Genetic Phenomena Commons^™

Genetic And Serological Markers In Colorectal Cancer Surgery, Adrian Silaghi, Vlad Denis Constantin, Dragos Serban, Dragos Epistatu, Ioana Paunica, Daniela Gabriela Bălan, Laura Florentina Rebegea

Journal of Mind and Medical Sciences

Colon cancer is relatively asymptomatic in the early stages, the manifestations appearing and intensifying with the evolution of the disease, especially when associated with local and/or systemic complications. In such cases, surgical interventions are often emergency and involve more extensive operations (on metabolically and immune-stressed organisms), so that an early diagnosis (endoscopy, tumor markers, etc.) remains not only desirable but even a priority, especially in predisposed patients (genetic factors, lifestyle, etc.). As a consequence, the involvement of tumor markers in colon neoplasms has become more and more investigated in recent times. This review investigates the roles of serological and genetic …

Gene By Environment Interaction: The Social Determinants Of Health And Depression, Sowmya Duddu, Eron Manusov, Vincent Diego, Marcio Almeida, Sandra Laston, John Blangero, Sarah Williams-Blangero

Research Symposium

Background: Social Determinants of Health (SDoH) influence health through psychological, social, environmental, and cultural domains according to the psychosocial-cultural model of health. This report provides evidence of the intricate relationship between genetics, depression, and the Social Determinants of Health (SDoH). We applied a joint interaction model to account for G×Sex and G×SDoH interaction in the face of depression to establish if both types of interactions are important and independent of one another in the setting of depression. We estimated the corresponding genetic effect and extracted envophenotypes using Best Linear Unbiased Prediction to remove the influence of genetic variation on expression. …

Genome-Based Pathogenicity Potential Of Salmonella Isolated From Diverse Sources, Jared Mr Crocco

Theses and Dissertations (Comprehensive)

Bacterial human pathogens are among the leading causes of death around the world, especially in low income and developing countries. One important element in a bacterium’s ability to cause disease are genes that directly contribute to pathogenicity called virulence factors. A second significant aspect are antimicrobial resistance genes which allow microorganisms to persist in the presence of antimicrobial agents. In this project I aimed to determine if Salmonella isolated from different sources differed in pathogenicity profiles based on the complement of genes identified through genomic analysis. Accordingly, Salmonella genomes were organized into 8 groups: animal, clinical, human, environmental, food, water …

Plasma Protein Signatures Of Adult Asthma, Gordon J. Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B. Wyss, Julie D. White, Sinjini Sikdar, Jianping Jin, Andrew J. Grant, Alison A. Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J. London

Mathematics & Statistics Faculty Publications

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with …

Review Of: Pull Through Blessings: The Colorful Tapestry Of Hirschsprung’S Disease—Lisa Sensenig And Helen Zimmerman, Adin Stauffer

Journal of Amish and Plain Anabaptist Studies

Hirschsprung’s Disease (HD) is a genetic condition found in a child born without ganglion cells in part of the intestines. Ganglion cells send signals to intestinal muscles to contract to help pass bowel movements. No signal means no bowel movement, which results in babies not eating, becoming uncomfortable and sleepy, spitting up, and if not treated, eventually dying. [First paragraph.]

Dpyd Pathogenic Variants Associated With Fluoropyrimidines Toxicity, Diana Cristina Pérez-Ibave, Noé Israel Oliva-García, Irasema Ramos-Martínez, Francisco Javier Villarreal Alvarado, Valeria Jimena Gómez Ordaz, Jonatán Isaí Cortes Alfaro, Carlos Horacio Burciaga-Flores, Juan Francisco González-Guerrero, Oscar Vidal-Gutiérrez, Maria De Lourdes Garza-Rodriguez

Research Symposium

Background: Genetic variants in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism. DPYD contributes to the development of severe FPs-related toxicity, and pathogenic DPYD variants detection reduces side effects and complications associated with FP-toxicity. The allelic frequency of these variants in the Mexican population is currently unknown.

