DOCSLIB.ORG

Redalyc.Bases Moleculares De Hemoglobinopatías En Argentina

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Redalyc.Bases Moleculares De Hemoglobinopatías En Argentina Acta Bioquímica Clínica Latinoamericana ISSN: 0325-2957 [email protected] Federación Bioquímica de la Provincia de Buenos Aires Argentina Scheps, Karen Gabriela; Varela, Viviana Bases moleculares de hemoglobinopatías en Argentina Acta Bioquímica Clínica Latinoamericana, vol. 51, núm. 3, 2017, pp. 333-342 Federación Bioquímica de la Provincia de Buenos Aires Buenos Aires, Argentina Disponible en: http://www.redalyc.org/articulo.oa?id=53553013008 Cómo citar el artículo Número completo Sistema de Información Científica Más información del artículo Red de Revistas Científicas de América Latina, el Caribe, España y Portugal Página de la revista en redalyc.org Proyecto académico sin fines de lucro, desarrollado bajo la iniciativa de acceso abierto Hematología Reconocimiento a la trayectoria de la Prof. Dra. Nilda Fink Bases moleculares de hemoglobinopatías en Argentina* Molecular basis of hemoglobinopathies in Argentina Bases moleculares de hemoglobinopatias na Argentina ` Karen Gabriela Scheps1,a, Viviana Varela2,a 1 Dra. de la Universidad de Buenos Aires, Área Resumen Biología Molecular. Durante el desarrollo de un individuo se expresan distintas cadenas de globina 2 Dra. de la Universidad de Buenos Aires, Área de tipo y no- , que se combinan en tetrámeros para formar hemoglobina. Los Biología Molecular. Profesora Adjunta de la α α genes que las codifican se organizan en familias. Distintas mutaciones afectan Cátedra de Genética. Facultad de Farmacia y los genes que codifican las cadenas de globina: si provocan alteraciones cua- Bioquímica, Universidad de Buenos Aires. litativas originan cuadros de hemoglobinopatías estructurales, si disminuyen las síntesis de las cadenas de globina, talasemias, y si tienen ambos efectos, a Universidad de Buenos Aires, Cátedra de Ge- hemoglobinopatías talasémicas. El propósito de este trabajo es presentar las nética, INIGEM, Facultad de Farmacia y Bio- bases moleculares de las hemoglobinopatías en Argentina, en un total de 862 química, CONICET, Ciudad Autónoma de Bue- muestras, en base a los estudios moleculares realizados en este laboratorio a nos Aires, Argentina. partir del estudio de 910 muestras de pacientes. En nuestro medio, la Hb S * Subcomisión de Eritropatías, Sociedad Argen- es la hemoglobinopatía estructural más frecuente, las -talasemias presentan tina de Hematología. β una distribución similar a la cuenca del Mediterráneo y las α-talasemias están intrínsecamente relacionadas a la ascendencia de los afectados. Las bases mo- leculares de las hemoglobinopatías son variadas. Mientras que en las hemoglo- binopatías estructurales y β-talasemias predominan las mutaciones puntuales, en las α-talasemias predominan las deleciones. Se describen mutaciones nó- veles (cambios puntuales, deleciones y duplicaciones) que se presentan como eventos aislados con herencia recesiva o dominante. Es necesaria la interacción entre el médico hematólogo, el laboratorio bioquímico, el laboratorio molecular y el médico genetista, para llegar al diagnóstico certero de estos cuadros que permitirán reducir la incidencia de las formas severas. Palabras clave: hemoglobina * variantes estructurales * β-talasemia * α-talasemia * genética Acta Bioquímica Clínica Latinoamericana Abstract Incorporada al Chemical Abstract Service. Functional hemoglobin is a tetramer composed of 2 α and 2 non-α chains, Código bibliográfico: ABCLDL. encoded by genes that are organized in clusters and are expressed sequentially through development. There are multiple mutations described that affect these ISSN 0325-2957 genes: if the sequence variant leads to a qualitative alteration, the resulting