Genetics Commons^™

Investigating The Molecular Etiologies Of Sporadic Als (Sals) Using Rna-Sequencing, David G. Brohawn

Theses and Dissertations

ALS is an often lethal disease involving degeneration of motor neurons in the brain and spinal cord. Current treatments only extend life by several months, and novel therapies are needed. We combined RNA-Sequencing, systems biology analyses, and molecular biology assays to elucidate sporadic ALS group-specific differences in postmortem cervical spinal sections (7 sALS and 8 control samples) that may be relevant to disease pathology. >55 million 2X150 RNA-sequencing reads per sample were generated and processed.

In Chapter 2, we used bioinformatics tools to identify nuclear differentially expressed genes (DEGs) between our two groups. Further, we used Weighted Gene Co-Expression Network …

Genome Wide Epigenetic Analyses Of Araptus Attenuatus, A Bark Beetle, Chitra Seshadri

Theses and Dissertations

Phylogeographic studies have relied on surveying neutral genetic variation in natural populations as a way of gaining better insights into the evolutionary processes shaping present day population demography. Recent emphasis on understanding putative adaptive variation have brought to light the role of epigenetic variation in influencing phenotypes and the mechanisms underlying local adaptation. While much is known about how methylation acts at specific loci to influence known phenotypes, there is little information on the spatial genetic structure of genome-wide patterns of methylation and the extent to which it can extend our understanding of both neutral and putatively adaptive processes. This …

Genetic Structure And Connectivity Of The Endangered Giant Kangaroo Rat (Dipodomys Ingens) In A Heterogeneous Environment, Nathan Alexander

Cal Poly Humboldt theses and projects

Movement ecology and dispersal are important aspects of species’ life histories that can inform conservation and management. Dispersal is often cryptic and difficult to detect, but recent advances genetic technology and applications have provided new approaches to identifying and describing dispersal patterns. Giant kangaroo rats (Dipodomys ingens) are an endangered heteromyid that appear to persist in small subpopulations in a heterogeneous environment of their northern range, the Ciervo-Panoche Natural Area, California. Previous work suggested high levels of genetic diversity between populations with genetic distances not being correlated to geographic distances. Here, I identified landscape population structure through clustering …

Examining Genetic And Environmental Influences On Alcohol Use And Externalizing Behaviors In African American Adolescents, Neeru Goyal

Theses and Dissertations

The aim of this thesis is to expand our understanding of the etiology of alcohol misuse and related disorders in African Americans using genetically informative study designs. Specifically, we take advantage of the candidate-gene approach and polygenic score analysis to extend the literature specific to African American populations. Chapter 2 explores gene x environment (GxE) interactions through the candidate gene approach to explore the relationship between two genes chosen on their potential relevance to stress response and adolescent alcohol use and misuse, among African American youth living in highly impoverished neighborhoods, as moderated by stressful life events. Chapter 3 implements …

Adducins Are Negative Regulators Of Migration And Invasion Of Normal Lung Epithelial Cells And Lung Cancer Cells, Parth Hitenbhai Amin, Parth Amin

Theses and Dissertations

Cell migration is an important component of many physiological and pathological processes such as tissue and organ morphogenesis during development, wound healing, inflammatory immune response, and tumor metastasis. The actin cytoskeleton is the basic engine driving cell migration. In the present study, we elucidate the role of an important actin interacting proteins, Adducins, in motility of normal lung epithelium and lung cancer cells. Adducins are the family of cytoskeleton protein capping the fast growing end and facilitating the bundling of actin filaments. Adducins are encoded by the three closely related genes namely alpha (ADD1), beta (ADD2) and gamma (ADD3) Adducin. …

Functional Significance Of Mtdna Cytosine Modification Tested By Genome Editing, Jason M. Robinson

Theses and Dissertations

The field of epigenetics is gaining popularity and speed, due in part to its capability to answer lingering questions about the root cause of certain diseases. Epigenetics plays a crucial role in regulation of the cell and cell survival, particularly by cytosine methylation. It remains controversial if DNMT’s which facilitate methylation are present in mammalian mitochondria and what the functional significance they may have on modification of mitochondrial DNA. CRISPR-Cas9 technology enabled genome editing to remove the MTS (mitochondrial targeting sequence) from DNMT1 of HCT116 cells, purposefully minimizing effects on nuclear cytosine methylation, while exclusively impacting mitochondrial modification. Removal of …

