Life Sciences Commons^™

Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal programming is the area of study that focuses on the prenatal origins of adult onset disorders. Previous studies have associated an adverse prenatal environment with the onset of physiologic and metabolic diseases during adulthood. Fetal malnutrition, hypoxia, and exposure to drugs - such as cocaine and nicotine - have been associated with adult disease states. Cigarette smoking is the number one cause of preventable death in the developed world. Among the many dangerous chemicals found in tobacco products is nicotine, the compound responsible for the addictive nature of tobacco use. Nicotine use during pregnancy is a known cause of …

A Family-Based Association Study Of Conduct Disorder., Xueqiu Jian

Electronic Theses and Dissertations

Conduct disorder (CD) is a psychiatric syndrome in childhood and adolescence that is one of the most common childhood disorders with continuously increasing prevalence but uncertain pathogenesis. We performed a genome-wide, family-based association study of CD using P2BAT/FBAT software. The data is gathered from Collaborative Study on the Genetics of Alcoholism (COGA) and International Multi-Center ADHD Genetics Project (IMAGE).

Using COGA data, we identified 20 markers which showed suggestive associations (p<10^-3) with CD. Nine of them are located in known genes. Two genes, ADAM10 and CAMK2A, which had been reported associated with Alzheimer's disease (AD), bipolar disorder, …

Error Correcting Codes And The Human Genome., Suzanne Mclean Lyle

Electronic Theses and Dissertations

In this work, we study error correcting codes and generalize the concepts with a view toward a novel application in the study of DNA sequences. The author investigates the possibility that an error correcting linear code could be included in the human genome through application and research. The author finds that while it is an accepted hypothesis that it is reasonable that some kind of error correcting code is used in DNA, no one has actually been able to identify one. The author uses the application to illustrate how the subject of coding theory can provide a teaching enrichment activity …

The Functional Role Of The Drosophila Gypsy Insulator In The Regulation Of Gene Expression, Hyuck Joon Kang

Doctoral Dissertations

Chromatin insulators are short DNA sequences that, together with enhancers and silencers, orchestrate gene transcription through DNA-protein interactions in eukaryotic genomes. It has been proposed that insulators operate at the chromatin level by generating functionally independent higher-order chromatin domains. Insulators may maintain the integrity of such domains using two properties: blocking enhancer-promoter interactions and blocking heterochromatin spreading. The gypsy insulator of Drosophila was identified as a region of the gypsy retrovirus responsible for the production of tissue-specific mutations in many genes. The Suppressor of Hairy wing [Su(Hw)] protein contains 12 zinc fingers that specifically bind the gypsy insulator. Upon DNA …

Evaluation Of Genetic Diversity Of Flowering Dogwood (Cornus Florida L.) In The Eastern United States Using Microsatellites., Denita Hadziabdic

Doctoral Dissertations

Flowering dogwood (Cornus florida L.) populations have experienced severe declines caused by dogwood anthracnose in the past three decades. Mortality has ranged from 48 to 98%, raising the concern that genetic diversity of this native tree has been reduced significantly. Microsatellite data were used to evaluate the level and distribution of genetic variation throughout much of the native range of the tree. In the first conducted study, we found that genetic variation in areas affected by anthracnose was as high as or higher than areas without die-offs. We found evidence of four widespread, spatially contiguous genetic clusters. However, there was …

Factors Associated With Early Versus Late Development Of Breast And Ovarian Cancer In Brca1 And Brca2 Positive Women, Justine M. Cooper

Dissertations & Theses (Open Access)

Hereditary breast and ovarian cancer (HBOC) is caused by a mutation in the BRCA1 or BRCA2 genes. Women with a BRCA1/2 mutation are at increased risks for breast and ovarian cancer and often develop cancer at an earlier age than the general population. However, some women with a BRCA1/2 mutation do not develop breast or ovarian cancer under the age of 50 years. There have been no specific studies on BRCA positive women with no cancer prior to age 50, therefore this study sought to investigate factors within these women with no cancer under age 50 with respect to reproductive …

Xenobiotic Metabolism Genes And Clubfoot, Amy M. Sommer

Dissertations & Theses (Open Access)

Idiopathic or isolated clubfoot is a common orthopedic birth defect that affects approximately 135,000 children worldwide. It is characterized by equinus, varus and adductus deformities of the ankle and foot. Correction of clubfoot involves months of serial manipulations, castings and bracing, with surgical correction needed in forty percent of cases. Multifactorial etiology has been suggested in numerous studies with both environmental and genetic factors playing an etiologic role. Maternal smoking during pregnancy is the only common environmental factor that has consistently been shown to increase the risk for clubfoot. Moreover, a positive family history of clubfoot and maternal smoking increases …

Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock

Dissertations & Theses (Open Access)

Mounting an effective response to tissue damage requires a concerted effort from a number of systems, including both the immune and nervous systems. Immune-responsive blood cells fight infection and clear debris from damaged tissues, and specialized pain receptors become hypersensitive to promote behavior that protects the damaged area while it heals. To uncover the cellular and molecular mechanisms underlying these processes, we have developed a genetically tractable invertebrate model of damage-induced inflammation and pain hypersensitivity using Drosophila larvae.