ISSN 1851-6114 en línea effect is a structural hemoglobinopathy, if it decreases the synthesis of the ISSN 1852-396X (CD-ROM) globin chains, thalassemia, and if it affects both the quality and quantity of Acta Bioquím Clín Latinoam 2017; 51 (3): 333-42 334 Scheps KG y Varela V the globin chain, the consequence is a thalassemic hemoglobinopathy. The aim of this paper is to present the molecular bases of hemoglobinopathies in Argentina, determined in 862 patients, based on the results of the molecular studies carried out in our laboratory from the analysis of 910 samples. Hb S is the most frequent structural hemoglobinopathy, β-thalassemia mutations exhibit a pattern similar to the one displayed by Mediterranean basin populations, and α-thalassemia mutations are intrinsically related to the ancestry of those affected. These syndromes exhibit diverse molecular bases: structural hemoglobinopathies and β-thalassemia are a consequence, mostly of point mutations, whereas in α-thalassemia deletions prevail. Novel mutations (point changes, deletions and duplications) that occurred as isolated events, with recessive or dominant inheritance, were described. Interaction between the hematologist, the geneticist and both the clinical and molecular biology laboratories is necessary to reach an accurate diagnosis of these syndromes and reduce the incidence of severe forms. Keywords: hemoglobin * structural variants * β-thalassemia * α-thalassemia * genetics Resumo Durante o desenvolvimento de um indivíduo expressam-se diversas cadeias de globina de tipo α e não-α, que se combinam em tetrámeros para formar hemoglobina. Os genes que as codificam são organizados em famílias. Diferentes mutações afetam os genes que codificam as cadeias de globina: se provocarem altera- ções qualitativas originam quadros de hemoglobinopatias estruturais, se diminuírem as sínteses das cadeias de globina, talassemias, e se tiverem ambos os efeitos, hemoglobinopatias talassêmicas. O propósito deste trabalho é apresentar as bases moleculares das hemoglobinopatias na Argentina, num total de 862 amostras, com base nos estudos moleculares realizados neste laboratório a partir do estudo de 910 amostras de pacien- tes. No nosso meio, a Hb S é a hemoglobinopatia estrutural mais frequente, as β-talassemias apresentam uma distribuição similar à bacia do Mediterrâneo e as α-talassemias estão intrinsecamente relacionadas com a ascendência dos afetados. As bases moleculares das hemoglobinopatias são variadas. Enquanto nas hemoglobinopatias estruturais e β-talassemias predominam as mutações pontuais, nas α-talassemias predo- minam as deleções. Descrevem-se mutações incipientes (mudanças pontuais, deleções e duplicações) que se apresentam como eventos isolados com herança recessiva ou dominante. É necessária a interação entre o médico hematólogo, o laboratório bioquímico, o laboratório molecular e o médico geneticista, para chegar ao diagnóstico certo desses quadros que permitirão reduzir a incidência das formas severas. Palavras-chave: hemoglobina * variantes estruturais * β-talassemia * α-talassemia * genética Introducción codifican cadenas de globina funcionales de 146 ami- noácidos. Los desórdenes hereditarios que comprometen la El orden de los genes en el cluster en dirección 5’ a 3’ síntesis de la hemoglobina (Hb) representan el gru- es: HBE1-HBG2-HBG1-HBBP-HBD-HBB (3). po más común de alteraciones genéticas que afectan La expresión de los genes de la familia está regulada una sola copia de un gen: se estima que nacen más de por la presencia de elementos reguladores en cis, proxi- 350.000 afectados por año (1) y que al menos el 5,2% males y distales. El locus de la región de control (Locus de la población mundial es portadora de alguna va- Control Region, LCR), es un elemento regulador distal, riante de importancia