Genetics and Genomics Commons^™

Conservation And Variation Of Dna Methylation In Lactuca Sativa And Lactuca Serriola, Trudi A. Baker

Graduate Doctoral Dissertations

Molecular techniques for guiding plant breeding have successfully used wild progenitors of domestic crops as sources of genetic variants conveying desirable traits. However, epigenetic variation, in particular DNA methylation, is a significant source of phenotypic variation and epigenetic effects of plant domestication are poorly understood. Described herein are the first single-base pair resolution methylomes of the highly valued crop iceberg lettuce (Lactuca sativa cv. Salinas) and its close relative, and ubiquitous weed, L. serriola. This work suggests several roles for acquisition and inheritance of methylation in the evolution of Lactuca spp. in response to stress. The Lactuca spp. have conserved …

Unseen Science: Modern Discoveries Too Far Away Or Tiny For Human Eyes, Lucy Huang

Capstones

As science has progressed, scientists have realized that evidence goes beyond the realms of physical sight. Whether it is too small or difficult to find, scientists have developed different ways to get around this problem. We see this in cancer genomics and in extrasolar planetary research. Scientists use what they know and what they measure to validate their work.

https://lucy-huang-9tge.squarespace.com/

Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande

KGI Theses and Dissertations

Huntington’s disease (HD) is a debilitating neurodegenerative disorder with a complex pathophysiology. Despite extensive studies to study the disease, the sequence of events through which mutant Huntingtin (mHtt) protein executes its action still remains elusive. The phenotype of HD is an outcome of numerous processes initiated by the mHtt protein along with other proteins that act as either suppressors or enhancers of the effects of mHtt protein and PolyQ aggregates. Utilizing an integrative systems biology approach, I construct and analyze a Huntington’s disease integrome using human orthologs of protein interactors of wild type and mHtt protein. Analysis of this integrome …

Prospective Associations Of Homocysteine, Executive Function, And Depressive Symptoms, Peter J. Dearborn

Electronic Theses and Dissertations

Associations of cardiovascular risk factors, cognitive performance, and depressive symptoms have been well established. However, the directionality of these associations as well as the specificity of these associations with respect to executive function are less clear. Additionally few studies have determined whether genetic risk factors, such as apolipoprotein-E4 (APOE-E4) genotype, and age moderate the associations of cardiovascular risk factors such as homocysteine with changes in depressive symptoms and how these associations may be mediated by cognitive performance. The primary aim of this study was to analyze the bidirectional associations of a full range of cognitive domains and symptoms of depression …

Comparative Molecular Characterization Of Typical And Exceptional Responders In Glioblastoma, Kristin Wipfler

Theses & Dissertations

Glioblastoma (GBM) is the most common and the deadliest type of primary brain tumor, with a median survival time of only 15 months despite aggressive treatment. Although most patients have an extremely poor prognosis, a small number of patients survive far beyond the median survival time. Investigation of these “exceptional responders” has sparked a great deal of interest and is becoming an important focus in the field of cancer research. To investigate the molecular differences between typical and exceptional responders in GBM, comparative analyses of copy number, methylation, gene expression, miRNA expression, and protein expression data sets from The Cancer …

Mechanism Of Gene Regulation By Coding Polya Tracks, Laura Lea Arthur

Arts & Sciences Electronic Theses and Dissertations

Regulation of gene expression is essential for cellular development and survival. The great variety and complexity of regulatory mechanisms underscores this fact. Messenger RNA stability and translational efficiency are often key determinants of gene expression. mRNA surveillance pathways, discovered for their role in degradation of aberrant mRNA, are now known to be instrumental in the regulation of physiologically correct mRNA stability. Thus, the study of cis elements in a transcript that can induce mRNA surveillance pathways has become an area of particular interest.

