Genetics and Genomics Commons^™

Structural And Functional Characterization Of The Mbd2-Nurd Co-Repressor Complex, Megha Desai

Theses and Dissertations

The MBD2-NuRD co-repressor complex is an epigenetic regulator of the developmental silencing of embryonic and fetal β-type globin genes in adult erythroid cells as well as aberrant methylation-dependent silencing of tumor suppressor genes in neoplastic diseases. Biochemical characterization of the MBD2-NuRD complex in chicken erythroid cells identified RbAp46/48, HDAC1/2, MTA1/2/3, p66α/β, Mi2α/β and MBD2 to comprise this multi-protein complex.

In the work presented in Chapter 2, we have pursued biophysical and molecular studies to describe a previously uncharacterized domain of human MBD2 (MBD2_IDR). Biophysical analyses show that MBD2_IDR is an intrinsically disordered region (IDR). Despite this inherent …

Characterization And Identification Of Novel Regulators Of The Synthesis Of Phospholipids, Cunqi Ye

Wayne State University Dissertations

Phospholipids are the most abundant lipids in cell membranes. The synthesis of phospholipids is crucial for cellular membrane biogenesis and nearly all aspects of cellular processes. Understanding the regulation of synthesis of phospholipids is beneficial to our fundamental knowledge of cell biology as well as human health.

Regulation of the synthesis of phospholipids is intensively studied in the yeast S. cerevisiae. Most notably, the synthesis of phospholipids is coordinated with the synthesis of inositol, a precursor of inositol-containing lipids, by controlling expression of the genes encoding phospholipid biosynthetic enzymes. In addition to this well-characterized regulatory circuit controlled by the …

Regulation Of Immune Response Genes By Vitamin D In Mammary Epithelial Cells With An Emphasis On Cd14, Katrina Marie Simmons

Legacy Theses & Dissertations (2009 - 2024)

Vitamin D is primarily known for its role in bone health, however recently vitamin D has been identified as a potent immunomodulator. Most research studying the effects of vitamin D on immune properties have focused on immune cells. Few have evaluated how vitamin D affects the immune functions of barrier epithelial cells, such as human mammary epithelial (HME) cells, that are exposed to pathogens both locally and systemically. The goals of the studies described in this thesis were to comprehensively and mechanistically evaluate the immune effects of vitamin D metabolites, 1α,25-dihydroxyvitamin D (1,25D) and 25-hydroxyvitamin D (25D), on HME cells. …

Regulation Of Ty1 Retrovirus-Like Transposon Rna Localization And Translation, Ryan Joseph Palumbo

Legacy Theses & Dissertations (2009 - 2024)

Replication of the Ty1 retrovirus-like transposon of the yeast Saccharomyces cerevisiae is stringently regulated to reduce the frequency of deleterious retrotransposition events. However, under stress conditions, Ty1 retrotransposition can lead to adaptive genomic alterations. To characterize host regulation of Ty1 retrotransposition, I analyzed ribosome profiling data and showed that Ty1 RNA is efficiently translated. Moreover, the ribosome biogenesis factors BUD21, DBP7, HCR1, LOC1, MRT4, and PUF6 are required for optimal expression of the Ty1 protein Gag.

Genetic Diversity And Population Structure Of Brook Trout (Salvelinus Fontinalis) In A Remote Adirondack Watershed, Spencer A. Bruce

Legacy Theses & Dissertations (2009 - 2024)

In conservation genetics, the importance of understanding how historical and contemporary processes have contributed to geographic patterns of genetic structure is key to preserving diversity. In New York State there are currently eleven remaining known populations of native brook trout (Salvelnius fontinalis) that inhabit the watersheds for which they are named. These populations are known as "heritage strains", and are currently managed under regulations set by the New York State Department of Environmental Conservation.

Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta

Legacy Theses & Dissertations (2009 - 2024)

1,25-Dihydroxyvitamin D (1,25D) exerts anti-cancer actions through the vitamin D receptor (VDR) but the specific targets that mediate these effects remain to be defined. In these studies, growth and genomic responses to 1,25D were evaluated in a cellular model system derived from mammary tumors generated in VDR knockout (KO) and wildtype (WT) mice. WT145 cells (derived from WT tumors) expressed VDR and were growth inhibited by 1,25D, whereas KO240 cells (derived from VDRKO tumors) lacked VDR and were not growth inhibited by 1,25D. KO240 cell clones stably expressing VDR (KOhVDR cells) were sensitized to 1,25D mediated growth arrest. Genomic profiling …

Multiple Roles For Hoxa3 In Regulating Thymus And Parathyroid Differentiation And Morphogenesis In Mouse, Jena L. Chojnowski, Kyoko Masuda, Heidi A. Trau, Kirk Thomas, Mario Capeechi, Nancy R. Manley

Natural Sciences Faculty Publications

Hoxa3 was the first Hox gene to be mutated by gene targeting in mice and is required for the development of multiple endoderm and neural crest cell (NCC)-derived structures in the pharyngeal region. Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. …

Origins Of The Classical Gene Concept, 1900–1950: Genetics, Mechanistic, Philosophy, And The Capitalization Of Agriculture, Garland E. Allen

Biology Faculty Research

In the period of “classical genetics” (roughly 1915–1950), the common view of the gene was mechanistic—that is, genes were seen as individual, atomistic units, as material components of the chromosomes. Although it was recognized early on that genes could interact and influence each other’s expression, they were still regarded as individually functioning units, much like the chemists’ atoms or molecules. Although geneticists in particular knew the story was more complex, the atomistic gene remained the central view for a variety of reasons. It fit the growing philosophy of mechanistic materialism in the life sciences, as biologists tried to make their …

Parents' Dreams For Their Young Adults With Down Syndrome: What Resources Are Needed To Achieve Them?, Julianna Elise Hudnall

Theses and Dissertations

This study sought to identify the goals parents have for their young adult sons and daughters with Down syndrome, the factors that help to achieve those goals, and parents' perceived barriers to successful attainment of those objectives. While many supports are readily available to youths with Down syndrome in primary and secondary school, many of these supports disappear as these individuals transition into adulthood. When combined with the inherent challenges of emerging adulthood, significant gaps in resources become evident for this population. In order to identify areas in need of improvement, this study surveyed parents of post- and peri-transitional young …

Phenotypes And Variants In Cases Submitted For X-Linked Intellectual Disability (Xlid) Gene Panel Testing, Michael J. Friez

Theses and Dissertations

Intellectual disability (ID) refers to reduced cognitive function, apparent before the age of 18, that negatively affects a person's learning and adaptive capacity. Approximately 1-3% of the population is affected with ID, males more than females, and most in the mild-to-moderate range. ID creates financial, logistical and psychosocial challenges for affected persons and their families and caregivers. It is estimated that up to 50% of ID has a genetic cause. Molecular genetic diagnosis may help in obtaining services and has important implications for family members, but can be elusive. Genes causing ID are known to be over-represented on the X …

The Use Of Social Media And The Impact Of Support On The Well-Being Of Adult Cystic Fibrosis Patients, Margaret Anne Faust

Theses and Dissertations

Cystic fibrosis (CF) is the most common, life-limiting autosomal recessive condition disorder of Caucasians. CF is a chronic condition that requires daily treatment of symptoms, the stress of which can have mental health consequences. Due to the potential for cross contamination of bacterial infections, individuals with CF are discouraged from meeting in person and must find other venues to receive support. Social media provides the opportunity for individuals with CF to communicate and provide support. We hypothesized a positive correlation between the patients' health-related quality of life and the amount of time spent on CF-related social media sites. We expected …

Parental Satisfaction And Teacher Perspectives On Inclusive Education Of Students With Asperger Syndrome: An Educational Tool, Hannah Warren

Theses and Dissertations

Purpose: This study aimed to evaluate parental satisfaction and anxiety regarding the high school educational experiences of their child with a previous diagnosis of Asperger syndrome (AS), as well as educators' understanding of the diagnosis and what information they deemed important to know about the student. The goal of this study was to develop an educational tool that would aid in initiating communication between parents of a student with AS, or with a new diagnosis of high-functioning autism (HFA), and their teachers. This would be an additional resource of use to pediatric genetic counselors that frequently see families regarding a …

Investigating The Interactions Between Cyanobacteria And Vibrio Parahaemolyticus, Caroline E. Ward

Honors Theses and Capstones

One well-known pathogen that has been the topic of many recent studies is Vibrio parahaemolyticus, which causes thousands of foodborne illnesses a year, mostly from the ingestion of raw or undercooked oysters. It has been shown cyanobacteria can act as a long-term reservoir of Vibrio cholerae, another pathogenic Vibrio, by encasing the cells within mucilaginous sheaths during which Vibrios enter a viable but non-culturable state. In this study we investigated the interaction of V. parahaemolyticus with cyanobacteria to determine whether cyanobacteria aid in the longevity and survival of V. parahaemolyticus. We found that non-pathogenic V. parahaemolyticus …

