Medical Sciences Commons^™

Mechanism Of Rare Variant In Acta2, P.Arg149cys, Driving Diverse Vascular Disease, Kaveeta Kaw

Dissertations & Theses (Open Access)

Heterozygous variants in ACTA2 (smooth muscle (SM) α-actin) predispose to thoracic aortic aneurysms and dissections (TAAD) and early-onset coronary artery disease (CAD). The most common ACTA2 mutation is a genetic alteration of arginine 149 to a cysteine, ACTA2 p.Arg149Cys, which accounts for disease in 24% of all ACTA2 mutation carriers.(1) ACTA2 p.Arg149Cys mutation carriers present with either TAAD or CAD but rarely have both diseases. To identify the molecular mechanisms dictating whether an individual with ACTA2 p.Arg149Cys develops TAAD or CAD, CRISPR/Cas9 technology was used to generate the mutant mouse, Acta2^R149C/+, in a C57BL6 background. Acta2^R149C/+ mice …

Mechanisms Of Mitochondrial Promoter Recognition In Humans And Other Mammalian Species, Angelica Zamudio-Ochoa, Yaroslav I Morozov, Azadeh Sarfallah, Michael Anikin, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

Recognition of mammalian mitochondrial promoters requires the concerted action of mitochondrial RNA polymerase (mtRNAP) and transcription initiation factors TFAM and TFB2M. In this work, we found that transcript slippage results in heterogeneity of the human mitochondrial transcripts in vivo and in vitro. This allowed us to correctly interpret the RNAseq data, identify the bona fide transcription start sites (TSS), and assign mitochondrial promoters for > 50% of mammalian species and some other vertebrates. The divergent structure of the mammalian promoters reveals previously unappreciated aspects of mtDNA evolution. The correct assignment of TSS also enabled us to establish the precise register of …

Investigating Gene-Environment Interaction In A Double-Hit Model For Autism Spectrum Disorder, Melvin Maroon

Undergraduate Student Research Internships Conference

With the exponential advancements seen in the field of sequencing technology, the science community has come to identify hundreds of potential genetic risk factors for neuropsychiatric disorders. Despite our knowledge that such risk factors exist, we have yet to understand their specific influences on the behavioral profile of an individual. In addition, maternal infection during pregnancy can have longstanding detrimental outcomes on a child’s development. This is especially impactful with the present threat of viral infection during the pandemic. Our study aims to understand the influence of a specific genetic and environmental factor on a preclinical rodent model’s behavioral development. …

Living With It: A Patient’S And A Biochemist’S Perspective On Kidney Disease; A Historical Review Of Alport Syndrome, Jacob Olson

WWU Honors College Senior Projects

A review paper on the origin of health studies around Alport Syndrome, including aspects of genetics, pharmacy, and biochemistry, from the past to today and beyond. This report deals with important aspects of health development with regards to kidney disease overall, but narrows its focus on Alport Syndrome specifically due to the personal nature of the topic for the author. While this paper includes no personal testimony, as it is strictly meant to be formal, the author shares a deep connection with the material.

Autoimmunity In Psoriatic Arthritis: Pathophysiological And Clinical Aspects, Hakan Emmungi̇l, Ufuk İlgen, Rafi̇ Haner Di̇reskeneli̇

Turkish Journal of Medical Sciences

Psoriatic arthritis (PsA) is an underdiagnosed entity with a broad impact on the quality of life. Although the pathogenesis is largely unknown, autoimmune footprints of the inflammation in PsA have increasingly been recognized. Most of the genetic variation predisposing to PsA is mapped to the class I major histocompatibility complex (MHC) region and shared by a variety of autoimmune diseases. Polymorphisms in the genes IL12B, IL23R, IL13, TNIP1, TRAF3IP2, TYK2, and many others explain the nonHLA genetic risk with little known functional consequences. Entheseal and synovial cellular infiltrate with oligoclonal CD8+ T cells and occasional germinal centers, loss of regulatory …

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …

The Association Between Chronic Spontaneous Urticaria And Hla Class I And Class Ii Antigen, Nesli̇han Doğan, Songül Çi̇ldağ, Çi̇ğdem Yeni̇sey, Taşkin Şentürk

