Genetics and Genomics Commons^™

Acquired Epigenetic And Chromosomal Changes In Women Treated For Breast Cancer, Noran Aboalela

Theses and Dissertations

Improved survival for women receiving chemotherapy for breast cancer (BC) has been accompanied by the development/persistence of psychoneurological symptoms (PNS) that compromise their quality of life. The biological basis for these PNS is unknown, but could reflect the acquisition of soma-wide chromosomal/epigenetic alterations. An important first step in testing this hypothesis is to determine if somatic genetic/epigenetic changes arise and persist following treatment. To answer this question we longitudinally studied 71 women (ages 23-71) with early-stage BC and collected measures before chemotherapy (baseline), and 4 weeks (mid-chemo); six months (during radiation therapy for a subset of women); and one year …

Methods For Integrative Analysis Of Genomic Data, Paul Manser

Theses and Dissertations

In recent years, the development of new genomic technologies has allowed for the investigation of many regulatory epigenetic marks besides expression levels, on a genome-wide scale. As the price for these technologies continues to decrease, study sizes will not only increase, but several different assays are beginning to be used for the same samples. It is therefore desirable to develop statistical methods to integrate multiple data types that can handle the increased computational burden of incorporating large data sets. Furthermore, it is important to develop sound quality control and normalization methods as technical errors can compound when integrating multiple genomic …

I Wish I Had Known This!: Impact Of Age On Life Choices And Testing Satisfaction For Brca1/2 Mutation Carriers Who Underwent Genetic Testing By Age 25, Sarah Elaine King

Theses and Dissertations

Objective: To examine if BRCA1/2 mutation carriers who received their positive genetic test result by age 25 were satisfied with their decision to undergo genetic testing and with the choices made regarding family planning, surveillance, and surgery. Methods: 72 participants recruited via social media completed a survey hosted by SurveyMonkey.com. Sixty-three met study criteria and were asked 40 quantitative and qualitative questions designed to assess family planning, surveillance, and surgery needs of young BRCA carriers, which included a six question Satisfaction with Decision Scale. Results: Regardless of age, participants were very satisfied with the decision to undergo genetic testing. Recommendations …

The Paternal Age Effect: A Preliminary Study Of Current Challenges For Prenatal Genetics Care, Andrew Tyler Gunter

Theses and Dissertations

Advanced paternal age (APA) is related to various genetic conditions, behavioral disorders, and adverse pregnancy outcomes. Since the publication of ACMG's practice guidelines on APA in 2008, much has been learned about the causes of paternal age effect (PAE) mutations and their clinical implications. However, no guidelines exist to refer these high-risk pregnancies to prenatal genetics care, nor are effective screening techniques presently available. As such, many patients are not fully-informed about the risks to their pregnancies due to possible APA effects, and neither are are the men who have fathered these pregnancies.

Our findings support that limited APA principles …

Walking The Edge With Controversial Use Of Preimplantation Genetic Diagnosis (Pgd): Opinions And Attitudes Of Genetic Counselors, Kristen Everton

Theses and Dissertations

Purpose: This study explored opinions and attitudes of genetic counselors regarding three controversial applications of preimplantation genetic diagnosis (PGD): PGD for early-onset Alzheimer, use of embryos that are BRCA positive after PGD revealed no disease-free embryos to be available, and PGD to select against a variant of unknown significance (VUS) for Marfan syndrome. Methods: Genetic counselors were contacted through the National Society of Genetic Counselors (NSGC) electronic mailing list. Inclusion criteria required that a participant was currently practicing as a genetic counselor, was a member of the NSGC, and has counseled patients about PGD. Twenty-nine participants volunteered to participate and …

The Impact Of Culture & Ethnicity On The Counseling Process: Perspectives Of Genetic Counselors From Minority Ethnic Groups, Brittanie Morris

Theses and Dissertations

In the genetic counseling profession, discussions about cross-cultural counseling and cultural competence emphasize the importance of patient culture as well as counselor culture in a counseling session. A culturally competent counselor should be aware of the influence of her own cultural values on interactions with patients and peers (Weil, 2000; & Uhlmann, Schuette, & Yashar, 2011). Focusing specifically on counselors from cultural/ethnic minorities, this mixed-methods study sought to empirically evaluate the influence of a counselor's cultural values and ethnic identity on the genetic counseling process. 162 genetic counselors, 58 of whom self-identified as being from an ethnic minority group, completed …

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 …

Multi-Species Gene Networks And Drosophila Ethanol Sedation, Arnavaz Kollah

Theses and Dissertations

Alcohol use disorders (AUDs) are major health issues with few known genetic explanations. This project used the fruit fly (Drosophila melanogaster) model to identify genes and gene networks that influence alcohol intoxication, a phenotype related to alcohol abuse in humans. We used bioinformatic tools to build gene networks based on 24 published Drosophila ethanol-responsive genes with human orthologs. We then assessed the role of these networks in ethanol sedation by testing two of the networks seeded on IP3K2, a gene that regulates calcium signaling, and CG14630, a gene involved in carnitine biosynthesis. We knocked down several genes in each of …

