Medical Genetics Commons^™

Ribonucleotide Reductase Inhibitor 3-Ap Induces Oncogenic Virus Infected Cell Death And Represses Tumor Growth, Lu Dai, Jungang Chen, Yueyu Cao, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human malignancies, particularly Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation while still lacking of effective therapeutic options. We recently found that the ribonucleotide reductase (RR) subunit M2 is potentially regulated by the key oncogenic HGF/c-MET pathway in KSHV-related lymphoma cells. One of RR inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) effectively induced apoptosis of KSHV+ lymphomas and suppressed tumor progression . In the current study, we found that 3-AP treatment selectively inhibited the proliferation of KSHV-infected endothelial cells, the major cellular components of KS, through inducing DNA …

Regulators Of Oncogenic Mutant Tp53 Gain Of Function., Satomi Yamamoto, Tomoo Iwakuma

Manuscripts, Articles, Book Chapters and Other Papers

The tumor suppressor p53 (TP53) is the most frequently mutated human gene. Mutations in TP53 not only disrupt its tumor suppressor function, but also endow oncogenic gain-of-function (GOF) activities in a manner independent of wild-type TP53 (wtp53). Mutant TP53 (mutp53) GOF is mainly mediated by its binding with other tumor suppressive or oncogenic proteins. Increasing evidence indicates that stabilization of mutp53 is crucial for its GOF activity. However, little is known about factors that alter mutp53 stability and its oncogenic GOF activities. In this review article, we primarily summarize key regulators of mutp53 stability/activities, including genotoxic stress, post-translational modifications, ubiquitin …

Precision Medicine In Pediatric Cancer: Current Applications And Future Prospects., Atif Ahmed, Divya S. Vundamati, Midhat S. Farooqi, Erin M. Guest

Manuscripts, Articles, Book Chapters and Other Papers

Precision oncologic medicine is an emerging approach for cancer treatment that has recently taken giant steps in solid clinical practice. Recent advances in molecular diagnostics that can analyze the individual tumor's variability in genes have provided greater understanding and additional strategies to treat cancers. Although tumors can be tested by several molecular methods, the use of next-generation sequencing (NGS) has greatly facilitated our understanding of pediatric cancer and identified additional therapeutic opportunities. Pediatric tumors have a different genetic make-up, with a fewer number of actionable targets than adult tumors. Nevertheless, precision oncology in the pediatric population has greatly improved the …

Subject Level Clustering Using A Negative Binomial Model For Small Transcriptomic Studies., Qian Li, Janelle R. Noel-Macdonnell, Devin C. Koestler, Ellen L. Goode, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Unsupervised clustering represents one of the most widely applied methods in analysis of high-throughput 'omics data. A variety of unsupervised model-based or parametric clustering methods and non-parametric clustering methods have been proposed for RNA-seq count data, most of which perform well for large samples, e.g. N ≥ 500. A common issue when analyzing limited samples of RNA-seq count data is that the data follows an over-dispersed distribution, and thus a Negative Binomial likelihood model is often used. Thus, we have developed a Negative Binomial model-based (NBMB) clustering approach for application to RNA-seq studies.

RESULTS: We have developed a Negative …

Notch Signaling Regulates Mitochondrial Metabolism And Nf-Κb Activity In Triple-Negative Breast Cancer Cells Via Ikkα-Dependent Non-Canonical Pathways, Fokhrul Hossain, Claudia Sorrentino, Deniz A. Ucar, Yin Peng, Margarite Matossian, Dorota Wyczechowska, Judy Crabtree, Jovanny Zabaleta, Silvana Morello, Luis Del Valle, Matthew Burow, Bridgette Collins-Burow, Antonio Pannuti, Lisa M. Minter, Todd E. Golde, Barbara A. Osborne, Lucio Miele

School of Medicine Faculty Publications

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown. We studied the role of the AKT pathway and mitochondrial metabolism downstream of Notch signaling in TNBC CSC from cell lines representative of different TNBC molecular subtypes as well as …

Autoimmune Hyperphosphatemic Tumoral Calcinosis In A Patient With Fgf23 Autoantibodies., Mary Scott Roberts, Peter D. Burbelo, Daniela Egli-Spichtig, Farzana Perwad, Christopher J. Romero, Shoji Ichikawa, Emily G. Farrow, Michael J. Econs, Lori C. Guthrie, Michael T. Collins, Rachel I. Gafni

Manuscripts, Articles, Book Chapters and Other Papers

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 …

Genetic Predisposition To Necrotizing Enterocolitis In Premature Infants: Current Knowledge, Challenges, And Future Directions., Alain Cuna, Lovya George, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

