Genetics and Genomics Commons^™

Maintenance Of Genetic And Epigenetic Stability During Dna Double-Strand Break Repair And Dna Replication, Nathaniel Edward Wiest

Biomedical Sciences ETDs

Eukaryotic genomes are assembled into a complex of DNA and proteins known as chromatin. The packaging of DNA into chromatin is the foundational strategy that cells use to both compress genomic DNA into nuclei and regulate access to its contents. The basic repeating subunit of chromatin is the nucleosome, composed of an octamer of two copies of each of the core histone proteins H2A, H2B, H3, and H4 around which 146 bp of DNA are tightly wrapped. While the compaction of genomes into chromatin offers cells significant advantages, it also presents serious challenges to fundamental processes that maintain genome integrity, …

Root Hair Single Cell Type Specific Profiles Of Gene Expression And Alternative Polyadenylation Under Cadmium Stress, Jingyi Cao, Congting Ye, Guijie Hao, Carole Dabney-Smith, Arthur G. Hunt, Qingshun Q. Li

Plant and Soil Sciences Faculty Publications

Transcriptional networks are tightly controlled in plant development and stress responses. Alternative polyadenylation (APA) has been found to regulate gene expression under abiotic stress by increasing the heterogeneity at mRNA 3′-ends. Heavy metals like cadmium pollute water and soil due to mining and industry applications. Understanding how plants cope with heavy metal stress remains an interesting question. The Arabidopsis root hair was chosen as a single cell model to investigate the functional role of APA in cadmium stress response. Primary root growth inhibition and defective root hair morphotypes were observed. Poly(A) tag (PAT) libraries from single cell types, i.e., root …

Characterization Of Bacterial Isolates Obtained From Commercial Poultry Feed And Retail Food Using Whole Genome Sequence Analysis And Selected Biochemical Tests, Elena George Olson

Electronic Theses & Dissertations

The goals of this study is two-fold. The first part investigates bacterial isolates from commercial poultry feed and the second part deals with bacterial isolates recovered from retail food. In order to reduce pathogen contamination in poultry products identification of overall microbial populations in poultry production processing steps have always been considered an important monitoring tool for assessing sanitizer effectiveness and the corresponding responses of bacteria load levels on poultry carcasses. Bacterial isolates recovered from corn-based chicken feed were purified on aerobic plate count agar and eleven morphologically different colonies were selected for whole genome sequencing. In this part, the …

What Lies Beneath? Molecular Evolution During The Radiation Of Caecilian Amphibians, María Torres-Sánchez, David J. Gower, David Alvarez-Ponce, Christopher J. Creevey, Mark Wilkinson, Diego San Mauro

Neuroscience Faculty Publications

Background: Evolution leaves an imprint in species through genetic change. At the molecular level, evolutionary changes can be explored by studying ratios of nucleotide substitutions. The interplay among molecular evolution, derived phenotypes, and ecological ranges can provide insights into adaptive radiations. Caecilians (order Gymnophiona), probably the least known of the major lineages of vertebrates, are limbless tropical amphibians, with adults of most species burrowing in soils (fossoriality). This enigmatic order of amphibians are very distinct phenotypically from other extant amphibians and likely from the ancestor of Lissamphibia, but little to nothing is known about the molecular changes underpinning their radiation. …

Rising Rural Body-Mass Index Is The Main Driver Of The Global Obesity Epidemic In Adults, Con Burns, Tara Coppinger, Janette Walton, Et Al

Publications

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to …

Extracellular Vesicle Encapsulated Micrornas In Patients With Type 2 Diabetes Are Affected By Metformin Treatment., Vikas Ghai, Taek-Kyun Kim, Alton Etheridge, Trine Nielsen, Torben Hansen, Oluf Pedersen, David Galas, Kai Wang

Articles, Abstracts, and Reports

Recently, microRNAs (miRNAs) in circulating extracellular vesicles (EVs), have emerged as a source of potential biomarkers for various pathophysiological conditions, including metabolic disorders such as diabetes. Type 2 diabetes mellitus (T2DM), is the most prevalent form of diabetes in the USA, with 30 million diagnosed patients. Identifying miRNA biomarkers that can be used to assess response to glucose lowering treatments would be useful. Using patient plasma samples from a subset of the Danish Metagenomics of the Human Intestinal Tract (MetaHIT) cohort, we characterized miRNAs from whole plasma, plasma-derived EVs, and EV-depleted plasma by small RNA-sequencing to identify T2DM associated miRNAs. …

