Genetics and Genomics Commons^™

Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray

Pharmacology and Nutritional Sciences Faculty Publications

Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …

The Microbiome Of The Built Environment: A Large-Scale Citizen Science Genomics Project, Christopher Garrett Wilson

Honors Capstone Projects and Theses

No abstract provided.

Global Genetic Connectivity And Diversity In A Shark Of High Conservation Concern, The Oceanic Whitetip, Carcharhinus Longimanus, Cassandra L. Ruck

HCNSO Student Theses and Dissertations

The oceanic whitetip shark, Carcharhinus longimanus, is a circumtropical pelagic shark of high conservation concern (IUCN Red List: “Critically Endangered” in the Western North and Western Central Atlantic and “Vulnerable” globally). I present the first, population genetic assessment of the oceanic whitetip shark on a global scale, based on analysis of two mitochondrial genome regions (entire 1066-1067 bp control region and 784 bp partial ND4 gene), and nine nuclear microsatellite loci. No population structure was detected within the Western Atlantic. However, highly significant population structure was detected between Western Atlantic and Indo-Pacific Ocean sharks across all markers. Additionally, a …

Biology, Gene Flow, And Management Of Glyphosate-Resistant Common Waterhemp (Amaranthus Rudis Sauer) In Nebraska, Debalin Sarangi

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Common waterhemp is the most troublesome weed in the midwestern United States. Growers from Nebraska reported failure to control common waterhemp following sequential applications of glyphosate in glyphosate-tolerant corn and soybean, which led to moderate to severe yield loss; justifying the need to confirm resistance and study the biology and management of common waterhemp. The objectives of this research were: 1) to confirm the presence of glyphosate-resistant (GR) common waterhemp biotypes in Nebraska and to evaluate their sensitivity to herbicides belonging to alternative sites-of-action; 2) to evaluate the response of common waterhemp to water stress; 3) to quantify pollen-mediated gene …

The Asian Arowana (Scleropages Formosus) Genome Provides New Insights Into The Evolution Of An Early Lineage Of Teleosts, Chao Bian, Yinchang Hu, Vydianathan Ravi, Inna S. Kuznetsova, Xueyan Shen, Xidong Mu, Ying Sun, Xinxin You, Jia Li, Xiaofeng Li, Ying Qiu, Boon-Hui Tay, Natascha May Thevasagayam, Aleksey S. Komissarov, Vladimir Trifonov, Marsel Kabilov, Alexey Tupikin, Jianren Luo, Yi Liu, Hongmei Song, Chao Liu, Xuejie Wang, Dangen Gu, Yexin Yang, Wujiao Li, Gianluca Polgar, Guangyi Fan, Peng Zeng, He Zhang, Zijun Xiong, Zhujing Tang, Chao Peng, Zhiqiang Ruan, Hui Yu, Jieming Chen, Mingjun Fan, Yu Huang, Min Wang, Xiaomeng Zhao, Guojun Hu, Huanming Yang, Jian Wang, Jun Wang, Xun Xu, Linsheng Song, Gangchun Xu, Junmin Xu, Stephen J. O'Brien, Laszlo Orban, Byrappa Venkatesh, Qiong Shi

Biology Faculty Articles

The Asian arowana (Scleropages formosus), one of the world’s most expensive cultivated ornamental fishes, is an endangered species. It represents an ancient lineage of teleosts: the Osteoglossomorpha. Here, we provide a high-quality chromosome-level reference genome of a female golden-variety arowana using a combination of deep shotgun sequencing and high-resolution linkage mapping. In addition, we have also generated two draft genome assemblies for the red and green varieties. Phylogenomic analysis supports a sister group relationship between Osteoglossomorpha (bonytongues) and Elopomorpha (eels and relatives), with the two clades together forming a sister group of Clupeocephala which includes all the remaining …

A Tale Of Two Theories: Using An Engineered Strain Of E. Coli To Bridge The Gap Between Quorum Sensing And Diffusion Sensing, Cortney E. Wilson

HCNSO Student Theses and Dissertations

Cooperation is a trait that is found at all levels of biological organization. Interestingly, cooperation appears to occur in bacteria that produce small, easily diffusible molecules called autoinducers. To understand why bacteria produce these autoinducers, the scientific community has focused on one predominant theory called quorum sensing. Under this theory, bacteria produce autoinducers so they can sense the density of the population. Once a sufficiently high population density is reached, autoinducers initiate the production of a costly gene product that serves to benefit the population. In contrast, a competing theory called diffusion sensing suggests that autoinducers are used by the …

