cancer tissues, with randomization to fresh-frozen (FF) or FFPE conditions. To comprehensively evaluate the FFPE RNA-seq data quality for expression profiling, we developed multiple computational methods for assessment, such as the uniformity and continuity …

Non-Coding Rnas Identify The Intrinsic Molecular Subtypes Of Muscle-Invasive Bladder Cancer, Andrea E. Ochoa

Dissertations and Theses (Open Access)

NON-CODING RNAS IDENTIFY THE INTRINSIC MOLECULAR SUBTYPES OF MUSCLE-INVASIVE BLADDER CANCER

Andrea Elizabeth Ochoa, B.S.

Advisory Professors: David J. McConkey, Ph.D. and Joya Chandra, Ph.D.

There has been a recent explosion of genomics data in muscle-invasive bladder cancer (MIBC) to better understand the underlying biology of the disease that leads to the high amount of heterogeneity that is seen clinically. These studies have identified relatively stable intrinsic molecular subtypes of MIBC that show similarities to the basal and luminal subtypes of breast cancer. However, previous studies have primarily focused on protein-coding genes or DNA mutations/alterations.

There is emerging evidence implicating …

Systematic Analysis Of Whole Exome Sequencing Determines Ret G691s Polymorphism As Germline Variant In Melanoma, Brent J. Smith Jr, Jennifer D. Hintzsche, Carol M. Amato, Aik-Choon Tan, Keith R. Wells, Allison J. Applegate, Rita T. Gonzalez, Jodie R. Barr, William A. Robinson

Marshall Journal of Medicine

Abstract

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA …

Accumulation And Expression Of Multiple Antibiotic Resistance Genes In Arcobacter Cryaerophilus That Thrives In Sewage, Jess A. Millar, Rahul Raghavan

Biology Faculty Publications and Presentations

We explored the bacterial diversity of untreated sewage influent samples of a wastewater treatment plant in Tucson, AZ and discovered that Arcobacter cryaerophilus, an emerging human pathogen of animal origin, was the most dominant bacterium. The other highly prevalent bacteria were members of the phyla Bacteroidetes and Firmicutes, which are major constituents of human gut microbiome, indicating that bacteria of human and animal origin intermingle in sewage. By assembling a near-complete genome of A. cryaerophilus, we show that the bacterium has accumulated a large number of antibiotic resistance genes (ARGs) probably enabling it to thrive in the wastewater. We also …

Rseqrep: Rna-Seq Reports, An Open-Source Cloud-Enabled Framework For Reproducible Rna-Seq Data Processing, Analysis, And Result Reporting, Travis L. Jensen, Michael Frasketi, Kevin Conway, Leigh Villarroel, Heather Hill, Konstantinos Krampis, Johannes B. Goll

Publications and Research

RNA-Seq is increasingly being used to measure human RNA expression on a genome-wide scale. Expression profiles can be interrogated to identify and functionally characterize treatment-responsive genes. Ultimately, such controlled studies promise to reveal insights into molecular mechanisms of treatment effects, identify biomarkers, and realize personalized medicine. RNA-Seq Reports (RSEQREP) is a new open-source cloud-enabled framework that allows users to execute start-to-end gene-level RNA-Seq analysis on a preconfigured RSEQREP Amazon Virtual Machine Image (AMI) hosted by AWS or on their own Ubuntu Linux machine. The framework works with unstranded, stranded, and paired-end sequence FASTQ files stored locally, on Amazon Simple Storage …