Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina

Over 700 samples from carriers of structural hemoglobinopathies and thalassemia, and affected individuals with these syndromes, were analyzed.\nThe frequency of ?-thalassemia was updated: mutations were detected in 417 families; 9 mutations were described for the first time in Argentina.\nFive mutat...

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Autor principal: Scheps, Karen Gabriela
Otros Autores: Varela, Viviana
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2015
Materias:
Hemoglobinopatías
Talasemia
Genética
Ciencia de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1162
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1162.dir/1162.PDF
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-HWA_1162
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spelling I28-R145-HWA_11622019-09-25 Over 700 samples from carriers of structural hemoglobinopathies and thalassemia, and affected individuals with these syndromes, were analyzed.\nThe frequency of ?-thalassemia was updated: mutations were detected in 417 families; 9 mutations were described for the first time in Argentina.\nFive mutations associated with dominant forms of ?-thalassemia were detected: Hb Durham-N.C., and 4 novel mutations: Hbs Tavapy(HBB:c.182_187delCTCATG), JC-Paz(HBB:c.34_42delGTTACTGCC), Wilde (HBB:c.270_273delTGAG) and Patagonia(HBB:c.296_297dupGT).\nDeletions are the most common ?-thalassemic mutations (-?3,7, --MEDI, --CAL/CAMP and ?SEA). Three novel deletions were characterized: --BA, --PA and ?LU. The last one was identified in a boy with phenotypic features consistent with ATR-16. Point mutations were detected in both HBA genes; 3 novel mutations were detected: HBA1:c.301-2A>T, HBA1:c.187delG(p.W62fsX66) and HBA1:c.237delC(p.Asn78Lysfs*6).\nHb S is the most frequent structural hemoglobinopathy; mutations leading to unstable hemoglobins, hemoglobins with increased oxygen affinity and Hb M were detected, sporadically.\nGenotype-Phenotype association studies were performed to evaluate loci involved in Hb F levels variation.\nPrimary, secondary and tertiary genetic modifiers were analyzed in patients with thalassemia intermedia. Two novel ?-globin cluster duplications were detected.\nGenotype-Phenotype profiles were made and algorithms for molecular characterization were established.\nHopefully, this work will result in benefit of the affected families. Fil: Scheps, Karen Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Facultad de Farmacia y Bioquímica Varela, Viviana Scheps, Karen Gabriela 2015-04-29 Se analizaron más de 700 muestras de pacientes con fenotipos hematológicos portadores de hemoglobinopatías estructurales, de talasemias menor, mayor y no transfusión dependiente.\nSe actualizó la frecuencia de ?-talasemia en 417 familias: 9 mutaciones se describieron por primera vez en Argentina.\nSe caracterizaron 5 mutaciones con fenotipo de talasemia dominante: Hb Durham-N.C., y 4 nóveles: Hbs Tavapy(HBB:c.182_187delCTCATG), JC-Paz(HBB:c.34_42delGTTACTGCC), Wilde (HBB:c.270_273delTGAG) y Patagonia(HBB:c.296_297dupGT).\nLas deleciones son las mutaciones ?-talasémicas más frecuentes (-?3,7, --MEDI, --CAL/CAMP y ?SEA). Se detectaron 3 deleciones nóveles: --BA, --PA y --LU, esta última en un paciente con retraso mental y rasgos de ATR-16. Se caracterizaron mutaciones puntuales, 3 nóveles: HBA1:c.301-2A>T, HBA1:c.187delG(p.W62fsX66) y HBA1:c.237delC(p.Asn78Lysfs*6).\nLa Hb S fue la hemoglobinopatía estructural prevalente y en forma esporádica se detectaron hemoglobinas inestables, con afinidad aumentada por el oxígeno y metahemoglobinas.\nSe hicieron estudios de asociación genotipo-fenotipo para marcadores asociados a variación de Hb F.\nEn pacientes con talasemia intermedia, se estudiaron modificadores primarios, secundarios y terciarios. Se detectaron 2 duplicaciones del cluster de ?-globina, una caracterizada por array-CGH, ((arr[hg19]Chr16(16p13.3; 88165- 230724)x3).\nSe confeccionaron perfiles genotipo-fenotipo, y algoritmos de trabajo para la caracterización molecular.\nSe espera que estos conocimientos sean en beneficio de las familias afectadas. application/pdf Adamo, Ana Chiappe, Gustavo Slavutsky, Irma Hemoglobinopatías Talasemia Genética spa info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencia de la vida Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1162 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1162.dir/1162.PDF
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Español
orig_language_str_mv spa
topic Hemoglobinopatías
Talasemia
Genética
Ciencia de la vida
spellingShingle Hemoglobinopatías
Talasemia
Genética
Ciencia de la vida
Scheps, Karen Gabriela
Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina
topic_facet Hemoglobinopatías
Talasemia
Genética
Ciencia de la vida
description Over 700 samples from carriers of structural hemoglobinopathies and thalassemia, and affected individuals with these syndromes, were analyzed.\nThe frequency of ?-thalassemia was updated: mutations were detected in 417 families; 9 mutations were described for the first time in Argentina.\nFive mutations associated with dominant forms of ?-thalassemia were detected: Hb Durham-N.C., and 4 novel mutations: Hbs Tavapy(HBB:c.182_187delCTCATG), JC-Paz(HBB:c.34_42delGTTACTGCC), Wilde (HBB:c.270_273delTGAG) and Patagonia(HBB:c.296_297dupGT).\nDeletions are the most common ?-thalassemic mutations (-?3,7, --MEDI, --CAL/CAMP and ?SEA). Three novel deletions were characterized: --BA, --PA and ?LU. The last one was identified in a boy with phenotypic features consistent with ATR-16. Point mutations were detected in both HBA genes; 3 novel mutations were detected: HBA1:c.301-2A>T, HBA1:c.187delG(p.W62fsX66) and HBA1:c.237delC(p.Asn78Lysfs*6).\nHb S is the most frequent structural hemoglobinopathy; mutations leading to unstable hemoglobins, hemoglobins with increased oxygen affinity and Hb M were detected, sporadically.\nGenotype-Phenotype association studies were performed to evaluate loci involved in Hb F levels variation.\nPrimary, secondary and tertiary genetic modifiers were analyzed in patients with thalassemia intermedia. Two novel ?-globin cluster duplications were detected.\nGenotype-Phenotype profiles were made and algorithms for molecular characterization were established.\nHopefully, this work will result in benefit of the affected families.
author2 Varela, Viviana
author_facet Varela, Viviana
Scheps, Karen Gabriela
format Tesis doctoral
Tesis doctoral
acceptedVersion
author Scheps, Karen Gabriela
author_sort Scheps, Karen Gabriela
title Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina
title_short Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina
title_full Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina
title_fullStr Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina
title_full_unstemmed Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina
title_sort bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina
publisher Facultad de Farmacia y Bioquímica
publishDate 2015
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1162
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1162.dir/1162.PDF
work_keys_str_mv AT schepskarengabriela basesmolecularesdelasalteracionesgeneticasqueafectanlasintesisdehemoglobina
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