Chromosomal-Level Assembly Of The Asian Seabass Genome Using Long Sequence Reads And Multi-Layered Scaffolding, Shubha Vij, Heiner Kuhl, Inna S. Kuznetsova, Aleksey Komissarov, Andrey A. Yurchenko, Peter Van Heusden, Siddharth Singh, Natascha May Thevasagayam, Sai Rama Sridatta Prakki, Kathiresan Purushothaman, Jolly M. Saju, Junhui Jiang, Stanley Kimbung Mbandi, Mario Jonas, Amy Hin Yan Tong, Sarah Mwangi, Doreen Lau, Si Yan Ngoh, Woei Chang Liew, Xueyan Shen, Lawrence S. Hon, James P. Drake, Matthew Boitano, Richard Hall, Chen-Shan Chin, Ramkumar Lachumanan, Jonas Korlach, Vladimir Trifonov, Marsel Kabilov, Alexey Tupikin, Darrell Green, Simon Moxon, Tyler Garvin, Fritz J. Sedlazeck, Gregory W. Vurture, Gopikrishna Gopalapillai, Vinaya Kumar Katneni, Tansyn H. Noble, Vinod Scaria, Sridhar Sivasubbu, Dean R. Jerry, Stephen J. O'Brien, Michael C. Schatz, Tamas Dalmay, Stephen W. Turner, Si Lok, Alan Christoffels, Laszlo Orban

Biology Faculty Articles

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species’ native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications …

Comparative Error-Free And Error-Prone Translesion Synthesis Of N2‑2′-Deoxyguanosine Adducts Formed By Mitomycin C And Its Metabolite, 2,7-Diaminomitosene, In Human Cells, Arindam Bose, Chaitra Surugihalli, Paritosh Pande, Elise Champeil, Ashis K. Basu

Publications and Research

Mitomycin C (MC) is a cytotoxic and mutagenic antitumor agent that alkylates DNA upon reductive activation. 2,7-Diaminomitosene (2,7-DAM) is a major metabolite of MC in tumor cells, which also alkylates DNA. MC forms seven DNA adducts, including monoadducts and inter- and intrastrand cross-links, whereas 2,7-DAM forms two monoadducts. Herein, the biological effects of the dG-N2 adducts formed by MC and 2,7-DAM have been compared by constructing single-stranded plasmids containing these adducts and replicating them in human embryonic kidney 293T cells. Translesion synthesis (TLS) efficiencies of dG-N2-MC and dG-N2-2,7-DAM were 38 ± 3 and 27 …

A Patient With Constitutional Ring 1 Chromosome Characterized By Snp Array Cgh, Sheila Saliganan, Joanna Lee, Sainan Wei

Pathology and Laboratory Medicine Faculty Publications

We present a male patient with constitutional ring 1 chromosome and subsequent 6 Mb deletion at 1q43q44. The patient displays overlapping clinical features with reported patients with ring 1 chromosome and 1q43q44 microdeletion syndrome. To our knowledge, this is the first patient with ring 1 chromosome characterized by comparative genomic hybridization.

Non-Essentiality Of Alr And Muri Genes In Mycobacteria, Philion L. Hoff, Denise Zinniel, Raúl G. Barletta

UCARE: Research Products

Amino acids are the building blocks of life. If DNA is the blueprint, amino acids are the lumber that proteins are built with. Proteins are built with left-handed, L- forms of amino acids. Bacteria have an essential cell wall component that happens to be an exception: peptidoglycan. Bacteria have enzymes called racemases that convert L- amino acid forms into right-handed, D- forms. Amino acids participate in many reactions with keto acids. Transaminases allow conversion between amino acids by transfer of an amino group.

