Life Sciences Commons^™

Two Fields, One Pellet: Combining Demographics And Population Genetics Through Non-Invasive Sampling Of Snowshoe Hare Fecal Pellets In Michigan., Genelle Nicole Uhrig

Theses and Dissertations

As climate continues to change at a rapid rate, species are increasingly vulnerable to the resulting environmental changes. This is especially true for species whose fitness is closely linked to climate-associated environmental conditions. One of these vulnerable species is snowshoe hare, Lepus americanus, who depends on the timing and duration of snowfall to provide camouflage when they go through seasonal pelage changes from brown in the summer to white in the winter. Whereas snowshoe hare are stable across the core of their range, populations along the southern range edge are experiencing declines due to climate driven environmental changes that cause …

An Autism-Causing Variant Misregulates Selective Autophagy To Alter Axon Targeting And Behavior, Tyler Buddell

Theses and Dissertations

Neurodevelopmental disorders cause debilitating disruptions to the cellular mechanisms that underlie development of the brain. Unfortunately, the complexities of neurodevelopmental disorders make them difficult to study, and the molecular mechanisms perturbed by these disorders remain elusive. Better understanding of neurodevelopmental mechanisms, and the related genes involved, will likely yield new insight into neurodevelopmental disorders. A gene that has been associated with a number of neurodevelopmental disorders is the calcium voltage-gated channel subunit alpha1 C (CACNA1C) gene. Common and rare variants of the CACNA1C gene have been associated with autism and other neurodevelopmental disorders including schizophrenia, bipolar disorder and ADHD. However, …

A Seascape Genetics Approach To Studying Genetic Differentiation In The Bull Kelp Nereocystis Luetkeana, Lily G. Gierke

Theses and Dissertations

The brown alga Nereocystis luetkeana is a foundation species found from Alaska to California. In the Salish Sea, N. luetkeana is declining, but little is known about its population structure. We explored N. luetkeana 1) allelic dissimilarity and richness using seven microsatellite markers, and 2) tested models of gene flow in the Salish Sea using a hydrodynamic transport model. Our results suggest that the N. luetkeana distribution is comprised of four genetic co-ancestry groups that are geographically coherent, apart from the separation of the Strait of Georgia/Puget Sound by the Strait of Juan de Fuca. Our model supported that environmental …

Chromatin Digestion By The Chemotherapeutic Agent Bleomycin Produces Nucleosome And Transcription Factor Footprinting Patterns Similar To Micrococcal Nuclease, Joshua Michael Stolz

Theses and Dissertations

Bleomycin (BLM), a glycopeptide antibiotic commonly used in chemotherapeutic treatments, has been shown to produce single and double stranded DNA breaks. Subsequent analysis of DNA fragmentation patterns has demonstrated preferential digestion of chromatin in the TSS of active genes and the ability to produce nucleosome-sized fragments within intact chromatin. Nucleosome positioning plays a critical role in the regulation of gene activation. Currently, micrococcal nuclease (MNase) is used as the standard for mapping the position of nucleosomes in the genome. In order to identify whether BLM can be used as an effective nucleosome-mapping agent, BLM was used to digest chromatin in …

Dissection Of Floral Organ Development And Sterility In Sorghum Bicolor, Ashley R. Smith

Theses and Dissertations

Sorghum bicolor is a drought resistant cereal grain commonly grown for use in food, feed, fiber, and fuel production. Due to its versatility and modest sized genome it is poised to become an increasingly important research organism within the C4 plants. Sorghum produces spikelet pairs with one fertile sessile spikelet and one to two sterile pedicellate spikelets. One major area of interest in sorghum production is maximizing seed yield. While the importance of the grain is obvious there are several large gaps in the study of sorghum that prevent researchers and growers from maximum productivity. The first gap is that …

Receptor-Mediated Maturation Of Olfactory Sensory Neurons: A Time Course Evaluation Of Neuronal Maturation In Neomorphic Mutants, Elizabeth Miller

Theses and Dissertations

How expression of odorant receptors affects the maturation of olfactory sensory neurons (OSNs) is not known. In a time course experiment, we show that wild type OSNs mature significantly more than those expressing Neomorphic mutant receptors. We conclude that functional receptors are critical to the differentiation and survival of OSNs.

