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Comprehensive Array CGH of Normal Karyotype Myelodysplastic
Leukemia (2011) 25, 387–399 & 2011 Macmillan Publishers Limited All rights reserved 0887-6924/11 www.nature.com/leu LEADING ARTICLE Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance A Thiel1, M Beier1, D Ingenhag1, K Servan1, M Hein1, V Moeller1, B Betz1, B Hildebrandt1, C Evers1,3, U Germing2 and B Royer-Pokora1 1Institute of Human Genetics and Anthropology, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany and 2Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Duesseldorf, Germany About 40% of patients with myelodysplastic syndromes (MDSs) 40–50% of MDS cases have a normal karyotype. MDS patients present with a normal karyotype, and they are facing different with a normal karyotype and low-risk clinical parameters are courses of disease. To advance the biological understanding often assigned into the IPSS low and intermediate-1 risk groups. and to find molecular prognostic markers, we performed a high- resolution oligonucleotide array study of 107 MDS patients In the absence of genetic or biological markers, prognostic (French American British) with a normal karyotype and clinical stratification of these patients is difficult. To better prognosticate follow-up through the Duesseldorf MDS registry. Recurrent these patients, new parameters to identify patients at higher risk hidden deletions overlapping with known cytogenetic aberra- are urgently needed. With the more recently introduced modern tions or sites of known tumor-associated genes were identi- technologies of whole-genome-wide surveys of genetic aberra- fied in 4q24 (TET2, 2x), 5q31.2 (2x), 7q22.1 (3x) and 21q22.12 tions, it is hoped that more insights into the biology of disease (RUNX1, 2x). -
Germline Risk of Clonal Haematopoiesis
REVIEWS Germline risk of clonal haematopoiesis Alexander J. Silver 1,2, Alexander G. Bick 1,3,4,5 and Michael R. Savona 1,2,4,5 ✉ Abstract | Clonal haematopoiesis (CH) is a common, age-related expansion of blood cells with somatic mutations that is associated with an increased risk of haematological malignancies, cardiovascular disease and all-cause mortality. CH may be caused by point mutations in genes associated with myeloid neoplasms, chromosomal copy number changes and loss of heterozygosity events. How inherited and environmental factors shape the incidence of CH is incompletely understood. Even though the several varieties of CH may have distinct phenotypic consequences, recent research points to an underlying genetic architecture that is highly overlapping. Moreover, there are numerous commonalities between the inherited variation associated with CH and that which has been linked to age-associated biomarkers and diseases. In this Review, we synthesize what is currently known about how inherited variation shapes the risk of CH and how this genetic architecture intersects with the biology of diseases that occur with ageing. Haematopoietic stem cells Haematopoiesis, the process by which blood cells are gen- First, advances in next-generation sequencing technolo- (HSCs). Cells that are erated, begins in embryogenesis and continues through- gies have enabled the identification of mutations with responsible for the creation of out an individual’s lifespan1. Haematopoietic stem cells high resolution (that is, single base-pair changes) even all blood cells in the human (HSCs) are responsible for the creation of all mature when these lesions are present in just a fraction of sampled body and are multipotent in blood cells, including red blood cells, platelets, and the cells. -
Crucial Role of the SH2B1 PH Domain for the Control of Energy Balance
Diabetes Page 2 of 46 1 Crucial Role of the SH2B1 PH Domain for the Control of 2 Energy Balance 3 4 Anabel Floresa, Lawrence S. Argetsingerb+, Lukas K. J. Stadlerc+, Alvaro E. Malagab, Paul B. 5 Vanderb, Lauren C. DeSantisb, Ray M. Joea,b, Joel M. Clineb, Julia M. Keoghc, Elana Henningc, 6 Ines Barrosod, Edson Mendes de Oliveirac, Gowri Chandrashekarb, Erik S. Clutterb, Yixin Hub, 7 Jeanne Stuckeyf, I. Sadaf Farooqic, Martin G. Myers Jr. a,b,e, Christin Carter-Sua,b,e, g * 8 aCell and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA 9 bDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA 10 cUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, 11 Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK 12 dMRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, 13 Cambridge, UK 14 eDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA 15 fLife Sciences Institute and Departments of Biological Chemistry and Biophysics, University of Michigan, Ann Arbor, 16 MI 48109, USA 17 +Authors contributed equally to this work 18 gLead contact 19 *Correspondence: [email protected] 20 21 Running title: Role of SH2B1 PH Domain in Energy Balance 22 23 24 25 26 27 28 1 Diabetes Publish Ahead of Print, published online August 22, 2019 Page 3 of 46 Diabetes 29 30 Abstract 31 Disruption of the adaptor protein SH2B1 is associated with severe obesity, insulin resistance and 32 neurobehavioral abnormalities in mice and humans. -
