Genetics and Genomics Commons^™

Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy

Dissertations and Theses (Open Access)

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. All of these thiol-modifiers have been demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of thiol stress toxicity responsible for these outcomes are largely unknown. Furthermore, I hypothesize proteins identified as redox-active are prone to misfolding and aggregation by thiol-specific …

Higher Order Chromosome Organization And Recombination Dynamics Of Meiotic Prophase I In Mouse Spermatocytes, Rhea Kang

Dissertations and Theses (Open Access)

Meiotic recombination is required for parental chromosomes to find each other (pairing/synapsis) and to exchange genetic information thus allowing faithful segregation of chromosomes and the production of haploid gametes. At the start of meiotic prophase I, meiotic chromosomes organize into loop arrays that extrude out of the chromosome axis. Then, a large number of programmed double-strand breaks (DSBs) are formed at specific chromosomal locations or “hotspots” on parental chromosomes, which are repaired by homologous recombination (HR). HR produces either crossovers, which result in the exchange of flanking markers between homologs, or noncrossovers, which are short regions ofgene conversion to the …

Sequence-Specific Gene Correction Of Cystic Fibrosis Airway Basal Cells, Varada Anirudhan

Dissertations and Theses (Open Access)

Cystic fibrosis (CF) is a lethal monogenic disease resulting from mutations in the CFTR gene which encodes a protein involved in regulating anion trans-epithelial transport. A three-base deletion in CFTR (termed as ΔF508 mutation), wherein CFTR protein is misfolded leading to its pre-mature degradation in the endoplasmic reticulum (ER), is the most common cause of this debilitating disease. Since CFTR is expressed in multiple body systems, CF affects different organs, but lung pathology is the greatest cause of death in affected patients. We achieved site-specific gene correction with an efficiency of ~10 % in CF airway basal cells homozygous for …

Cellular Localization Of Rad51d Mutant Proteins And The Application Of Art To Increase Scientific Literacy In America, Claire L. Chabot

Senior Theses

Ovarian cancers are the leading cause of death from cancer of the female reproductive system. Approximately 50% of ovarian cancers have defects in the homologous recombination (HR) DNA repair pathway that is required for the repair of DNA double-stranded breaks. The status of HR genes, such as BRCA1, BRCA2, and the RAD51 family, contributes to ovarian cancer development as well as treatment decisions regarding chemotherapy, radiation, and immunotherapy. The overarching goal of this project is to identify new insights into HR that can integrate with Precision Medicine Initiatives and align with the goals of the Cancer Moonshot 2020 Program. I …

Characterization Of Macrophomina Phaseolina Infecting Chia Plants, Cailyn Sakurai, Hagop S. Atamian, Julien Besnard

Student Scholar Symposium Abstracts and Posters

Microbial organisms have caused detrimental effects to agricultural plants by significantly decreasing their plant growth yield and it’s nutritional qualities, leading to high levels of economic losses in society. Salvia Hispanica L., commonly known as chia, is becoming a rising agricultural crop because of its favorable nutritional qualities. Chia seeds have a high concentration of α-linolenic acid, commonly known as omega-3 fatty acids) which provide several different health benefits, in addition to being a rich source of protein and fiber. Chia field trial conducted by the Atamian lab during summer 2018, experienced high levels of disease incidence characterized by …

Streptococcus Agalactiae Strains With Chromosomal Deletions Evade Detection With Molecular Methods, Isabella A. Tickler, Fred C. Tenover, Scott Dewell, Victoria M. Le, Rachel N. Blackman, Richard V. Goering, Amy E. Rogers, Heather Piwonka, Brittney D. Jung-Hynes, Derrick J. Chen, Michael J. Loeffelholz, Devasena Gnanashanmugam, Ellen Jo Baron

Biology Faculty Publications

Surveillance of circulating microbial populations is critical for monitoring the performance of a molecular diagnostic test. In this study, we characterized 31 isolates of Streptococcus agalactiae (group B Streptococcus [GBS]) from several geographic locations in the United States and Ireland that contain deletions in or adjacent to the region of the chromosome that encodes the hemolysin gene cfb, the region targeted by the Xpert GBS and GBS LB assays. PCR-negative, culture-positive isolates were recognized during verification studies of the Xpert GBS assay in 12 laboratories between 2012 and 2018. Whole-genome sequencing of 15 GBS isolates from 11 laboratories revealed …

