Genetics Commons^™

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

The Association Between The Il-1 Pathway, Isaac C. Wun

Dissertations and Theses (Open Access)

Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The …

Childhood Obesity And Familial Hypercholesterolemia: Genetic Diseases That Contribute To Cardiovascular Disease, Alyssa Caudle

Senior Honors Theses

Childhood obesity occurs as the result of an imbalance between caloric intake and energy expenditure. Genetic risk factors for obesity have become an area of research due to its permanency. Mutated genes such as Fat Mass and Obesity Associated (FTO), Leptin (LEP), Leptin Receptor (LEPR), Melanocortin 4 Receptor (MC4R), Adiponectin C1Q and Collagen Domain Containing (ADIPOQ), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1), and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) all contribute to the development of childhood obesity. In the presence of high cholesterol caused by obesity, the genetic condition known as familial hypercholesterolemia is exacerbated. Familial hypercholesterolemia is caused by a …

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

Working Papers on Science in a Changing World

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

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

Dartmouth Scholarship

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

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

Dissertations and Theses

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

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

USF Tampa Graduate Theses and Dissertations

Abstract

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

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

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

Human Biology Open Access Pre-Prints

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

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

Faculty Scholarship

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

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 …

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 …

Linking Molecular, Electrical And Anatomical Properties Of Human Epileptic Brain, Shruti Bagla

Wayne State University Dissertations

Epilepsy is a common neurological disorder of recurrent unprovoked seizures. It affects almost 1% of the world population. Although there is a wide range of anti-epileptic drugs (AEDs) available, they only treat the seizure symptoms and do not cure the disease itself. The poor role of AEDs can be attributed to the lack of knowledge of exact mechanisms and networks that produce epileptic activities in the neocortex. At present, the best cure for epilepsy is surgical removal of electrically localized epileptic brain tissue. Surgically removed brain tissue presents an excellent opportunity to discover the molecular and cellular basis of human …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Genetic Sex Conditions And Redefining Sex, Jayce O'Shields

Student Scholarship

Western culture has a tendency to value binaries and discreet categories that separate its social structure and provide a sense of order and organization. The value placed on binaries and categories may be advantageous in some aspects, but when it starts to infringe upon the legal and medical rights of individuals not easily placed in either binary category, it can become less advantageous.

A baby is usually classified as either male or female shortly after birth, and all future legal, social, and economic actions and rights of that individual are more or less decided according to this classification. A problem …

Single Nucleotide Polymorphisms Linked To Essential Hypertension In Kasigau, Kenya, Julia Carol Freeman

Masters Theses & Specialist Projects

Hypertension, or high blood pressure (BP), is an ever-growing epidemic in the developing world. Understanding the genetics behind essential hypertension (EH), or hypertension with no known cause, is especially important. In this study, three single nucleotide polymorphisms (SNPs) known to be linked to an increase in susceptibility to EH were quantified from a cohort of Kenyans living in the Kasigau region. The SNPs are located in three genes that are part of the renin angiotensin system, the primary regulatory pathway in humans controlling BP. They include: AGT (rs699), AGTR1 (rs5186), and HSD11β2 (rs5479). Overall, by using a fluorescent-based RT-PCR technique, …

Electrotransfer Of Single-Stranded Or Double-Stranded Dna Induces Complete Regression Of Palpable B16.F10 Mouse Melanomas, Loree Heller, Vesba Todorovic, Maja Cemazar

Bioelectrics Publications

Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both …

Sex Determination Using Discriminant Function Analysis In Hispanic Children And Adolescents: A Lateral Cephalometric Study, Alyssa E. Sprowl

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lateral cephalometric radiographs have been used for years to help diagnose skeletal and dental patterns in Orthodontics. Within the last decade, these radiographs have caught the interest of the department of Anthropology for the identification of gender within the adult and adolescent population. Numerous publications have been made but failed to identify sexual dimorphism in the pre-adolescent population. 303 lateral cephalograms of pre and post Latino adolescence age ranging from 6.5 to 17.9 years old were obtained from University of Nevada, Las Vegas (UNLV) digital database. 25 variables were identified and plotted with all linear and angular measurements transferred into …

