Genetics and Genomics Commons^™

Special Muscles, Annamaria C. Scaccia

Capstones

Special Muscles is a documentary that explores living with Duchenne muscular dystrophy, a fatal degenerative disease that weakens the muscles at an aggressive rate. The film will give an uncensored look at how one family copes with inevitability of the disease and their journey chasing a promising experimental cure.

Special Muscles follows 7-year-old Pietro Scarso and his family as they face the challenges, complications and promise of treating Pietro’s progressive muscle disorder. The film travels from New York to Los Angeles to Philadelphia to document the Scarso family’s race against time as Pietro undergoes a 96-week clinical trial for Eteplirsen, …

Phylogenetic Investigation Of Enteric Bovine Coronavirus In Ireland Reveals Partitioning Between European And Global Strains, Lynda Gunn, P. J. Collins, M. J. O'Connell, Helen O'Shea

Department of Biological Sciences Publications

Background

Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies.

Findings

In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was …

Alternative Use Of Dna Binding Domains By The Neurospora White Collar Complex Dictates Circadian Regulation And Light Responses, Bin Wang, Xiaoying Zhou, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

In the Neurospora circadian system, the White Collar complex (WCC) of WC-1 and WC-2 drives transcription of the circadian pacemaker gene frequency (frq), whose gene product, FRQ, as a part of the FRQ-FRH complex (FFC), inhibits its own expression. The WCC is also the principal Neurospora photoreceptor; WCC-mediated light induction of frq resets the clock, and all acute light induction is triggered by WCC binding to promoters of light-induced genes. However, not all acutely light-induced genes are also clock regulated, and conversely, not all clock-regulated direct targets of WCC are light induced; the structural determinants governing the shift …

Elimination Of Chromosomal Island Spycim1 From Streptococcus Pyogenes Strain Sf370 Reverses The Mutator Phenotype And Alters Global Transcription, Christina Hendrickson, Chad W. Euler, Scott V. Nguyen, Maliha Rahman, Kimberly A. Mccullor, Catherine J. King, Vincent A. Fischetti, W. Michael Mcshan

Publications and Research

Streptococcus pyogenes chromosomal island M1 (SpyCIM1) integrates by site-specific recombination into the 5’ end of DNA mismatch repair (MMR) gene mutL in strain SF370SmR, blocking transcription of it and the downstream operon genes. During exponential growth, SpyCIM1 excises from the chromosome and replicates as an episome, restoring mutL transcription. This process is reversed in stationary phase with SpyCIM1 re-integrating into mutL, returning the cells to a mutator phenotype. Here we show that elimination of SpyCIM1 relieves this mutator phenotype. The downstream MMR operon genes, multidrug efflux pump lmrP, Holliday junction resolution helicase ruvA, and DNA base excision …

Mechanisms Of Adaptation In The Newly Invasive Species Brachypodium Sylvaticum (Hudson) Beauv., Gina Lola Marchini

Dissertations and Theses

It is common knowledge that invasive species cause worldwide ecological and economic damage, and are nearly impossible to eradicate. However, upon introduction to a novel environment, alien species should be the underdogs: They are present in small numbers, possess low genetic diversity, and have not adapted to the climate and competitors present in the new habitat. So, how are alien species able to invade an environment occupied by native species that have already adapted to the local environment? To discover some answers to this apparent paradox I conducted four ecological genetic studies that utilized the invasive species Brachypodium sylvaticum (Hudson) …

Period-1 Encodes An Atp-Dependent Rna Helicase That Influences Nutritional Compensation Of The Neurospora Circadian Clock, Jillian M. Emerson, Bradley M. Bartholomai, Carol S. Ringelberg, Scott E. Baker, Jennifer Loros, Jay Dunlap

Dartmouth Scholarship

Mutants in the period-1 (prd-1) gene, characterized by a recessive allele, display a reduced growth rate and period lengthening of the developmental cycle controlled by the circadian clock. We refined the genetic location of prd-1 and used whole genome sequencing to find the mutation defining it, confirming the identity of prd-1 by rescuing the mutant circadian phenotype via transformation. PRD-1 is an RNA helicase whose orthologs, DDX5 [DEAD (Asp-Glu-Ala-Asp) Box Helicase 5] and DDX17 in humans and DBP2 (Dead Box Protein 2) in yeast, are implicated in various processes, including transcriptional regulation, elongation, and termination, ribosome biogenesis, and mRNA decay. …