Analyzing The Effect Of Apoptotic Mutations On The State Of The Nascent-Polypeptide Associated Complex In Caenorhabditis Elegans, Monica Gerber

Senior Honors Projects, 2010-2019

Cells experiencing misfolded protein stress can become debilitated and die, contributing to the onset of disease. The nascent polypeptide-associated complex (NAC) is a heterodimeric translational chaperone that protects against misfolded protein stress by mediating proper protein folding and localization during translation. Depletion of this complex results in misfolded protein accumulation in the endoplasmic reticulum (ER). To determine the importance of the NAC to proteostasis, we have previously depleted the complex in C.elegans via RNA interference and observed numerous dose-dependent effects, including apoptosis of neuronal cells and changes in gene expression of hypodermal cells. While we have observed these cell-specific responses …

Detecting The Cold: Do Innexins Function In Cold Nociception?, Rachel Barborek

Senior Honors Projects, 2010-2019

Nociception is the perception of and response to harmful stimuli. Nociception is essential for minimizing tissue damage, but aberrant nociceptive pathways can result in chronic pain. Chronic pain in the U.S. is commonly managed with wide-acting opioids, and precisely defining the components of nociceptive pathways could uncover novel targets for pain therapies. I hypothesize that the vitally quick process of nociception would utilize electrical synapses because they transmit signals between neurons more quickly than chemical synapses do. This study, therefore, aims to uncover the potential role of the eight Drosophila melanogaster gap junction proteins, the Innexins, in cold nociception. Wild …

Genetic Diversity Of Local Canines Assessed By Derived Cleaved Amplified Polymorphic Sequences, Nicole Benmoshe, Jeremy Seto

Publications and Research

Breeding of the dog, Canis Iupus familiaris, over centuries has given rise to the selection of certain traits including size, shape, coat length, color and many behavioral traits. Inbreeding within dog breeds has resulted in the increase of genetic diseases, many of which are similar to human diseases making the dog an exemplary model organism to study. Using dCAPS (Derived Cleaved Amplified Polymorphic Sequences) we can identify SNPs (Single Nucleotide Polymorphisms) in the dog genome using buccal samples collected from four local dogs of different breeds, both large and small. After performing DNA extractions, PCR (Polymerase Chain Reaction), restriction enzyme …

Loop-Ligation Of Dna Nanoswitch For Sensitivity Increase, Lillie Carnell

CURCE Annual Undergraduate Conference

DNA nanoswitches are tools to detect nucleic acids such as microRNAs and viral RNAs. The DNA nanoswitch is a linear duplex structure created from single-stranded circular viral M13 DNA using a DNA origami approach. Each nanoswitch can be designed to have explicit detector strands that bind to a specific DNA sequence. In the presence of a particular target sequence, the DNA nanoswitch will undergo a conformational change in which it switches from a linear “off” state to a looped “on” state. The shape of the DNA nanoswitch can then be detected using standard gel electrophoresis, a cheap and simple test. …

Yeast Mitochondrial Protein Pet111p Binds Directly To Two Distinct Targets In Cox2 Mrna, Suggesting A Mechanism Of Translational Activation, Julia L Jones, Katharina B Hofmann, Andrew T Cowan, Dmitry Temiakov, Patrick Cramer, Michael Anikin

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The genes in mitochondrial DNA code for essential subunits of the respiratory chain complexes. In yeast, expression of mitochondrial genes is controlled by a group of gene-specific translational activators encoded in the nucleus. These factors appear to be part of a regulatory system that enables concerted expression of the necessary genes from both nuclear and mitochondrial genomes to produce functional respiratory complexes. Many of the translational activators are believed to act on the 5'-untranslated regions of target mRNAs, but the molecular mechanisms involved in this regulation remain obscure. In this study, we used a combination of in vivo and in …

Genetic Predisposition Impacts Clinical Changes In A Lifestyle Coaching Program., Niha Zubair, Matthew P Conomos, Leroy Hood, Gilbert S Omenn, Nathan D Price, Bonnie J Spring, Andrew T Magis, Jennifer C Lovejoy

