Genetic Phenomena Commons^™

Extrinsic Allergic Alveolitis: A Systematic Review Of Hla-Dr In Pigeon Breeder’S Disease, Dylan Thibaut, Ryan A. Witcher, Anitha Kunnath, James Toldi

Advances in Clinical Medical Research and Healthcare Delivery

Abstract

Introduction: Pigeon Breeder’s Pneumonitis (PBP) results due to a complex pathophysiology that includes exposure to avian antigens. Susceptibility has been linked to human leukocyte antigen (HLA) class II, though consensus has not been reached. The goal of this systematic review is to further elucidate the association between PBP and HLA-DR subtypes.

Methods: Databases utilized included PubMed, Google Scholar, ScienceDirect, and Cochrane Library. Inclusion required a minimum of three studies in English presenting HLA-DR alleles of PBP and control subgroups. Exclusion was due to insufficient data or non-feasible control groups. Forest plots were created for HLA-DR subtypes’ association …

Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters

Undergraduate Honors Theses

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD⁺) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD⁺ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPR^mt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD⁺ and through increasing levels …

Decoupling Body Shape And Mass Distribution In Birds And Their Dinosaurian Ancestors, Sophie Macaulay, Tatjana Hoehfurtner, Samuel R.R. Cross, Ryan D. Marek, John R. Hutchinson, Emma R. Schachner, Alice E. Maher, Karl T. Bates

School of Medicine Faculty Publications

It is accepted that non-avian theropod dinosaurs, with their long muscular tails and small forelimbs, had a centre-of-mass close to the hip, while extant birds, with their reduced tails and enlarged wings have their mass centred more cranially. Transition between these states is considered crucial to two key innovations in the avian locomotor system: crouched bipedalism and powered flight. Here we use image-based models to challenge this dichotomy. Rather than a phylogenetic distinction between ‘dinosaurian’ and ‘avian’ conditions, we find terrestrial versus volant taxa occupy distinct regions of centre-of-mass morphospace consistent with the disparate demands of terrestrial bipedalism and flight. …

Nature, Nurture, And The Meaning Of Educational Attainment: Differences By Sex And Socioeconomic Status, Thalida Em Arpawong, Margaret Gatz, Catalina Zavala, Tara L. Gruenewald, Ellen E. Walters, Carol A. Prescott

Psychology Faculty Articles and Research

Estimated heritability of educational attainment (EA) varies widely, from 23% to 80%, with growing evidence suggesting the degree to which genetic variation contributes to individual differences in EA is highly dependent upon situational factors. We aimed to decompose EA into influences attributable to genetic propensity and to environmental context and their interplay, while considering influences of rearing household economic status (HES) and sex. We use the Project Talent Twin and Sibling Study, drawn from the population-representative cohort of high school students assessed in 1960 and followed through 2014, to ages 68−72. Data from 3552 twins and siblings from 1741 families …

Interactions Of Snps In Folate Metabolism Related Genes On Prostate Cancer Aggressiveness In European Americans And African Americans, Hui Yi Lin, Susan E. Steck, Indrani Sarkar, Elizabeth T.H. Fontham, Alan Diekman, Lora J. Rogers, Calvin T. Ratliff, Jeannette T. Bensen, James L. Mohler, L. Joseph Su

School of Public Health Faculty Publications

Background: Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study’s objective is to evaluate SNP–SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. Methods: We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP–SNP interactions were analyzed. Results: None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP–SNP …

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

Breast Cancer Subtyping Of The Cancer Genome Atlas (Tcga) Samples, Spencer E. Yu, Alfred B. Amendolara, Steven T. Tung, Alexander P. Sheppert, Nasif Islam, Mindy Cook, Lena Diprizito, Nicole Lashiker, Roshni Jogin, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …

Hereditary Angioedema: Diagnosis, Clinical Implications, And Pathophysiology, Evan S. Sinnathamby, Peter P. Issa, Logan Roberts, Haley Norwood, Kevin Malone, Harshitha Vemulapalli, Shahab Ahmadzadeh, Elyse M. Cornett, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene. HAE affects 1/50,000 people worldwide. Three main types of HAE exist: type I, type II, and type III. Type I is characterized by a deficiency in C1-INH. C1-INH is important in the coagulation complement, contact systems, and fibrinolysis. Most HAE cases are type I. Type I and II HAE result from a mutation in the SERPING1 gene, which encodes C1-INH. Formally known as type III HAE is typically an estrogen-dependent or hereditary angioedema with normal C1-INH activity. Current guidelines now recommend subdividing …

Effects That The Methylenetetrahydrofolate Gene Mutation (Both The C677t And A1298c Polymorphisms) Have On Both Men And Women’S Fertility Abilities And Subsequent Fetal Development, As Well As What Nutritional Changes Can Possibly Do To Aid In Reversing These Supposed Negative Effects., Elizabeth Simkanin