Therapeutic Efficacy Of P53 Restoration In Mdm2-Overexpressing Tumors, Qin Li

Dissertations and Theses (Open Access)

The TP53 tumor suppressor is the most mutated gene in human cancers. Recent studies using genetically modified mouse models have shown that restoring the expression of wild-type p53 has led to tumor growth suppression in various types of tumors lacking p53. Other mechanisms, e.g. upregulation of Mdm2 levels, exist in tumors to inactivate the p53 pathway. Mdm2, an E3 ubiquitin-ligase that targets p53 for proteasomal degradation, is present at high levels in many tumors with wild-type p53. In this study, we probed the effects of restoring p53 activity in Mdm2-overexpressing tumors genetically using animal models. Here we demonstrated high levels …

Maternal Genital Tract Colonisation By Group-B Streptococcus: A Hospital Based Study, Nida Najmi, Rozina Sikandar, Nadeem F. Zuberi, Imtiaz Jehan

Department of Obstetrics & Gynaecology

Objectives: To determine the prevalence of Group B Streptococcus genital tract infection in pregnant women and to determine the risk factors for its colonisation.
Methods: The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi and Sobhraj Hospital, Karachi, from May to August 2007. Pregnant women at 35-37 weeks gestation attending antenatal clinic at these hospitals constituted the study population. Based on stratified sampling, 405 patients were recruited. High vaginal swabs of these patients were taken in order to calculate the prevalence of infection at each hospital. Logistic regression was used to evaluate the risk factor association. SPSS …

Development Of Tools To Assess The Effects Of Lunasin On Normal Development And Tumor Progression In Drosophila Melanogaster, Gillian E. Jones

Masters Theses & Specialist Projects

Soy contains many bioactive molecules known to elicit anti-cancer effects. One such peptide, Lunasin, has been shown to selectively act on newly transformed cells while having no cytotoxic effect on non-tumorigenic or established cancer cell lines. In this study we attempt to understand the developmental effects of Lunasin overexpression in vivo and create reagents that will help us understand Lunasin’s anti tumorigenic effects in an intact organism. cDNA encoding lunasin and EGFP-lunasin were cloned into pUAST and microinjected into Drosophila embryos. Tissue-specific overexpression of EGFP-Lun in the resulting transgenic lines was accomplished by crossing transgenics to various GAL4 driver lines. …

Relationship Of Global Dna Methylation With Cardiovascular Fitness And Body Composition, Michael Steele Jarrett

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: Global DNA Methylation (GDM), an epigenomic modification has been linked to the development of Cardiovascular Disease and its risk factors. Purpose: The purpose of this study was to determine if there is a significant correlation between GDM and cardiovascular fitness, as well as, measures of body composition. Methodology: 26 apparently healthy, adults (11 males) completed a physical activity and diet questionnaire, as well as, had a small blood sample (600μL) collected via finger prick for the determination of GDM. Body composition was assessed by means of a Dual-Energy X-ray Absorptiometry (DEXA) scan, while cardiovascular fitness was evaluated by the …

Prkca: Identification Of A Novel Downstream Target Of Wt1, Devin Jones

Dissertations and Theses (Open Access)

Wilms tumor is a childhood tumor of the kidney arising from the undifferentiated metanephric mesenchyme. Tumorigenesis is attributed to a number of genetic and epigenetic alterations. In 20% of Wilms tumors, Wilms tumor gene 1 (WT1) undergoes inactivating homozygous mutations causing loss of function of the zinc finger transcription factor it encodes. It is hypothesized that mutations in WT1 result in dysregulation of downstream target genes, leading to aberrant kidney development and/or Wilms tumor. These downstream target genes are largely unknown, and identification is important for further understanding Wilms tumor development. Heatmap data of human Wilms tumor protein …

Knowledge And Expectations Of Support People In Prenatal Genetic Counseling Sessions, Michelle A. Mcdougle

Dissertations and Theses (Open Access)

Prenatal genetic counseling patients have the ability to choose from a myriad of screening and diagnostic testing options, each with intricacies and caveats regarding accuracy and timing. Decisions regarding such testing can be difficult and are often made on the same day that testing is performed. Therefore, it is reasonable to consider that the support people brought to an appointment may have a role in the decision-making process. We aimed to better define this potential role by examining the incoming knowledge and expectations of support people who attended prenatal genetic counseling appointments.