Rna Sequencing Analysis Of The Msl2msl3, Crl, And Ggps1 Mutants Indicates That Diverse Sources Of Plastid Dysfunction Do Not Alter Leaf Morphology Through A Common Signaling Pathway, Darron R. Luesse, Margaret E. Wilson, Elizabeth S. Haswell

Biology Faculty Research

Determining whether individual genes function in the same or in different pathways is an important aspect of genetic analysis. As an alternative to the construction of higher-order mutants, we used contemporary expression profiling methods to perform pathway analysis on several Arabidopsis thaliana mutants, including the mscS-like (msl)2msl3 double mutant. MSL2 and MSL3 are implicated in plastid ion homeostasis, and msl2msl3 double mutants exhibit leaves with a lobed periphery, a rumpled surface, and disturbed mesophyll cell organization. Similar developmental phenotypes are also observed in other mutants with defects in a range of other chloroplast or mitochondrial functions, including …

Rnai-Mediated Control Of Aflatoxins In Peanut: Method To Analyze Mycotoxin Production And Transgene Expression In The Peanut/Aspergillus Pathosystem, Renee S. Arias, Phat M. Dang, Victor S. Sobolev

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

The Food and Agriculture Organization of the United Nations estimates that 25% of the food crops in the world are contaminated with aflatoxins. That represents 100 million tons of food being destroyed or diverted to non-human consumption each year. Aflatoxins are powerful carcinogens normally accumulated by the fungi Aspergillus flavus and A. parasiticus in cereals, nuts, root crops and other agricultural products. Silencing of five aflatoxin-synthesis genes by RNA interference (RNAi) in peanut plants was used to control aflatoxin accumulation following inoculation with A. flavus. Previously, no method existed to analyze the effectiveness of RNAi in individual peanut transgenic events, …

Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari

Theses & Dissertations

Cyclic adenosine monophosphate (cAMP) is a second messenger responsive to many external stimuli, playing an important role in cellular gene expression, metabolism, migration, differentiation, hypertrophy, apoptosis and secretion. All of these cellular functions are important in many diseases including cancer. Most of its effects were initially attributed to the classical protein kinase A (PKA) protein, but cellular functions such as proliferation and migration were found to be PKA independent and dependent on the newly discovered exchange proteins directly activated by cAMP (EPACs). EPACs are single polypeptides that primarily function as guanine exchange factors (GEFs) for Rap proteins that allow the …

Finding Function In The Unknown, Kelly Boyd, Emma Highland, Amanda Misch, Amber Hu, Sushma Reddy, Catherine Putonti

Bioinformatics Faculty Publications

Through high-throughput RNA sequencing (RNAseq), transcriptomes for a single cell, tissue, or organism(s) can be ascertained at a high resolution. While a number of bioinformatic tools have been developed for transcriptome analyses, significant challenges exist for studies of non-model organisms. Without a reference sequence available, raw reads must first be assembled de novo followed by the tedious task of BLAST searches and data mining for functional information. We have created a pipeline, PyRanger, to automate this process. The pipeline includes functionality to assess a single transcriptome and also facilitate comparative transcriptomic studies.

Are Immune Modulating Single Nucleotide Polymorphisms Associated With Necrotizing Enterocolitis?, Ashanti L Franklin, Mariam Said, Clint D Cappiello, Heather Gordish-Dressman, Zohreh Tatari-Calderone, Stanislav Vukmanovic, Khodayar Rais-Bahrami, Naomi L C Luban, Joseph M Devaney, Anthony D Sandler

Genomics and Precision Medicine Faculty Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over …

Leveraging Global Gene Expression Patterns To Predict Expression Of Unmeasured Genes, James Rudd, René A. Zelaya, Eugene Demidenko, Ellen L. Goode, Casey S. Greene S. Greene, Jennifer A. Doherty

Dartmouth Scholarship

BackgroundLarge collections of paraffin-embedded tissue represent a rich resource to test hypotheses based on gene expression patterns; however, measurement of genome-wide expression is cost-prohibitive on a large scale. Using the known expression correlation structure within a given disease type (in this case, high grade serous ovarian cancer; HGSC), we sought to identify reduced sets of directly measured (DM) genes which could accurately predict the expression of a maximized number of unmeasured genes.