Methods: The study was carried out at the Centro Universitario Contra el Cáncer (CUCC) of the Universidad Autónoma de Nuevo León (UANL) in Monterrey México. Genomic DNA was isolated from 154 subjects using the QIAamp DNA Blood Midi kit (QIAGEN) following the manufacturer's recommendations. We …

Pca-Clf: A Classifier Of Prostate Cancer Patients Into Patients With Indolent And Aggressive Tumors Using Machine Learning, Yashwanth Karthik Kumar Mamidi, Tarun Karthik Kumar Mamidi, Md Wasi Ul Kabir, Jiande Wu, Md Tamjidul Hoque, Chindo Hicks

School of Medicine Faculty Publications

A critical unmet medical need in prostate cancer (PCa) clinical management centers around distinguishing indolent from aggressive tumors. Traditionally, Gleason grading has been utilized for this purpose. However, tumor classification using Gleason Grade 7 is often ambiguous, as the clinical behavior of these tumors follows a variable clinical course. This study aimed to investigate the application of machine learning techniques (ML) to classify patients into indolent and aggressive PCas. We used gene expression data from The Cancer Genome Atlas and compared gene expression levels between indolent and aggressive tumors to identify features for developing and validating a range of ML …

Clinical Manifestation For Immunoglobulin A Deficiency: A Systematic Review And Metaanalysis, Ahmad Vosughimotlagh, Seyed Erfan Rasouli, Hosein Rafiemanesh, Molood Safarirad, Niusha Sharifinejad, Atossa Madanipour, Maria Marluce Dos Santos Vilela, Edyta Heropolitańska-Pliszka, Gholamreza Azizi

Department of Neurology Faculty Papers

OBJECTIVES: Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal subclasses, and specific antibodies. Patients with this disorder represent a spectrum of clinical manifestations including infections, autoimmune disorders, malignancy, and allergic diseases. The current study aimed to evaluate their prevalence and categorized them.

METHODS: We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2022 with standard keywords. Pooled estimates of clinical manifestations prevalence and the corresponding 95% confidence intervals were calculated using random-effects …

Comparing Antimicrobial Resistant Genes And Phenotypes Across Multiple Sequencing Platforms And Assays For Enterobacterales Clinical Isolates, Rebecca Rose, David J. Nolan, Deborah Ashcraft, Amy K. Feehan, Leonor Velez-Climent, Christopher Huston, Benjamin Lain, Simon Rosenthal, Lucio Miele, Gary B. Fogel, George Pankey, Julia Garcia-Diaz, Susanna L. Lamers

School of Medicine Faculty Publications

Introduction: Whole genome sequencing (WGS) of bacterial isolates can be used to identify antimicrobial resistance (AMR) genes. Previous studies have shown that genotype-based AMR has variable accuracy for predicting carbapenem resistance in carbapenem-resistant Enterobacterales (CRE); however, the majority of these studies used short-read platforms (e.g. Illumina) to generate sequence data. In this study, our objective was to determine whether Oxford Nanopore Technologies (ONT) long-read WGS would improve detection of carbapenem AMR genes with respect to short-read only WGS for nine clinical CRE samples. We measured the minimum inhibitory breakpoint (MIC) using two phenotype assays (MicroScan and ETEST) for six antibiotics, …

A Cryptic Microdeletion Del(12)(P11.21p11.23) Within An Unbalanced Translocation T(7;12)(Q21.13;Q23.1) Implicates New Candidate Loci For Intellectual Disability And Kallmann Syndrome, Afif Ben-Mahmoud, Shotaro Kishikawa, Vijay Gupta, Natalia T. Leach, Yiping Shen, Oana Moldovan, Himanshu Goel, Bruce Hopper, Kara Ranguin, Nicolas Gruchy, Saskia M. Maas, Yves Lacassie, Soo Hyun Kim, Woo Yang Kim, Bradley J. Quade, Cynthia C. Morton, Cheol Hee Kim, Lawrence C. Layman, Hyung Goo Kim