Turkish Journal of Medical Sciences

Background/aim: Chronic spontaneous urticaria (CSU) is a chronic disease with an unknown etiology. In human leukocyte antigen (HLA) system, the association of class I and class II antigens with autoimmune diseases has been identified and HLA antigens that have a tendency to or can prevent chronic urticaria have been studied. The aim of this study is to investigate the association between chronic spontaneous urticaria and HLA class I and class II antigens.Materials and methods: A total of 80 subjects, 40 patients with CSU and 40 healthy individuals were enrolled in the study. DNA sample isolation from blood was primarily done …

Control Of Ccnd1 Ubiquitylation By The Catalytic Saga Subunit Usp22 Is Essential For Cell Cycle Progression Through G1 In Cancer Cells., Victoria J. Gennaro, Timothy J. Stanek, Amy R. Peck, Yunguang Sun, Feng Wang, Shuo Qie, Karen E. Knudsen, Hallgeir Rui, Tauseef Butt, J. Alan Diehl, Steven B. Mcmahon

Department of Biochemistry and Molecular Biology Faculty Papers

Overexpression of the deubiquitylase ubiquitin-specific peptidase 22 (USP22) is a marker of aggressive cancer phenotypes like metastasis, therapy resistance, and poor survival. Functionally, this overexpression of USP22 actively contributes to tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro, and inhibits tumor progression in animal models of lung, breast, bladder, ovarian, and liver cancer, among others. Current models suggest that USP22 mediates these biological effects via its role in epigenetic regulation as a subunit of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional cofactor complex. Challenging the dogma, we report here a nontranscriptional role for USP22 via a direct effect on the …

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 Faculty Scholarship

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 …

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 Faculty Scholarship

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 …

Silencing Of The Pink1 Gene Expression By Conditional Rnai Does Not Induce Dopaminergic Neuron Death In Mice., Hongxia Zhou, Björn H Falkenburger, Jörg B Schulz, Kim Tieu, Zuoshang Xu, Xu Gang Xia

Kim Tieu

Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson's disease. The expression of the shRNA …

Discussing History Of Mental Illness During Prenatal Genetic Counseling: Patient Interest And Comfort, Sarah Nimrichter

Theses and Dissertations

Purpose: This study aimed to explore patient interest in and comfort with discussing a personal and/or family history of mental illness with a genetic counselor during a prenatal genetic counseling session. Methods: Participants included pregnant women who met with a genetic counselor for routine prenatal screening/testing counseling at Palmetto Health USC Medical Group Department of OB/GYN. Following their appointment, they were given a copy of the invitation to participate, questionnaire, and mental health resource page by the genetic counselor who performed their genetic counseling. Results: Forty participants completed questionnaires. 70% of participants indicated some level of interest in discussing mental …

Mechanism Of Transcription Anti-Termination In Human Mitochondria., Hauke S Hillen, Andrey V Parshin, Karen Agaronyan, Yaroslav I Morozov, James J Graber, Aleksandar Chernev, Kathrin Schwinghammer, Henning Urlaub, Michael Anikin, Patrick Cramer, Dmitry Temiakov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA-the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream "sliding clamp," providing high processivity to the EC. …

Epigenetic Suppression Of Hippocampal Calbindin-D28k By Δfosb Drives Seizure-Related Cognitive Deficits., Jason C. You, Kavitha Muralidharan, Jin W. Park, Iraklis Petrof, Mark S. Pyfer, Brian F. Corbett, John J. Lafrancois, Yi Zheng, Xiaohong Zhang, Carrie A. Mohila, Daniel Yoshor, Robert A. Rissman, Eric J. Nestler, Helen E. Scharfman, Jeannie Chin

Department of Neuroscience Faculty Papers

The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer's disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. …

Genome- And Cd4+ T-Cell Methylome-Wide Association Study Of Circulating Trimethylamine-N-Oxide In The Genetics Of Lipid Lowering Drugs And Diet Network (Goldn), Stella Aslibekyan, Marguerite R. Irvin, Bertha A. Hidalgo, Rodney T. Perry, Elias J. Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N. Hopkins, Michael A. Province, Hemant K. Tiwari, Jose M. Ordovas, Devin M. Absher, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels.