The Distribution Of Fitness Effects Of Spontaneous Mutations In Vibrio Fischeri, Chelsea K. Jones

Honors Theses and Capstones

Mutations are the ultimate source of the biological diversity on which natural selection acts, but the vast majority of these mutations are harmful. As such, mutations lead to disease states like cancer, extinction of small populations, and can drive pathogen evolution. Unfortunately, because mutations are rare and past studies have been subject to detection biases, very little is known about the distribution of fitness effects from naturally occurring mutations. In this study, we used mutation accumulation and full genome sequencing to capture naturally occurring mutations before they were exposed to the sieve of natural selection in Vibrio fischeri. We …

Integrating Mitosis, Toxicity, And Transgene Expression In A Telecommunications Packet-Switched Network Model Of Lipoplex-Mediated Gene Delivery, Timothy M. Martin, Beata Wysocki, Jared P. Beyersdorf, Tadeusz A. Wysocki, Angela K. Pannier

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Gene delivery systems transport exogenous genetic information to cells or biological systems with the potential to directly alter endogenous gene expression and behavior with applications in functional genomics, tissue engineering, medical devices, and gene therapy. Nonviral systems offer advantages over viral systems because of their low immunogenicity, inexpensive synthesis, and easy modification but suffer from lower transfection levels. The representation of gene transfer using models offers perspective and interpretation of complex cellular mechanisms, including nonviral gene delivery where exact mechanisms are unknown. Here, we introduce a novel telecommunications model of the nonviral gene delivery process in which the delivery of …

The Pleiotropic Effects Of Beneficial Mutations Of Adapted Escherichia Coli Populations, Brian Scott Van Dam

Honors Theses and Capstones

Mutations that improve fitness in one environment can often be beneficial, deleterious, or neutral in alternative environments. When a single mutation effects fitness in multiple environments, it is said to be a pleiotropic, which can have important consequences for niche specialization, niche expansion, speciation, and even extinction in the face of environmental change. While previous studies have revealed that pleiotropy is nearly universal, the role of adaptive history in the spectrum of pleiotropic effects has yet to undergo detailed experimental observation. Using experimental evolution we gathered beneficial mutations in a previously adapted strain of Escherichia coli growing in the same …

Exploration Of The Genetic Epidemiology Of Asthma: A Review, With A Focus On Prevalence In Children And Adolescents In The Caribbean, A. Mohan, A. J. Roberto, B. C. Whitehill, A. Mohan, A. Kumar

Biological Sciences Faculty Publications

Asthma is a chronic disease caused by the inflammation of the main air passages of the lungs. This paper outlines a review of the published literature on asthma. While a few studies show a trend of rising asthma cases in the Caribbean region, even fewer have explored the genetic epidemiological factors of asthma. This is a literature review that seeks to sum the body of knowledge on the epidemiology of asthma. Specifically, the major objective of the literature review is to provide a unified information base on the current state of factors involved in the genetic epidemiology of asthma. 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% …

Basin Isolation And Oceanographic Features Influencing Lineage Divergence In The Humbug Damselfish (Dascyllus Aruanus) In The Coral Triangle, J. M. Raynal, E. D. Crandall, P. H. Barber, G. N. Mahardika, M. C. Lagman, Kent E. Carpenter

Biological Sciences Faculty Publications

The Coral Triangle is a hotspot for marine species diversity as well as for intraspecific genetic diversity. Here, we used nuclear RAG2 and mitochondrial D-Loop genes to identify deep genetic divergence among Dascyllus aruanus (Linnaeus, 1758) populations across relatively short scales within the Coral Triangle. Mitochondrial clades different by >20 mutational steps were completely isolated from one another across the distance between Java and the Lesser Sunda Islands, and also showed frequency differences in the eastern and western Philippines. Evidence for population structure in the Sulu Sea and at the Lesser Sunda Islands was also identified. Our results suggest that …

Renal Humoral, Genetic And Genomic Mechanisms Underlying Spontaneous Hypertension, Jason A. Collett

Theses and Dissertations--Biology

In spite of significant progress in our knowledge of mechanisms that control blood pressure, our understanding of the pathogenesis of hypertension, its genetics, and population efforts to control blood pressure, hypertension remains the leading risk factor for mortality worldwide. It’s estimated that 1 out of every 3 adults has hypertension. Hypertension is a major risk factor for cardiovascular disease and stroke, and is considered a primary or contributing cause of death to more than 2.4 million US deaths each year. Although spontaneous hypertension has been the subject of substantial research, many critical questions remain unanswered.

