Accelerating Functional Gene Discovery in Osteoarthritis
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Influencers on Thyroid Cancer Onset: Molecular Genetic Basis
G C A T T A C G G C A T genes Review Influencers on Thyroid Cancer Onset: Molecular Genetic Basis Berta Luzón-Toro 1,2, Raquel María Fernández 1,2, Leticia Villalba-Benito 1,2, Ana Torroglosa 1,2, Guillermo Antiñolo 1,2 and Salud Borrego 1,2,* 1 Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain; [email protected] (B.L.-T.); [email protected] (R.M.F.); [email protected] (L.V.-B.); [email protected] (A.T.); [email protected] (G.A.) 2 Centre for Biomedical Network Research on Rare Diseases (CIBERER), 41013 Seville, Spain * Correspondence: [email protected]; Tel.: +34-955-012641 Received: 3 September 2019; Accepted: 6 November 2019; Published: 8 November 2019 Abstract: Thyroid cancer, a cancerous tumor or growth located within the thyroid gland, is the most common endocrine cancer. It is one of the few cancers whereby incidence rates have increased in recent years. It occurs in all age groups, from children through to seniors. Most studies are focused on dissecting its genetic basis, since our current knowledge of the genetic background of the different forms of thyroid cancer is far from complete, which poses a challenge for diagnosis and prognosis of the disease. In this review, we describe prevailing advances and update our understanding of the molecular genetics of thyroid cancer, focusing on the main genes related with the pathology, including the different noncoding RNAs associated with the disease. -
Genome-Wide Analysis of Host-Chromosome Binding Sites For
Lu et al. Virology Journal 2010, 7:262 http://www.virologyj.com/content/7/1/262 RESEARCH Open Access Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1) Fang Lu1, Priyankara Wikramasinghe1, Julie Norseen1,2, Kevin Tsai1, Pu Wang1, Louise Showe1, Ramana V Davuluri1, Paul M Lieberman1* Abstract The Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1) protein is required for the establishment of EBV latent infection in proliferating B-lymphocytes. EBNA1 is a multifunctional DNA-binding protein that stimulates DNA replication at the viral origin of plasmid replication (OriP), regulates transcription of viral and cellular genes, and tethers the viral episome to the cellular chromosome. EBNA1 also provides a survival function to B-lymphocytes, potentially through its ability to alter cellular gene expression. To better understand these various functions of EBNA1, we performed a genome-wide analysis of the viral and cellular DNA sites associated with EBNA1 protein in a latently infected Burkitt lymphoma B-cell line. Chromatin-immunoprecipitation (ChIP) combined with massively parallel deep-sequencing (ChIP-Seq) was used to identify cellular sites bound by EBNA1. Sites identified by ChIP- Seq were validated by conventional real-time PCR, and ChIP-Seq provided quantitative, high-resolution detection of the known EBNA1 binding sites on the EBV genome at OriP and Qp. We identified at least one cluster of unusually high-affinity EBNA1 binding sites on chromosome 11, between the divergent FAM55 D and FAM55B genes. A con- sensus for all cellular EBNA1 binding sites is distinct from those derived from the known viral binding sites, sug- gesting that some of these sites are indirectly bound by EBNA1. -
Gene Regulation and Speciation in House Mice
Downloaded from genome.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Research Gene regulation and speciation in house mice Katya L. Mack,1 Polly Campbell,2 and Michael W. Nachman1 1Museum of Vertebrate Zoology and Department of Integrative Biology, University of California, Berkeley, California 94720-3160, USA; 2Department of Integrative Biology, Oklahoma State University, Stillwater, Oklahoma 74078, USA One approach to understanding the process of speciation is to characterize the genetic architecture of post-zygotic isolation. As gene regulation requires interactions between loci, negative epistatic interactions between divergent regulatory elements might underlie hybrid incompatibilities and contribute to reproductive isolation. Here, we take advantage of a cross between house mouse subspecies, where hybrid dysfunction is largely unidirectional, to test several key predictions about regulatory divergence and reproductive isolation. Regulatory divergence between Mus musculus musculus and M. m. domesticus was charac- terized by studying allele-specific expression in fertile hybrid males using mRNA-sequencing of whole testes. We found ex- tensive regulatory divergence between M. m. musculus and M. m. domesticus, largely attributable to cis-regulatory changes. When both cis and trans changes occurred, they were observed in opposition much more often than expected under a neutral model, providing strong evidence of widespread compensatory evolution. We also found evidence for lineage-specific positive se- lection on a subset of genes related to transcriptional regulation. Comparisons of fertile and sterile hybrid males identified a set of genes that were uniquely misexpressed in sterile individuals. Lastly, we discovered a nonrandom association between these genes and genes showing evidence of compensatory evolution, consistent with the idea that regulatory interactions might contribute to Dobzhansky-Muller incompatibilities and be important in speciation. -