The role of genetics in the pathogenesis of necrotizing enterocolitis (NEC) was initially informed by epidemiological data indicating differences in prevalence among different ethnic groups as well as concordance in twins. These early observations, together with major advances in genomic research, paved the way for studies that begin to reveal the contribution of genetics to NEC. Using the candidate gene or pathway approach, several potential pathogenic variants for NEC in premature infants have already been identified. More recently, genome-wide association studies and exome-sequencing based studies for NEC have been reported. These advances, however, are tempered by the lack of adequately …

On The Verge Of Diagnosis: Detection, Reporting, And Investigation Of De Novo Variants In Novel Genes Identified By Clinical Sequencing., Isabelle Thiffault, Maxime Cadieux-Dion, Emily G. Farrow, Raymond Caylor, Neil A. Miller, Sarah E. Soden, Carol J. Saunders

Manuscripts, Articles, Book Chapters and Other Papers

The variable evidence supporting gene-disease associations contributes to the difficulty of accurate variant reporting in a clinical setting. An evidence-based scoring system for evaluating the clinical validity of gene-disease associations, proposed by ClinGen, considers experimental as well as genetic evidence. De novo variants are heavily weighted, given the overall rarity in the genome and their contribution to human disease, however they are reported as "genes of unknown significance" in our center when there is insufficient evidence for the gene-disease assertion. We report a collection of 21 de novo variants in genes of unknown clinical significance ascertained via clinical testing, of …

Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples.

METHODS: Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3, NTCP, OCT1, OATP1B1, OATP1B3, OATP2B1 and ATP1A1 were quantified with LC-MS/MS in isolated crude membrane fractions of snap-frozen post-mortem fetal and pediatric, and surgical adult liver samples. mRNA expression was quantified using RNA sequencing, and genetic variants with TaqMan assays. We explored relationships between protein expression and age …

Antibody Epitope Specificity For Dsdna Phosphate Backbone Is An Intrinsic Property Of The Heavy Chain Variable Germline Gene Segment Used, Tatjana Srdic-Rajic, Heinz Kohler, Vladimir Jurisic, Radmila Metlas

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously …

Cysteine Residues Contribute To The Dimerization And Enzymatic Activity Of Human Nuclear Dutp Nucleotidohydrolase (Ndut)., Shawna M Rotoli, Julia L Jones, Salvatore J Caradonna

Rowan-Virtua School of Osteopathic Medicine Departmental Research

dUTPase is an enzyme found in all organisms that have thymine as a constituent of DNA. Through evolution, humans have two major isoforms of dUTPase: a mitochondrial (mDut) and a nuclear (nDut) isoform. The nuclear isoform of dUTPase is a 164-amino-acids-long protein containing three cysteine residues. nDut's starting methionine is post-translationally cleaved, leaving four unique amino acids on its amino-terminus including one cysteine residue (C3). These are not present in the mitochondrial isoform (mDut). Using mass spectrometry analyses of recombinant dUTPase constructs, we have discovered an intermolecular disulfide bridge between cysteine-3 of each nDut monomer. We have found that these …

Identification Of Chst9 As A Candidate Gene For Schizophrenia From Whole Genome Sequencing, Christopher Sharp, Jingchun Chen, Marvi Moreno, Mahtab Hamid, Francisco Servin, Bita Bashy, Travis Mize

LSAMP Poster Presentations

Recent results imply that rare variants contribute to the risk of schizophrenia. We conducted whole genome sequencing for 99 subjects from 20 Chinese families (parents and at least two siblings with a schizophrenia diagnosis and one unaffected sibling). Of the 9 frameshift mutations identified in more than 2 families, one was at chromosome 10:125780762 on the Carbohydrate Sulfotransferase 15 (CHST15) gene and another at chromosome 18:24722723 on the Carbohydrate Sulfotransferase 9 (CHST9) gene. We observed these deletions in 4 affected persons of two families from whole. At least two types of mutations (one or three bases insertion) have been identified …

Knockdown Of Crispld2 In Zebrafish Identifies A Novel Network For Nonsyndromic Cleft Lip With Or Without Cleft Palate Candidate Genes, Brett T Chiquet, Qiuping Yuan, Eric C Swindell, Lorena Maili, Robert Plant, Jeffrey Dyke, Ryan Boyer, John F Teichgraeber, Matthew R Greives, John B Mulliken, Ariadne Letra, Susan H Blanton, Jacqueline T Hecht