To investigate mechanisms underlying spontaneous …

Use Of Genomic Tools To Discover The Cause Of Champagne Dilution Coat Color In Horses And To Map The Genetic Cause Of Extreme Lordosis In American Saddlebred Horses, Deborah G. Cook

Theses and Dissertations--Veterinary Science

Champagne dilution of coat color in horses is caused by dominant gene action. Three sire families were identified as segregating for this trait. Genome wide linkage analysis using 104 microsatellite DNA markers was used to map the gene to ECA14 (LOD > 11.0). Four genes, namely SPARC, SLC36A1, SLC36A2 and SLC36A3, were selected from the region implicated by linkage and their exons sequenced. DNA sequences were compared for two homozygotes for Champagne dilution, two heterozygotes and two horses without dilution. A single base change in exon 2 of SLC36A1 was found unique to horses exhibiting Champagne dilution. This change in base …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

Data From: Further Examination Of The Geographic Range Of Eriogonum Corymbosum Var. Nilesii (Polygonaceae), Mark W. Ellis, Paul G. Wolf, Shannon Bardot, James A. Walton, Carol A. Rowe, Sarah Kulpa, Karen E. Mock

Browse all Datasets

The buckwheat Eriogonum corymbosum is widely distributed throughout the southwestern United States, forming a complex of eight varieties. Eriogonum corymbosum var. nilesii is a primarily yellow-flowered taxon reported only from Clark County, Nevada. A previous genetic study by our research group found that variety nilesii is genetically distinct from other E. corymbosum varieties, based on a limited number of populations. Here, we assess genetic variation in 14 newly sampled yellow-flowered populations from southern Nevada, southern Utah, and northern Arizona, and compare them to genetic variation in six populations of previously determined E. corymbosum varieties. Of the new populations, we identified …

Dna From Chewed Vegetation: A Noninvasive Collection Strategy For Golden-Handed Tamarins (Saguinus Midas), Jennifer E. Humphreys

All Master's Theses

Noninvasive genetic sampling was first used in wild animals more than two decades ago, although since that time there have been advancements in both sampling strategies and amplification technology [Hoss et al., 1992; Taberlet and Bouvet, 1992]. Feces, hair, and urine are examples of biomaterials that are collected noninvasively [Beja-Pereira et al., 2009]. These materials provide clear advantages over the more invasive DNA sampling techniques such as blood collection; researchers can study nonhuman subjects without contacting, disturbing, or even seeing them. This advantage becomes greater in habitats disturbed by human activities such as agriculture or mining. The Republic of Suriname, …

The Use Of Dna Sequencing To Discover Novel Pathogens Of Aquatic Invertebrates With Focus On Mosquitoes (Culicidae), Dale Robert Jansons

All Master's Theses

The use of DNA sequencing to discover fungal pathogens of aquatic invertebrates, including mosquito larvae, was explored. Mosquito-borne diseases kill millions of people every year, mostly children. One method used to control the spread of mosquito-borne diseases has been to use mosquito-killing fungi to reduce mosquito populations. Locating and identifying pathogens of mosquitoes can be difficult, but with phylum specific primers, novel pathogens can be found, identified, and compared to known isolates without rearing mosquitoes, setting baited traps for pathogens, or culturing microbes associated with mosquito larvae. Mosquito larvae and other aquatic invertebrates were subjected to PCR and DNA sequencing …

Value Of Mendelian Laws Of Segregation In Families: Data Quality Control, Imputation, And Beyond, Elizabeth M. Blue, Lei Sun, Nathan L. Tintle, Ellen M. Wijsman

Faculty Work Comprehensive List

When analyzing family data, we dream of perfectly informative data, even whole-genome sequences (WGSs) for all family members. Reality intervenes, and we find that next-generation sequencing (NGS) data have errors and are often too expensive or impossible to collect on everyone. The Genetic Analysis Workshop 18 working groups on quality control and dropping WGSs through families using a genome-wide association framework focused on finding, correcting, and using errors within the available sequence and family data, developing methods to infer and analyze missing sequence data among relatives, and testing for linkage and association with simulated blood pressure. We found that single-nucleotide …