Associations Of Circulating Very-Long-Chain Saturated Fatty Acids And Incident Type 2 Diabetes: A Pooled Analysis Of Prospective Cohort Studies, Amanda M. Fretts, Fumiaki Imamura, Matti Marklund, Renata Micha, Jason H. Y. Wu, Rachel A. Murphy, Kuo-Liong Chien, Barbara Mcknight, Nathan L. Tintle, Nita G. Forouhi, Waqas T. Qureshi, Jyrki K. Virtanen, Kerry Wong, Alexis C. Wood, Maria Lankinen, Kalina Rajaobelina, Tamara B. Harris, Luc Djousse, Bill Harris, Nick J. Wareham, Lyn M. Steffen, Markku Laakso, Jenna Veenstra, Cecilia Samieri, Ingeborg A. Brouwer, Chaoyu Ian Yu, Albert Koulman, Brian T. Steffen, Catherine Helmer, Nona Sotoodehnia, David Siscovick, Vilmunder Gudnason, Interact Consortium, Lynne Wagenknecht, Sari Voutilainen, Michael Y. Tsai, Matti Uusitupa, Anya Kalsbeek, Claudine Berr, Dariush Mozaffarian, Rozenn N. Lemaitre

Faculty Work Comprehensive List

Background: Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed.

Objective: We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies.

Methods: Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. …

Dna Double Strand Breaks: To Repair, Or Not To Repair, Susiyan Jiang

NYMC Student Theses and Dissertations

DNA damages that cause double-strand breaks (DSBs) to the chromosome are most harmful. Subsequent choices have critical consequences for cell fate. Without repair, cells will face certain death. Low-fidelity repair will introduce mutations that could transform the cells, leading to carcinogenesis.

How cells make the decision is not well-understood. A single DSB can lead to apoptosis for some cells, whereas others can repair up to 25 DSBs and survive. It has been postulated that decision to repair DSBs is a stochastic process.

In the nucleus, DSBs elicit a cascade of signaling events that require the recognition, protection, processing, and subsequent …

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential …

Investigating Comt Influence On The Proactive-Reactive Stress Coping Axis In Zebrafish, Sean T. Bresnahan, Ryan Y. Wong

UNO Student Research and Creative Activity Fair

Individuals of the same species often display differences in correlated suites of behaviors which are made conspicuous when challenges – stressful, fear-inducing, etc. – are presented. In many species, a specific suite of behaviors (risk-aversion, aggression, exploration, learning, and memory) characterize an alternative set of stress coping styles (proactive and reactive). Such behaviors are regulated in the brain by specific neurotransmitters along with proteins that regulate them. One neurotransmitter regulator protein, catechol-O-methyltransferase (COMT) shows higher baseline whole-brain expression in proactive relative to reactive animals. However, it is not known whether its expression is a cause or a consequence of the …

Diversity Of Resistance Mechanisms In Carbapenem-Resistant Enterobacteriaceae At A Health Care System In Northern California, From 2013 To 2016, Fiona Senchyna, Rajiv L. Gaur, Johanna Sandlund, Cynthia Truong, Guillaume Tremintin, Dietmar Kültz, Carlos A. Gomez, Fiona B. Tamburini, Tessa Andermann, Ami Bhatt, Isabella A. Tickler, Nancy Watz, Indre Budvytiene, Gongyi Shi, Fred C. Tenover, Niaz Banaei

Biology Faculty Publications

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) bla_KPC, 20.8% (5/24) bla_NDM, 20.8% (5/24) bla_SME, 8.3% (2/24) bla_IMP, and 4.2% (1/24) bla_VIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing bla_KPC were 100% susceptible to ceftazidime–avibactam, meropenem–vaborbactam, …

Investigating The Dna-Binding Site For Virb, A Key Transcriptional Regulator Of Shigella Virulence Genes, Using An In Vivo Binding Tool, Monika M.A. Karney, Joy A. Mckenna, Natasha Weatherspoon-Griffin, Alexander D. Karabachev, Makensie E. Millar, Eliese A. Potoceck, Helen J. Wing

Life Sciences Faculty Research

The transcriptional anti-silencing and DNA-binding protein, VirB, is essential for the virulence of Shigella species and, yet, sequences required for VirB-DNA binding are poorly understood. While a 7-8 bp VirB-binding site has been proposed, it was derived from studies at a single VirB-dependent promoter, icsB. Our previous in vivo studies at a different VirB-dependent promoter, icsP, found that the proposed VirB-binding site was insufficient for regulation. Instead, the required site was found to be organized as a near-perfect inverted repeat separated by a single nucleotide spacer. Thus, the proposed 7-8 bp VirB-binding site needed to be re-evaluated. Here, we engineer …

