Genetics Commons^™

Redox Regulation Of Protein Translation In Eukaryotes, Maxim Gerashchenko

Department of Biochemistry: Dissertations, Theses, and Student Research

Gene expression may be controlled at multiple levels, e.g., through genomic architecture, transcription and translation. In the current work, we focused on regulation of protein synthesis. Historically, the investigation of the regulation of gene expression at the level of translation lagged behind the transcriptional control because of the lack of accessible high-throughput methods. Our research has begun with the finding of the use of alternative non-AUG start codon in thioredoxin-glutathione reductase (TGR), a selenoprotein involved in redox control during male reproduction. The use of this codon, CUG, relies on the Kozak consensus sequence and ribosomal scanning mechanism. However, the CUG …

Naturalized Offspring From An 85-Year-Old Chinese Chestnut (Castanea Mollissima) Planting: Stand Dynamics And Genetic Relationships, Amy Christel Miller

Open Access Theses

Chestnuts, members of the genus Castanea , family Fagaceae, are valuable worldwide, and all species have noteworthy ecological, economic, and cultural importance in their native ranges. Historically, American chestnut (Castanea dentata (Marshall) Borkh.) was an abundant tree species in eastern North America until its decimation in the early 20 th century by chestnut blight, caused by the fungus Cryphonectria parasitica . To regain the benefits of this prized species in North America, efforts are ongoing to produce and introduce blight-resistant hybrids of C. dentata and the blight-resistant Chinese chestnut ( C. mollissima Blume). It is important that the C. …

Stress Responses And Energy Storage In Drosophila Melanogaster Selected For Resistance To A Gram-Positive Bacillus Cereus Spores, Zhen Hu

School of Biological Sciences: Dissertations, Theses, and Student Research

A survival response study was carried out by using D. melanogaster and the opportunistic pathogen B. cereus as the agent of selection. The spores of B. cereus, a gram-positive bacteria that can cause the human pathogen disease, were applied in our artificial laboratory selection. Selected lines were treated with B. cereus spores. Wound control lines were punctured with a needle dipped into sterile H₂O. Control lines did not apply any treatment. Three different environmental treatments were used within each line type (autoclaved spores of B.cereus, sterile H₂O and no treatment). The autoclaved spores were …

Heterogeneity, Not Randomness, Sets Challenges For Quantitative Genetics And Epidemiology: A Response To Davey Smith’S “Gloomy Prospect”, Peter J. Taylor

Working Papers on Science in a Changing World

Social epidemiologist Davey Smith (2011) argues that epidemiologists should accept a gloomy prospect: considerable randomness at the individual level means that they should keep their focus on modifiable causes of disease at the population level. The difficulty epidemiology has had in moving from significant population-level risk factors to improved prediction of cases at an individual level is analogous to the lack of success in the search for systematic aspects of the non-shared environmental influences that human quantitative genetics claims overshadow common environmental influences (e.g., the family’s socioeconomic status which siblings have in common). This article responds to the argument and …

Multilocus Coalescent Analyses Reveal The Demographic History Of Mouse Lemur Sister Species., Christopher Blair, Kellie L. Heckman, Amy L. Russell, Anne D. Yoder

Publications and Research

Debate continues as to whether allopatric speciation or peripatric speciation through a founder effect is the predominant force driving evolution in vertebrates. The mouse lemurs of Madagascar are a system in which evolution has generated a large number of species over a relatively recent time frame. Here, we examine speciation patterns in a pair of sister species of mouse lemur, Microcebus murinus and M. griseorufus. These two species have ranges that are disparately proportioned in size, with M. murinus showing a much more extensive range that marginally overlaps that of M. griseorufus. Given that these two species are …

Five Fundamental Gaps In Nature-Nurture Science, Peter J. Taylor

Working Papers on Science in a Changing World

Difficulties identifying causally relevant genetic variants underlying patterns of human variation have been given competing interpretations. The debate is illuminated in this article by drawing attention to the issue of underlying heterogeneity—the possibility that genetic and environmental factors or entities underlying a trait are heterogeneous—as well as four other fundamental gaps in the methods and interpretation of classical quantitative genetics: "Genetic" and "environmental" fractions of variation in traits are distinct from measurable genetic and environmental factors underlying the traits’ development; Standard formulas for partitioning variation in human traits are unreliable; Methods for translation from fractions of variation to measurable …