clínica. Las hemoglobinopatías que se ubica aproximadamente de 6 a 20 kb corriente representan, además, el 3,4% de las muertes en niños arriba de HBE1 y es necesario para que haya alta efi- menores de 5 años (2). ciencia transcripcional de los genes. En este cluster se Los genes que codifican para las cadenas de las distin- producen 2 eventos de switch (eventos de “apagado” y tas Hbs que se observan a lo largo del desarrollo de un “prendido” de genes) durante el desarrollo (4). individuo, presentan una organización típica de genes eu- La familia de los genes de α-globina se ubica en la re- cariotas y poseen una estructura general similar, donde la gión subtelomérica del brazo pequeño del cromosoma 16 secuencia codificante está repartida en tres exones. (16p13.3). Al igual que los genes que codifican para Los genes están agrupados en familias (clusters) mul- cadenas tipo β, son pequeños (aproximadamente tigénicas (familia de β-globina y de α-globina). 1.500 pb), y codifican cadenas de globina funcionales La familia de los genes de β-globina se ubica en el de 141 aminoácidos. brazo pequeño del cromosoma 11 (11p15.5); son rela- El orden de los genes en dirección 5’ a 3’, es: HBZ- tivamente pequeños (aproximadamente 1.500 pb), y HBZP-HBM-HBAP1-HBA2-HBA1-HBQ1 (3). Acta Bioquím Clín Latinoam 2017; 51 (3): 333-42 Bases moleculares de hemoglobinopatías en Argentina 335 Los genes HBA2 y HBA1 surgieron de una duplica- tructurales en el territorio americano en la era preco- ción ancestral, por lo que son idénticos en la secuencia lombina (12). Las mutaciones se introdujeron a partir codificante. Existen pequeñas diferencias a nivel del de distintas corrientes migratorias de Europa occiden- intrón 2 y difieren en mayor grado en las regiones 3’ tal, desde el siglo XVI y por el tráfico de esclavos de UTR (5). África occidental a fines del siglo XVI. Al igual que los genes de la familia de β-globina, los En función del perfil migratorio en Argentina y de genes de esta familia que se expresan durante la onto- estudios de laboratorios, se podría afirmar que, hasta el genia se encuentran sujetos
Load more

Recommended publications
  • Analysis of Genetic Determinants Associated with Persistent Synthesis of Fetal Hemoglobin
    UNIVERSITÀ DEGLI STUDI DI SASSARI PhD School in Biomolecular and Biotechnological Sciences Curriculum: Biochemistry and Molecular Biology Director: Prof. Claudia Crosio “XXVI Ciclo” Analysis of genetic determinants associated with Persistent Synthesis of Fetal Hemoglobin Supervisor: Monica Pirastru, PhD Director: Prof. Claudia Crosio PhD Student: Sandro Trova ................................................................................................................................................. INDEX INDEX ABSTRACT ................................................................................... 3 INTRODUCTION ......................................................................... 4 1. Hemoglobin .......................................................................................... 4 1.1 Structure and function of Hemoglobin ........................................ 4 1.2 Structure of globin genes and their cluster organization ............. 5 1.3 Genomic context of the α– and β–globin gene clusters .............. 9 2. Globin gene switching ....................................................................... 12 2.1 Regulatory regions and transcription factors of globin genes ... 13 2.2 The β–Globin Locus Control Region (β–LCR) role in globin expression ....................................................................... 20 2.3 Chromatin role in β–like globin gene expression: the PYR role .............................................................................. 25 2.4 Summary on the fetal to adult switch .......................................