Here I report on the mechanism of gene regulation by coding polyA tracks, defined as a sequence …

Knowledge Driven Approaches And Machine Learning Improve The Identification Of Clinically Relevant Somatic Mutations In Cancer Genomics, Benjamin John Ainscough

Arts & Sciences Electronic Theses and Dissertations

For cancer genomics to fully expand its utility from research discovery to clinical adoption, somatic variant detection pipelines must be optimized and standardized to ensure identification of clinically relevant mutations and to reduce laborious and error-prone post-processing steps. To address the need for improved catalogues of clinically and biologically important somatic mutations, we developed DoCM, a Database of Curated Mutations in Cancer (http://docm.info), as described in Chapter 2. DoCM is an open source, openly licensed resource to enable the cancer research community to aggregate, store and track biologically and clinically important cancer variants. DoCM is currently comprised of 1,364 variants …

Analysis Of Argonaute-Small Rna-Transcription Factor Circuits Controlling Leaf Development, John Steen Hoyer

Arts & Sciences Electronic Theses and Dissertations

Experimental studies of plant development have yielded many insights into gene regulation, revealing interactions between core transcriptional and post-transcriptional regulatory pathways present in all land plants. This work describes a direct connection between the three main small RNA-transcription factor circuits controlling leaf shape dynamics in the reference plant Arabidopsis thaliana. We used a high-throughput yeast 1-hybrid platform to identify factors directly binding the promoter of the highly specialized ARGONAUTE7 silencing factor. Two groups of developmentally significant microRNA-targeted transcription factors were the clearest hits from these screens, but transgenic complementation analysis indicated that their binding sites make only a small contribution …

Effects Of Crude Oil On Tumor Suppressor P53 Polymorphisms In Laboratory-Exposed Atlantic Killifish, Fundulus Heteroclitus, Allison Margaret Nadler

Seton Hall University Dissertations and Theses (ETDs)

Polycyclic aromatic hydrocarbons (PAHs), constituents of crude oil, are implicated as a potent source of adverse toxicological effects on living organisms. To model the effects of PAHs in response to environmental oil spill disasters a species of killifish (Fundulus heteroclitus) was captured and exposed to crude oil in a laboratory-controlled setting. Over a period of 7 days, fish were dosed with crude oil by gavage, culled, and organs were harvested for analysis. Excitation-emission matrix spectroscopy (EEMS) of gall bladder tissue homogenates was used to verify exposure. Effects of PAHs on the p53 gene were evaluated as an indicator …

The Role Of Orphan Nuclear Receptor Dax-1 (Nr0b1) In Human Breast Cancer Cells: Expression, Proliferation And Metastasis, Erin Dishington

Master's Theses

The orphan nuclear hormone receptor DAX-1 (Dosage Sensitive Sex Reversal, Adrenal Hypoplasia Congenita on the X Chromosome, gene 1) plays an important role in the development of adrenal and gonadal tissues and functions as a global negative-regulator of steroidogenesis. In addition, it is known to be involved in several diseases including some cancers. Herein, we describe our examination of the role of DAX-1 in breast cancer, specifically its influence on proliferation and metastasis and its expression during progressive stages of disease. In an effort to understand how DAX-1 influences breast cancer cell proliferation and metastasis, we used MCF7 breast cancer …

Nuclear Genome Size Diversity Of Marine Invertebrate Taxa Using Flow Cytometric Analysis, Kyle Roebuck

HCNSO Student Theses and Dissertations

Genomic analysis provides a substantial amount of information on evolutionary history, novel genes, transcriptomic expression and regulation in response to environmental stimuli, how efficiently organisms utilize their genome, and directional genome evolution. Genome size analysis serves as the first step in the sequencing process, because sequencing and annotation costs are directly correlated with genome size. Invertebrates represent the vast majority of faunal diversity on the planet, and, to a greater extent, the marine environment, although they are vastly understudied when compared to vertebrate genomes. Flow cytometry is a widely used, reliable, and accurate means of estimating genome sizes and has …

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis

HCNSO Student Capstones

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of early …

Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh

Dissertations & Theses (Open Access)

Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …

Bioinformatic And Experimental Approaches For Deeper Metaproteomic Characterization Of Complex Environmental Samples, Ramsunder Mahadevan Iyer