Identifying Gene-Gene Interactions That Are Highly Associated With Body Mass Index Using Quantitative Multifactor Dimensionality Reduction (Qmdr), Rishika De, Shefali S. Verma, Fotios Drenos, Emily R. Holzinger

Dartmouth Scholarship

Despite heritability estimates of 40–70% for obesity, less than 2% of its variation is explained by Body Mass Index (BMI) associated loci that have been identified so far. Epistasis, or gene-gene interactions are a plausible source to explain portions of the missing heritability of BMI. Using genotypic data from 18,686 individuals across five study cohorts – ARIC, CARDIA, FHS, CHS, MESA – we filtered SNPs (Single Nucleotide Polymorphisms) using two parallel approaches. SNPs were filtered either on the strength of their main effects of association with BMI, or on the number of knowledge sources supporting a specific SNP-SNP interaction in …

Genomic Legacy Of The African Cheetah, Acinonyx Jubatus, Pavel Dobrynin, Shiping Liu, Gaik Tamazian, Zijun Xiong, Andrey A. Yurchenko, Ksenia Krasheninnikova, Sergey Kliver, A. Schmidt-Kunzel, Klaus-Peter Koepfli, Warren E. Johnson, Lukas F. K. Kuderna, Raquel Garcia-Perez, Marc De Manuel, Ricardo Godinez, Aleksey Komissarov, Alexey Makunin, Vladimir Brukhin, Weilin Qiu, Long Zhou, Fang Li, Jian Yi, Carlos A. Driscoll, Agostinho Antunes, T. K. Oleksyk, Eduardo Eizirik, Polina Perelman, Melody E. Roelke, David E. Wildt, Mark Diekhans, Tomas Marques-Bonet, Laurie Marker, Jong Bhak, Jun Wang, Guojie Zhang, Stephen J. O'Brien

Biology Faculty Articles

Background

Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations.

Results

Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years …

Prenatal Genetic Testing: An Overview Of History, Advancements, And Impacts On Health Care, Jessica Neumann

University Honors Program

The purpose of this research is to study prenatal genetic testing and the advancements that have been made since the human genome project has made the testing process simpler and less invasive. Prenatal genetic testing is a screen or a test that is performed in order to determine if an embryo or fetus has a certain disease or condition before its birth. A variety of different prenatal tests and screens have been studied to evaluate what genetic conditions are screened for and when. The scope of this paper focuses on the historical overview, advancements, patients, tests, and impacts related to …

The Importance Of Physicochemical Characteristics And Nonlinear Classifiers In Determining Hiv-1 Protease Specificity, Timmy Manning, Paul Walsh

Department of Biological Sciences Publications

This paper reviews recent research relating to the application of bioinformatics approaches to determining HIV-1 protease specificity, outlines outstanding issues, and presents a new approach to addressing these issues. Leading machine learning theory for the problem currently suggests that the direct encoding of the physicochemical properties of the amino acid substrates is not required for optimal performance. A number of amino acid encoding approaches which incorporate potentially relevant physicochemical properties of the substrate are identified, and are evaluated using a nonlinear task decomposition based neuroevolution algorithm. The results are evaluated, and compared against a recent benchmark set on a nonlinear …

Genetic Parameters For Docility, Weaning Weight, Yearling Weight, And Intramuscular Fat Percentage In Hereford Cattle, J. A. Torres-Vázquez, Matthew L. Spangler

Department of Animal Science: Faculty Publications

Cattle behavior, including measures of docility, is important to beef cattle producers not only from a human safety perspective but also due to potential correlations to economically relevant traits. Field data from the American Hereford Association was used to estimate genetic parameters for chute score (CS; n = 25,037), weaning weight (WW; n = 24,908), yearling weight (YW; n = 23,978), and intramuscular fat percentage (IMF; n = 12,566). Single-trait and bivariate animal models were used to estimate heritabilities and genetic correlations. All models included fixed effects of sex and contemporary group, defined as herd–year–season, and direct genetic and residual …

The Development Of A Platform For Expression And Purification Of The Mammalian Transmembrane Transporter Abca4, Amaryllis Ortiz

Graduate School of Biomedical Sciences Theses and Dissertations

Purpose- ABCA4 is an ATP Binding Cassette (ABC) protein localized at cone and rod photoreceptor outer segments of the retina. Though mutations in ABCA4 have been found to cause a broad spectrum of disorders, ABCA4's high molecular weight (~210 kDa) and biochemical transmembrane properties have made ABCA4 functional studies unsuccessful. Identifying how ABCA4 functions might have significant clinical impact and open unanticipated avenues for therapeutic interventions. Thus, the objective of this study was to develop a new expression system able to produce the full-length, correctly folded and fully functional ABCA4 protein.