Williams Honors College, Honors Research Projects

This study discusses the perceived negative effects of variants (C677T and A1298C) of the methylenetetrahydrofolate (MTHFR) gene on male and female fertility and fetal development, as well as the potential for nutrition changes to aid in reversing these negative effects. This research project was completed in order to discuss the possible association with and connection between nutrition and fertility in both male and female individuals who have either of the two most common MTHFR gene polymorphisms, 677C>T and 1298A>C. These two polymorphisms are of particular interest because they are associated with the most decreased activity of the MTHFR …

The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman

Undergraduate Research Posters

This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …

Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib

Undergraduate Student Research Internships Conference

Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional …

Induced Cytotoxicity In Crebbp/Ep300mut Head And Neck Squamous Cell Carcinoma, Thomaia Pamplin

Dissertations and Theses (Open Access)

INDUCED CYOTOXICTY IN CREBBP/EP300mut HEAD AND NECK SQUAMOUS CELL CARCINOMA

Thomaia Pamplin

Advisor: Curtis Pickering, Ph.D.

Background: Head and neck squamous cell carcinoma HNSCC is the most common malignancy in the head and neck. Most cases are found in advanced stages and depending on the location can be treated with surgical resection and/or radiation (XRT), chemotherapy, or chemoradiation. Our lab groups have identified that HNSCC with a mutation in its CREBBP/EP300 genes can be sensitized to XRT when the histone acetyltransferase activity of CREBBP/EP300 is inhibited. This radiosensitization manifests in the form of increased cell death for …

Whole Genome Sequence Association Analysis Of Fasting Glucose And Fasting Insulin Levels In Diverse Cohorts From The Nhlbi Topmed Program, Daniel Dicorpo, Sheila M. Gaynor, Emily M. Russell, Kenneth E. Westerman, Laura M. Raffield, Marcio Almeida, Juan M. Peralta, John Blangero, Joanne E. Curran, Ravindranath Duggirala

School of Medicine Publications and Presentations

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well …

Utility Of The Motivation To Change Lifestyle And Health Behaviors For Dementia Risk Reduction Scale (Mclhb-Drr) Based On A North American Sample, Angelina E. Witbeck

Dissertations

As the population ages, the prevalence rates of dementia continue to increase. Without a cure or promising treatment for dementia, the best course of lowering the prevalence rates of dementia is through preventative measures. Through an electronic survey, the study utilized the MCLHB-DRR scale to determine whether (1) gender, age, educational background, and socioeconomic status will impact the motivational factors to change lifestyle and health behaviors to reduce the risk of developing dementia and (2) direct experiences with individuals that have a dementia diagnosis are likely to impact one's motivational factors to change lifestyle and health behaviors to reduce the …

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 …

Iron Effects On Clostridioides Difficile Toxin Production And Antimicrobial Susceptibilities, Jason Yamaki, Swati Chawla, Shirley Tong, Kate Alison Lozada, Sun Yang

Pharmacy Faculty Articles and Research

Despite the benefits of red blood cell (RBC) transfusion therapy, it can render patients vulnerable to iron overload. The excess iron deposits in various body tissues cause severe complications and organ damage such as cardiotoxicity and mold infections. Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea among cancer patients and is associated with significant morbidity and mortality. Our study aims to determine the role of iron overload and the effects of iron chelators on CDI. Our results demonstrated that iron (Fe³⁺) stimulated the growth of C. difficile with increased colony formation units (CFU) in …

Mendelian Randomization Supports Bidirectional Causality Between Telomere Length And Clonal Hematopoiesis Of Indeterminate Potential, Tetsushi Nakao, Alexander G. Bick, Margaret A. Taub, Seyedeh M. Zekavat, Md M. Uddin, Abhishek Niroula, Juan M. Peralta, Joanne E. Curran, John Blangero

School of Medicine Publications and Presentations

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies …

Epigenetic Pathogenesis Of Neurological Disorders In Utero And Considerations For Genetic Counseling, Lauren Juga

Senior Honors Theses

Epigenetic modifications are a major focus of study in the pathogenesis of many disorders regarding metabolism, aging, neurodevelopment, and neurodegeneration. Epigenetic mechanisms are present throughout life but are especially vital to guiding fetal development. The precise timing of gene activation and deactivation guides stem cell differentiation through each embryonic stage. After exposure to environmental stimuli, gene expression can be altered by transcription factors, resulting in observable phenotypes and even pathology. Here, the epigenetic mechanisms responsible for the pathogenesis of neurodevelopmental and neuropsychiatric disorders are explored in response to environmental perturbations in utero. The present goal is to identify correlations between …

Assessing Identification Of Newly Diagnosed Breast Cancer Patients For Referral To Genetic Counseling, Corinne Marie Locke

Theses and Dissertations

Since 1998, the National Comprehensive Cancer Network (NCCN) guidelines have specified clinical indications for genetic testing for breast cancer susceptibility genes, but retrospective studies have shown that, despite meeting the NCCN criteria, patients are not always advised of the option of genetic testing. Further compounding this issue, studies have shown that cancer family history intake and documented family history can be incomplete even when taken by oncology providers. At this study site and other cancer centers in the country, patients with a new diagnosis of breast cancer are referred for genetic counseling by their cancer care team if they are …