The Genome Of Cañahua: An Emerging Andean Super Grain, Hayley Jennifer Mangelson

Theses and Dissertations

Chenopodium pallidicaule, known commonly as cañahua, is a semi-domesticated crop grown in high-altitude regions of the Andes. It is an A-genome diploid (2n = 2x = 18) relative of the allotetraploid (AABB) Chenopodium quinoa and shares many of its nutritional benefits. Both species contain a complete protein, a low glycemic index, and offer a wide variety of nutritionally important vitamins and minerals. Due to its minor crop status, few genomic resources for its improvement have been developed. Here we present a fully annotated, reference-quality assembly of cañahua. The reference assembly was developed using a combination of established techniques, including multiple …

Exploring Patient Perceptions And Misconceptions: Beliefs Regarding Hereditary Cancer, Margaret Flach

Theses and Dissertations

Many patients who enter a genetic counseling session have preconceived notions about why they or their family members developed a genetic condition. Often these perceptions are deeply rooted in personal, familial, and/ or cultural beliefs; individuals typically have a personal framework, or schema, into which they incorporate new information. There is limited research on what information patients are retaining during a genetic counseling session and how they are assimilating that knowledge into their existing views. We attempted to characterize these patient perceptions with respect to hereditary cancer, in order to assess how patients are adopting the information presented in a …

Impact Of Service Delivery Model On Patient Perceptions And Utility Of Genetic Counseling For Hereditary Breast And Ovarian Cancer: An Exploration Of Group Genetic Counseling, Alyssa M. Gates

Theses and Dissertations

Patients at risk for hereditary breast and ovarian cancer (HBOC) traditionally participate in individual cancer genetic counseling sessions to be educated about cancer genetics concepts, their personal cancer risks and genetic testing. With expanding technology and increased public awareness of HBOC, referrals to cancer genetic counseling services have grown. The current number of practicing genetic counselors struggles to meet the demands of increased referrals, so new service delivery models need to be explored. The purpose of this study is to assess the utility of group genetic counseling for HBOC by evaluating the perspectives of patients that received group genetic counseling …

Evaluating The Social Informational Needs Of Emerging Adults With Genetic Conditions, Courtney Whitmore

Theses and Dissertations

Purpose: This study evaluated the healthcare provider’s role during the social development of emerging adults with a genetic condition. The study also identified the type of information and ways that these adolescents hope to receive information on the potential side effects or complications from engaging in risk taking behaviors and lifestyle choices.

Methods: Participants included both males and females aged 18-26 with achondroplasia, sickle cell disease, cystic fibrosis, or Marfan syndrome. Respondents were recruited to complete an anonymous online questionnaire via social media support groups or email notification.

Results: There were 103 total respondents that completed the questionnaire and met …

Amish Perspectives Of The Genetic Counseling Process, Brianna Teapole

Theses and Dissertations

The Amish are a population with a high concentration of genetic disorders who have informed our understanding of several genetic conditions. This culturally unique group has special need for genetic services. While clinics have been established to care for Amish individuals, such as the Community Health Clinic in Indiana, little research has been done on Amish perspectives of these services, specifically genetic counseling. Amish individuals who received genetic counseling from the Community Health Clinic were sent recruitment letters and a questionnaire via mail. The questionnaire consisted of demographic questions, a 7-item adapted Genetic Counseling Satisfaction Scale (GCSS), and open-response questions. …

Reproductive-Aged Adults Diagnosed With Tuberous Sclerosis Complex (Tsc): Understanding Of Clinical Variability, Perceived Disease Burden, And Reproductive Decision-Making, Diane L. Biederman

Theses and Dissertations

Tuberous Sclerosis Complex (TSC) is a highly variable autosomal dominant multisystem disorder characterized by the growth of benign tumors, epilepsy, and TSC- associated neuropsychiatric disorders (TAND). There is a high level of clinical variability, even within the same family. While reproductive decisions always carry a level of uncertainty, individuals with highly variable genetic conditions like TSC must consider both the chance of passing on the condition and the uncertain clinical presentation. There is currently no literature on factors influencing reproductive decisions of adults with TSC. To address this gap in understanding, we conducted an exploratory mixed-methods survey utilizing an anonymous …

The Perspectives Of Emerging Adults With Hereditary Diffuse Gastric Cancer, Carrie Anderson

Theses and Dissertations

Individuals with hereditary diffuse gastric cancer (HDGC) caused by a CDH1 mutation have a high lifetime risk of developing gastric cancer. National guidelines recommend CDH1 carriers undergo a prophylactic total gastrectomy (PTG)— a surgery that greatly reduces the risk of developing gastric cancer but has significant comorbidities. This study explores the impact of a diagnosis of HDGC in the transitional life stage between the ages of 18-29 deemed “emerging adulthood.” We surveyed 21 CDH1 carriers and conducted semi-structured phone interviews with 6 CDH1 carriers between the ages of 18-29 to learn about their life experiences regarding education, career, relationships, and …

Brca1 And Brca2 Mutation Carrier Perspectives On Direct-To- Consumer Genetic Testing For Brca Mutations, Caitlyn E. Mitchell

Theses and Dissertations

Recently the FDA authorized one direct-to-consumer genetic testing (DTC-GT) company to begin reporting certain genetic variants in the BRCA1 and BRCA2 genes. Pathogenic variants in these genes confer lifetime risks for breast and ovarian cancer in women as high as 87% and 62%, respectively. Historically, genetic testing for these mutations has been offered in a clinical setting where genetic counseling is part of the testing process. Genetic counseling is not routinely a part of DTC-GT, raising concern that those undergoing DTC-GT for BRCA1/2 mutations may not fully understand what is being tested, the implications of results, or that they may …

Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon

Theses and Dissertations

This study phylogenetically analyzed 30 AMY-related genes from 11 primates. The results show the gradual expansion of the AMY gene family which could have allowed primates to adapt to various ecological landscapes and maximize energy intake from starch-rich foods in periods of food scarcity.

Aeg-1 Knockout Sensitizes Hepatocellular Carcinoma (Hcc) Cells To Ionizing Radiation, Maheen Khan

Theses and Dissertations

Liver cancer is the fourth leading cause of cancer-associated deaths globally, and among primary liver cancers, hepatocellular carcinoma (HCC) encompasses 75-85% of all cases. HCC is a highly lethal disease due to limited treatment options – only a small subset of patients qualify for surgical resection or transplantation; the remaining patients often display resistance to radiation therapy or chemotherapy. Overexpression of the oncogene astrocyte elevated gene-1 (AEG-1) is associated with poorer survival and increased tumor recurrence in HCC, and numerous studies show its role in initiation of hepatocarcinogenesis. A prior study also demonstrated AEG-1 expression inhibits senescence by diminishing the …

Spatial Genetic Structure And Local Adaptation Within And Among Foxtail Pine (Pinus Balfouriana Subsp. Balfouriana) Populations Located In The Klamath Mountains, California, Rebecca D. Piri

Theses and Dissertations

Foxtail pine (Pinus balfouriana) is a subalpine conifer endemic to California, notably separated into two disjunct subspecies. Previous studies have described the northern subspecies,Pinus balfouriana subsp. balfouriana,as having an uncommonly high level of genetic differentiation and no discernible spatial patterns in phenotypic variation. This study seeks to characterize the spatial genetic structure and patterns of selection of the northern subspecies (Pinus balfouriana subsp. balfouriana) using genome-wide data and to identify the influence of ecology and environment on the unique genetic patterns. I show that genetic differentiation among populations is much less than previously estimated …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Regulation Of Cancer-Specific Mirnas By Mda-7/Il-24, Danielle Scheunemann

Theses and Dissertations

Melanoma differentiation associated gene 7/Interleukin-24 (MDA-7/IL-24) is a secreted cytokine which acts as a tumor suppressor. It is capable of selectively killing cancer cells, regardless of anatomic origin, while sparing normal cells. miRNAs are master regulators of gene expression that can play two roles in cancer: tumor-suppression and oncogenesis. We identified a number of miRNAs that are regulated by MDA-7/IL-24 using a PCR plate array containing probes for miRNAs known to play a role in prostate cancer. We independently validated the array with qRT-PCR to identify three miRNAs which are downregulated by MDA-7/IL-24 treatment in DU145, PC3, and PC3ML prostate …

Co-Localization Of Polycystic Ovary Syndrome Candidate Gene Products In Human Theca Cells Suggests Novel Signaling Pathways, Rewa M. Kulkarni

Theses and Dissertations

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility and the most common endocrinopathy of women of reproductive age. Genome-wide association studies (GWAS) identified a number of loci associated PCOS in different ethnic populations, including women with Asian and European ancestry. Replication studies have confirmed some of these associations. Among the loci identified are those located near the LH receptor gene (LHCGR), a clathrin-binding protein gene (DENND1A) that also functions as a guanine nucleotide exchange factor, and the gene encoding RAB5B, a GTPase and protein involved in vesicular trafficking. The functional significance of one …

Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee

Theses and Dissertations

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …

Genetic And Environmental Factors Influence Drosophila Ethanol Sedation, Rebecca E. Schmitt

Theses and Dissertations

Alcohol use disorder is a global health issue that affects a significant portion of the population, with affects including both negative mental and physical consequences. Currently, there are few treatment options available to those who suffer from alcohol use disorder, alcohol abuse, or alcohol dependence. Identifying candidate genes or environmental influences would therefore improve the means for possible treatments or identification of those people at risk for alcohol use disorder. Previous studies in humans have demonstrated an inverse association between initial sensitivity and risk for alcohol abuse. This connection allows investigators, and our laboratory, to investigate genetic and environmental factors …

Translational Insights Into The Genetic Etiology Of Mental Health Disorders: Examining Risk Factor Models, Neuroimaging, And Current Dissemination Practices, Jessica L. Bourdon

Theses and Dissertations

Psychiatric genetics is a basic science field that has potential for practical application and effective translation. To date, translational frameworks utilized by this field have been linear (e.g., sequential) in nature, focusing on molecular genetic information. It is proposed that non-linear (e.g., socio-ecological) frameworks are a better way to immediately translate non-molecular genetic information. This dissertation explored the translation of psychiatric genetic information in two ways. First, a survey was sent to academic stakeholders to assess the state of the science regarding the translation of genetic information to the clinical care of mental health disorders. Findings from this indicate a …

The Increased Frequency Of Micronuclei Seen In Women With A History Of Childhood Sexual Abuse Reflects More Numerical Than Structural Acquired Chromosomal Events: A Discordant Identical Co-Twin Study, Kaitlyn M. Dochelli

Theses and Dissertations

Childhood sexual abuse (CSA) is a stressful life experience with lasting/far-reaching health and psychopathological consequences. Our laboratory recently identified a significantly increased frequency of acquired chromosomal anomalies (assessed using the cytokinesis-blocked micronucleus assay) in adult female twins exposed to CSA when compared to their unexposed co-twin. The primary aim of this study was to evaluate potential mechanism(s) underlying the observed increases in levels of micronuclei in an expanded group of 90 female identical twins (61 CSA+ females and 29 CSA- females [including a total of 27 MZ co-twin pairs]) using fluorescence in situ hybridization (FISH) methodologies, with PNA probes specific …

Phenotypic Characterization Of Pnpase Mutation And Overexpression In C. Elegans, Brian J. Hur

Theses and Dissertations

PNPase, polynucleotide phosphorylase, is a multifunctional exoribonuclease protein with 3` terminal oligonucleotide polymerase activity. Coded by the PNPT1 gene, the protein is associated with mitochondrial homeostasis and functions as a possible target for cancer therapy. In this study, C. elegans was used to investigate the effect of mutation and overexpression of pnpt-1, the gene that encodes PNPase. It was determined that two specific mutations in pnpt-1 did not affect PNPase expression nor did they produce deleterious phenotypes that affected polycistronic transcript accumulation or ROS production. Creation of a stable overexpression model was achieved through Fusion PCR. However, different transgenic …