Medical Genetics Commons^™

Patient-Reported Barriers & Outcomes Of Cardiovascular Genetic Counseling In Diverse Populations Of New York City, Marisa M. Thornburg, Alynn M. Kruse

Human Genetics Theses

Hereditary cardiomyopathies and cardiac arrhythmias can be inherited in an autosomal dominant pattern, which puts a patient with a positive genetic test result at a 50% chance to pass this variant onto any children. Our pilot study with Montefiore Medical Center aims to understand how confident patients feel about their cardiology genetic test results and how participants can share information with relevant family members and healthcare professionals. This study attempts to qualify the physical and emotional barriers patients face and understand the psychosocial burden they face following their results session. For our study, 43 participants were contacted via phone call …

Genetic Origins Of Polycystic Ovarian Syndrome (Pcos): An Analysis Of The Genetic Correlation Between Pcos And Insulin Receptor Mutations, Lauren Henry

Undergraduate Theses

Polycystic Ovarian Syndrome (PCOS) remains an extremely common, yet understudied syndrome experienced by 6-12% of females of reproductive age. Not only does it cause painful side effects manifesting both physically and mentally, but it also poses a threat to the fertility of those affected. For this reason, a more in-depth analysis to better understand how to detect this condition early and prevent fertility complications later is certainly warranted. PCOS is suspected to be primarily genetic due to correlations among immediate female family members. Based on previous research, a good starting point for analysis is the INSR gene. Various mutations within …

The Significance Of Cell-Surface Α2,3-Linked Sialic Acid In Osteoclasts, Christopher S. Harding

EWU Masters Thesis Collection

Osteoclasts are giant, multinucleated cells that, alongside osteoblasts, are central to maintaining physiologically healthy bone. The functions of osteoclasts and osteoblasts-degrading and depositing bone matrix, respectively-are paired in healthy bone tissue, thereby yielding no net bone loss or deposition. When these functions become imbalanced, it results in net bone loss or gain, depending on which cell type is being outcompeted. Osteoporosis is one of the most common pathologies stemming from such an imbalance, and predominantly affects postmenopausal women, as the ablation of circulating estrogen-a pro-death signal for osteoclasts-causes a prolongation of osteoclast lifespan and consequent lengthening of their resorptive activity. …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Genetic Mechanisms Of Transcriptional Regulation In Childhood Acute Lymphoblastic Leukemia, Xujie Zhao

Theses and Dissertations (ETD)

Introduction. Advances in genomic profiling and sequencing studies have identified germline and somatic variations that are associated with childhood ALL, improving our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL). Recent genome-wide association studies (GWAS) have identified germline genetic variations of ARID5B and, more recently, IGF2BP1 that are associated with susceptibility to ALL. Genome-wide sequencing studies also discovered a new ALL subtype characterized of ZNF384-mediated chromosomal translocations, providing new insights into genetic heterogeneity in childhood ALL. However, the underlying mechanism by which these genetic variants contribute to the transcriptional regulatory circuitries of ALL is still poorly understood. …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …

Clincial Translational Science Research Of The Functional Role Of Large Conductance Potassium Channels In Selective Destruction Of Triple Negative Breast Cancer Cells, Gina Sizemore

Graduate Theses, Dissertations, and Problem Reports

ABSTRACT

The preliminary background that puts this research into context is threefold; it is the aggressive nature of triple negative breast cancer (TNBC), the complexity surrounding its pathology, and the significant lack of targeted treatment for this disease. To clarify the focus of my research, I have concentrated on identifying a targeted treatment for TNBC. In the process, I have identified cycles of reciprocity between treatment, clinical diagnosis, staging, and pathology that will be addressed in smaller papers. However, the weight of this work is in the discovery of a novel target for triple negative breast cancer. The value of …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …

Revealing A Non-Canonical Role Of Anti-Apoptotic Mcl-1 In Early Embryonic Development, Xue Yang

Theses and Dissertations (ETD)

MCL-1, a well-known pro-survival BCL-2 family member, is indispensable for the survival of various cellular lineages and is also among the most frequently amplified genes in a variety of human malignancies. Gene ablation studies previously revealed that Mcl-1 deficiency leads to embryonic lethality around E3.5 during peri-implantation stage. Strikingly, the study did not detect any increase in apoptotic cells of the blastocyst, indicating a function of MCL-1 beyond regulating apoptosis. Our previous studies revealed an unrecognized role of MCL-1 in promoting mitochondrial physiology, which is independent of its classical anti-apoptotic function and requires being imported into the mitochondrial matrix. In …

Functional Analysis Of Genomic Variation And Impact On Molecular And Higher Order Phenotypes, Ashutosh Kumar Pandey

Theses and Dissertations (ETD)

Reverse genetics methods, particularly the production of gene knockouts and knockins, have revolutionized the understanding of gene function. High throughput sequencing now makes it practical to exploit reverse genetics to simultaneously study functions of thousands of normal sequence variants and spontaneous mutations that segregate in intercross and backcross progeny generated by mating completely sequenced parental lines. To evaluate this new reverse genetic method we resequenced the genome of one of the oldest inbred strains of mice—DBA/2J—the father of the large family of BXD recombinant inbred strains. We analyzed ~100X wholegenome sequence data for the DBA/2J strain, relative to C57BL/6J, the …

Obstetrician And Gynecologist Utilization Of The Nipt Expanded Testing Option, Sarah Mayes Ba

Dissertations & Theses (Open Access)