Mrub_3019 Casa Gene Is An Ortholog To E. Coli B2760, Kelsey Heiland, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This research is part of the Meiothermus ruber genome annotation project which aims to predict gene function with various bioinformatics tools. We investigated the function of Mrub_3019, which encodes the CasA protein involved in the multi-subunit effector complex for the CRISPR-Cas immunity system and predicted it to be an ortholog of E. coli K12 MG1655 b2760 (casA). We predicted that Mrub_3019 encodes the protein CasA, which is involved in PAM recognition of CRISPR interference pathway. Foreign DNA will bind to CasA, which signals Cas3 for helicase-mediated DNA degradation. Our hypothesis is supported by low E-values for pairwise alignment in NCBI …

Mrub_3015 Is Orthologous To The B2757 Gene Found In Escherichia Coli Coding For Casd, Ramona Collins, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of the gene Mrub_3015, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system. We predict that Mrub_3015 (DNA coordinates 3055550...3056245) encodes the the CRISPR-associated protein cas5, which is integral in maintaining the crRNA-DNA structure, keeping the complex from base pairing with the target phage DNA. Our hypothesis is supported by identical hits for Mrub_3015 and b2527 to the KEGG, Pfam, TIGRfam, CDD and PDB databases as well as a …

Mrub_3018 Is Orthologous To E. Coli B2759 (Casb), Kyle Parker, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We studied the biological activity of the Mrub_3018 gene, which we hypothesize is orthologous to E. coli gene B2759. We predicted that Mrub_3018(DNA coordinates 3057916… 3058524) encodes the protein CasB. CasB is a protein in the CRISPR CASCADE that will function as a structural protein. When the rest of the proteins form an “S” formation CasB will connect the front and back of the “S” creating a back bone for the structure. It will help bind DNA …

Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon

Theses and Dissertations

This study phylogenetically analyzed 30 AMY-related genes from 11 primates. The results show the gradual expansion of the AMY gene family which could have allowed primates to adapt to various ecological landscapes and maximize energy intake from starch-rich foods in periods of food scarcity.

Cyclin C: The Story Of A Non-Cycling Cyclin, Jan Jezek, Daniel G J Smethurst, David C Stieg, Z A C Kiss, Sara E Hanley, Vidyaramanan Ganesan, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit …

An Albino Mutant In Brassica Rapa Maps To The Pdx2 Locus On Chromosome 10, Beatriz M. Garcia

STAR Program Research Presentations

We have identified an albino mutant in the plant Brassica rapa. This recessive mutation could provide insights into the photosynthetic pathways of all plants. Previously the mutation was mapped to chromosome 10 of Brassica rapa. To narrow down the chromosomal region containing the albino mutation, we grew a segregating population of plants. DNA was extracted from albino and wildtype (green) plants and genotyped using PCR markers on chromosome 10. The genotype detected using the INDEL2 marker perfectly predicted whether a plant was albino or WT. This indicates that the INDEL2 marker is tightly linked to the albino mutation. INDEL2 is …

Dna Methylation Associated With Postpartum Depressive Symptoms Overlaps Findings From A Genome-Wide Association Meta-Analysis Of Depression, Dana M. Lapato, Roxann Roberson-Nay, Robert M. Kirkpatrick, Bradley T. Webb, Timothy P. York, Patricia A. Kinser

Human and Molecular Genetics Publications

Background Perinatal depressive symptoms have been linked to adverse maternal and infant health outcomes. The etiology associated with perinatal depressive psychopathology is poorly understood, but accumulating evidence suggests that understanding inter-individual differences in DNA methylation (DNAm) patterning may provide insight regarding the genomic regions salient to the risk liability of perinatal depressive psychopathology.

Results Genome-wide DNAm was measured in maternal peripheral blood using the Infinium MethylationEPIC microarray. Ninety-two participants (46% African-American) had DNAm samples that passed all quality control metrics, and all participants were within 7 months of delivery. Linear models were constructed to identify differentially methylated sites and regions, …

Mrub_3014 Is Orthologous To B2756, Samir Abdelkarim, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of the gene Mrub_3014, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system. We predict that Mrub_3014 (DNA coordinates 3054943..3055575) encodes CRISPR-associated protein Cse3/case which function as an endonuclease. Our hypothesis is supported by identical hits for Mrub_3014 and b2756 to the KEGG, Pfam, TIGRfam, CDD and PDB databases, as well as a low E-value for a pairwise NCBI BLAST comparison. Both protein products are predicted to be localized …

M. Ruber Mrub_3013 Is Orthologous To E. Coli B2755, Laura Butcher, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of gene Mrub_3013, which we hypothesize is orthologous to b2755 in E. coli K12 MG1655 (a.k.a. Cas1). We investigated the biological function of a gene with the M. ruber locus tag of Mrub_3013, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system in M. ruber. We predict that Mrub_3013 (DNA coordinates 3,053,978-3,054,940) encodes the protein Cas1 which as part of the CRISPR-Cas system, selects and cuts the foreign …