Prenatal Decision-Making Process Of Patients In Three Cities In South Carolina, Kimberly Marie Hamann

Theses and Dissertations

Purpose: Noninvasive prenatal testing (NIPT) has changed the landscape of prenatal genetic evaluation. This novel test can be performed as early as 10 weeks gestation without risk of pregnancy complication and has evoked questions about its applicability, appropriate use, and patient response. The purpose of this study was to evaluate patient decision-making processes about prenatal testing options as NIPT is integrated into the clinical realm. Method: Prenatal patients who were offered NIPT during genetic counseling (N = 105) in three cities in South Carolina completed a survey to address the goals of this study. Results: The top five factors most …

Unique Perspectives And Struggles Of Parents Rearing Children With Phenylketonuria With Unaffected Siblings, Cassandra Nicole Hollinger

Theses and Dissertations

Phenylketonuria (PKU) is an autosomal metabolic condition that is screened for via newborn screening. Individuals who are identified as having PKU require a protein-restricted diet to protect against neurological damage. Many parents who learn their child has PKU may already have children who are not affected, or may have children later who are not affected. This creates a unique situation in which parents are rearing children that require a strict protein-restricted diet with children who do not. Parents who are currently rearing children with and without PKU were surveyed to learn what unique perspectives and struggles they face, especially regarding …

A Qualitative Study On How Prenatal Genetic Counselors Prioritize Cultural Issues When Counseling Patients, Darcy Katherine Berry

Theses and Dissertations

The genetic counseling community has long recognized that the successful outcome of a session with a patient whose cultural background differs from the genetic counselor's is best achieved through recognition of the cultural differences and implementation of specific skills to overcome cultural barriers. Although research has examined the need and effects of cultural competency in genetic counseling, no prior study has evaluated how genetic counselors perceive the importance of addressing cultural issues in a genetic counseling session. Prenatal genetic counselors were recruited by emailing all NSGC members. For this study, sixteen prenatal genetic counselors were interviewed and asked to prioritize …

Use Of Social Media As A Support Network In Families With A Child Diagnosed With Trisomy 13, 18, Or 21, Ginger Elizabeth Edwardsen

Theses and Dissertations

Social media is a web based technology that allows individuals to communicate with other individuals, organizations, and communities about common interests and experiences. Recently, social media use has expanded into the healthcare field and many individuals are using social media to connect with others in similar situations and find support. Family members of children or pregnancies with trisomy 13, 18, or 21 were invited to participate in an online survey that explored the use of social media as a support network including their purposes for using social media as a support network, how often the use social media, and what …

Examining The Differences In Rapport Between Male And Female Cancer Genetic Counselors And Female Clients, John Abernethy

Theses and Dissertations

Genetic counseling is a field in which client-counselor rapport plays a critical role in client satisfaction with the genetic counseling process. One factor that may impact this rapport is gender of the genetic counselor. Previous studies in the field of psychological counseling suggest that gender is not a significant moderator of this rapport. To the best of our knowledge, no study has been published in the field of genetic counseling examining the impact that the gender of the genetic counselor has on client-counselor rapport. To study this effect, an amended version of Horvath & Greenberg's (1989) Working Alliance Inventory tool …

Working With Patients At Risk For Hereditary Degenerative Brain Disorders, Stephen John White

Theses and Dissertations

Hereditary degenerative brain disorders (HDBDs) are a unique class of genetic conditions that result in progressive loss of function within the nervous system, many of which present during adulthood. Given this, the diagnosis of a HDBD can be daunting for both the patient and the genetic counselor assisting in medical care. The purpose of this study was to find themes among genetic counselors who see this patient population and help provide a framework to counselors entering this field by recognizing verified methods of HDBD counseling. Sixteen genetic counselors who routinely see patients at-risk for HDBDs were interviewed concerning how they …

Transcriptional Profiling Of Aphid Resistant And Susceptible Melon (Cucumis Melo) Following Cotton -Melon Aphid (Aphis Gossypii) Feeding, Preethi Samuel

Theses and Dissertations

The interaction between phloem feeding aphids Aphis gossypii (cotton-melon aphid) and Cucumis melo (melon) provides an opportunity to elucidate the means by which a host plant defends itself against aphid attack. The relationship is of scientific as well as economic importance since A. gossypii is among the most destructive insects to agriculture in the U.S. and abroad. The resistance to A. gossypii in melon is controlled at the Vat (Virus aphid transmission) locus by a major dominant gene, Vat that has the unique feature of conferring resistance to A. gossypii and resistance to transmission of non-persistent viruses by A. gossypii …

Comparing Clustering Algorithms For Use With Genomic And Proteomic Data, Rebecca A. Olson