Deletion Mutant Library For Investigation Of Functional Outputs Of Cyclic Diguanylate Metabolism In Pseudomonas Aeruginosa Pa14, Dae-Gon Ha, Megan E. Richman, George A. O'Toole

Dartmouth Scholarship

We constructed a library of in-frame deletion mutants targeting each gene in Pseudomonas aeruginosa PA14 predicted to participate in cyclic di-GMP (c-di-GMP) metabolism (biosynthesis or degradation) to provide a toolkit to assist investigators studying c-di-GMP-mediated regulation by this microbe. We present phenotypic assessments of each mutant, including biofilm formation, exopolysaccharide (EPS) production, swimming motility, swarming motility, and twitch motility, as a means to initially characterize these mutants and to demonstrate the potential utility of this library.

How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos

Dartmouth Scholarship

Whole-genome profiling of gene expression is a powerful tool for identifying cancer-associated genes. Genes differentially expressed between normal and tumorous tissues are usually considered to be cancer associated. We recently demonstrated that the analysis of interindividual variation in gene expression can be useful for identifying cancer associated genes. The goal of this study was to identify the best microarray data–derived predictor of known cancer associated genes. We found that the traditional approach of identifying cancer genes—identifying differentially expressed genes—is not very efficient. The analysis of interindividual variation of gene expression in tumor samples identifies cancer-associated genes more effectively. The results …

Investigating A Role For The Ccaat/Enhancer-Binding Protein Δ In The Developing Zebrafish, Alisha Jennifer Beirl

Dissertations and Theses

The CCAAT/enhancer-binding protein delta (C/EBPδ) is a highly conserved transcription factor capable of regulating numerous cell fate processes, such as cell growth, differentiation, proliferation and apoptosis. C/EBPδ is inducible during cellular stress responses, including inflammation and responses to growth factor deprivation or thermal stress. C/EBPδ is stress-inducible in a diversity of fishes, including the zebrafish Danio rerio; however, little is known about its role in fish development. Here I show that overexpression of C/EBPδ leads to severe developmental defects, including reduced body length, edema, liver malformation and retinal abnormalities. The proportion of individuals that display developmental abnormalities is significantly …

Is Sickle Cell Trait As Benign As Is Usually Assumed?, Carroll Nicole Flansburg

USF Tampa Graduate Theses and Dissertations

Abstract

Introduction Sickle cell trait carriers may experience sickling events, which can cause severe health problems. Some sickle cell haplotypes contain genetic modifiers that are associated with increased levels of fetal hemoglobin, which is resistant to sickling. The aim of this study is to determine if sickle cell trait individuals who do not carry these modifiers are more likely to experience sickling episodes than those who do carry the modifiers.

Methods: Participants were eligible for inclusion in this study if they were male, 18 years of age or older, a sickle cell trait carrier, and had previously played any level …

Did Pre-Clovis People Inhabit The Paisley Caves (And Why Does It Matter)?, Stuart J. Fiedel

Human Biology Open Access Pre-Prints

The date and processes of initial human colonization of the Americas are crucial issues for the understanding of human biological and cultural development. For example, Soares et al. (2009) cited the American archaeological record to validate their proposed revision of the human mitochondrial molecular clock. Their suggested mutation rate puts the date of rapid expansion of Native American clades at around 13,500–15,000 cal BP. Similarly, Poznik et al. (2013) have used the “high-confidence archaeological dating” of the initial peopling of the Americas to calibrate the rates of both Y-chromosome and mtDNA mutation and thereby to reconcile the ages of the …

Student Identity Considerations And Implications Associated With Socioscientific Issues Instruction, Mitchel James Ruzek

USF Tampa Graduate Theses and Dissertations

The purpose of this investigation was to explore how aspects of identity, perceived levels of controversy, and the strength of a student's attachment to their controversial identity relate to conceptual understanding and knowledge acquisition during socioscientific issues (SSI) based instruction in a biology classroom. The knowledge gained from this study will have the capacity to enhance our understanding of the role that attachment to identity plays during SSI negotiation. Additionally, insight was gained into the role played by aspects of identity in conceptual understanding of scientifically controversial topics during SSI based instruction.