The Impact Of Oxygen On Bacterial Enteric Pathogens, Nathan Wallace, Ashley N. Zani, Elizabeth A. Abrams, Yvonne Sun

Biology Faculty Publications

Bacterial enteric pathogens are responsible for a tremendous amount of foodborne illnesses every year through the consumption of contaminated food products. During their transit from contaminated food sources to the host gastrointestinal tract, these pathogens are exposed and must adapt to fluctuating oxygen levels to successfully colonize the host and cause diseases. However, the majority of enteric infection research has been conducted under aerobic conditions. To raise awareness of the importance in understanding the impact of oxygen, or lack of oxygen, on enteric pathogenesis, we describe in this review the metabolic and physiological responses of nine bacterial enteric pathogens exposed …

Characterization Of Insertion Sequence Is605 In Halanaerobium Hydrogeniformans, Michael C. Sadler

Masters Theses

"Insertion sequences are the smallest prokaryotic transposable elements. These genes play a significant evolutionary role by promoting genome plasticity. Insertion sequences are highly diverse elements that have largely been uncharacterized. As such, the ability to accurately identify, annotate, and infer genomic impact of insertion sequences is lacking. The study of new insertion sequences contributes knowledge to their annotation and evolution. Halanaerobium hydrogeniformans is a unique organism with an abnormally high number of insertion sequences. A family of insertion sequences, IS200/605, showed several interesting distinctions from other elements in the genome, including severe open reading frame degradation, and was characterized in …

Endohelminth Parasites Of Some Midwater And Benthopelagic Stomiiform Fishes From The Northern Gulf Of Mexico, Michael J. Andres, Mark S. Peterson, Robin M. Overstreet

Gulf and Caribbean Research

: Mesopelagic fishes represent significant ecological links between mesozooplankton and the larger pelagic squids, fishes, and marine mammals. As such, these fishes also play a significant role as intermediate or paratenic hosts for parasites that require a crustacean intermediate host and mature in marine mammals or pelagic fishes. We examined a total of 208 individuals representing 5 species of Sternoptychidae and 88 individuals representing 2 species of Phosichthyidae from 20 locations in the northern Gulf of Mexico (nGOM). Six of the 7 species we examined are mesopelagic and one species was benthopelagic. We found the larval stages of Anisakis brevispiculata …

Isolation And Characterization Of Eight Polymorphic Microsatellites For The Spotted Spiny Lobster, Panulirus Guttatus, Nathan Truelove, Donald C. Behringer, Mark J. Butler Iv, Richard F. Preziosi

Biological Sciences Faculty Publications

Microsatellite sequences were isolated from enriched genomic libraries of the spotted spiny lobster, Panulirus guttatus using 454 pyrosequencing. Twenty-nine previously developed polymerase chain reaction primer pairs of Panulirus argus microsatellite loci were also tested for cross-species amplification in Panulirus guttatus. In total, eight consistently amplifying, and polymorphic loci were characterized for 57 individuals collected in the Florida Keys and Bermuda. The number of alleles per locus ranged from 8 to 20 and observed heterozygosities ranged from 0.409 to 0.958. Significant deviations from Hardy–Weinberg equilibrium were found in one locus from Florida and three loci from Bermuda. Quality control testing indicated …

Fuzzy Unheritance: A Novel Form Of Somatic Cell Inheritance That Regulates Cell Population Heterogeneity, Batoul Abdallah

Wayne State University Dissertations

Multi-level heterogeneity is a characteristic feature of cancer cell populations. However, how a cell population regulates and maintains its cell population heterogeneity is not well understood. Based on conventional theories of genetic inheritance, cell division is precise, where a daughter cell inherits an identical karyotype from its mother cell. Therefore, errors that are generated during cell division occur at low frequencies that take prolonged time periods to accumulate. However, the overwhelming heterogeneity found in unstable cancers is largely inconsistent with current models of genetic inheritance. In order to determine the mechanism of how heterogeneity is regulated, the pattern of inherited …

Effective Drug Treatment Induces Drug Resistance Through Rapid Genome Alteration-Mediated Cancer Evolution, Steven Horne

Wayne State University Dissertations

The central paradox associated with current cancer therapeutic strategies is initially effective treatment, which eliminates a high tumor cell count, consistently results in successful drug resistance. Mathematical and evolutionary modeling have previously suggested that therapeutic intervention could provide selective pressure for the expansion of resistant variants. Drug-related stress has been associated with genome chaos, a common phenomenon in cancer characterized as rapid, stochastic genomic fragmentation and reorganization. Since cancer represents an evolutionary process, analysis within the context of genome-mediated cancer evolution can shed light on this key problem of therapeutics. We propose that genomic change is a general response to …