Faculty, Staff and Student Publications

Orofacial development is a multifaceted process involving tightly regulated genetic signaling networks, that when perturbed, lead to orofacial abnormalities including cleft lip and/or cleft palate. We and others have shown an association between the cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) gene and nonsyndromic cleft lip with or without cleft palate (NSCLP). Further, we demonstrated that knockdown of Crispld2 in zebrafish alters neural crest cell migration patterns resulting in abnormal jaw and palate development. In this study, we performed RNA profiling in zebrafish embryos and identified 249 differentially expressed genes following knockdown of Crispld2. In silico pathway analysis identified …

Promoting Clinical Breast Evaluations In A Lower Middle–Income Country Setting: An Approach Toward Achieving A Sustainable Breast Health Program, Roziya Buribekova, Irina Shukurbekova, Surayo Ilnazarova, Nekruz Jamshevov, Guldarbogh Sadonshoeva, Saleem Sayani, Aliya Aminmuhammad, Farin Amersi, Sheemain Asaria, Mansoor Saleh, Zohray Talib

Medical College Documents

PURPOSE:
To promote a systems-based approach for the early detection and downstaging of breast cancer at presentation in the remote mountainous region of Gorno Badakhshan Autonomous Oblast (GBAO), Tajikistan, by introducing breast cancer awareness into the community and training health care professionals in clinical breast evaluation (CBE).
METHODS:
Through a public-private partnership between the Ministry of Health, the Aga Khan Health Services, Tajikistan, and the Aga Khan Health Board, we organized breast cancer screening in the community and trained family medicine doctors (FMDs) and family medicine nurses (FMNs) in CBE. We identified and trained CBE master trainers, who, in turn, …

Distinct Neuropsychological Profile And Associated Neurochemical Changes In Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, And Stroke-Like Episodes (Melas), Emily B. Leaffer

Dissertations, Theses, and Capstone Projects

Background: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) is a maternally inherited progressive multisystemic disorder. Occurrence of seizure and/or stroke-like episode, as well as classic biomarkers (i.e., cerebral lactic acidosis, depleted N-acetylaspartate (NAA)), have been linked to neuropsychological deficit and trigger the developmental cascade of neurodegeneration affecting posterior prior to anterior brain regions. While a pattern of global deterioration has been reported, systematic examination in a large MELAS cohort has not been conducted.

Objective: First, we examined verbal and visual memory function and its relationship to brain metabolites (lactate, NAA) in individuals with MELAS. Second, we hypothesized that MELAS …

Lafora Disease Masquerading As Hepatic Dysfunction, Faisal Inayat, Waqas Ullah, Hanan T. Lodhi, Zarak H. Khan, Ghulam Ilyas, Nouman Safdar Ali, Hafez Mohammad A. Abdullah

Abington Jefferson Health Papers

Lafora disease is fatal intractable progressive myoclonic epilepsy. It is frequently characterized by epileptic seizures, difficulty walking, muscle spasms, and dementia in late childhood or adolescence. We chronicle here an unusual case of an asymptomatic young male soccer player who presented with elevated liver enzymes. Neurological examination was unremarkable. The diagnostic workup for hepatitis, infectious etiologies, autoimmune disorders, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, and other related diseases was inconclusive. He subsequently underwent an uneventful percutaneous liver biopsy. Based on the pathognomonic histopathological findings, Lafora disease was considered the likely etiology. The present study is a unique illustration of this …

N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The N-terminal domain (NTD) of nuclear human uracil DNA glycosylase (hUNG2) assists in targeting hUNG2 to replication forks through specific interactions with replication protein A (RPA). Here, we explored hUNG2 activity in the presence and absence of RPA using substrates with ssDNA-dsDNA junctions that mimic structural features of the replication fork and transcriptional R-loops. We find that when RPA is tightly bound to the ssDNA overhang of junction DNA substrates, base excision by hUNG2 is strongly biased toward uracils located 21 bp or less from the ssDNA-dsDNA junction. In the absence of RPA, hUNG2 still showed an 8-fold excision bias …

An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome., Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle T. Mcnulty, Nephrotic Syndrome Study Network (Neptune), Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian "Deterministic Approximation of Posteriors" (DAP) to fine-map …

Review Of Karyotypic Data From Low Grade Glial Brain Tumors, Specifically Pilocytic Astrocytomas, And Correlation Of Genetic Aberrations With Tumor Recurrence., Linda D. Cooley, Scott C. Smith, Lisa Warren, Melissa Gener, Kevin Ginn, John Herriges

Posters

Abstract: Brain tumors are the most common solid tumor of childhood. Approximately 50% of pediatric CNS tumors are low grade gliomas (WHO grade I or II) and Pilocytic astrocytoma (PA) is the most common accounting for 33% of all gliomas in children 0-14 years and ~18% of all childhood brain tumors. Prognosis with this slow-growing tumor is excellent; 10 year overall survival of ~95%. However, event free survival averages ~50%. Patient age and extent of tumor resection are key prognostic factors; tumor location and size impact resection and outcome. Histopathological features indicate PA is a benign tumor and rarely are …

Approaches To Carrier Testing And Results Disclosure In Translational Genomics Research, Ellen Wright Clayton, Kathryn M. Porter, Et Al.