Doctoral Dissertations

The coupling of high performance multi-dimensional liquid chromatography and tandem mass spectrometry for characterization of microbial proteins from complex environmental samples has paved the way for a new era in scientific discovery. The field of metaproteomics, which is the study of protein suite of all the organisms in a biological system, has taken a tremendous leap with the introduction of high-throughput proteomics. However, with corresponding increase in sample complexity, novel challenges have been raised with respect to efficient peptide separation via chromatography and bioinformatic analysis of the resulting high throughput data. In this dissertation, various aspects of metaproteomic characterization, including …

Investigating The Regulation Of Indole-3-Acetic Acid Production By The Plant Associated Microbe Pantoea Sp. Yr343, Kasey Noel Estenson

Doctoral Dissertations

The auxin indole-3-acetic acid (IAA) plays a central role in plant growth and development and many plant-associated microbes produce IAA. Several IAA biosynthetic pathways have been identified in microbes which use the precursor tryptophan. Pantoea sp. YR343, which was isolated from the Populus deltoides rhizosphere, is a robust plant root colonizer that produces IAA. Using genomic and metabolomics analyses, we predicted that the indole-3-pyruvate (IPA) pathway is the major pathway in Pantoea sp. YR343 for IAA production. To better understand IAA biosynthesis and the effects of IAA exposure on cell physiology, we performed proteomics on Pantoea sp. YR343 grown in …

Systematics And Biogeography Of The Cortinarius Violaceus Group And Sequestrate Evolution In Cortinarius (Agaricales), Emma Harrower

Doctoral Dissertations

Phylogenetics is a powerful tool used for illuminating the diversity of life on Earth, their evolution and their ecology. I created a multi-gene phylogenetic tree of Cortinarius section Cortinarius and uncovered five previously overlooked species, increasing the number of species in the section from seven to twelve. All members of the clade possess both cheilocystidia and pleurocystidia and possess a pigment known as (R)-39,49-dihydroxybphenylalanine. Ancestral state reconstruction estimated that the ancestral host was most likely an angiosperm, switching hosts when encountering novel host species in new lands, and only C. violaceus associating with the Pinaceae in North America. Biogeographic analysis …

Evaluating The Therapeutic Efficacy Of Restoring Wild-Type P53 Activity In P53-Mutant Tumors, Connie A. Larsson

Dissertations & Theses (Open Access)

The p53 transcription factor is the most frequently altered in human cancers usually via missense mutations that undermine its transcriptional activity. Clinically, TP53 mutations have been shown to be remarkably predictive of refractoriness to treatment, resulting in poor outcome. Consequently, the development of p53 pathway activating agents is rapidly evolving and gaining more attention in cancer therapeutics research, with several small molecule compounds currently in preclinical and clinical trials. However, it remains largely unknown what types or proportions of p53-mutant tumors will respond to p53 restoration-based therapies.

Using a mouse model of Li Fraumeni syndrome, we genetically restored wild-type …

Mediation And Moderation Of Intergenerational Epigenetic Effects Of Trauma, Stefanie Renee Pilkay

Doctoral Dissertations

Trauma and early-life stress have been linked to poor mental and physical health outcomes. In fact, research has identified trauma and stress can influence epigenetic marks on genes that can alter gene activity. It is suspected that epigenetically altered gene activity is involved in behavior and mental health. This may help explain why some individuals don’t experience great benefit from treatment for the effects of stress, and severe mental health symptoms can be chronic for decades or a lifetime. Moreover, some trauma-related mental health symptoms have shown generational patterns that appear linked to epigenetic marks. Therefore, this study sought to …

Identifying Genetic Factors Influencing Sperm Mobility Phenotype In Chicken Using Genome Wide Association Studies, Primordial Germ Cell Transplantation, And Rnaseq., Sohita Ojha