Clonal Hematopoietic Mutations Linked to Platelet Traits and the Risk Of
REVIEW ARTICLE Clonal hematopoietic mutations linked to Ferrata Storti Foundation platelet traits and the risk of thrombosis or bleeding Alicia Veninga, 1,* Ilaria De Simone, 1,* Johan W.M. Heemskerk, 1 Hugo ten Cate, 1,2,3 and Paola E.J. van der Meijden 1,2 1Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht; 2Thrombosis Expertise Center, Heart and Vascular Haematologica 2020 Center, Maastricht University Medical Center, Maastricht and 3Department of Internal Volume 105(8):2020-2031 Medicine, Maastricht University Medical Center, Maastricht, the Netherlands *AV and IDS contributed equally as co-first authors. ABSTRACT latelets are key elements in thrombosis, particularly in atherosclero - sis-associated arterial thrombosis (atherothrombosis), and hemosta - Psis. Megakaryocytes in the bone marrow, differentiated from hematopoietic stem cells are generally considered as a uniform source of platelets. However, recent insights into the causes of malignancies, includ - ing essential thrombocytosis, indicate that not only inherited but also somatic mutations in hematopoietic cells are linked to quantitative or qualitative platelet abnormalities. In particular cases, these form the basis of thrombo-hemorrhagic complications regularly observed in patient groups. This has led to the concept of clonal hematopoiesis of indetermi - nate potential (CHIP), defined as somatic mutations caused by clonal expansion of mutant hematopoietic cells without evident disease. This concept also provides clues regarding the importance of platelet function Correspondence: in relation to cardiovascular disease. In this summative review, we present an overview of genes associated with clonal hematopoiesis and altered P.E.J. VAN DER MEIJDEN platelet production and/or functionality, like mutations in JAK2 . We con - [email protected] sider how reported CHIP genes can influence the risk of cardiovascular disease, by exploring the consequences for platelet function related to Received: January 31, 2020. -
Diagnostic Workflow for Hereditary Erythrocytosis and Thrombocytosis
Diagnostic workflow for hereditary erythrocytosis and thrombocytosis McMullin, M. F. (2019). Diagnostic workflow for hereditary erythrocytosis and thrombocytosis. Hematology (United States), 2019(1), 391-396. https://doi.org/10.1182/hematology.2019000047 Published in: Hematology (United States) Document Version: Peer reviewed version Queen's University Belfast - Research Portal: Link to publication record in Queen's University Belfast Research Portal Publisher rights Copyright 2019 American Society of Hematology. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher. General rights Copyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The Research Portal is Queen's institutional repository that provides access to Queen's research output. Every effort has been made to ensure that content in the Research Portal does not infringe any person's rights, or applicable UK laws. If you discover content in the Research Portal that you believe breaches copyright or violates any law, please contact [email protected]. Download date:29. Sep. 2021 Diagnostic workflow for hereditary erythrocytosis and thrombocytosis Mary Frances McMullin, Centre for Medical Education, Queen’s University Belfast, Belfast BT9 7AB, N. Ireland. Email [email protected] Abstract In the patient presenting with an elevated blood count who does not have an acquired clonal disorder causing a myeloproliferative neoplasm, hereditary erythrocytosis or hereditary thrombocytosis needs to be considered as a possible explanation. -
Insight Into the Brain-Specific Alpha Isoform of the Scaffold Protein SH2B1 and Its Rare Obesity-Associated Variants
Insight into the Brain-Specific Alpha Isoform of the Scaffold Protein SH2B1 and its Rare Obesity-Associated Variants By Ray Morris Joe A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Cellular and Molecular Biology) in the University of Michigan 2017 Doctoral Committee: Professor Christin Carter-Su, Chair Professor Ken Inoki Professor Benjamin L. Margolis Professor Donna M. Martin Professor Martin G. Myers © Ray Morris Joe ORCID: 0000-0001-7716-2874 [email protected] All rights reserved 2017 Acknowledgements I’d like to thank my mentor, Christin Carter-Su, for providing me a second opportunity and taking a chance on me after my leave of absence without hesitation. It is an honor to have a mentor guide me through the many challenges I have faced as a graduate student. She has taught me to find passion in my profession, and to strive to push through obstacles and find ways to reach my goals. In addition, she has given me insight to find a balance between work and life by giving me freedom to independently perform my research as well as stories on family and child-rearing. Throughout the many countless days and nights writing grants, manuscripts, and analyzing/interpreting data, it was wonderful to share our past cultural identities with one another. I look forward to having Christy as a mentor, colleague, and friend for all my future endeavors I have after I leave her laboratory. I want to thank my thesis committee, Ken Inoki, Ben Margolis, Donna Martin, and Martin Myers for the numerous insights for my scientific training. -