    [Show full text]
  • Rayra Pereira Santiago Acidente Vascular...2016.Pdf
    0 UNIVERSIDADE FEDERAL DA BAHIA FACULDADE DE MEDICINA FUNDAÇÃO OSWALDO CRUZ CENTRO DE PESQUISAS GONÇALO MONIZ UFBA FIOCRUZ CURSO DE PÓS-GRADUAÇÃO EM PATOLOGIA HUMANA E EXPERIMENTAL DISSERTAÇÃO DE MESTRADO ACIDENTE VASCULAR CEREBRAL NA HEMOGLOBINOPATIA SC (HBB GLU6VAL E GLU6LYS): AVALIAÇÃO DE MARCADORES DE PROGNÓSTICO RAYRA PEREIRA SANTIAGO Salvador – Bahia 2016 1 FUNDAÇÃO OSWALDO CRUZ CENTRO DE PESQUISAS GONÇALO MONIZ Curso de Pós-Graduação em Patologia Humana e Experimental ACIDENTE VASCULAR CEREBRAL NA HEMOGLOBINOPATIA SC (HBB GLU6VAL E GLU6LYS): AVALIAÇÃO DE MARCADORES DE PROGNÓSTICO RAYRA PEREIRA SANTIAGO Orientadora: Profª Drª Marilda de Souza Gonçalves Co-orientadora: Profª Drª Dalila Luciola Zanette Dissertação apresentada ao Curso de Pós-Graduação em Patologia Humana e Experimental para a obtenção do título de Mestre. Salvador – Bahia 2016 2 Ficha Catalográfica elaborada pela Biblioteca do Centro de Pesquisas Gonçalo Moniz / FIOCRUZ - Salvador - Bahia. Santiago, Rayra Pereira S235a Acidente Vascular Cerebral na Hemoglobinopatia SC (HBB glu6val e glu6lys): avaliação de marcadores de prognóstico. / Rayra Pereira Santiago. - 2016. 182 f. : il. ; 30 cm. Orientador: Profª Drª Marilda de Souza Gonçalves, Laboratório de Hematologia, Genética e Biologia Computacional. Dissertação (Mestrado em Patologia) – Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, 2016. 1. Doença SC. 2. Doppler. 3. Acidente vascular cerebral. I. Título. CDU 616.831-005.1 3 “ACIDENTE VASCULAR CEREBRAL NA HEMOGLOBINOPATIA SC (HBB GLU6VAL E GLU6LYS): AVALIAÇÃO DE MARCADORES DE PROGNÓSTICO” RAYRA PEREIRA SANTIAGO FOLHA DE APROVAÇÃO Salvador, 11 de março de 2016 COMISSÃO EXAMINADORA 4 Vamos agradecer a todos, por que nessa vida a gente não faz nada sozinho. Saulo Fernandes 5 Dedico este trabalho aos pacientes com hemoglobinopatia SC, que superam dificuldades todos os dias.
    [Show full text]
  • Expresión Del Cluster De Β-Globina Issn 0025-7680383
    EXPRESIÓN DEL CLUSTER DE β-GLOBINA ISSN 0025-7680383 ARTÍCULO ESPECIAL MEDICINA (Buenos Aires) 2016; 76: 383-389 REGULACIÓN DE EXPRESIÓN DE GENES DE LA FAMILIA DE β-GLOBINA HUMANA, ÚTIL EN LA BÚSQUEDA DE NUEVOS BLANCOS TERAPÉUTICOS PARA TRATAMIENTO DE HEMOGLOBINOPATÍAS KAREN G. SCHEPS1, 2, VIVIANA VARELA1, 2 1Cátedra de Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 2INIGEM (Instituto de Inmunología, Genética y Metabolismo), CONICET- Universidad de Buenos Aires, Argentina Resumen Durante la etapa embrionaria, el desarrollo fetal y la vida posnatal se expresan isoformas funcional- mente distintas de hemoglobina, producto de la combinación de cadenas polipeptídicas sintetizadas a partir de los distintos genes que componen las familias de α- y β-globina. En función de que la presencia de altos niveles de hemoglobina fetal (Hb F) es beneficiosa en síndromes falciformes y talasémicos graves, se plantea revisar las bases de la regulación de la expresión de los genes de la familia de β-globina, en particular los genes que codifican las cadenas de γ-globina (HBG1 y HBG2). En este trabajo se revisan los conocimientos sobre factores de transcripción y reguladores epigenéticos que gobiernan los eventos de encendido y apagado de los genes de la familia de β-globina. Se espera que la consolidación de estos conocimientos permita hallar nuevos blancos terapéuticos para el tratamiento de hemoglobinopatías. Palabras clave: Hb F, cluster de β-globina, genética, epigenética Abstract Regulation of the β-globin gene family expression, useful in the search for new therapeutic targets for hemoglobinopathies. Different hemoglobin isoforms are expressed during the embry- onic, fetal and postnatal stages.