Graduate Theses and Dissertations

Sperm mobility is a major determinant of male fertility in chicken. In spite of low heritability of reproductive traits, sperm mobility has high heritability index which suggests presence of quantitative trait loci (QTLs) governing the trait. Our research focused on three objectives: i) to identify the QTLs affecting low mobility phenotype in chicken, ii) to understand the impact of Sertoli-cells and germ cells interactions in influencing the mobility phenotype and iii) to identify the genes and gene networks differentially expressed in male and female PGCs. To detect the QTLs, genome wide association studies (GWAS) was conducted which revealed the presence …

Transcriptome-Based Gene Networks For Systems-Level Analysis Of Plant Gene Functions, Chirag Gupta

Graduate Theses and Dissertations

Present day genomic technologies are evolving at an unprecedented rate, allowing interrogation of

cellular activities with increasing breadth and depth. However, we know very little about how the

genome functions and what the identified genes do. The lack of functional annotations of genes

greatly limits the post-analytical interpretation of new high throughput genomic datasets. For plant

biologists, the problem is much severe. Less than 50% of all the identified genes in the model plant

Arabidopsis thaliana, and only about 20% of all genes in the crop model Oryza sativa have some

aspects of their functions assigned. Therefore, there is an …

A Neuroprotective Role For Mir-1017, A Non-Canonical Mirna, Matthew De Cruz

Master's Theses

miRNAs are post-transcriptional regulators of gene expression, with numerous being involved in neurobiology. Within the human genome a quarter of the identified miRNA loci derive from a class of miRNAs termed tailed mirtrons. Despite the identification of this large population of miRNA, no functional studies have been conducted to identify their role. In this study we examined the highly expressed and deeply conserved Drosophila 3’ tail mirtron, miR-1017, as a candidate to elucidate tailed mirtron functionality. We identified acetylcholine receptor transcripts, Da5 and Da2, as bona fide targets for miR-1017. Interestingly, Da2 is also the host transcript for miR-1017. We …

Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, Pravin Raghunath Kaldhone

Graduate Theses and Dissertations

Foodborne illnesses are a leading cause of infectious diseases in the world. Among enteric organisms Salmonella is a key pathogen. It’s high prevalence in poultry and other food-animal sources make it imperative to study. Salmonella has the ability to modify its genetic content with help of mobile genetic elements such as plasmids. Incompatibiltiy group 1 (IncI1) plasmids are commonly reported in Salmonella. This study evaluates role on IncI1 plasmids in antimicrobial resistance and virulence in Salmonella. Genetic determinants of resistance and virulence are noted among our IncI1-containing Salmonella isolates. These genetic elements are also transferable and reported to carry respective …

This Is Just A Phase : The Impact Of Population Structure On Haplotype Phasing And Linkage Disequilibrium Measures At Functional Genetic Sites., Roxanne Kaaren Leiter

Electronic Theses and Dissertations

The block-like structure of the human genome has been the subject of many scientific papers and is of practical significance in large-scale genome-wide association studies. How stringent haplotype block boundaries are within and between populations has been the subject of ongoing debate within human population genetics. This thesis will contribute to the description of universal and population-specific haplotype blocks at functional sites, namely across the IL-10 gene family (including IL-10, IL-19, IL-20 and IL-24), which is involved in a number of immune system processes, and MAPKAP-K2, an adjacent and functionally significant kinase gene. Beyond the description of blocks across these …

Development Of New Bioinformatic Approaches For Human Genetic Studies, Jose Andres Guevara Coto

All Dissertations

The development of bioinformatics methods for human genetic studies utilizes the vast amount of data to generate new valuable information. Machine learning and statistical coupling analysis can be used in the study of human diseases. These diseases include intellectual disabilities (ID), prevalent in 1-3% of the population and caused primarily by genetics. Although many cases of ID are caused by mutations in protein-coding genes, the possible involvement of long non-coding RNAs (lncRNAs) in ID due to their role in gene expression regulation, has been explored. In this study, we used machine learning to develop a new expression-based model trained using …

Development, Evaluation, And Application Of A Novel Error Correction Method For Next Generation Sequencing Data, Isaac Akogwu

Dissertations

Tremendous evolvement in sequencing technologies and the vast availability of data due to decreasing cost of Next-Generation-Sequencing (NGS) has availed scientists the opportunity to address a wide variety of evolutionary and biological issues. NGS uses massively parallel technology to accelerate the process at the expense of accuracy and read length in comparison to earlier Sanger methods. Therefore, computational limitations exist in how much analysis and information can be gleaned from the data without performing some form of error correction.