Jawaharlal Nehru University, New Delhi
Jawaharlal Nehru University, New Delhi Evaluative Report of the Department (science) Name of the School/Spl. Center Pages 1 School of Life Sciences 1-45 2. School of Biotechnology 46-100 3 School of Computer and systems Sciences 101-120 4 School of Computational and Integrative Sciences 121-141 5. School of Physical Sciences 142-160 6 School of Environmental Sciences 161-197 7 Spl. Center for Molecular Medicine 198-256 8 Spl Center for Nano Sciences 257-268 Evaluation Report of School of Life Sciences In the past century, biology, with inputs from other disciplines, has made tremendous progress in terms of advancement of knowledge, development of technology and its applications. As a consequence, in the past fifty years, there has been a paradigm shift in our interpreting the life process. In the process, modern biology had acquired a truly interdisciplinary character in which all streams of sciences have made monumental contributions. Because of such rapid emergence as a premier subject of teaching and research; a necessity to restructure classical teachings in biology was recognised by the academics worldwide. In tune with such trends, the academic leadership of Jawaharlal Nehru University conceptualised the School of Life Sciences as an interdisciplinary research/teaching programme unifying various facets of biology while reflecting essential commonality regarding structure, function and evolution of biomolecules. The School was established in 1973 and since offering integrated teaching and research at M. Sc/ Ph.D level in various sub-disciplines in life sciences. Since inception, it remained dedicated to its core objectives and evolved to be one of the top such institutions in India and perhaps in South East Asia. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
RET/PTC Activation in Papillary Thyroid Carcinoma
European Journal of Endocrinology (2006) 155 645–653 ISSN 0804-4643 INVITED REVIEW RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture Massimo Santoro1, Rosa Marina Melillo1 and Alfredo Fusco1,2 1Istituto di Endocrinologia ed Oncologia Sperimentale del CNR ‘G. Salvatore’, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, University ‘Federico II’, Via S. Pansini, 5, 80131 Naples, Italy and 2NOGEC (Naples Oncogenomic Center)–CEINGE, Biotecnologie Avanzate & SEMM, European School of Molecular Medicine, Naples, Italy (Correspondence should be addressed to M Santoro; Email: [email protected]) Abstract Papillary thyroid carcinoma (PTC) is frequently associated with RET gene rearrangements that generate the so-called RET/PTC oncogenes. In this review, we examine the data about the mechanisms of thyroid cell transformation, activation of downstream signal transduction pathways and modulation of gene expression induced by RET/PTC. These findings have advanced our understanding of the processes underlying PTC formation and provide the basis for novel therapeutic approaches to this disease. European Journal of Endocrinology 155 645–653 RET/PTC rearrangements in papillary growth factor, have been described in a fraction of PTC thyroid carcinoma patients (7). As illustrated in figure 1, many different genes have been found to be rearranged with RET in The rearranged during tansfection (RET) proto-onco- individual PTC patients. RET/PTC1 and 3 account for gene, located on chromosome 10q11.2, was isolated in more than 90% of all rearrangements and are hence, by 1985 and shown to be activated by a DNA rearrange- far, the most frequent variants (8–11). They result from ment (rearranged during transfection) (1).As the fusion of RET to the coiled-coil domain containing illustrated in Fig. -
RET Gene Fusions in Malignancies of the Thyroid and Other Tissues