    [Show full text]
  • Sickle Cell Aneamia in Cameroon
    Sickle Cell Anaemia in Cameroon: Co-Inheritance of α- Thalassemia, HBB Gene Haplotypes, Clinical & Haematological Characterisation s MARYAM RUMANEY (RMNMAR005) MSc in Human Genetics University of Cape Town FACULTY OF HEALTH SCIENCES SUPERVISED BY: Associate Professor Ambroise Wonkam CO-SUPERVISED BY: Ms Anna Alvera Vorster, and Professor Raj Ramesar 1 The copyright of this thesis vests in the author. No quotation from it or information derived from it is to be published without full acknowledgement of the source. The thesis is to be used for private study or non- commercial research purposes only. Published by the University of Cape Town (UCT) in terms of the non-exclusive license granted to UCT by the author. University of Cape Town DECLARATION I, MISS MARYAM BIBI RUMANEY, hereby declare that the work on which this dissertation/thesis is based is my original work (except where acknowledgements indicate otherwise) and that neither the whole work nor any part of it has been, is being, or is to be submitted for another degree in this or any other university. I empower the university to reproduce for the purpose of research either the whole or any portion of the contents in any manner whatsoever. Signature:__________Date: 25 May 2015 2 ACKNOWLEDGEMENTS "Smooth seas do not make skilful sailors." - African Proverb First, I acknowledge my Lord, my Creator, Allah, for giving me the strength to complete this study. It was through His Guidance and Mercy that I was able to succeed. I would like to express my warmest gratitude to my wonderful parents, Ismail Cassiem and Suraya Rumaney, and brothers, Hishamuddin and Nizamuddin Rumaney, who have supported me unconditionally in all my endeavours in life.
    [Show full text]
  • Assessing the Role of Genetic Variations at the Β-Globin Gene Cluster in Levels of Fetal Hemoglobin
    Assessing the role of genetic variations at the β-globin gene cluster in levels of fetal hemoglobin Catarina Rocha Pacheco Mestrado em Genética Forense Departamento de Biologia 2020 Orientador Maria João Prata, PhD, Faculdade de Ciências da Universidade do Porto (FCUP); Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP); Instituto de Investigação e Inovação em Saúde (i3S). Coorientador Verónica Gomes, PhD, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP); Instituto de Investigação e Inovação em Saúde (i3S). Todas as correções determinadas pelo júri, e só essas, foram efetuadas. O Presidente do Júri, Porto, ______/______/_________ FCUP ii Assessing the role of genetic variations at the β–globin gene cluster in levels of fetal hemoglobin Agradecimentos A toda a equipa do grupo de Genética Populacional e Evolução, do Instituto de Investigação e Inovação em Saúde (i3S), pela hospitalidade com que me receberam. À minha orientadora Professora Doutora Maria João Prata, pela excelente orientação que me proporcionou, por todos os conhecimentos que me transmitiu, pela total dedicação, preocupação e compreensão. Pelo tempo que dispensou para me ajudar. Obrigada por todas as sugestões, incentivo e ajuda na elaboração desta dissertação. Foi sem dúvida um privilégio poder aprender consigo. À minha coorientadora Doutora Verónica Gomes, por todo o auxílio e acompanhamento na parte laboratorial deste trabalho e pela incansável disponibilidade e paciência. Ao Doutor Licínio Manco, pela amabilidade e disponibilidade prestada e cuja ajuda foi indispensável para a concretização deste trabalho. Aos meus pais por todo o carinho e amor incondicional, por acreditarem em mim e me motivarem sempre a seguir os meus sonhos.