Error correction process is laborious and consumes a lot of computational resources. Despite the existence of many NGS data error correction …

Quality Of Life: Socio-Demographic And Genetic Determinants As Well As Links With Cancer Outcomes, Jeanne Pierzynski

Dissertations & Theses (Open Access)

Quality of life (QOL) is an independent prognostic factor for cancer. Lung cancer is the leading cause of cancer death. Breast cancer is the most diagnosed. Bladder cancer is the most expensive cancer to treat because of its high recurrence rate. We set to perform comprehensive analyses of predictors of QOL in these cancer sites with the future goal of improving QOL and outcomes.

In 6,456 newly diagnosed lung cancer patients, we investigated the relationship between baseline patient characteristics and QOL to identify determinants of QOL. A QOL questionnaire (SF-12v1) measured patients’ physical component summary (PCS) and mental component summary …

A Deep Learníng-Based Data Minimization Algorithm For Big Genomics Data In Support Of Lot And Secure Smart Health Services, Mohammed Aledhari

Dissertations

In the age of Big Genomics Data, institutes such as the National Human Genome Research Institute (NHGRI),1000-Genomes project, and the international cancer sequencing consortium are faced with the challenge of sharing large volumes of data between internationallydispersed sample collectors, data analyzers, and researchers, a process that up until now has been plagued by unreliable transfers and slow connection speeds. These occur due to the inherent throughput bottlenecks of traditional transfer technologies. One suggested solution is using the cloud as an infrastructure to solve the store and analysis challenges. However, the transfer and share of the genomics datasets between biological laboratories …

Stressing Out: Dynamics Of Chromatin Insulator Body Formation In Eukaryotes Under Osmotic Stress, Shannon Marie Garland

Masters Theses

Higher order genome organization and the role it plays in governing cell dynamics and protein expression has become a widely studied field. Chromatin insulators are important to this organization in their ability to form long range contacts between distant regions on the genome. During times of osmotic stress, insulator proteins leave their binding sites on the DNA to form insulator bodies in the nucleus. This phenomenon relieves the DNA of its structure and is rapidly reversible. Using a variety of immunofluorescent staining methods, this work looked to further characterize this process while attempting to identify molecular mechanisms that mediate chromatin …

Chromatin Accessibility Dynamics In The Arabidopsis Root Epidermis And Endodermis During Cold Acclimation, Shawn Hoogstra

Electronic Thesis and Dissertation Repository

Understanding cell-type specific transcriptional responses to environmental conditions is limited by a lack of knowledge of transcriptional control due to epigenetic dynamics. Additionally, cell-type analyses are limited by difficulties in applying current technologies to single cell-types. A novel DNase-seq protocol and analysis procedure, deemed DNase-DTS, was developed to identify DHSs in the Arabidopsis epidermis and endodermis under control and cold acclimation conditions. Results identified thousands of DHSs within each cell-type and experimental condition. DHSs showed strong association to gene expression, DNA methylation, and histone modifications. A priori mapping of existing DNA binding motifs within accessible genes and the cold C-repeat/dehydration …

Transcriptomic Regulation Of Alternative Phenotypic Trajectories In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Amie L. Romney

Dissertations and Theses

The Annual Killifish, Austrofundulus limnaeus, survives the seasonal drying of their pond habitat in the form of embryos entering diapause midway through development. The diapause trajectory is one of two developmental phenotypes. Alternatively, individuals can "escape" entry into diapause and develop continuously until hatching. The alternative phenotypes of A. limnaeus are a form of developmental plasticity that provides this species with a physiological adaption for surviving stressful environments. The developmental trajectory of an embryo is not distinguishable morphologically upon fertilization and phenotype is believed to be influenced by maternal provisioning within the egg based on observations of offspring phenotype …