Articles, Abstracts, and Reports

Both genetic and lifestyle factors contribute to an individual's disease risk, suggesting a multi-omic approach is essential for personalized prevention. Studies have examined the effectiveness of lifestyle coaching on clinical outcomes, however, little is known about the impact of genetic predisposition on the response to lifestyle coaching. Here we report on the results of a real-world observational study in 2531 participants enrolled in a commercial "Scientific Wellness" program, which combines multi-omic data with personalized, telephonic lifestyle coaching. Specifically, we examined: 1) the impact of this program on 55 clinical markers and 2) the effect of genetic predisposition on these clinical …

Receptor-Mediated Maturation Of Olfactory Sensory Neurons: A Time Course Evaluation Of Neuronal Maturation In Neomorphic Mutants, Elizabeth Miller

Theses and Dissertations

How expression of odorant receptors affects the maturation of olfactory sensory neurons (OSNs) is not known. In a time course experiment, we show that wild type OSNs mature significantly more than those expressing Neomorphic mutant receptors. We conclude that functional receptors are critical to the differentiation and survival of OSNs.

Times Of Action And Evolutionary Conservation Of Heterochronic Genes, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

Specific genes called heterochronic genes control the timing and sequence of developmental events during larval stages of C. elegans. Mutations in heterochronic genes can cause skipping or reiteration of cell fates associated with certain larval stages. lin-14 and lin-28 are two well-studied heterochronic genes. LIN-14 acts during the first larval stage (L1) and controls events of the L1 and L2 stages, LIN-28 acts during the L2 stage and controls its events.

Acute Promyelocytic Leukemia: A Case Study Correlating Cytogenetic Abnormality With Prognosis, Alyssa Lamond, Theresa Tellier-Castellone

Senior Honors Projects

Advancements in medical technology today have positively impacted the diagnosis, treatment, and prognosis of cancers. Particularly acute promyelocytic leukemia (APL) has completely improved from having the poorest prognosis to one of the best. Acute promyelocytic leukemia is a malignant disease of hematopoietic tissue classified by WHO as leukemia with >20% blasts from the myeloid lineage, specifically promyelocytes. Determined in 1976, FAB classified AML subtypes M1-M7, with APL being M3. Specific characteristics classify the subtype of AML, with each resulting from a different genetic abnormality. The focus of APL diagnosis, treatment, and prognosis occurs around the known PML-RARα fusion gene. Flow …

Do Metabolic Networks Follow A Power Law? A Psamm Analysis, Ryan Geib, Lubos Thoma, Ying Zhang

Senior Honors Projects

Inspired by the landmark paper “Emergence of Scaling in Random Networks” by Barabási and Albert, the field of network science has focused heavily on the power law distribution in recent years. This distribution has been used to model everything from the popularity of sites on the World Wide Web to the number of citations received on a scientific paper. The feature of this distribution is highlighted by the fact that many nodes (websites or papers) have few connections (internet links or citations) while few “hubs” are connected to many nodes. These properties lead to two very important observed effects: the …

Enhancing Face Validity Of Mouse Models Of Alzheimer's Disease With Natural Genetic Variation., Kristen D Onos, Asli Uyar, Kelly J Keezer, Harriet M Jackson, Christoph Preuss, Casey J Acklin, Rita O'Rourke, Rebecca Buchanan, Travis L Cossette, Stacey J Sukoff Rizzo, Ileana Soto Reyes, Gregory W Carter, Gareth R Howell

College of Science & Mathematics Departmental Research

Classical laboratory strains show limited genetic diversity and do not harness natural genetic variation. Mouse models relevant to Alzheimer's disease (AD) have largely been developed using these classical laboratory strains, such as C57BL/6J (B6), and this has likely contributed to the failure of translation of findings from mice to the clinic. Therefore, here we test the potential for natural genetic variation to enhance the translatability of AD mouse models. Two widely used AD-relevant transgenes, APPswe and PS1de9 (APP/PS1), were backcrossed from B6 to three wild-derived strains CAST/EiJ, WSB/EiJ, PWK/PhJ, representative of three Mus musculus subspecies. These new AD strains were …

A Genetic Counseling Needs Assessment Of Mexico., Daiana Bucio, Kelly E Ormond, Daisy Hernandez, Carlos D Bustamante, Arturo Lopez Pineda

Articles, Abstracts, and Reports

BACKGROUND: While genetic counseling has expanded globally, Mexico has not adopted it as a separate profession. Given the rapid expansion of genetic and genomic services, understanding the current genetic counseling landscape in Mexico is crucial to improving healthcare outcomes.