Mrub_3020, A Paralog Of Mrub_1489, Is Orthologous To E. Coli Casc (Locus Tag B2761), Alfred Dei-Ampeh, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological functions of two genes: mrub_3020 and mrub_1489. We make two hypotheses in this investigation: a) mrub_3020 is orthologous to the gene b2761 in E. coli K12 MG1655 (a.k.a. casC); b) mrub_1489 is a paralog of mrub_3020. We also predict that the two genes encode unique proteins: mrub_3020 with DNA coordinates 3060491…3063190 encodes a CRISPR – associated helicase (Cas3) that supports the Cascade complex of the CRISPR – Cas adaptive immune system …

Effects Of Temperature On Crispr/Cas System, Eddie Beckom, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the effect of temperature on the complexity of CRISPR/Cas systems in bacterial organisms across temperature classifications. We predict that temperature extremes would result in CRISPR/Cas systems with multiple operons, repeating cas genes, and complex systems. CRISPR/Cas systems can be classified into three types with a number of subtypes based on the CRISPR-associated genes, cas genes, present in a given organism. Our hypothesis is supported by the presence of multiple operons in thermophilic organisms based on …

An Investigation Into The Relationship Between Mrub_3013, Mrub_1477, And Mrub_0224: Are They Paralogs?, Melette Devore, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of mrub_3013 and the nature of its relationship with mrub_1477 and mrub_0224. We hypothesized that mrub_3013 is orthologous to b2755 in E. coli K12 MG1655 (a.k.a. cas1). We predict that mrub_3013 encodes the enzyme Cas1, which is involved in spacer acquisition in the CRISPR-Cas prokaryotic defense system. Our hypothesis is supported by identical hits for b2755, mrub_3013, mrub_1477, and mrub_0224 from the CDD and Pfam databases and highly similar hits from …

Comparative Analysis Of Four Dna Preparation Kits For Quercus Falcata, Palustris, And Rubra Dna Extractions And Subsequent Dna Sequencing, Devin Cummins, Timothy D. Trott

Research in Biology

In 2011, of the 8.7 million species of lif suspected to populate the globe only 1.2 million had been catalogued and it was estimated that 1,200 years would pass before the remainder were processed, allowing the possibility that some species would go extinct before they were even discovered (Mora, Tittensor, Adl, Simpson, & Worm, 2011). DNA barcoding may provide an answer to this problem. According to Hebert and Gregory, “DNA barcoding will accelerate the pace of species discovery by allowing taxonomists to rapidly sort specimens... by highlighting divergent taxa that may represent new species… and by making species identifications more …

Evolution Of The Zhx Transcription Factor Family And Analysis Of Zhx2 Target Genes Cyp2a4 And Cyp2a5 In Mouse Liver, Alexandra Nichole Nail

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

The liver is the largest internal organ and performs a wide variety of functions to maintain organismal homeostasis. While some liver functions are carried out by all hepatocytes, other functions are restricted to certain populations of hepatocytes within the liver. This phenomenon, called zonal gene regulation or liver zonation, controls may metabolic processes within the liver including ammonia detoxification; glucose homeostasis; bile acid and glutamine synthesis; and metabolism of xenobiotics, lipids, and amino acids. The liver also expresses many genes in a developmental or sex-biased manner. Some genes are expressed at higher levels early or late in development, or alternatively, …

Insects And The Evolution Of Developmental Pathways: Functional Analysis Of Genetic Sex Determination Mechanisms In Oncopeltus Fasciatus, Josefine Just

Honors Theses

Natural selection alters genetic pathways over evolutionary time. However, different pathways have been shown to maintain mutations at varying rates, leading to different levels of conservation across developmental pathways. Sex determination pathways, in particular, show vast diversity across animals despite the fundamental conservation of biological sex itself. Here, I investigated the sex determination pathway of the hemimetabolous insect, Oncopeltus fasciatus. The large milkweed bug, O. fasciatus, is part of the order Hemiptera, which provides a relevant outgroup study to other insects in which sex determination has been studied to date. I studied three sex determination genes, intersex, fruitless …

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …

Exploration Of Sonic Hedgehog Gene Expression In Fathead Minnows (Pimephales Promelas), Brooke Renee Greiner

Undergraduate Honors Theses

Pollutants, as a result of wastewater treatments, have been shown to have negative impacts on aquatic ecosystems. To better understand the possible consequences caused by effluents on ecosystems, it is important to examine ecotoxicology data. One of the most commonly used species for water quality testing is the fathead minnow, Pimephales promelas. Ecotoxicology can then be taken one step further to understand the effects of pollutants on a molecular level. Previous research had identified effluents as causes for abnormal minnow fin morphology. In order to collect additional data on development, tanks with fathead minnows were placed at the Charleston …