Methods- the ABCA4 gene was amplified from the PCMV6-ABCA4 …

Review Of "Race Unmasked: Biology And Race In The Twentieth Century" By M. Yudell, John B. Jenkins

Biology Faculty Works

No abstract provided.

Expression Of Insulin Responsive Genes In Insulin Resistant Conditions, And The Effect Of Selenium On Gene Expression, David L. Ruff

Masters Theses

Chronically high blood glucose levels lead to many problems, such as insulin resistance, the hallmark of Type II diabetes. Increased flux through the hexosamine biosynthesis pathway is one mechanism by which high glucose as well as glucosamine has been shown to induce insulin resistance. This study tests the effects of glucosamine induced insulin resistance on insulin regulation of the metabolic genes glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) as well as insulin responsive proteins tribbles homolog (TRIB3) and sterol regulatory element binding protein (SERBP-1c) 1c.

Selenium, a micronutrient has been shown to be an effective insulin mimetic in Type …

Role Of B Cell Receptor Signaling In Il-10 Production By Normal And Malignant B-1 Cells., Sara S Alhakeem, Vishal J Sindhava, Mary K Mckenna, Beth W Gachuki, John C Byrd, Natarajan Muthusamy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells are considered innate immune cells, which produce the majority of natural antibodies. B-1 cell responses to B cell receptor (BCR) and Toll-like receptor ligation are tightly regulated owing to the cross-reactivity to self-antigens. CD5 has been shown to play a major role in downregulation of BCR responses in B-1 cells. Here, we provide evidence for another mechanism by which BCR response is regulated in B-1 cells. B-1 cells, as well as their malignant counterpart, B cell chronic lymphocytic leukemia (B-CLL) cells, produce interleukin-10 (IL-10) constitutively. IL-10 secretion by normal B-1 cells downregulates their proliferation responses to BCR ligation. …

Microrna-Mediated Plant Development And Response To Environmental Stress In Perennial Grasses, Shuangrong Yuan

All Dissertations

World population will pass nine billion by 2050, while the agricultural land area will not increase dramatically in the coming decades. To meet the ever-increasing food demand, genetically engineered crops have been rapidly adopted for crop productivity. MicroRNAs have become increasingly attractive as targets in crop genetic modification due to their regulatory role in fine-tuning many essential biological processes. My research explores the potentials of microRNA528 (miR528) and miR396 for use in genetic modifications of the important agronomic traits of plant development, abiotic stress response, and/or flowering time control in an economically and environmentally important perennial monocot species, creeping bentgrass …

Post Operative Fungal Endopthalmitis Due To Geotrichum Candidum, Thein Myint, Matthew J. Dykhuizen, Carolyn H. Mcdonald, Julie A. Ribes

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Geotrichum species have been rarely reported as the cause of sepsis, disseminated infection in immunosuppressed patients. The patient we describe developed indolent endophthalmitis four months after her routine right eye cataract surgery. The intraoperative sample from right vitreous fluid grew Geotrichum candidum. The patient underwent vitrectomy, artificial lens explantation and intravitreal injection of amphotericin B followed by oral voriconazole. Despite these interventions, she underwent enucleation. This is the first published case of Geotrichum candidum endophthalmitis.