Theses and Dissertations

The Human Genome Project and related projects have resulted in the development of a number of new experimental and analytic tools for use in genomic and proteomic research. In the area of toxicogenomics, researchers are concerned with how genes react to exposure to certain chemicals. The United States Air Force is interested in the effect of exposure to mission-essential chemicals. Although military personnel may come into contact with chemicals such as hydrazine, risk assessment is usually very limited. On the genomic level, risk assessment is a multi-stop and multi-disciplinary process. The process begins with an experiment that exposes cells to …

Sjögren-Larsson Syndrome: Genetic Studies And Biochemical Characterization Of Human Fatty Aldehyde Dehydrogenase, Todd L. Kelson

Theses and Dissertations

Sjögren-Larsson syndrome (SLS) is an autosomal recessive disorder due to deficiency of the fatty aldehyde dehydrogenase (FALDH) component of fatty alcohol:NAD⁺ oxidoreductase (FAO). We investigated the enzymatic defect in SLS in order to elucidate the role of FALDH in fatty aldehyde and fatty alcohol metabolism.

Genetic studies were performed to investigate carrier detection for SLS. Cultured skin fibroblasts from normal controls, SLS obligate heterozygotes, and SLS homozygotes were assayed for FAO and FALDH activities using 18-carbon substrates. In SLS homozygotes, mean FAO and FALDH activities were 8% of normal, and there was no overlap between the homozygote and heterozygote …

Molecular And Cytogenetic Characterization Of De Novo Acrocentric Rearrangements In Humans, Lisa Gail Shaffer

Theses and Dissertations

I have studied 26 children who have a de novo rearrangement of the acrocentric chromosomes in order to understand the formation of these aberrations. The families include '25 probands ascertained for Robertsonian-type translocations, 13 between nonhomologous chromosomes and 12 between homologs, and one rea(21;21)(q22;q22). The parental origins of the de novo rearrangements were determined in 26/26 families using QFQ and NOR variants and/or RFLP analyses. While there was no overall difference in the sex distribution of the parents of origin, there were more maternally derived nonhomologous ("true" Robertsonian) translocations (8 mat: 5 pat) and more paternally derived homologous rearrangements (4 …

Genetic Studies Of Questionnaire Data From A Residential School For The Deaf, Frederick Robert Bieber

Theses and Dissertations

A self-administered thirteen page Hearing Loss Questionnaire (HLQ) was designed in order to systematically collect medical and family history data on deaf children and their families. Data were collected from over 400 families with one or more children enrolled in September 1979 at the Maryland School for the Deaf (MSD). Almost 70% of the parents provided pedigree and family history information by completing the detailed HLQ. Computer analyses of the collected data allowed a thorough examination of almost 200 medical and family history variables, providing useful reference data on the MSD probands. Parental responses to a four-step rating scale of …

Genetic Heterogeneity In Complementation Groups Of Propionic Acidemia, Catherine Mckeon

Theses and Dissertations

Propionic acidemia is an autosomal recessively inherited disorder of organic acid metabolism caused by deficient activity of propionyl CoA carboxylase. This enzyme is required for the catabolism of the odd-chain fatty acids, the side chain of cholesterol and the amino acids: isoleucine, methionine, and threonine. Although the clinical expression of this disorder is variable, affected children usually develop ketoacidosis and hyperammonemia which may progress to seizures, coma and possibly death. Some patients may exhibit vomiting, lethargy and hypotonia in the first few weeks of life whereas others may remain asymptomatic for months or even years.(1) The degree of residual enzyme …

Sex-Linked Mental Retardation Without Physical Stigmata (Martin-Bell Or Renpenning Type) : A Genetic And Psychometric Approach, Craig L. Hanis

Theses and Dissertations

Screening the Utah State Training School (a resident institution for the mentally retarded) for kindreds having at least two institutionalized sibs generated 54 sib groups. Of these, 20-male only sibships had histories compatible with sex-linked mental retardation without physical stigmata (Martin-Bell or Renpenning type). Affected males had no characteristic physical stigmata (an appreciable number did have speech problems and/or seizure disorders) and exhibited IQs ranging from 5 to 74 with a mean of 34.2. Obligate carrier females had a mean IQ score of 91.9 (range, 79 to 106), which is as would be predicted due to random X-inactivation. Carrier females …

The Serlogical Specificity Of The Lectin From Lens Culinaris, Deborah Ward Heritage

Theses and Dissertations

Lens culinaris, the common lentil, contains a lectin which has been shown to be specific for a glycoprotein saliva antigen and a glycolipoprotein serum antigen. Both the saliva and serum precipitin reactions with the lectin are directly inhibited with saccharides, especially those related to D-mannose. Electrophoresis of the serum antigen showed that it migrates as three bands, while appearing as a single band in double diffusion precipitin patterns. Quantitative studies of the saliva antigen levels by hemagglutination inhibition titration indicated a polygenic, quantitative mode of inheritance with a minimum heritability of O. 34. Blood group ABH secretor individuals were found …