This study contributed to the existing knowledge base …

Comparing Partial Least Square Approaches In Gene-Or Region-Based Association Study For Multiple Quantitative Phenotypes, Zhongshang Yuan, Xiaoshuai Zhang, Fangyu Li, Jinghua Zhao, Fuzhong Xue

Human Biology Open Access Pre-Prints

On thinking quantitatively of complex diseases, there are at least three statistical strategies for association study: single SNP on single trait, gene-or region (with multiple SNPs) on single trait and on multiple traits. The third of which is the most general in dissecting the genetic mechanism underlying complex diseases underpinning multiple quantitative traits. Gene-or region association methods based on partial least square (PLS) approaches have been shown to have apparent power advantage. However, few attempts are developed for multiple quantitative phenotypes or traits underlying a condition or disease, and the performance of various PLS approaches used in association study for …

Genetic Origins Of Lactase Persistence And The Spread Of Pastoralism In Africa, Michael Campbell

Department of Biology Faculty Publications

In humans, the ability to digest lactose, the sugar in milk, declines after weaning because of decreasing levels of the enzyme lactase-phlorizin hydrolase, encoded by LCT. However, some individuals maintain high enzyme amounts and are able to digest lactose into adulthood (i.e., they have the lactase-persistence [LP] trait). It is thought that selection has played a major role in maintaining this genetically determined phenotypic trait in different human populations that practice pastoralism. To identify variants associated with the LP trait and to study its evolutionary history in Africa, we sequenced MCM6 introns 9 and 13 and ∼2 kb of the …

Chip-Seq And Rna-Seq Reveal An Amrz-Mediated Mechanism For Cyclic Di-Gmp Synthesis And Biofilm Development By Pseudomonas Aeruginosa, Christopher J. Jones, David Newsom, Benjamin Kelly, Yasuhiko Irie, Laura K. Jennings, Binjie Xu, Dominique H. Limoli, Joe J. Harrison, Matthew R. Parsek, Peter White, Daniel J. Wozniak

Biology Faculty Publications

The transcription factor AmrZ regulates genes important for P. aeruginosa virulence, including type IV pili, extracellular polysaccharides, and the flagellum; however, the global effect of AmrZ on gene expression remains unknown, and therefore, AmrZ may directly regulate many additional genes that are crucial for infection. Compared to the wild type strain, a ΔamrZ mutant exhibits a rugose colony phenotype, which is commonly observed in variants that accumulate the intracellular second messenger cyclic diguanylate (c-di-GMP). Cyclic di-GMP is produced by diguanylate cyclases (DGC) and degraded by phosphodiesterases (PDE). We hypothesized that AmrZ limits the intracellular accumulation of c-di-GMP through transcriptional repression …

Quantitative Field Testing Heterodera Glycines From Metagenomic Dna Samples Isolated Directly From Soil Under Agronomic Production., Yan Li, Gary W. Lawrence, Shien Lu, Clarissa Balbalian, Vincent P. Klink

CALS Publications

A quantitative PCR procedure targeting the Heterodera glycines ortholog of the Caenorhabditis elegans uncoordinated-78 gene was developed. The procedure estimated the quantity of H. glycines from metagenomic DNA samples isolated directly from field soil under agronomic production. The estimation of H. glycines quantity was determined in soil samples having other soil dwelling plant parasitic nematodes including Hoplolaimus, predatory nematodes including Mononchus, free-living nematodes and biomass. The methodology provides a framework for molecular diagnostics of nematodes from metagenomic DNA isolated directly from field soil.

Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold

Dartmouth Scholarship

Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can …

Direct-To-Consumer Genetic Testing In The College Classroom: Knowledge, Attitudes, And Concerns Of Introductory Biology Students, Nicanor Austriaco

Biology Faculty Publications

Pioneered by companies like 23andMe.com, deCODEme.com, and Navigenics.com, direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print media, or the Internet. This kind of testing provides access to a customer’s genetic information without necessarily involving either a medical health care professional or a genetic counselor in the process. In recent years, a course offered to medical and graduate students at Stanford University has included an option for students to undergo personal genotyping, raising the possibility that direct-to-consumer genetic testing could also be incorporated into undergraduate biology courses to enhance student learning. In this …