Previous reports claimed there is no D-ala transaminase activity in mycobacteria and thus alr and murI genes …

Gene Expression Profiling In An Alzheimer's Disease Mouse Model, Matthew R. Dalton

Senior Honors Theses

Explaining precisely how Alzheimer’s disease (AD)—the world’s most common form of dementia—materializes in the human brain has proven to be one of the most elusive ends in modern medicine. Progressive memory loss, neurodegeneration, and the presence of abnormal protein aggregates of amyloid-beta (Aβ) and neurofibrillary tangles (NFT) characterize this disease. Genome sequencing provides researchers with the ability to better identify disease-related changes in gene expression, some of which may play a role in the initiation and progression toward the AD-like state. Intimate interactions between tissues have been observed in many diseases, particularly between the brain and blood. This analysis seeks …

Effects Of Choline On Dna Methylation And Macronutrient Metabolic Gene Expression In In Vitro Models Of Hyperglycemia, Xinyin Jiang, Esther Greenwald, Chauntelle Jack-Roberts

Publications and Research

Choline is an essential nutrient that plays an important role in lipid metabolism and DNA methylation. Studies in rodents suggest that choline may adversely affect glycemic control, yet studies in humans are lacking. Using the human hepatic and placental cells, HepG2 and BeWo, respectively, we examined the interaction between choline and glucose treatments. In HepG2 cells, choline supplementation (1 mM) increased global DNA methylation and DNA methyltransferase expression in both low-glucose (5 mM) and high-glucose (35 mM) conditions. Choline supplementation increased the expression of peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), which mediates fatty acid β-oxidation, especially in the high-glucose condition. …

Genetic Moderators Of Cognitive Decline In The Health And Retirement Study, Shannon K. Runge

USF Tampa Graduate Theses and Dissertations

The current dissertation used a gene x environment (G x E) approach to examine the independent and interactive effects of specific genetic variants and participation in physical and cognitive/social activities (PA and CSA) on cognitive performance in 4,764 participants of the Health and Retirement Study. Using three-wave data, three sets of multi-level growth models were conducted to examine baseline, longitudinal, and interactive effects of genotype (i.e., ApoE, COMT, and BDNF) and CSA/PA on performance across five cognitive measures: immediate, delayed and total word recall, and serial 7s and backwards counting.

At baseline, the ApoE ε4 allele predicted …

Gibsonville Healthy Forest Restoration Project: Silviculture Report, Dan Roskopf

Aspen Bibliography

The Forest Service proposes to reduce the risk of wildfire, to protect, restore, and enhance forest ecosystem components (i.e., streams, meadows, aspen areas) in the vicinity of Gibsonville, California. A combination of hazard tree removal, forest health, and fuels reduction treatments are proposed on 1,200 acres of Forest Service system lands. These actions are proposed to be implemented on the Feather River Ranger District of the Plumas National Forest.

The Effects Of Chronic Partial Sleep Deprivation On Alcohol Consumption And Delta Fos B Accumulation, Kristian Ponder

Showcase of Graduate Student Scholarship and Creative Activities

The present study explores the relation between sleep restriction and alcohol use and the neural substrates that result from chronic behaviors, such as transcription factors. Transcription factor activity is suggested as a possible outcome of chronic behaviors, such as addiction. Sleep is discussed as possible mediating factor in the relationship between specific transcription factors and alcohol. Analysis will focus on brain areas related to both sleep and reward.

Detecting Gene-Gene Interactions Using A Permutation-Based Random Forest Method, Jing Li, James D. Malley, Angeline S. Andrew, Margaret R. Karagas, Jason H. Moore

Dartmouth Scholarship

Identifying gene-gene interactions is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Here, we aimed at developing a permutation-based methodology relying on a machine learning method, random forest (RF), to detect gene-gene interactions. Our approach called permuted random forest (pRF) which identified the top interacting single nucleotide polymorphism (SNP) pairs by estimating how much the power of a random forest classification model is influenced by removing pairwise interactions.

Nonreplicative Dna Helicases Involved In Maintaining Genome Stability, Salahuddin Syed

USF Tampa Graduate Theses and Dissertations

Double-strand breaks and stalled forks arise when the replication machinery encounters damage from exogenous sources like DNA damaging agents or ionizing radiation, and require specific DNA helicases to resolve these structures. Sgs1 of Saccharomyces cerevisiae is a member of the RecQ family of DNA helicases and has a role in DNA repair and recombination. The RecQ family includes human genes BLM, WRN, RECQL4, RECQL1, and RECQL5. Mutations in BLM, WRN, and RECQL4 result in genetic disorders characterized by developmental abnormalities and a predisposition to cancer. All RecQ helicases have common features including a …