Pathway Analysis Approaches For Rare And Common Variants: Insights From Genetic Analysis Workshop 18, Stella Aslibekyan, Marcio Almeida, Nathan L. Tintle

Faculty Work Comprehensive List

Pathway analysis, broadly defined as a group of methods incorporating a priori biological information from public databases, has emerged as a promising approach for analyzing high-dimensional genomic data. As part of Genetic Analysis Workshop 18, seven research groups applied pathway analysis techniques to whole-genome sequence data from the San Antonio Family Study. Overall, the groups found that the potential of pathway analysis to improve detection of causal variants by lowering the multiple-testing burden and incorporating biologic insight remains largely unrealized. Specifically, there is a lack of best practices at each stage of the pathway approach: annotation, analysis, interpretation, and follow-up. …

A Course-Based Research Experience: How Benefits Change With Increased Investment In Instructional Time, Christopher D. Shaffer, Consuelo J. Alvarez, April E. Bednarski, David Dunbar, Anya L. Goodman, Catherine Reinke, Anne G. Rosenwald, Michael J. Wolyniak, Cheryl Bailey, Daron Barnard, Christopher Bazinet, Dale L. Beach, James E.J. Bedard, Satish Bhalla, John Braverman, Martin Burg, Vidya Chandrasekaran, Hui-Min Chung, Kari Clase, Randall J. Dejong, Justin R. Diangelo, Chunguang Du, Todd T. Eckdahl, Heather Eisler, Julia A. Emerson, Amy Frary, Donald Frohlich, Yuying Gosser, Shubha Govind, Adam Haberman, Amy T. Hark, Charles Hauser, Arlene Hoogewerf, Laura L.M. Hoopes, Carina E. Howell, Diana Johnson, Christopher J. Jones, Lisa Kadlec, Marian Kaehler, S. Catherine Silver Key, Adam Kleinschmit, Nighat P. Kokan, Olga Kopp, Gary Kuleck, Judith Leatherman, Jane Lopilato, Christy Mackinnon, Juan Carlos Martinez-Cruzado, Gerard Mcneil, Stephanie Mel, Hemlata Mistry, Alexis Nagengast, Paul Overvoorde, Don W. Paetkau, Susan Parrish, Celeste N. Peterson, Mary Preuss, Laura K. Reed, Dennis Revie, Srebrenka Robic, Jennifer Roecklein-Canfield, Michael R. Rubin, Kenneth Saville, Stephanie Schroeder, Karim Sharif, Mary Shaw, Gary Skuse, Christopher D. Smith, Mary A. Smith, Sheryl T. Smith, Eric Spana, Mary Spratt, Aparna Sreenivasan, Joyce Stamm, Paul Szauter, Jeffrey S. Thompson, Matthew Wawersik, James Youngblom, Leming Zhou, Elaine R. Mardis, Jeremy Buhler, Wilson Leung, David Lopatto, Sarah C.R. Elgin

Faculty Publications

There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant …

Evaluation And Integration Of Genetic Signature For Prediction Risk Of Nasopharyngeal Carcinoma In Southern China, Xiuchan Guo, Cheryl Winkler, Ji Li, Li Guan, Minzhong Tang, Jian Liao, Hong Deng, Guy De The, Yi Zeng, Stephen J. O'Brien

Biology Faculty Articles

Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted. Seven SNPs in ITGA9 at 3p21.3 and 9 SNPs within the 6p21.3 HLA region were genotyped. To explore the potential clinical application of these genetic markers in NPC, we further evaluate the predictive/diagnostic role of significant SNPs by calculating the area under the curve (AUC). Results …

Genetic Variation, Local Adaptation And Population Structure In North American Red Oak Species, Quercus Rubra L. And Q. Ellipsoidalis E. J. Hill, Jennifer F. Lind-Riehl

Dissertations, Master's Theses and Master's Reports - Open

Forest trees, like oaks, rely on high levels of genetic variation to adapt to varying environmental conditions. Thus, genetic variation and its distribution are important for the long-term survival and adaptability of oak populations. Climate change is projected to lead to increased drought and fire events as well as a northward migration of tree species, including oaks. Additionally, decline in oak regeneration has become increasingly concerning since it may lead to decreased gene flow and increased inbreeding levels. This will in turn lead to lowered levels of genetic diversity, negatively affecting the growth and survival of populations. At the same …