Vanderbilt Law School Faculty Publications

Background: Clinical genome and exome sequencing (CGES) is primarily used to address specific clinical concerns by detecting risk of future disease, clarifying diagnosis, or directing treatment. Additionally, CGES makes possible the disclosure of autosomal recessive and X-linked carrier results as additional secondary findings, and research about the impact of carrier results disclosure in this context is needed.

Methods: Representatives from 11 projects in the clinical sequencing exploratory research (CSER) consortium collected data from their projects using a structured survey. The survey focused on project characteristics, which variants were offered and/or disclosed to participants as carrier results, methods for carrier results …

Building A Bridge Between Genetics And Outcomes Research: Application In Autism (The Autgo Study)., Zohreh Talebizadeh, Ayten Shah, Pcori Eain-2419 Working Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Concerns over the need to improve translational aspects of genetics research studies and engaging community members in the research process have been noted in the literature and raised by patient advocates. In addition to the work done by patient advocacy groups, organizations such as the Patient-Centered Outcomes Research Institute advocate for a change in the culture of research from being researcher-driven to becoming more patient-driven.

OBJECTIVE: Our project, Autism Genetics and Outcomes (AutGO), consists of two phases. The goal for phase I was to initiate a general discussion around the main topic (i.e., linking genetics and outcomes research). We …

Polymorphisms Within Ryr3 Gene Are Associated With Risk And Age At Onset Of Hypertension, Diabetes, And Alzheimer's Disease, Shaoqing Gong, Brenda Bin Su, Hugo Tovar, Chunxiang Mao, Valeria Gonzalez, Ying Liu, Yongke Lu, Ke-Sheng Wang, Chun Xu

Pharmacology, Physiology and Toxicology

Background: Hypertension affects 33% of Americans while type 2 diabetes and Alzheimer's disease (AD) affect 10% of Americans, respectively. Ryanodine receptor 3 gene (RYR3) codes for the RYR which functions to release stored endoplasmic reticulum calcium ions (Ca2+) to increase intracellular Ca2+ concentration. Increasing studies demonstrate that altered levels of intracellular Ca2+ affect cardiac contraction, insulin secretion, and neurodegeneration. In this study, we investigated associations of the RYR3 genetic variants with hypertension, AD, and diabetes.

Methods: Family data sets were used to explore association of RYR3 polymorphisms with risk and age at onset (AAO) of hypertension, diabetes, and AD.

Results: …

Evaluation Of The Illumigene Mycoplasma Direct Dna Amplification Assay, Neena Kanwar, Morgan A. Pence, Donna Mayne, Jeff Michael, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

Copyright © 2018 Kanwar et al. Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. The illumigene Mycoplasma Direct (IMD) DNA amplification assay is a qualitative in vitro test utilizing loop-mediated isothermal amplification (LAMP) technology for the direct detection of M. Pneumoniae DNA in respiratory specimens. The IMD assay does not require the preextraction of nucleic acids from specimens, which is a prerequisite step for the previously approved illumigene Mycoplasma (iM) assay. The aim of this prospective multicenter study was to evaluate the performance characteristics of the newly developed IMD assay, compared with the iM assay. Subjects with symptoms of …

A Humanized Hypertrophic Cardiomyopathy Model To Elucidate Molecular Mechanism In Disease Pathology, Ragavi Vijayakumar, Maxine Hong

The International Student Science Fair 2018

Hypertrophic cardiomyopathy (HCM), that clinically manifests as an enlarged heart is a highly prevalent cardiac disorder with propensity towards arrhythmia-induced sudden cardiac death. The mechanism of HCM remains poorly defined, necessitating further understanding of the disease for improved therapeutic strategies. As it is challenging to obtain cardiac biopsies from human subjects, using induced pluripotent stem cells technology, we generated cardiomyocytes (CMs) in a dish from HCM patients. These HCM-CMs presented the clinical manifestation in that they were significantly larger in size in comparison to control (healthy)-CMs. Furthermore, gene expression profiling of cardiac ion channels revealed increased transcripts encoding for calcium …