A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi

Wayne State University Dissertations

In humans and fruit flies, males have one X chromosome while females have two. This imbalance in gene dosage is potentially lethal, and the process of dosage compensation corrects it. The MSL (Male Specific Lethal) complex, which is composed of five proteins and one of two functionally redundant long non-coding roX (RNA on the X) RNAs, brings about dosage compensation in Drosophila melanogaster. In fruit fly dosage compensation, all the genes on the single male X chromosome are upregulated approximately twofold, via chromatin modifications, to equalize gene dosage with the two X chromosomes of females. This process calls for highly …

An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu

Wayne State University Dissertations

Chromatin modification and cellular metabolism are tightly connected. The mechanism for this cross-talk, however, remains incompletely understood. SIN3 controls histone acetylation through association with the histone deacetylase RPD3. In this study, my major goal is to explore the mechanism of how SIN3 regulates cellular metabolism.

Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. In collaboration with others, I report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality, as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone …

Modeling The Mechanism Underlying Environmental And Genetic Determinants Of Gene Expression And Complex Traits, Gregory Alan Moyerbrailean

Wayne State University Dissertations

Advances in next-generation sequencing technologies and functional genomics strategies have allowed researchers to identify both common and rare genetic variation, to deeply profile gene expression, and even to determine regions of active gene transcription.

While these technologies and strategies have contributed greatly to our understanding of complex traits and diseases, there are many biological questions and analytical issues to be addressed.

Genome-wide association studies (GWAS) have successfully identified large numbers of genetic variants associated with complex traits and diseases. However, in many cases the mechanistic link between the phenotype and associated variant remains unclear. This may be because most variants …

System Genetic Analysis Of Mechanisms Underlying Excessive Alcohol Consumption, Maren L. Smith

Theses and Dissertations

Increased alcohol consumption over time is one of the characteristic symptoms of Alcohol Use Disorder (AUD). The molecular mechanisms underlying this escalation in intake is still the subject of study. However, the mesocortical and mesolimbic dopamine pathways, and the extended amygdala, because of their involvement in reward and reinforcement are believed to play key roles in these behavioral changes. Multiple gene expression studies have shown that alcohol affects the expression of thousands of genes in the brain. The studies discussed in this document use the systems biology technique of co-expression network analysis to attempt to find

patterns within genome-wide expression …

Time To Diagnosis Of Second Primary Cancers Among Patients With Breast Cancer, Edward Okezie Irobi

Walden Dissertations and Doctoral Studies

Many breast cancer diagnoses and second cancers are associated with BRCA gene mutations. Early detection of cancer is necessary to improve health outcomes, particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading …

Population Genetic Structure Of Necturus Maculosus In Central And Eastern Kentucky, Mason Owen Murphy

Theses and Dissertations--Biology

Population structure is influenced by extrinsic factors, such as landscape architecture and dispersal barriers. Lotic network architecture is known to constrain ecological, demographic and evolutionary processes, including population genetic structure. I assessed the population structure of a widespread aquatic salamander, Necturus maculosus, across three river basins in central and eastern Kentucky. I examined the role of network architecture, anthropogenic barriers, and spatial scale on patterns of population structure. I also provided a review of N. maculosus capture methods and offer an improved trap design. I identified significant structuring between the combined Licking/Kinniconick basin and the Kentucky River basin, with …

Analysis Of Fy Promoter And Hepatocystis Load In South African Vervet Monkeys (Chlorocebus Aethiops), Benjamin J. Gombash

All Master's Theses

There are species of Hepatocystis and Plasmodium, related blood parasites, that enter the cell through a chemokine receptor, coded for by the Duffy antigen/receptor for chemokines in humans, and the FY*0 (FY Null) allele in the promoter of this gene results in the absence of this receptor on the exterior of the cell (Miller et al., 1977; Miller et al., 1975; Miller et al., 1976; Barnwell et al., 1989; Perkins and Schall, 2002; Martinsen et al., 2008; Tung et al., 2009). Humans without the receptor show resistance to multiple strains of Plasmodium (Tournamelle, et al., 1995; Zimmerman, et al. …

Low-Head Dams On Habitat, Fish Functional Guilds And Genetic Structuring In A Midwestern River System, Shannon Cassandra Frary Smith