Clonality Identified by Targeted Sequencing
RESEARCH ARTICLE Idiopathic hypereosinophilia is clonal disorder? Clonality identified by targeted sequencing Jee-Soo Lee1¤, Heewon Seo2,3, Kyongok Im4, Si Nae Park4, Sung-Min Kim4, Eun Kyoung Lee4, Jung-Ah Kim1, Joon-hee Lee1, Sunghoon Kwon5, Miyoung Kim6, Insong Koh7, Seungwoo Hwang8, Heung-Woo Park9, Hye-Ryun Kang9, Kyoung Soo Park9, Ju Han Kim2,3, Dong Soon Lee1,4* 1 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea, 2 Division of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul a1111111111 National University College of Medicine, Seoul, Republic of Korea, 3 Division of Biomedical Informatics, a1111111111 Systems Biomedical Informatics National Core Research Center, Seoul National University College of a1111111111 Medicine, Seoul, Republic of Korea, 4 Cancer Research Institute, Seoul National University College of a1111111111 Medicine, Seoul, Republic of Korea, 5 Department of Electrical Engineering, Seoul National University, a1111111111 Seoul, Republic of Korea, 6 Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea, 7 Department of Physiology, College of Medicine, Hanyang University, Seoul, Republic of Korea, 8 Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea, 9 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea OPEN ACCESS ¤ Current address: Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Citation: Lee J-S, Seo H, Im K, Park SN, Kim S-M, * [email protected] Lee EK, et al. (2017) Idiopathic hypereosinophilia is clonal disorder? Clonality identified by targeted sequencing. PLoS ONE 12(10): e0185602. -
Sex-Specific Association of SH2B3 and SMARCA4 Polymorphisms With
www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 35), pp: 59397-59407 Research Paper Sex-specific association ofSH2B3 and SMARCA4 polymorphisms with coronary artery disease susceptibility Yuqiang Ji1,2,3,*, Yanbin Song1,2,4,*, Qingwen Wang5, Pengcheng Xu5, Zhao Zhao3, Xia Li3, Nan Wang3, Tianbo Jin1,2 and Chao Chen1,2 1Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xi’an, Shaanxi 710069, China 2School of Life Sciences, Northwest University, Xi’an, Shaanxi 710069, China 3Department of Cardiovascular Medicine, First Hospital of Xi’an, Xi’an 710002, China 4Department of Cardiovascular Medicine, Affiliated Hospital Yan’an University, Yan’an 716000, China 5Department of Hand Surgery, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, Hebei 061001, China *These authors have contributed equally to this work Correspondence to: Tianbo Jin, email: [email protected] Chao Chen, email: [email protected] Keywords: coronary artery disease, SH2B3, SMARCA4, single nucleotide polymorphism, gene Received: February 06, 2017 Accepted: June 03, 2017 Published: July 31, 2017 Copyright: Ji et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT To determine whether sex differences affect the association between genetic polymorphisms and coronary artery disease (CAD) in the Chinese Han population, we conducted a study comparing the frequency of SH2B3 and SMARCA4 variants in 456 CAD patients (291 men, 165 women) and 685 age-matched controls (385 men, 300 women). -
Characterization of Drosophila Lnk an Adaptor Protein Involved in Growth Control
Research Collection Doctoral Thesis Characterization of Drosophila Lnk an adaptor protein involved in growth control Author(s): Werz, Christian Publication Date: 2009 Permanent Link: https://doi.org/10.3929/ethz-a-006073429 Rights / License: In Copyright - Non-Commercial Use Permitted This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use. ETH Library DISS. ETH Nr. 18640 Characterization of Drosophila Lnk – An Adaptor protein involved in growth control ABHANDLUNG Zur Erlangung des Titels DOKTOR DER WISSENSCHAFTEN der ETH ZÜRICH vorgelegt von CHRISTIAN WERZ Dipl. Biol. Geboren am 13.02.1977 von Neckarsulm, Deutschland Angenommen auf Antrag von Prof. Dr. Ernst Hafen Prof. Dr. Konrad Basler Prof. Dr. Markus Affolter Zürich 2009 Table of Contents Table of Contents Summary: .................................................................................................................. 4 Zusammenfassung: .................................................................................................. 5 Introduction: ............................................................................................................. 7 The fundamental process of growth control ............................................................ 7 The Insulin/IGF and TOR pathway.......................................................................... 9 Signaling downstream of the receptor................................................................... 11 Insulin -