Methods and results: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans. TMAO was not associated with other plasma markers of cardiovascular disease, …

The Transcriptional Regulation Of The Human Angiotensinogen Gene After High-Fat Diet Is Haplotype-Dependent: Novel Insights Into The Gene-Regulatory Networks And Implications For Human Hypertension, A Rana, S Jain, N Puri, M Kaw, N Sirianni, D Eren, Brahma Mopidevi, Anand Kumar

NYMC Faculty Publications

Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have …

The Serotonin Transporter Promoter Polymorphism Moderates The Continuity Of Behavioral Inhibition In Early Childhood., Victoria C Johnson, Katie R Kryski, Haroon I Sheikh, Heather J Smith, Shiva M Singh, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures …

Neurogenesis-Mediated Forgetting Minimizes Proactive Interference., Jonathan R Epp, Rudy Silva Mera, Stefan Köhler, Sheena A Josselyn, Paul W Frankland

Brain and Mind Institute Researchers' Publications

Established memories may interfere with the encoding of new memories, particularly when existing and new memories overlap in content. By manipulating levels of hippocampal neurogenesis, here we show that neurogenesis regulates this form of proactive interference. Increasing hippocampal neurogenesis weakens existing memories and, in doing so, facilitates the encoding of new, conflicting (but not non-conflicting) information in mice. Conversely, decreasing neurogenesis stabilizes existing memories, and impedes the encoding of new, conflicting information. These results suggest that reduced proactive interference is an adaptive benefit of neurogenesis-induced forgetting.

Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik

Journal Articles: Biochemistry & Molecular Biology

Changes in lipid metabolism and iron content are observed in the livers of patients with fatty liver disease. The expression of hepcidin, an iron-regulatory and acute phase protein synthesized by the liver, is also modulated. The potential interaction of lipid and iron metabolism is largely unknown. We investigated the role of lipid intermediate, ceramide in the regulation of human hepcidin gene, HAMP. Human hepatoma HepG2 cells were treated with cell-permeable ceramide analogs. Ceramide induced significant up-regulation of HAMP mRNA expression in HepG2 cells. The effect of ceramide on HAMP expression was mediated through transcriptional mechanisms because it was completely blocked …

Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik

Journal Articles: Biochemistry & Molecular Biology

Changes in lipid metabolism and iron content are observed in the livers of patients with fatty liver disease. The expression of hepcidin, an iron-regulatory and acute phase protein synthesized by the liver, is also modulated. The potential interaction of lipid and iron metabolism is largely unknown. We investigated the role of lipid intermediate, ceramide in the regulation of human hepcidin gene, HAMP. Human hepatoma HepG2 cells were treated with cell-permeable ceramide analogs. Ceramide induced significant up-regulation of HAMP mRNA expression in HepG2 cells. The effect of ceramide on HAMP expression was mediated through transcriptional mechanisms because it was completely blocked …

The Dna Structure And Sequence Preferences Of Wrn Underlie Its Function In Telomeric Recombination Events, Deanna N. Edwards, Amrita Machwe, Li Chen, Vilhelm A. Bohr, David K. Orren

Toxicology and Cancer Biology Faculty Publications

Telomeric abnormalities caused by loss of function of the RecQ helicase WRN are linked to the multiple premature ageing phenotypes that characterize Werner syndrome. Here we examine WRN's role in telomeric maintenance, by comparing its action on a variety of DNA structures without or with telomeric sequences. Our results show that WRN clearly prefers to act on strand invasion intermediates in a manner that favours strand invasion and exchange. Moreover, WRN unwinding of these recombination structures is further enhanced when the invading strand contains at least three G-rich single-stranded telomeric repeats. These selectivities are most pronounced at NaCl concentrations within …

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 …

Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains, Zhongle Liu, Lawrence C. Myers

Dartmouth Scholarship

Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their …

Disrupting Sumoylation Enhances Transcriptional Function And Ameliorates Polyglutamine Androgen Receptor-Mediated Disease., Jason P Chua, Satya L Reddy, Zhigang Yu, Elisa Giorgetti, Heather L Montie, Sarmistha Mukherjee, Jake Higgins, Richard C Mceachin, Diane M Robins, Diane E Merry, Jorge A Iñiguez-Lluhí, Andrew P Lieberman