METHODS: Our needs assessment strategy has two components. First, we gathered quantitative data about genetics education and medical geneticists' geographic distribution through an exhaustive compilation of available information across several medical schools and public databases. Second, we conducted semi-structured interviews of 19 key-informants from 10 Mexican states remotely with digital recording and transcription.

RESULTS: Across 32 states, ~54% of enrolled medical …

A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …

Detection Of Genetic Thrombophilia (Fa V Leiden & Pt20210 Mutation) Using Genexpert Technology With Iqcp Implementation, Mariegrace Saquilayan

Natural Sciences and Mathematics | Clinical Laboratory Sciences

Abstract

Individuals having Genetic Thrombophilia pose a higher risk of having a thrombotic event. It is crucial to determine these gene variants to prevent a possible episode of thromboembolism. With the current PCR method, it involves individual processing of DNA isolation, amplification, and detection using three (3) different instruments resulting to an increased turnaround time of 5 to 7 days and additional staff utilization. It is performed by repetitive manual sample pipetting and preparation of reagent master mixes in small vials. Results interpretations are entered manually to a worklist built initially for final verification. These processes increase the risk of …

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …

Identification Of Genes Involved In Iron Metabolism In Rhizobium Leguminosarum Atcc 14479 Genome Through The Use Of In-Silico Analysis, Shuaib A. Siddiqui

Undergraduate Honors Theses

The complete genomic sequence of Rhizobium leguminosarum ATCC 14479 has been determined. Its genome size is 7,935,223 base-pairs of DNA (bp). This multipartite genome contains 5 distinct replicons: a chromosome of 4,883,137 bp and four mega-plasmids of size 1,234,209 bp, 415,988 bp, 771,583 bp, and 630,306 bp. In silico (literally: on computer) analysis was done on the complete genome to detect genes relating to iron metabolism by bacteria. Seven iron-related operons and genes were found: nodulation genes, the Tol operon, the hmuPSTUV operon, iron response regulator genes, the cycHJKL operon, genes for bacterial cyclic glucans, and vicibactin genes.

Investigation Of Lipid Metabolism Dysregulation And The Effects On Immune Microenvironments In Pan-Cancer Using Multiple Omics Data., Yang Hao, Daixi Li, Yong Xu, Jian Ouyang, Yongkun Wang, Yuqi Zhang, Baoguo Li, Lu Xie, Guangrong Qin

Articles, Abstracts, and Reports

BACKGROUND: Lipid metabolism reprogramming is a hallmark for tumor which contributes to tumorigenesis and progression, but the commonality and difference of lipid metabolism among pan-cancer is not fully investigated. Increasing evidences suggest that the alterations in tumor metabolism, including metabolite abundance and accumulation of metabolic products, lead to local immunosuppression in the tumor microenvironment. An integrated analysis of lipid metabolism in cancers from different tissues using multiple omics data may provide novel insight into the understanding of tumorigenesis and progression.

RESULTS: Through systematic analysis of the multiple omics data from TCGA, we found that the most-widely altered lipid metabolism pathways …

Beaver And Aspen: Synergy Among Keystone Species, Stephen N. Bennett, Nicolaas Bouwes, Paul C. Rogers

Aspen Bibliography

In the West, climate change is likely to increase the frequency, intensity, and duration of drought. Restoration of soils and water storage capacity can help create resilient uplands and riverscapes (i.e., streams and the valley bottoms). Over the past two centuries, common land uses, the removal of beaver and wood, straightening of streams, and damage to riparian areas have created simplified, structurally starved, riverscapes. Degraded streams are very efficient at transporting water, sediment, and nutrients downstream. Aspen forests are also biological hotspots that have been degraded by past land uses such as overbrowsing ungulates, land clearing, fire suppression, and outright …