    [Show full text]
  • Human Gene Evolution the HUMAN MOLECULAR GENETICS Series
    Human Gene Evolution The HUMAN MOLECULAR GENETICS series Series Advisors D.N. Cooper, Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK S.E. Humphries, Division of Cardiovascular Genetics, University College London Medical School, London, UK T. Strachan, Department of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, UK Human Gene Mutation From Genotype to Phenotype Functional Analysis of the Human Genome Molecular Genetics of Cancer Environmental Mutagenesis HLA and MHC: Genes, Molecules and Function Human Genome Evolution Gene Therapy Molecular Endocrinology Venous Thrombosis: from Genes to Clinical Medicine Protein Dysfunction in Human Genetic Disease Molecular Genetics of Early Human Development Neurofibromatosis Type 1: from Genotype to Phenotype Analysis of Triplet Repeat Disorders Molecular Genetics of Hypertension Human Gene Evolution Forthcoming title B Cells Human Gene Evolution David N. Cooper Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK. © BIOS Scientific Publishers Limited, 1999 First published in 1999 All rights reserved. No part of this book may be reproduced or transmitted, in any form or by any means, without permission. A CIP catalogue record for this book is available from the British Library. ISBN 1 859961 51 7 BIOS Scientific Publishers Ltd 9 Newtec Place, Magdalen Road, Oxford OX4 1RE, UK Tel. +44 (0)1865 726286. Fax +44 (0)1865 246823 World Wide Web home page: http://www.bios.co.uk/ Published in the United States, its dependent territories and Canada by Academic Press, Inc., A Harcourt Science and Technology Company, 525 B Street, San Diego, CA 92101–4495. www.academicpress.com TO PAUL, CATRIN AND DUNCAN O sweet spontaneous earth how often has the naughty thumb of science prodded thy beauty thou answereth them only with spring.
    [Show full text]
  • Open Dissertation.Pdf
    The Pennsylvania State University The Graduate School College of Engineering INFERENCE OF ORTHOLOGS, WHILE CONSIDERING GENE CONVERSION, TO EVALUATE WHOLE-GENOME MULTIPLE SEQUENCE ALIGNMENTS A Dissertation in Computer Science and Engineering by Chih-Hao Hsu © 2009 Chih-Hao Hsu Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December 2009 The dissertation of Chih-Hao Hsu was reviewed and approved* by the following: Webb Miller Professor of Biology and Computer Science and Engineering Dissertation Advisor Chair of Committee Raj Acharya Professor of Computer Science and Engineering Head of the Department of Computer Science and Engineering Wang-Chien Lee Associate Professor of Computer Science and Engineering Ross Hardison T. Ming Chu Professor of Biochemistry and Molecular Biology *Signatures are on file in the Graduate School iii ABSTRACT The problem of computing a multiple-sequence alignment (MSA) is very important for the analysis of biological sequences. An equally critical problem is to evaluate the quality of an alignment. In the preliminary project described here, alignments produced by Multiz and ROAST of the human genome to other vertebrate genomes are evaluated using orthologous genes in 13 gene clusters from 6 mammalian species, which are identified using maximum-likelihood phylogenetic tree reconstruction methods. Analysis of the α- and β-globin gene clusters show that inferred ortholog relationships are accurate. The orthologous β-globin genes from over 14 species are used to evaluate the performance of four MSA programs (MLAGAN, MAVID, TBA and ROAST). The results show that the performance of ROAST is superior to the others. Furthermore, differences among gene clusters and among species are studied.