Noninvasive prenatal testing (NIPT) enables the detection of common fetal aneuploidies such as trisomy 21, trisomy 18, trisomy 13, and sex chromosome abnormalities via analysis of cell-free fetal DNA circulating in maternal serum. Although the accuracy of NIPT for fetal aneuploidy is expected to be higher than that of currently available alternative maternal serum screening options, the implications of results are not straight forward. In October 2013, the option to screen for additional trisomies and select microdeletion syndromes, such as 22q11.2 deletion syndrome and 5 p- syndrome, became clinically available. Due to this rapidly evolving prenatal screening technology, clinicians must …

Genetics Of Obesity In Starr County, Texas Mexican Americans, Heather M. Highland

Dissertations & Theses (Open Access)

Currently, over two-thirds of Americans are classified as over-weight or obese. Obesity increases risk for many other diseases including type 2 diabetes, heart disease, stroke, and cancer, making obesity the largest public health problem in America and most other Westernized nations. Hispanics have a higher rate of both obesity and type 2 diabetes, making them a particularly interesting population in which to study obesity. For the last 33 years, the Starr County Health Studies has collected an array of phenotypes and biological samples from residents of Starr County, along Texas-Mexico border. This study includes 825 subjects who were not known …

Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff

Dissertations & Theses (Open Access)

Mutations in the BRCA1 or BRCA2 genes are associated with increased risks for breast, ovarian, and several other cancers. The purpose of this study was to evaluate the incidence of cancers in first and second degree relatives of BRCA mutation carriers compared to the general population. A total of 1086 pedigrees of BRCA mutation carriers were obtained from a prospectively maintained, internal review board approved study of persons referred for clinical genetic counseling at The University of Texas MD Anderson Cancer Center. We identified 9032 first and second degree relatives from 784 pedigrees which demonstrated a clear indication of parental …

Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin

Dissertations & Theses (Open Access)

There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB …

Latinas And The Traditional Genetic Counseling Model: A Qualitative Study, Stephanie Thompson

Dissertations & Theses (Open Access)

The traditional genetic counseling model reflects an individualized counseling session that includes the presentation of information about genes, chromosomes, personalized risk assessment, and genetic testing and screening options. Counselors are challenged to balance providing educational information with discussion of implications of this information in an allotted amount of time. The aim of this study was to explore the perceptions of pregnant Latinas on the benefits and limitations of the traditional prenatal genetic counseling model and to determine the specific preferences for receiving prenatal genetic counseling. Data were collected through focus groups and one-on-one, semi-structured interviews of twenty-five Spanish speaking Latinas …

Retinoic Acid Regulation Of Thyroid Hormone Action In Bone Cells, Anjali Babbar

Loma Linda University Electronic Theses, Dissertations & Projects

Retinoic acid and thyroid hormone are known to play key roles in the regulation of endochondral ossification. However, the issue of whether these two hormones interact with each other to regulate bone functions remains to be established. We investigated how thyroid hormone and retinoic acid interact to regulate cells involved in endochondral bone formation. We demonstrate that thyroid hormone treatment stimulates differentiation of ATDC5 chondrocytes and promotes formation of mineralized nodules while retinoic acid treatment at high dose inhibits chondrocyte differentiation and formation of mineralized nodules. Furthermore, thyroid hormone induced mineralized nodule formation is inhibited by co-treatment with retinoic acid …

Chemopreventive Effects Of Pterostilbene In Metastatic Prostate Cancer Cells, Phillip A. Zook

PCOM Biomedical Studies Student Scholarship

Recent studies find that pterostilbene (PTS) exhibits more favorable drug properties and similar chemopreventive effects to its structural analogue resveratrol (RSV). However, few studies describe the activity of PTS in prostate cancer (PCa). Here, we conducted cell count experiments to assess the effects of PTS on metastatic PCa cell viability and to compare the potency of PTS to RSV in this respect. We also performed experiments to assess the effects of PTS on the androgen receptor (AR) and AR-mediated events. We used qPCR to measure the mRNA levels of the androgenresponsive gene (ARG), prostate-specific antigen (PSA), and Western blots to …

Identification And Characterization Of Novel Sir3/Mecp2-Chromatin Interactions, Nicholas L. Adkins

Theses, Dissertations and Capstones

The eukaryotic genome is packaged into chromosomes that are made up of a highly organized and heavily regulated structure called chromatin. The proteins involved in the compaction of DNA into this condensed state are mostly understood at the level of the structure of the nucleosome. The higher order arrangement of chromatin and how it effects gene regulation is only partially understood and characterized. The compaction of nucleosomal arrays into 30-nm and higher structures are partially the responsibility of architectural, or structural, chromatin associated proteins. The following dissertation analyzes the individual chromatin contributions of two well studied architectural proteins, the yeast …

Maternal Immunomodulation Of Neonatal Alloantigen Response, Leh Chang

Loma Linda University Electronic Theses, Dissertations & Projects

Remarkable success has been achieved in the transplantation of allogeneic cardiac grafts into newborn infants at Loma Linda University Medical Center. The superior graft survival rate documented in these patients has not correlated with the degree of immunosuppression rendered, or the selection of genetically matched donors. However, the clinical success has correlated with the age of the recipient at the time of receiving a transplant. Patients receiving an allograft within the first few weeks of life are unique in that they seem to accept the alloantigens of their cardiac graft while responding aggressively to antigens in their environment. These observations …

The Basics Of Behavior Genetics: A Study Of Heredity, William Edwin Walker

Honors Theses

The general issue of the significance of genetic contributions to individual differences may be approached in two ways, through population genetics and through physiological genetics. The first has no logical meaning when applied to an individual, for his whole genotype and total life experience contribute to every aspect of his behavior, and their influences cannot be separated. The second is rather light on the emphasis of environment and its influence.

The two approaches to the problem on individual differences complement each other. Knowledge of heritability is paramount when one attempts to change phenotypes by selection. Possibly the most significant contribution …