G C A T T A C G G C A T genes Review RET Gene Fusions in Malignancies of the Thyroid and Other Tissues Massimo Santoro 1,*, Marialuisa Moccia 1, Giorgia Federico 1 and Francesca Carlomagno 1,2 1 Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, 80131 Naples, Italy; [email protected] (M.M.); [email protected] (G.F.); [email protected] (F.C.) 2 Institute of Endocrinology and Experimental Oncology of the CNR, 80131 Naples, Italy * Correspondence: [email protected] Received: 10 March 2020; Accepted: 12 April 2020; Published: 15 April 2020 Abstract: Following the identification of the BCR-ABL1 (Breakpoint Cluster Region-ABelson murine Leukemia) fusion in chronic myelogenous leukemia, gene fusions generating chimeric oncoproteins have been recognized as common genomic structural variations in human malignancies. This is, in particular, a frequent mechanism in the oncogenic conversion of protein kinases. Gene fusion was the first mechanism identified for the oncogenic activation of the receptor tyrosine kinase RET (REarranged during Transfection), initially discovered in papillary thyroid carcinoma (PTC). More recently, the advent of highly sensitive massive parallel (next generation sequencing, NGS) sequencing of tumor DNA or cell-free (cfDNA) circulating tumor DNA, allowed for the detection of RET fusions in many other solid and hematopoietic malignancies. This review summarizes the role of RET fusions in the pathogenesis of human cancer. Keywords: kinase; tyrosine kinase inhibitor; targeted therapy; thyroid cancer 1. The RET Receptor RET (REarranged during Transfection) was initially isolated as a rearranged oncoprotein upon the transfection of a human lymphoma DNA [1]. -
RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients Shumei Kato1, Vivek Subbiah2, Erica Marchlik3, Sheryl K
Published OnlineFirst September 28, 2016; DOI: 10.1158/1078-0432.CCR-16-1679 Personalized Medicine and Imaging Clinical Cancer Research RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients Shumei Kato1, Vivek Subbiah2, Erica Marchlik3, Sheryl K. Elkin3, Jennifer L. Carter3, and Razelle Kurzrock1 Abstract Purpose: Aberrations in genetic sequences encoding the tyrosine (52/88)], cell cycle–associated genes [39.8% (35/88)], the PI3K kinase receptor RET lead to oncogenic signaling that is targetable signaling pathway [30.7% (27/88)], MAPK effectors [22.7% with anti-RET multikinase inhibitors. Understanding the compre- (20/88)], or other tyrosine kinase families [21.6% (19/88)]. hensive genomic landscape of RET aberrations across multiple RET fusions were mutually exclusive with MAPK signaling cancers may facilitate clinical trial development targeting RET. pathway alterations. All 72 patients harboring coaberrations Experimental Design: We interrogated the molecular portfolio had distinct genomic portfolios, and most [98.6% (71/72)] of 4,871 patients with diverse malignancies for the presence of had potentially targetable coaberrations with either an FDA- RET aberrations using Clinical Laboratory Improvement Amend- approved or an investigational agent. Two cases with lung ments–certified targeted next-generation sequencing of 182 or (KIF5B-RET) and medullary thyroid carcinoma (RET M918T) 236 gene panels. thatrespondedtoavandetanib(multikinase RET inhibitor)- Results: Among diverse cancers, RET aberrations were iden- containing regimen are shown. tified in 88 cases [1.8% (88/4, 871)], with mutations being Conclusions: RET aberrations were seen in 1.8% of diverse the most common alteration [38.6% (34/88)], followed cancers, with most cases harboring actionable, albeit dis- by fusions [30.7% (27/88), including a novel SQSTM1-RET] tinct, coexisting alterations. -
Anti-SH3BP4 Polyclonal Antibody (CABT-B1932) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
Anti-SH3BP4 polyclonal antibody (CABT-B1932) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Immunogen Recombinant protein corresponding to human SH3BP4. Isotype IgG Source/Host Rabbit Species Reactivity Human Purification Affinity Conjugate Unconjugated Applications IHC Molecular Weight 107 kDa calculated Format Liquid Concentration Please refer to lot specific datasheet. Size 100 µL Buffer PBS (pH 7.2) with 0.02% sodium azide and 40% glycerol. Preservative 0.02% Sodium Azide Storage Stable for 1 year at -20°C from date of receipt. Handling Recommendations: Upon receipt and prior to removing the cap, centrifuge the vial and gently mix the solution. Aliquot into microcentrifuge tubes and store at -20°C. Avoid repeated freeze/thaw cycles, which may damage IgG and affect product performance. Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage. BACKGROUND Introduction SH3 domain-binding protein 4, also known as, EH-binding protein 10 or Transferrin receptor- trafficking protein, and encoded by the gene name(s), SH3BP4 or BOG25 or EHB10 or TTP, may function in transferrin receptor internalization at the plasma membrane through a cargo- specific control of clathrin-mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation; thereby may indirectly regulate cell growth, proliferation and autophagy. -
Using Genetically Isolated Populations to Understand the Genomic Basis of Disease Eleftheria Zeggini