Masters Theses

The natural flow regime of the majority of rivers in the United States has been altered by anthropogenic structures. This loss of connectivity plays a strong role in shaping river ecosystems by altering physical habitat characteristics and shaping fish community assemblages. Although the impacts of large dams on river systems are well documented and often easy to observe, there are fewer studies on the effects of smaller low-head dams. Additionally, the influences of low-head dams on the genetic structuring of small-bodied riverine fishes have yet to be fully explored. I assessed the effects of two low-head dams on the Vermilion …

Novel Regulatory Mechanisms Of Inositol Biosynthesis In Saccharomyces Cerevisiae And Mammalian Cells, And Implications For The Mechanism Underlying Vpa-Induced Glucose 6-Phosphate Depletion, Wenxi Yu

Wayne State University Dissertations

Myo-inositol is the precursor of all inositol containing molecules, including inositol phosphates, phosphoinositides and glycosylphosphatidylinositols, which are signaling molecules involved in many critical cellular functions. Perturbation of inositol metabolism has been linked to neurological disorders. Although several widely-used anticonvulsants and mood-stabilizing drugs have been shown to exert inositol depletion effects, the mechanisms of action of the drugs and the role of inositol in these diseases are not understood. Elucidation of the molecular control of inositol synthesis will shed light on the pathologies of inositol related illnesses.

In Saccharomyces cerevisiae, deletion of the four glycogen synthase kinase-3 genes, MCK1, MRK1, MDS1, …

Bois 412/812: Human Genetics—A Peer Review Of Teaching Project Benchmark Portfolio, Colin D. Meiklejohn

UNL Faculty Course Portfolios

This portfolio focuses on Human Genetics, an upper-division course taken primarily by biology majors to fulfill elective credit in their degree. This course studies the genetic basis for human variation, with the goal of placing this variation in the context of human evolutionary history and the consequences of this variation for medical understanding and treatments. In Human Genetics, students complete an original synthetic research paper on a human genetic disorder. Through writing this paper, students are expected to learn how to navigate electronic databases and online resources on human genetic diseases, and to read and synthesize the primary scientific literature. …

The Informational And Emotional Support Needs Of Grandparents Of Children With Pompe Disease, Natasha Lousie Rudy

Theses and Dissertations

The complex roles and experiences of grandparents of children with various diagnoses have been described, but previous studies have not investigated the roles and experiences of grandparents of children with treatable, Mendelian conditions such as Pompe disease. The availability of treatment and heritable nature of Pompe introduce the possibility for unique grandparent roles, experiences and needs. This is a particularly timely investigation given the advent of newborn screening for Pompe. This study aimed to characterize grandparents’ roles and involvement, identify grandparents’ information and emotional support needs, and explore the psychosocial impact felt by grandparents of children with Pompe. An online …

Clusters Of Alpha Satellite On Human Chromosome 21 Are Dispersed Far Onto The Short Arm And Lack Ancient Layers, William Ziccardi, Chongjian Zhao, Valery Shepelev, Lev Uralsky, Ivan Alexandrov, Tatyana Andreeva, Evgeny Rogaev, Christopher Bun, Emily Miller, Catherine Putonti, Jeffrey Doering

Bioinformatics Faculty Publications

Human alpha satellite (AS) sequence domains that currently function as centromeres are typically flanked by layers of evolutionarily older AS that presumably represent the remnants of earlier primate centromeres. Studies on several human chromosomes reveal that these older AS arrays are arranged in an age gradient, with the oldest arrays farthest from the functional centromere and arrays progressively closer to the centromere being progressively younger. The organization of AS on human chromosome 21 (HC21) has not been well-characterized. We have used newly available HC21 sequence data and an HC21p YAC map to determine the size, organization, and location of the …

Neuronal Insult Either By Exposure To Lead Or By Direct Neuronal Damage Cause Genome-Wide Changes In Dna Methylation And Histone 3 Lysine 36 Trimethylation, Arko Sen

Wayne State University Dissertations

Prenatal and postnatal exposure to pervasive neuro-toxicants such as Lead (Pb) has been reported to causes extensive and diverse changes in the epigenetic profile. Among epigenetic modification, DNA methylation (5mC) is perhaps the most widely studied and has been proposed to be potential early biomarkers for Pb toxicity. Several studies have demonstrated the association between Pb-exposure and 5mC. However most of these studies are restricted to looking at a specific set of target genes or repetitive elements. Therefore, one of the main objectives of our study was to use an unbiased genome-wide approach to look at Pb-exposure associated changes in …