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic state. …

Comparison Of Two Commercial Dna Extraction Kits For The Analysis Of Nasopharyngeal Bacterial Communities, Marcos Pérez-Losada, Keith Crandall, Robert J. Freishtat

Pediatrics Faculty Publications

Characterization of microbial communities via next-generation sequencing (NGS) requires an extraction ofmicrobial DNA. Methodological differences in DNA extraction protocols may bias results and complicate inter-study comparisons. Here we compare the effect of two commonly used commercial kits (Norgen and Qiagen)for the extraction of total DNA on estimatingnasopharyngeal microbiome diversity. The nasopharynxis a reservoir for pathogens associated with respiratory illnesses and a key player in understandingairway microbial dynamics.
Total DNA from nasal washes corresponding to 30 asthmatic children was extracted using theQiagenQIAamp DNA and NorgenRNA/DNA Purification kits and analyzed via IlluminaMiSeq16S rRNA V4 ampliconsequencing. The Norgen samples included more sequence reads …

Analysis Of Morphology And Secretion Mutants In Aspergillus Nidulans, Shelby N. Holaday, Steven D. Harris

UCARE: Research Products

Filamentous fungi are important economically and medically due to their capacity to produce secondary metabolites or as human and animal pathogens. The genes and molecular mechanism responsible for secretion is poorly understood. Using classical genetics, we derived temperature sensitive (Ts) fungal mutants in Aspergillis nidulans. These mutants were then analyzed for their secondary metabolite secretion capacity.

In this study, we used the Ts strains of A. nidulans to determine how knockouts affect morphological and protein secretion by examining the phenotypes under the microscope and also by staining the mutants with Congo red staining. Mutants were stained with Congo red to …

Is A Mitochondrial Plasmid Really A Virus?, Mackenzie Strehle

UCARE: Research Products

In addition to containing a large and complex mitochondrial genome, the mitochondria of several species of plants have been shown to contain an independent, self-replicating DNA molecule in the form of a plasmid. Plants in the Brassica genus contain a linear plasmid that is approximately 11.6 kilobases in length. The plasmid is characterized by the presence of terminal inverted repeats and covalently bonded proteins at its termini (Handa 2008). The plasmid also contains six ORFs that encode DNA and RNA polymerases and a number of unknown proteins (Figure 1). Currently, both the function of this plasmid and the mechanisms by …

Genetic Factors Affecting Hybrid Male Sterility Leading To Speciation, Patrick Opperman, Colin D. Meiklejohn

UCARE: Research Products

The process whereby speciation occurs can come about through the evolution of barriers to gene flow. One of these barriers to gene flow can be an incompatibility, which leaves hybrids dead or sterile. Two theories underlie the work of this experiment, Haldane’s Rule and the large X effect. Haldane’s Rule is the observation that unisexual inviability or sterility among species’ hybrids is almost always found in the heterogametic sex. The large X effect is the observation that substitution of one species’ X-chromosome for another’s has a disproportionately large effect on hybrid fitness compared to similar substitution of an autosome. For …

Examining Maternal Obesity Effects On Oogenesis, Follicular Development, And Embryonic Myogenesis, Chris Lindeman, Jennifer Wood

UCARE: Research Products

The CDC estimates that more than one-third of U.S. adults (approximately 78.6 million) are obese. Despite national efforts to combat this with diet and exercise, the number of obese adults and children continues to climb. It is critical to emphasize that obesity can lead to lifelong, chronic complications and health risks including hypertension, heart disease, and diabetes.

Diet and obesity also have important impacts on the reproductive health of female including the ability to become pregnant (fertility) and risk for complications during pregnancy. Furthermore, for women who do become pregnant, obesity can affect the development of the embryo and fetus, …

Transgenerational Plasticity Is Sex-Dependent And Persistent In Yellow Monkeyflower (Mimulus Guttatus), Kayla C. Akkerman, Arash Sattarin, John K. Kelly, Alison G. Scoville

Student Published Works

Transgenerational phenotypic plasticity, whereby environmental cues experienced by parents alter the phenotype of their progeny, has now been documented in diverse organisms. Transmission of environmentally determined responses is known to occur through both maternal and paternal gametes, but the underlying mechanisms have rarely been compared. In addition, the persistence of induction over multiple generations appears to vary widely, but has been characterized for relatively few systems. Yellow monkeyflower (Mimulus guttatus) is known to exhibit transgenerational induction of increased glandular trichome production in response to simulated insect damage. Here, we test for differences between maternal and paternal transmission of …