Deletion Of Aif1 But Not Of Yca1/Mca1 Protects Saccharomyces Cerevisiae And Candida Albicans Cells From Caspofungin-Induced Programmed Cell Death, Nicanor Austriaco, Christopher Chin, Faith Donaghey, Kathrine Helming, Morgan Mccarthy, Stephen Rogers

Biology Faculty Publications

Caspofungin was the first member of a new class of antifungals called echinocandins to be approved by a drug regulatory authority. Like the other echinocandins, caspofungin blocks the synthesis of β(1,3)-D-glucan of the fungal cell wall by inhibiting the enzyme, β(1,3)-D-glucan synthase. Loss of β(1,3)-D-glucan leads to osmotic instability and cell death. However, the precise mechanism of cell death associated with the cytotoxicity of caspofungin was unclear. We now provide evidence that Saccharomyces cerevisiae cells cultured in media containing caspofungin manifest the classical hallmarks of programmed cell death (PCD) in yeast, including the generation of reactive oxygen species (ROS), the …

Phylogeny And Population Genetics Of The Endangered Dwarf Bear-Poppy, Arctomecon Humilis Coville (Papaveraceae) Using Microsatellite Markers, Joshua Simpson

Dissertations, Theses, and Capstone Projects

The genus Arctomecon (Papaveraceae) is comprised of three narrowly endemic rare species that are largely restricted to gypsum soils of the eastern Mojave Desert. The small, remaining populations of these species have become increasingly isolated by urban development and habitat fragmentation. Arctomecon humilis is federally listed as endangered due to its limited distribution within a ~15 km radius of an actively expanding city. Organizations involved with land management and conservation have called for greater insight into the genetic variation and population structure of the remaining subpopulations as they make important decisions regarding where to focus their efforts and resources.

The …

Trip/Nopo E3 Ubiquitin Ligase Promotes Ubiquitylation Of Dna Polymerase Η, Heather A. Wallace, Julie A. Merkle, Michael C. Yu, Taloa G. Berg, Ethan Lee, Giovanni Bosco, Laura A. Lee

Dartmouth Scholarship

We previously identified a Drosophila maternal effect-lethal mutant named ‘no poles’ (nopo). Embryos from nopo females undergo mitotic arrest with barrel-shaped, acentrosomal spindles during the rapid cycles of syncytial embryogenesis because of activation of a Chk2-mediated DNA checkpoint. NOPO is the Drosophila homolog of human TNF receptor associated factor (TRAF)-interacting protein (TRIP), which has been implicated in TNF signaling. NOPO and TRIP contain RING domains closely resembling those of known E3 ubiquitin ligases. We herein sought to elucidate the mechanism by which TRIP/NOPO promotes genomic stability by performing a yeast two-hybrid screen to identify potential substrates/interactors. We identified members of …

Measuring Radiation Exposure In Human Blood Using Gene Expression, Krystal Naranjo, Melissa Bentley, Harsha Konery, Matthew Coleman

STAR Program Research Presentations

Mammalian cells are known to express genes that are associated with repairing damaged DNA. The transcript CDKN1A is one of several cell cycle regulator genes expressed in response to cell damage by ionizing radiation (IR). In this study, male and female lymphocytes; previously exposed ex vivo to IR, were used to demonstrate linear gene expression responses that may vary between genders. We used qRT-PCR to generate response curves for CDKN1A. No differences were identified for the endogenous control gene GAPDH. CDKN1A expression demonstrated average fold changes well above three fold for three of the four healthy patient donors at 24 …

Finding Fault?: Exploring Legal Duties To Return Incidental Findings In Genomic Research, Elizabeth R. Pike, Karen H. Rothenberg, Benjamin E. Berkman

Faculty Scholarship

The use of whole genome sequencing in biomedical research is expected to produce dramatic advances in human health. The increasing use of this powerful, data-rich new technology in research, however, will inevitably give rise to incidental findings (IFs), findings with individual health or reproductive significance that are beyond the aims of the particular research, and the related questions of whether and to what extent researchers have an ethical obligation to return IFs. Many have concluded that researchers have an ethical obligation to return some findings in some circumstances, but have provided vague or context-dependent approaches to determining which IFs must …

Relationships Between The Weedy (Amaranthaceae) And The Grain Amaranths [Abstract], Kiel D. Kielinski, Felix Jimenez, Eric N. Jellen, Peter J. Maughan, Scott M. Smith, Donald B. Pratt

Faculty Publications

No abstract provided.