Department of Biochemistry and Molecular Biology Faculty Papers

Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes neuromuscular degeneration in individuals with spinobulbar muscular atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits ligand-dependent proteotoxicity, features that have both been implicated in SBMA; however, the extent to which altered AR transcriptional function contributes to pathogenesis remains controversial. Here, we sought to dissociate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcriptional activity of polyQ AR. To accomplish this, we bypassed the inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like modifier) by mutating conserved lysines in the polyQ AR that …

Cohort Of Birth Modifies The Association Between Fto Genotype And Bmi, James Niels Rosenquist, Steven F. Lehrer, A. James O'Malley, Alan M. Zaslavsky, Jordan W. Smoller, Nicholas A. Christakis

Dartmouth Scholarship

A substantial body of research has explored the relative roles of genetic and environmental factors on phenotype expression in humans. Recent research has also sought to identify gene-environment (or g-by-e) interactions, with mixed success. One potential reason for these mixed results may relate to the fact that genetic effects might be modified by changes in the environment over time. For example, the noted rise of obesity in the United States in the latter part of the 20th century might reflect an interaction between genetic variation and changing environmental conditions that together affect the penetrance of genetic influences. To evaluate this …

Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield

Dartmouth Scholarship

Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes …

De Novo Assembly Of The Chimpanzee Transcriptome From Nextgen Mrna Sequences, Mnirnal D. Maudhoo, Jacob D. Madison, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the species most closely related to humans. For this reason, it is especially important to have complete and accurate chimpanzee nucleotide and protein sequences to understand how humans evolved their unique capabilities. We provide transcriptome data from four untransformed cell types derived from the reference Pan troglodytes, "Clint", to better annotate the chimpanzee genome and provide empirical validation for proposed gene models of this important species.

FINDINGS: RNA was extracted from primary cells cultured from four tissues: skin, adipose stroma, vascular smooth muscle and skeletal muscle. These four RNA samples …

Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu

Dartmouth Scholarship

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …

Contribution Of Teg49 Small Rna In The 5′ Upstream Transcriptional Region Of Sara To Virulence In Staphylococcus Aureus, Samin Kim, Dindo Reyes, Marie Beaume, Patrice Francois, Ambrose Cheung

Dartmouth Scholarship

High-throughput RNA sequencing technology has found the 5' untranslated region of sarA to contain two putative small RNAs (sRNAs), designated teg49 and teg48. Northern blot analysis disclosed that teg49 and teg48 were detectable within the P3-P1 and P1 sarA promoter regions, respectively. Focusing on teg49, we found that this sRNA, consisting of 196 nucleotides, is transcribed in the same direction as the sarA P3 transcript. The expression of both P3 and teg49 transcripts is dependent on sigB and cshA, which encodes a DEAD box RNA helicase. Within the sRNA teg49, there are two putative hairpin-loop structures, HP1 and HP2. Transversion …

Clinical And Biochemical Function Of Polymorphic Nr0b1 Ggaa-Microsatellites In Ewing Sarcoma: A Report From The Children's Oncology Group., Michael J. Monument, Kirsten M. Johnson, Elizabeth Mcilvaine, Lisa Abegglen, W. Scott Watkins, Lynn B. Jorde, Richard B. Womer, Natalie Beeler, Laura Monovich, Elizabeth R. Lawlor, Julia A. Bridge, Joshua D. Schiffman, Mark D Krailo, R. Lor Randall, Stephen L. Lessnick

Journal Articles: Pathology and Microbiology

BACKGROUND: The genetics involved in Ewing sarcoma susceptibility and prognosis are poorly understood. EWS/FLI and related EWS/ETS chimeras upregulate numerous gene targets via promoter-based GGAA-microsatellite response elements. These microsatellites are highly polymorphic in humans, and preliminary evidence suggests EWS/FLI-mediated gene expression is highly dependent on the number of GGAA motifs within the microsatellite.

OBJECTIVES: Here we sought to examine the polymorphic spectrum of a GGAA-microsatellite within the NR0B1 promoter (a critical EWS/FLI target) in primary Ewing sarcoma tumors, and characterize how this polymorphism influences gene expression and clinical outcomes.

RESULTS: A complex, bimodal pattern of EWS/FLI-mediated gene expression was observed …