Atmospheric Nitrogen Assimilation In Ustilago Maydis., Michael Cooper

Electronic Theses and Dissertations

Nitrogen is an essential nutrient for all living creatures. Ammonium is one of the most efficiently used and thus preferred, sources of nitrogen. As with other dimorphic fungi, yeast-like cells of Ustilago maydis, a fungal pathogen of maize, switches to filamentous growth when starved for nitrogen/ammonium. U. maydis carries two genes, ump1 and ump2, encoding ammonium transporters that facilitate both uptake of ammonium and the filamentous response to its absence. While no obvious phenotype is observed when ump1 is deleted, cells without ump2 are unable to filament in response to low ammonium, although they can still grow. Surprisingly, …

Genomic And Transcriptomic Analyses Of Microbotryum Lychnidis-Dioicae Provide Insights Into The Biology Of A Fascinating Fungal Phytopathogen., Su San Toh

Electronic Theses and Dissertations

This study made use of the Silene latifolia/Microbotryum lychnidis-dioicae phytopathogen system as the focal system to establish the first reference genome for Microbotryum violaceum sensu lato. In silico analysis was performed on the genome assembly to identify various characteristics of the genome. Using RNA-Sequencing technologies on the Illumina platform, we collected transcriptomic data for both in vitro and in planta life stages of the fungus, providing the most comprehensive look at the gene expression and regulation of this fungus. Due to a lack of identifiable domains on the predicted genes, gene set enrichment analysis was done in …

Genome Rearrangements Can Make And Break Small Rna Genes, Rahul Raghavan, Fenil R. Kacharia, Jess A. Millar, Christine Demko Sislak, Howard Ochman

Biology Faculty Publications and Presentations

Small RNAs (sRNAs) are short, transcribed regulatory elements that are typically encoded in the intergenic regions (IGRs) of bacterial genomes. Several sRNAs, first recognized in Escherichia coli, are conserved among enteric bacteria, but because of the regulatory roles of sRNAs, differences in sRNA repertoires might be responsible for features that differentiate closely related species. We scanned the E. coli MG1655 and Salmonella enterica Typhimurium genomes for nonsyntenic IGRs as a potential source of uncharacterized, species-specific sRNAs and found that genome rearrangements have reconfigured several IGRs causing the disruption and formation of sRNAs. Within an IGR that is present in …

Efficacy Of Galactooliosaccharide (Gos) And/Or Rhamnose-Based Synbiotics In Enhancing Ecological Performance Of Lactobacillus Reuteri In The Human Gut And Characterization Of Its Gos Metabolic System, Monchaya Rattanaprasert

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Probiotic L. reuteri has potential to produce antimicrobial compounds and secrete immunosuppressive factors. These metabolic attributes could benefit the human host by providing colonization resistance (competitive and metabolic exclusion) against enteropathogens and mitigating inflammation. As metabolically active cells are fundamental to such probiotic properties, synbiotic approaches that supply L. reuteri with a source(s) of carbon, energy, and/or external electron acceptor for cell growth in the gut environment could therefore prompt the probiotic to engage in beneficial activities. In this study, the efficacy of GOS and/or rhamnose-based synbiotic approaches in promoting colonization persistence and metabolic activity of L. reuteri was evaluated. …

A Survey Of The Common Loon (Gavia Immer) Genome Reveals Patterns Of Natural Selection, Zach G. Gayk

All NMU Master's Theses

With rapid advances in Next-Generation Sequencing technology, comparative genomics has become a viable method for studying the adaptation of species to their environment at the genome level. I investigated this in common loons (Gavia immer)—for which molecular adaptation has not been characterized—by finding signatures of positive selection as evidence for genomic adaptation.

I used Illumina short read sequencing data from a single female common loon to produce a fragmented assembly of the common loon (Gavia immer) genome. The resulting assembly had a contig N50 of 814 bp, a total length of 767,326,331 bp, and 45.7 % …

Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age, Michelle L. Bolner

Dissertations and Theses (Open Access)

The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the …

In Vivo Functional Significance Of Ccat2 Long Non-Coding Rna In Myelodysplastic Syndrome, Maitri Y. Shah

Dissertations and Theses (Open Access)

Long non-coding RNAs form the largest part of the mammalian non-coding transcriptome and control gene expression at various levels including chromatin modification, transcriptional and post-transcriptional processing. Although the underlying molecular mechanisms are not yet entirely understood, lncRNAs are implicated in initiation and progression of several cancers. CCAT2 is a lncRNA that spans the highly conserved 8q24 region associated with increased risk for various cancers. CCAT2 has been shown to play an important role in inducing chromosomal instability and supporting cell proliferation and cell cycle arrest. However, a causal role of CCAT2 in initiation of tumorigenesis and the importance of G/T …