Biodiversity Within Aspen Forests, Paul C. Rogers

Aspen Bibliography

Aspen have long been known for supporting lush vegetation and rich wildlife habitat. These features, alongside brilliant green and gold seasonal coloration, accompany a broadly appreciated aesthetic for aspen forests by the public-at-large. However, in earlier times timber producers in many locales considered aspen to have low value and actively eliminated them. More recent research has pointed out that relative moisture held within aspen communities facilitates a wide array of species – collectively, biodiversity – compared to surrounding vegetation types. Aspen groves in the Intermountain West, for example, are known to be second only to riparian forests is supporting the …

Role Of Wildfire And Topography In Shaping Aspen Regeneration After The Hayman Fire, Co, Usa, Arianna A. B. Porter

Aspen Bibliography

Unusually rapid and widespread mortality in Quaking aspen (Populus tremuloides) has been documented throughout the 21st century primarily as a result of warm, dry weather conditions. Although aspen are not drought-adapted, aspen are well adapted to wildfire. Increases in wildfire severity and extent as a result of climate change may provide opportunities for aspen regeneration, especially at mid- and high-elevation sites. Aspen's sensitivity to drought suggests that regeneration following fire might be constrained to cooler and wetter topographic locations on the landscape which reduce drought stress on vegetation. While aspen mortality is demonstrated to occur at low elevation sites, aspen …

Burn Severity And Fire History In The Northwestern Canadian Boreal Forest: Drivers And Ecological Outcomes, Ellen Whitman

Aspen Bibliography

Wildfire is the dominant stand-renewing disturbance in the northwestern Canadian boreal forest. Fires burn extensive areas in Canada, disturbing an average of 1.96 Mha yr−1, primarily in the boreal zone. Fires generally occur every ~30 – > 200 years in this region, due in part to a lack of fuel that allows young stands to resist reburning. Boreal understory plants and trees are adapted to stand-renewing wildfire through mechanisms such as serotiny, seed banking, and resprouting from roots and rhizomes of top-killed individuals. Such adaptations confer resilience to boreal forests, and post-fire vegetation communities generally resemble the pre-fire ones, following a …

Hiding In The Lianas Of The Tree Of Life: Molecular Phylogenetics And Species Delimitation Reveal Considerable Cryptic Diversity Of New World Vine Snakes, Robert C. Jadin, Christopher Blair, Michael J. Jowers, Anthony Carmona, John C. Murphy

Publications and Research

The Brown Vine Snake, Oxybelis aeneus, is considered a single species despite the fact its distribution covers an estimated 10% of the Earth’s land surface, inhabiting a variety of ecosystems throughout North, Central, and South America and is distributed across numerous biogeographic barriers. Here we assemble a multilocus molecular dataset (i.e. cyt b, ND4, cmos, PRLR) derived from Middle American populations to examine for the first time the evolutionary history of Oxybelis and test for evidence of cryptic lineages using Bayesian and maximum likelihood criteria. Our divergence time estimates suggest that Oxybelis diverged from its sister genus, Leptophis …

Surveying Apicomplexan Diversity And Dynamics In Narragansett Bay, Evelyn Spencer

Senior Honors Projects

Parasites play an important role in marine ecosystems and their diversity is generally understudied. Apicomplexans, a group of parasitic protists in the phylum Alveolata, infect a wide variety of animal hosts and are abundant in ecosystems spanning from Polar Regions to Neotropical rainforests. Previous data generated from marine sediments in Antarctica, Naples Bay, and off the coast of Oslo, exhibit high diversity and numbers of apicomplexans. Abundance and diversity of these protists are unknown for Narragansett Bay, despite the fact that they infect many commercially important species. The aim of my study was to obtain abundance data and understand genetic …

The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy

Dissertations, Theses, and Capstone Projects

Cellular homeostasis is achieved by the dynamic flux in gene expression. Post-transcriptional regulation of coding and non-coding RNA offers a fast method of adapting to a changing cellular environment, including deadenylation, microRNA (miRNA) pathway, and alternative polyadenylation (APA). In this dissertation, I explored some of the mechanisms involved in the post-transcriptional regulation of gene expression. The main hypothesis in these studies is that a single APA event after DNA damage is governed by specific conditions and factors outside of current known regulators of APA, and that the resultant transcript has a role in the DNA damage response (DDR). My aims …