Zeggini Genome Medicine 2014, 6:83 http://genomemedicine.com/content/6/10/83 RESEARCH HIGHLIGHT Using genetically isolated populations to understand the genomic basis of disease Eleftheria Zeggini Abstract use of next-generation association studies, a hybrid of genome-wide genotyping and whole genome sequencing Rare variation has a key role in the genetic etiology of (WGS) approaches, for complex disease gene mapping complex traits. Genetically isolated populations have [2,3]. In Iceland, numerous novel loci for complex dis- been established as a powerful resource for novel eases, such as type 2 diabetes (T2D) and prostate cancer locus discovery and they combine advantageous [4,5], have been identified through a combination of characteristics that can be leveraged to expedite WGS and long-range phasing-assisted imputation on a discovery. Genome-wide genotyping approaches genome-wide genotype scaffold, together with calcula- coupled with sequencing efforts have transformed the tion of genotype probabilities in approximately 300,000 landscape of disease genomics and highlight the untyped individuals by making use of the extended ge- potentially significant contribution of studies in nealogical information available. founder populations. More recently, novel insights into the biological path- ways underpinning T2D were achieved through the study of a Greenlandic founder population [6]. A non- Complex trait locus discovery in isolated TBC1D4 populations sense variant in the gene was found to be strongly associated with postprandial hyperglycemia, im- Genetically isolated or founder populations have recently paired glucose tolerance and T2D. These unique insights returned to the fore of genetic association studies as into the mechanism conferring muscle insulin resistance valuable resources for complex trait gene identification for this subset of T2D was afforded by studying the [1]. -
Biological Models of Colorectal Cancer Metastasis and Tumor Suppression
BIOLOGICAL MODELS OF COLORECTAL CANCER METASTASIS AND TUMOR SUPPRESSION PROVIDE MECHANISTIC INSIGHTS TO GUIDE PERSONALIZED CARE OF THE COLORECTAL CANCER PATIENT By Jesse Joshua Smith Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University In partial fulfillment of the requirements For the degree of DOCTOR OF PHILOSOPHY In Cell and Developmental Biology May, 2010 Nashville, Tennessee Approved: Professor R. Daniel Beauchamp Professor Robert J. Coffey Professor Mark deCaestecker Professor Ethan Lee Professor Steven K. Hanks Copyright 2010 by Jesse Joshua Smith All Rights Reserved To my grandparents, Gladys and A.L. Lyth and Juanda Ruth and J.E. Smith, fully supportive and never in doubt. To my amazing and enduring parents, Rebecca Lyth and Jesse E. Smith, Jr., always there for me. .my sure foundation. To Jeannine, Bill and Reagan for encouragement, patience, love, trust and a solid backing. To Granny George and Shawn for loving support and care. And To my beautiful wife, Kelly, My heart, soul and great love, Infinitely supportive, patient and graceful. ii ACKNOWLEDGEMENTS This work would not have been possible without the financial support of the Vanderbilt Medical Scientist Training Program through the Clinical and Translational Science Award (Clinical Investigator Track), the Society of University Surgeons-Ethicon Scholarship Fund and the Surgical Oncology T32 grant and the Vanderbilt Medical Center Section of Surgical Sciences and the Department of Surgical Oncology. I am especially indebted to Drs. R. Daniel Beauchamp, Chairman of the Section of Surgical Sciences, Dr. James R. Goldenring, Vice Chairman of Research of the Department of Surgery, Dr. Naji N. -
Evaluating the Glucose Raising Effect of Established Loci Via a Genetic Risk Score
RESEARCH ARTICLE Evaluating the glucose raising effect of established loci via a genetic risk score Eirini Marouli1*, Stavroula Kanoni1, Vasiliki Mamakou2, Sophie Hackinger3, Lorraine Southam3,4, Bram Prins3, Angela Rentari5, Maria Dimitriou5, Eleni Zengini2,6, Fragiskos Gonidakis7, Genovefa Kolovou8, Vassilis Kontaxakis9, Loukianos Rallidis10, Nikolaos Tentolouris11, Anastasia Thanopoulou12, Klea Lamnissou13, George Dedoussis5, Eleftheria Zeggini3, Panagiotis Deloukas1,14 1 William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom, 2 Dromokaiteio Psychiatric Hospital, Athens, Greece, 3 Wellcome Trust Sanger Institute, Hinxton, Cambridge, 4 Wellcome Trust Centre for Human Genetics, Oxford, United a1111111111 Kingdom, 5 Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio a1111111111 University, Athens, Greece, 6 Department of Oncology and Metabolism, University of Sheffield, Sheffield, a1111111111 United Kingdom, 7 1st Psychiatric Department, National and Kapodistrian University of Athens, Medical a1111111111 School, Eginition Hospital, Athens, Greece, 8 Department of Cardiology, Onassis Cardiac Surgery Center, a1111111111 Athens, Greece, 9 Early Psychosis Unit, 1st Department of Psychiatry, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece, 10 Second Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Attikon Hospital, Athens, Greece,