It’S In Your Genes, Cody Gowan

McNair Scholars Research Journal

There’s a vast misunderstanding of how cells function amongst the general public. Many people understand that our genes are what make us who we are. However, many people don’t understand how. Proteins are the functional units of the cell that allow the genome to express itself. The Central Dogma of biology is that DNA is transcribed to messenger RNA and then translated to protein, and everything about our physical being is a result of how proteins function—from the color of our eyes to life-threatening diseases that we endure, such as cancer. It is this idea (that the function of proteins …

Membrane Channel Gene Expression In Human Costal And Articular Chondrocytes, A. Asmar, R. Barrett-Jolley, A. Werner, R. Kelly Jr., M. Stacey

Bioelectrics Publications

Chondrocytes are the uniquely resident cells found in all types of cartilage and key to their function is the ability to respond to mechanical loads with changes of metabolic activity. This mechanotransduction property is, in part, mediated through the activity of a range of expressed transmembrane channels; ion channels, gap junction proteins, and porins. Appropriate expression of ion channels has been shown essential for production of extracellular matrix and differential expression of transmembrane channels is correlated to musculoskeletal diseases such as osteoarthritis and Albers-Sch€onberg. In this study we analyzed the consistency of gene expression between channelomes of chondrocytes from human …

Scalable Parallelization Of A Markov Coalescent Genealogy Sampler, Philip E. Davis

Masters Theses

Coalescent genealogy samplers are effective tools for the study of population genetics. They are used to estimate the historical parameters of a population based upon the sampling of present-day genetic information. A popular approach employs Markov chain Monte Carlo (MCMC) methods. While effective, these methods are very computationally intensive, often taking weeks to run. Although attempts have been made to leverage parallelism in an effort to reduce runtimes, they have not resulted in scalable solutions. Due to the inherently sequential nature of MCMC methods, their performance has suffered diminishing returns when applied to large-scale computing clusters. In the interests of …

Reducing The Potential For Acrylamide Formation In Wheat Products, Amy Hauver, P. Stephen Baenziger, Mary J. Guttieri

UCARE: Research Products

Acrylamide, a chemical formed from free asparagine and reducing sugars during high-temperature cooking via the Maillard reaction (i.e. frying or baking) of high starch foods is deemed ‘probably carcinogenic to humans’ based on its affect in mice. In April of 2002, a group of Swedish researchers reported findings that presented evidence that heat-treated, starch-rich foods contained high levels of acrylamide, later linking the production of acrylamide to the Maillard reaction. A number of other studies have been done to link dietary intake of acrylamide to human cancers and other health effects, although many have had inconclusive results. Nevertheless, the World …

The Genomic Cds Sandbox: An Assessment Among Domain Experts., Ayesha Aziz, Kensaku Kawamoto, Karen Eilbeck, Marc S Williams, Robert R Freimuth, Mark A Hoffman, Luke V Rasmussen, Casey L Overby, Brian H Shirts, James M Hoffman, Brandon M Welch

Manuscripts, Articles, Book Chapters and Other Papers

Genomics is a promising tool that is becoming more widely available to improve the care and treatment of individuals. While there is much assertion, genomics will most certainly require the use of clinical decision support (CDS) to be fully realized in the routine clinical setting. The National Human Genome Research Institute (NHGRI) of the National Institutes of Health recently convened an in-person, multi-day meeting on this topic. It was widely recognized that there is a need to promote the innovation and development of resources for genomic CDS such as a CDS sandbox. The purpose of this study was to evaluate …

Reinforcement Learning, Error-Related Negativity, And Genetic Risk For Alzheimer's Disease, Christina Marie Figueroa

Dissertations (1934 -)

Reinforcement learning (RL) has been widely used as a model of animal and human learning and decision-making. The neural networks underlying RL involve many of the same structures primarily affected by Alzheimer’s disease (AD) such as the hippocampus. Yet, RL and non-invasive evaluation of its neural underpinnings have been underutilized as a framework for understanding disease pathology and its pre-clinical states. This study aimed to provide a novel approach for assessing subtle changes in asymptomatic apolipoprotein-E (APOE) carriers and non-carriers. Electroencephalography was collected from forty APOE genotyped older adults (Male n = 11; Mage = 79.30; Meducation = 14.88 years) …