    [Show full text]
  • NGS4THAL, a One-Stop Molecular Diagnosis and Carrier Screening Tool for Thalassemia and Other Hemoglobinopathies by Next-Generation Sequencing
    NGS4THAL, a one-stop molecular diagnosis and carrier screening tool for thalassemia and other hemoglobinopathies by next-generation sequencing Yujie Cao Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong S.A.R., China Shau Yin Ha Department of Pathology, Hong Kong Children’s Hospital, Hong Kong S.A.R., China Chi-Chiu So Department of Pathology, Hong Kong Children’s Hospital, Hong Kong S.A.R., China Tong Ming For Clinical Genetic Service, Department of Health, The Government of the Hong Kong S.A.R., China Clara Sze-Man Tang Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong S.A.R., China Huoru Zhang Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong S.A.R., China Rui Liang Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong S.A.R., China Jing Yang Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong S.A.R., China Brian Hon-Yin Chung Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong S.A.R., China Godfrey Chi-Fung Chan Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong S.A.R., China Yu-Lung Lau Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong S.A.R., China Maria‐Mercè Garcia‐Barcelo Department of
    [Show full text]
  • Comparative Genome Analysis Delimits a Chromosomal Domain and Identifies Key Regulatory Elements in the Α Globin Cluster
    © 2001 Oxford University Press Human Molecular Genetics, 2001, Vol. 10, No. 4 371–382 Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the α globin cluster Jonathan Flint1, Cristina Tufarelli1,JohnPeden1,KevinClark1, Rachael J. Daniels1, Ross Hardison2, Webb Miller2, Sjaak Philipsen3,KianChenTan-Un4, Tara McMorrow3, Jonathan Frampton1,BlancheP.Alter5,+, Anna-Marie Frischauf6 and Douglas R. Higgs1,§ 1MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK, 2Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA, 3Faculteit der Geneeskunde en Gezondheids-Wetenschappen, Erasmus Universiteit, dr. Molewaterplein 50, Rotterdam, The Netherlands, 4School of Professional and Continuing Education, University of Hong Kong, Pokfulam Road, Hong Kong, 5Division of Pediatric Hematology/Oncology, Children’s Hospital, University of Texas Medical Branch, Galveston, TX, USA and 6Institut fuer Genetik und Allgemeine Biologie, Universitaet Salzburg, Austria Received 4 October 2000; Revised and Accepted 21 December 2000 We have cloned, sequenced and annotated segments availability of genomic regions that have been extensively of DNA spanning the mouse, chicken and pufferfish characterized at a number of levels, allowing genomic α globin gene clusters and compared them with the sequence to be related to function. We have previously corresponding region in man. This has defined a characterized the structure (2), epigenetic modifications (3–6) small segment (∼135–155 kb) of synteny and and function (summarized in refs 2 and 7) of a contiguous (376 kb) segment of DNA extending from the telomeric conserved gene order, which may contain all of the repeats of human chromosome 16p.
    [Show full text]
  • Screening of HBB Gene Mutations in Population Samples from Alentejo and Implementation of a ® Snapshot Based System for HBB*S Haplotyping
    MSc 2.º CICLO FCUP i3S Ipatimup 2017 implementation of a a of implementation Screening of Screening HBB gene mutations in population samplesfrom population in mutations gene Screening of HBB gene SNaPshot mutations in population ® based system system forbased samples from Alentejo and implementation of a ® HBB*S SNaPshot based system haplotyping for HBB*S haplotyping Alentejo and Cátia Sofia BotelhoSofia Cátia Couto Cátia Sofia Botelho Couto Dissertação de Mestrado apresentada à Faculdade de Ciências da Universidade do Porto Biologia 2017 Screening of HBB gene mutations in population samples from Alentejo and implementation of a ® SNaPshot based system for HBB*S haplotyping Cátia Sofia Botelho Couto Mestrado em Biologia Celular e Molecular Departamento de Biologia 2017 Orientador Maria João Prata, PhD, Faculdade de Ciências da Universidade do Porto (FCUP), Instituto de Patologia e Imunologia Molecular da Universidade do Poto (Ipatimup), Instituto de Investigação e Inovação em Saúde (i3S) Coorientador Luísa Azevedo, PhD, Faculdade de Ciências da Universidade do Porto (FCUP), Instituto de Patologia e Imunologia Molecular da Universidade do Poto (Ipatimup), Instituto de Investigação e Inovação em Saúde (i3S) All corrections determined by the jury, and only those, were incorporated. The President of the Jury, Porto, ______/______/_________ FCUP i Screening of HBB gene mutations in population samples from Alentejo and implementation of a SNaPshot® based system for HBB*S haplotyping Agradecimentos À equipa do Grupo de Genética Populacional e Evolução, do Instituto de Investigação e Inovação em Saúde (i3S), pela hospitalidade com a qual fui recebida, com especial agradecimento ao Professor Doutor António Amorim pela oportunidade concedida em realizar o projeto de mestrado neste grupo de investigação.
    [Show full text]