Complete Genome Sequence Of Anabaena Variabilis Atcc 29413, Teresa Thiel, Brenda Pratte, Jinshun Zhong, Lynne Goodwin, Alex Copeland, Susan Lucas, Cliff Han, Sam Pitluck, Miriam Land, Nikos Kyrpides, Tanja Woyke

Biology Department Faculty Works

Anabaena variabilis ATCC 29413 is a filamentous, heterocyst-forming cyanobacterium that has served as a model organism, with an extensive literature extending over 40 years. The strain has three distinct nitrogenases that function under different environmental conditions and is capable of photoautotrophic growth in the light and true heterotrophic growth in the dark using fructose as both carbon and energy source. While this strain was first isolated in 1964 in Mississippi and named Anabaena flos-aquae MSU A-37, it clusters phylogenetically with cyanobacteria of the genus Nostoc. The strain is a moderate thermophile, growing well at approximately 40° C. Here we provide …

Set-Based Tests For Genetic Association In Longitudinal Studies, Zihuai He, Min Zhang, Seunggeun Lee, Jennifer A. Smith, Xiuqing Guo, Walter Palmas, Sharon L.R. Kardia, Ana V. Diez Roux, Bhramar Mukherjee

The University of Michigan Department of Biostatistics Working Paper Series

Genetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint effect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set …

Frequency-Dependent Mate Selection In The Guppy (Poeciliidae: Poecilia Reticulata), Andre Porter, Jack Frankel

Department of Biology Faculty Publications

Heterogeneity within a population enhances its long-term survival. A fundamental method of maintaining population heterogeneity is the retention of rare or uncommon phenotypes by selective mating strategies. Employing two color morphs, red tuxedo and red, of the guppy (Poecilia reticulata, Poeciliidae), this study was designed to investigate whether P. reticulata females would preferentially seek out heterogeneous groupings of males exhibiting two color morphs. Adult female guppies were exposed simultaneously to two groups of males (n=10); one comprised of only the tuxedo color morph (n=5) and the other of both color morphs (n=5). For the latter group, the ratio of males …

The Mechanism Of Regulation Of Autosomal Heterochromatic Genes In Drosophila Melanogaster Males By Rox Rna And Msl Proteins, Satya Kiran Koya

Wayne State University Dissertations

In humans and flies, males and females have different set of sex chromosomes contributing to different levels of X-linked gene expression. To equalize X-linked gene dosage between sexes, both humans and flies developed independent strategies which are called dosage compensation. Human females randomly inactivate one of their X chromosome into barr body and Drosophila males up regulate their single X chromosome two fold. Both strategies equalize of X linked gene dose between sexes.

In Drosophila, dosage compensation is brought about by the ribonucleoprotein Male Specific Lethal (MSL) complex that binds hundreds of sites along the X chromosome and modifies …

Did Androgen-Binding Protein Paralogs Undergo Neo- And/Or Subfunctionalization As The Abp Gene Region Expanded In The Mouse Genome?, Robert C. Karn, Amanda G. Chung, Christina M. Laukaitis

Scholarship and Professional Work - LAS

The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the …

Fate Of Antimicrobials And Antimicrobial Resistance Genes In Simulated Swine Manure Storage, Stacey R. Joy, Xu Li, Daniel D. Snow, John Gilley, Bryan L. Woodbury, Shannon L. Bartelt-Hunt

School of Natural Resources: Faculty Publications

The behavior of three antibiotics (bacitracin, chlortetracycline, and tylosin) and two classes of antibiotic resistance genes (ARGs), tet and erm, were monitored in swine manure slurry under anaerobic conditions. First-order decay rates were determined for each antibiotic with half-lives ranging from1 day (chlortetracycline) to 10 days (tylosin). ARGs were monitored in the swine manure slurry, and losses of approximately 1 to 3 orders of magnitude in relative abundance were observed during the 40 day storage period. First-order degradation profiles were observed for chlortetracycline and its corresponding resistance genes, tet(X) and tet(Q). Tylosin was degraded to approximately 10% …