Apoe And Alzheimer’S Disease: Neuroimaging Of Metabolic And Cerebrovascular Dysfunction, Jason A. Brandon, Brandon C. Farmer, Holden C. Williams, Lance A. Johnson

Physiology Faculty Publications

Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset Alzheimer’s Disease (AD), and is associated with impairments in cerebral metabolism and cerebrovascular function. A substantial body of literature now points to E4 as a driver of multiple impairments seen in AD, including blunted brain insulin signaling, mismanagement of brain cholesterol and fatty acids, reductions in blood brain barrier (BBB) integrity, and decreased cerebral glucose uptake. Various neuroimaging techniques, in particular positron emission topography (PET) and magnetic resonance imaging (MRI), have been instrumental in characterizing these metabolic and vascular deficits associated with this important AD risk factor. In …

The Zinc Transporter Zipt-7.1 Regulates Sperm Activation In Nematodes, Yanmei Zhao, Chieh-Hsiang Tan, Amber Krauchunas, Andrea Scharf, Nicholas Dietrich, Kurt Warnhoff, Zhiheng Yuan, Marina Druzhinina, Sam Guoping Gu, Long Miao, Andrew Singson, Ronald E Ellis, Kerry Kornfeld

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7.1, regulates the induction of sperm activation in Caenorhabditis nematodes. The zipt-7.1 mutant hermaphrodites cannot self-fertilize, and males reproduce poorly, because mutant spermatids are defective in responding to activating …

Genes Associated With Mandibular Prognathism In The Chinese Population, Jacqueline Payne, Marie Tolarova M.D., Ph.D., D.Sc.

Excellence Day

Mandibular prognathism (MP) is the relationship of the mandible anteriorly positioned in relation to the cranial base. The prevalence of MP in Asians is estimated to be 15%, whereas American and European descent exhibit a 5% prevalence. Orthodontic treatment is lengthy and challenging, and severe cases require surgical intervention. However, when a treatment is planned well, the outcomes are predominantly successful. It has been known that genetics are involved in the etiology of prognathism and that greater genetic contribution corresponds to greater challenges to treatment. Thus, there is a desire to determine genes involved in the etiology of prognathism.

Banning Abortion In Cases Of Down Syndrome: Important Lessons For Advances In Genetic Diagnosis, Rebecca Reingold, Lawrence O. Gostin

Georgetown Law Faculty Publications and Other Works

In December 2017, Ohio passed into law legislation that prohibited physicians from performing abortions if the pregnant woman’s decision was influenced by her belief that the fetus has Down syndrome. Physicians who perform abortions in these cases would face fourth-degree felony charges and revocation of their medical license. No other state bans abortion specifically for Down syndrome, but several ban abortions in cases of genetic diseases. Lower courts have struck down most such laws, holding they violate the constitutional rights of women. In February 2018, a federal district court judge blocked enforcement of Ohio’s law pending a final determination.

This …

The State Of The Translational Chaperone Icd-1 During Apoptosis In Caenorhabditis Elegans, Kyle Cicalese

Senior Honors Projects, 2010-2019

The unfolded protein response (UPR) is a signal transduction cascade that mitigates low levels of misfolded protein stress in the endoplasmic reticulum (ER) in an effort to save the affected cell, while prolonged and/or acute ER stress leads to UPR-initiated apoptosis (programmed cell death). One putative step driving apoptosis is the cleavage of chaperones, proteins tasked to help misfolded proteins refold, by caspases, proteases essential to the execution of apoptosis. We are studying the nascent polypeptide-associated complex (NAC), a heterodimeric chaperone complex essential for viability, to determine if its beta subunit is cleaved by caspases during apoptosis to prevent the …

Optimization Of Braf V600 Assay As A 2-Step Real-Time Pcr Protocol, Mimi Phuong

Dissertations, Masters Theses, Capstones, and Culminating Projects

The QClamp® BRAF Codon Specific Mutation Detection Kit is a real-time PCR assay for the detection of somatic mutations in codon 600 Valine at exon 15 in the BRAF gene which encodes the serine/threonine protein kinase, using purified DNA. The V600E mutation is the most common BRAF gene mutation found in human cancers. This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell growth and division. Mutations in this gene have been found in cancers, including non-Hodgkin lymphoma, colorectal cancer, malignant melanoma, papillary thyroid carcinoma, non-small-cell lung carcinoma, gastric cancer, and even …