School of Medicine Faculty Publications

In a patient diagnosed with both Kallmann syndrome (KS) and intellectual disability (ID), who carried an apparently balanced translocation t(7;12)(q22;q24)dn, array comparative genomic hybridization (aCGH) disclosed a cryptic heterozygous 4.7 Mb deletion del(12)(p11.21p11.23), unrelated to the translocation breakpoint. This novel discovery prompted us to consider the possibility that the combination of KS and neurological disorder in this patient could be attributed to gene(s) within this specific deletion at 12p11.21-12p11.23, rather than disrupted or dysregulated genes at the translocation breakpoints. To further support this hypothesis, we expanded our study by screening five candidate genes at both breakpoints of the chromosomal translocation …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …

Mid-Life Leukocyte Telomere Length And Dementia Risk: An Observational And Mendelian Randomization Study Of 435,046 Uk Biobank Participants, Rui Liu, Luke C. Pilling, David Melzer, Lihong Wang, Kevin J. Manning, David C. Steffens, Jack Bowden, Richard H. Fortinsky, George A. Kuchel, Taeho G. Rhee, Breno S. Diniz, Chia-Ling Kuo

Health Science Faculty Publications

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data ( …

31-Gene Expression Profile Testing In Cutaneous Melanoma And Survival Outcomes In A Population-Based Analysis: A Seer Collaboration, Christine N. Bailey, Brian J. Martin, Valentina I. Petkov, Nicola C. Schussler, Jennifer L. Stevens, Suzanne Bentler, Rosemary D. Cress, Jennifer A. Doherty, Eric B. Durbin, Scarlett L. Gomez, Lou Gonsalves, Brenda Y. Hernandez, Lihua Liu, Bozena M. Morawski, Maria J. Schymura, Stephen M. Schwartz, Kevin C. Ward, Charles Wiggins, Xiao-Cheng Wu, Matthew S. Goldberg, Jennifer J. Siegel, Robert W. Cook, Kyle R. Covington, Sarah J. Kurley

School of Public Health Faculty Publications

PURPOSE: The DecisionDx-Melanoma 31-gene expression profile (31-GEP) test is validated to classify cutaneous malignant melanoma (CM) patient risk of recurrence, metastasis, or death as low (class 1A), intermediate (class 1B/2A), or high (class 2B). This study aimed to examine the effect of 31-GEP testing on survival outcomes and confirm the prognostic ability of the 31-GEP at the population level. METHODS: Patients with stage I-III CM with a clinical 31-GEP result between 2016 and 2018 were linked to data from 17 SEER registries (n = 4,687) following registries' operation procedures for linkages. Melanoma-specific survival (MSS) and overall survival (OS) differences by …

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 …

Orthologs Of The C. Elegans Heterochronic Genes Have Divergent Functions In C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

The heterochronic genes of C. elegans comprise the best-studied pathway controlling the timing of tissue and organ formation in an animal. To begin to understand the evolution of this pathway, the significance of each factor, and the relationships among the components, we characterized 11 C. briggsae orthologs of C. elegans heterochronic genes. Using CRISPR/Cas9, we made a variety of alleles and found that several mutant phenotypes differ in significant ways from those of C. elegans. Although most orthologs displayed defects in developmental timing, those phenotypes could differ in which stages they controlled, the penetrance and expressivity of the phenotypes, or …

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 …

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 …

The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S. Weinstock, Cecelia A. Laurie, Jai G. Broome, Kent D. Taylor, Xiuqing Guo, Alan R. Shuldiner, Jeffrey R. O'Connell, Ravi Duggirala, Joanne E. Curran, John Blangero

School of Medicine Publications and Presentations

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid …

Switch-Like Behavior Of Lysosomes And Vcp Supports Spermatocyte Health And Development In Drosophila, Tyler James Butsch

LSU Doctoral Dissertations

Changes to societal norms, such as the educational, marital, and child-bearing expectations have coincided with significant increases in infertility worldwide. Surprisingly, male infertility is responsible for approximately half of all infertility cases worldwide. Thus, a better understanding of sperm development, and how it is affected by age, may permit the design and application of therapeutics to treat various cases male infertility. Here, I have found that lysosomes acidify as germ cells enter the spermatocyte stage. Once active, lysosomes turn over E-cadherin, and likely other proteins, to support plasma membrane stability. Notably, aging negatively impacts lysosome acidification, which can be reversed …

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. …