Support people were asked to complete a survey …

Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due To Lynch Syndrome?, Katherine M. Dempsey

Dissertations and Theses (Open Access)

BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS.

HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients.

METHODS: 253 individuals with an …

Patterns Of Gene Expression From Human Costal Cartilage In Relation To The Chest Wall Deformity Pectus Carinatum, Janna E. Grubbs

Biological Sciences Theses & Dissertations

Cartilage deformities within the human chest wall, specifically pectus excavatum (PE) and pectus carinatum (PC) are common (1/400-1/1000) and yet, despite their clinical significance, are some of the least studied disorders pertaining to cartilage [1]. The costal cartilage connecting "false ribs" 8-10 to the sternum is often abnormally grown and can lead to formation of a severely sunken "funnel" chest (PE) or push outwards to form a "pigeon" chest (PC). Both conditions can have impact on the diaphragm, heart, lungs, and psychological function. An established ratio of PE and PC in males to females is 4:1, indicating a sex-linked male …

Reproductive Isolation In The Elegans-Group Of Caenorhabditis, Scott Everet Baird, Sara Rose Seibert

Biological Sciences Faculty Publications

Reproductive isolation is the basis of the Biological Species Definition and can be a driving force of speciation. Theoretical studies have provided models of how reproductive isolation can arise within individual species. Genetic tests of these models are limited to populations in which reproductive isolation is present but not complete. Here, reproductive isolation in the Elgans-Group of the nematode genus Caenorhabditis is reviewed. Pre-mating barriers, assortative fertilization and post-zygotic barriers all have been observed in this clade. In some combinations of species, fertile F1 hybrids can be obtained. Therefore, the Elegans-Group of Caenorhabditis is poised to become an important experimental …

Genome-Wide Analysis Reveals Selection For Important Traits In Domestic Horse Breeds, Jessica Lynn Petersen, James R. Mickelson, Aaron K. Rendahl, Stephanie K. Valberg, Lisa S. Andersson, Ernie Bailey, Danika L. Bannasch, Matthew M. Binns, Alexandre S. Borges, Pieter Brama, Artur Da Câmara Machado, Stefano Capomaccio, Katia Cappelli, E. Gus Cothran, Ottmar Distl, Laura Fox-Clipsham, Kathryn T. Graves, Gérard Guérin, Bianca Haase, Telhia Hasegawa, Karin Hemmann, Emmeline W. Hill, Tosso Leeb, Gabriella Lindgren, Hannes Lohi, Maria Susana Lopes, Beatrice A. Mcgivney, Sofia Mikko, Nicholas Orr, M. Cecilia T. Penedo, Richard J. Piercy, Marja Raekallio, Stefan Rieder, Knut H. Røed, June Swinburne, Teruaki Tozaki, Mark Vaudin, Claire M. Wade, Molly E. Mccue

Department of Animal Science: Faculty Publications

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F_ST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were …

Meckel Gruber Syndrome: Second Trimester Diagnosis Of A Case In A Non-Consanguineous Marriage, Areej Alam, Mehreen Adhi, Raffat Bano, Aisha Zubair, Ammara Mushtaq

Department of Obstetrics & Gynaecology

Meckel-Gruber Syndrome (MKS) is a rare, autosomal recessive genetic disorder, incompatible with life. It is characterized by enlarged polycystic kidneys and post axial polydactyly. Foetal or neonatal death is caused by pulmonary hypoplasia. We report a case of a 35 year old woman who presented at 7 weeks of gestation of her sixth pregnancy. A transabdominal anomaly ultrasound performed for her current pregnancy at 18 weeks of gestation showed features consistent with MKS. The termination of pregnancy was declined and a live newborn female was delivered via an emergency caeserean section at 34 weeks of gestation due to previous history …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …