Genetics and Genomics Commons^™

Unaffected Women’S Decisions To Have Prophylactic Risk-Reducing Mastectomies, Stephanie N. Galloway

Theses and Dissertations

When a woman is at an increased risk of developing breast cancer due to a pathogenic mutation or a significant family history of the disease, she will be faced with choosing from among multiple management options, including risk-reducing mastectomy (RRM). The relative rate of RRM for both diagnosed and unaffected high-risk women has increased in recent years. Previous research has investigated the factors that influence women diagnosed with the disease to undergo RRM, but has not fully addressed how unaffected women make their decisions to choose RRM as an option when they are still healthy. This study was designed to …

Re-Contacting Cancer Genetic Counseling Patients: Expectations Of Patients And Physicians, Zoe Elizabeth Siegel

Theses and Dissertations

The landscape of cancer genetic counseling and testing is rapidly evolving. Genetic testing technology is improving, management guidelines are evolving, and genetic testing options are expanding. These frequent updates to the components of cancer genetics have increased the complexity of managing patient care over time. In particular, this raises questions on the duty to re-contact patients as new information becomes available. This study explored healthcare providers’ duty to re-contact through the interests and expectations of patients, including which circumstances warrant re-contacting, which healthcare provider is responsible for re-contacting the patient, and the preferred method of re-contacting. Physicians’ opinions on whether …

Identification Of Xpa And Xpc Gene Mutations In Patients With Xeroderma Pigmentosum, Eman Abdelalim Sidky Rabie

Theses and Dissertations

The human body employs different DNA repair pathways to protect itself against cancers induced by DNA damage. The nucleotide excision repair (NER) pathway comprises different synchronously working DNA repair proteins; two of which are XPA and XPC. Mutations of any of the genes encoding the NER proteins cause an autosomal recessive genetic disorder called Xeroderma Pigmentosum (XP). XP patients present with characteristic dry atrophic freckle-like pigmentation of the skin, photosensitivity and photophobia. Some patients develop neurodegenerative symptoms early in life, including mental retardation. Patients have a 10,000-fold increased risk for UV-induced skin cancers, moreover, a higher risk for ocular, oral …

Effects Of Drift, Selection And Gene Flow On Immune Genes In Prairie Grouse, Zachary Bateson

Theses and Dissertations

Fragmentation of natural habitats is related to population decline in many species. The resulting small and isolated populations are expected to lose genetic variation at a rapid rate, which reduces the ability to adapt to environmental change. One concern is that small populations are more susceptible to emerging pathogens due to the loss of variation at immune genes. My dissertation examined the relative effects of gene flow, genetic drift and selection on immune genes in prairie-chickens (Tympanuchus cupido), a species that has undergone drastic population declines across their range. In the first chapter, I examined how artificial gene flow through …

Power Analysis In Applied Linear Regression For Cell Type-Specific Differential Expression Detection, Edmund Glass

Theses and Dissertations

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from any tissues suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. However, this variability may actually be advantageous, as heterogeneous gene expression measurements coupled with cell counts may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression. Yet, they do not consider many artifacts hidden in high-dimensional gene expression …

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 …

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 …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

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 …