To study wound-induced inflammation, we generated transgenic larvae with fluorescent epidermal cells and blood cells (hemocytes). Using live imaging, we monitored the …

Analysis Of Variation In Clubfoot Candidate Genes, Audrey R. Ester

Dissertations & Theses (Open Access)

Isolated clubfoot, a common birth defect occurring in more than 135,000 livebirths worldwide each year, is associated with significant health care and financial burdens. Clubfoot is defined by forefoot adduction, hindfoot varus, midfoot cavus and hindfoot equinus. Isolated clubfoot, which is the focus of these studies, is distinct from syndromic clubfoot because there are no other associated malformations. Population, family, twin and segregation analysis studies provide evidence that genetic and environmental factors play an etiologic role in isolated clubfoot. The studies described in this thesis were performed to define the role of genetic variation in isolated clubfoot. Interrogation of a …

Automated Discovery Of Pedigrees And Their Structures In Collections Of Str Dna Specimens Using A Link Discovery Tool, Alex Brian Haun

Masters Theses

In instances of mass fatality, such as plane crashes, natural disasters, or terrorist attacks, investigators may encounter hundreds or thousands of DNA specimens representing victims. For example, during the January 2010 Haiti earthquake, entire communities were destroyed, resulting in the loss of thousands of lives. With such a large number of victims the discovery of family pedigrees is possible, but often requires the manual application of analytical methods, which are tedious, time-consuming, and expensive. The method presented in this thesis allows for automated pedigree discovery by extending Link Discovery Tool (LDT), a graph visualization tool designed for discovering linkages in …

Validation Of The Activation Of Aurora B Kinase By Caenorhabditis Elegans Tousled-Like Kinase And The Identification Of Cyclin B3 As A Phospho-Specific Tlk-1 Interactor, Gary Michael Deyter

Dissertations & Theses (Open Access)

A hallmark of tumorigenesis and certain birth defect syndromes is the loss of ploidy that can result from incorrect chromosome segregation. Chromosomes that are not partitioned properly during mitosis are often fragmented, changing the genetic makeup of daughter cells. Inheriting extrachromosomal fragments that contain cell survival genes or losing chromosomal loci that encode tumor suppressors can promote tumor development. Thus, it is essential to elucidate molecular mechanisms required for correct chromosome segregation. Chromosomes are connected to mitotic spindle microtubules by way of a proteinacous, chromosome-bound organelle called the kinetochore. Two decades of research have confirmed that the conserved Aurora B/AIR-2 …

A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee

Dissertations & Theses (Open Access)

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease.

In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it …

Attitudes Of Parents At Risk Of Inheriting Li-Fraumeni Syndrome Towards Predictive Genetic Testing In Their Minor-Aged Children., Leslie A. Newman

Dissertations & Theses (Open Access)

Li-Fraumeni Syndrome (LFS) is a hereditary cancer syndrome which predisposes individuals to cancer beginning in childhood. These risks are spread across a lifetime, from early childhood to adulthood. Mutations in the p53 tumor suppressor gene are known to cause the majority of cases of LFS. The risk for early onset cancer in individuals with Li-Fraumeni Syndrome is high. Studies have shown that individuals with LFS have a 90% lifetime cancer risk. Children under 18 have up to a 15% chance of cancer development. Effectiveness of cancer screening and management in individuals with Li-Fraumeni Syndrome is unclear. Screening for LFS-associated cancers …

A Systems Genetics Approach To The Characterization Of Differential Low Dose Radiation Responses In Bxd Recombinant Inbred Mice, Rachel Marie Lynch

Doctoral Dissertations

High doses of radiation (HDR) are clearly detrimental to human health, but relatively little is known about the health consequences following exposure to low doses of radiation (LDR, <10cGy). Understanding the risks associated with LDR is of great importance to the general public due to the recent dramatic increase in diagnostic radiological imaging. While HDR clearly suppress immune function, there is evidence that LDR can be immunostimulatory. Within the organism, defining the consequences of LDR is further complicated by the impact of genetic background, particularly in systems such as the immune system for which both radiosensitivity and genetic effects are profound.

We addressed the issue of genetic susceptibility to LDR using the immune system as a target system and treated the LDR response as a complex trait analyzed using a systems genetics framework. Using the BXD recombinant inbred strain mouse panel as a genetic reference population allowed us to address the radiation response within the context of natural genetic variation. Our overarching hypothesis is that, within a population, the immunological effects of LDR …

Mapping Quantitative Trait Loci Associated With Chilling Requirement And Bloom Date In Peach, Shenghua Fan

All Dissertations

Chilling requirement (CR), together with heat requirement (HR), determines bloom date (BD), which impacts climatic distribution of genotypes of temperate tree species. The molecular basis of floral bud CR is poorly understood despite its importance to fruit tree adaptation and production. A peach F2 populations developed from two genotypes with contrasting CR values was used for QTL mapping for CR, HR and BD. Using the Contender × Fla.92-2c population, 20 QTLs with additive effects were identified for three traits including one major QTL for CR and two major QTLs for BD. Particularly, one genomic region of 2cM pleiotropic for the …