Epigenetic Age Prediction in Semen – Marker Selection and Model Development
www.aging-us.com AGING 2021, Vol. 13, No.15 Research Paper Epigenetic age prediction in semen – marker selection and model development Aleksandra Pisarek1, Ewelina Pośpiech1, Antonia Heidegger2, Catarina Xavier2, Anna Papież3, Danuta Piniewska-Róg4, Vivian Kalamara5, Ramya Potabattula6, Michał Bochenek1, Marta Sikora-Polaczek7, Aneta Macur8, Anna Woźniak9, Jarosław Janeczko8, Christopher Phillips10, Thomas Haaf6, Joanna Polaoska3, Walther Parson2,11, Manfred Kayser5, Wojciech Branicki1,9 on behalf of the VISAGE Consortium 1Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland 2Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck, Austria 3Department of Data Science and Engineering, The Silesian University of Technology, Gliwice, Poland 4Department of Legal Medicine, Medical College, Krakow, Poland 5Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands 6Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany 7The Fertility Partnership Macierzynstwo, Krakow, Poland 8PARENS Fertility Centre, Krakow, Poland 9Central Forensic Laboratory of the Police, Warsaw, Poland 10Department of Legal Medicine, Santiago de Compostela, Spain 11Forensic Science Program, The Pennsylvania State University, University Park, PA 16802, USA Correspondence to: Wojciech Branicki; email: [email protected] Keywords: semen, epigenetic age, DNA methylation, amplicon bisulfite sequencing, epigenetic age estimation Received: March 16, 2021 Accepted: July 17, 2021 Published: August 10, 2021 Copyright: © 2021 Pisarek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT DNA methylation analysis is becoming increasingly useful in biomedical research and forensic practice. -
A Graph-Theoretic Approach to Model Genomic Data and Identify Biological Modules Asscociated with Cancer Outcomes
A Graph-Theoretic Approach to Model Genomic Data and Identify Biological Modules Asscociated with Cancer Outcomes Deanna Petrochilos A dissertation presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2013 Reading Committee: Neil Abernethy, Chair John Gennari, Ali Shojaie Program Authorized to Offer Degree: Biomedical Informatics and Health Education UMI Number: 3588836 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. UMI 3588836 Published by ProQuest LLC (2013). Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, MI 48106 - 1346 ©Copyright 2013 Deanna Petrochilos University of Washington Abstract Using Graph-Based Methods to Integrate and Analyze Cancer Genomic Data Deanna Petrochilos Chair of the Supervisory Committee: Assistant Professor Neil Abernethy Biomedical Informatics and Health Education Studies of the genetic basis of complex disease present statistical and methodological challenges in the discovery of reliable and high-confidence genes that reveal biological phenomena underlying the etiology of disease or gene signatures prognostic of disease outcomes. This dissertation examines the capacity of graph-theoretical methods to model and analyze genomic information and thus facilitate using prior knowledge to create a more discrete and functionally relevant feature space. -
Haematological Malignancies
Thoennissen_relayout_EU Onc & Haem 08/02/2011 13:13 Page 59 Haematological Malignancies Leukaemic Transformation of Philadelphia-chromosome-negative Myeloproliferative Neoplasms – A Review of the Molecular Background Nils H Thoennissen1 and H Phillip Koeffler2 1. Post-doctoral Researcher, Division of Hematology/Oncology, Cedars-Sinai Medical Center; 2. Director, Division of Hematology/Oncology, Cedars-Sinai Medical Center, and Deputy Director of Cancer Research, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore Abstract Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs), including polycythaemia vera (PV), primary myelofibrosis (PMF) and essential thrombocythaemia (ET), are clonal haematopoietic stem cell disorders characterised by proliferation of one or more myeloid cell lineages. They are closely associated with the JAK2V617F mutation, whose detection is used as a clonal marker in the differential diagnosis of MPN. Despite recent improvements in the molecular diagnosis and therapeutic regimen of these chronic disorders, haematological evolution to blast phase remains a major cause of long-term mortality. The mechanism of MPN transformation is still a matter of some controversy because of insufficient insights into the underlying molecular pathogenesis. The purpose of this article is to summarise the increasing data concerning the mechanism of leukaemic evolution of patients diagnosed with chronic MPN. Chromosomal abnormalities and genes that have been shown to play a potential