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Genomic approaches to identifying targets for treating β hemoglobinopathies

Sickle cell disease and β thalassemia are common severe diseases with little effective pathophysiologically-based treatment. Their phenotypic heterogeneity prompted genomic approaches to identify modifiers that ultimately might be exploited therapeutically. Fetal hemoglobin (HbF) is the major modula...

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Autores principales: Ngo, Duyen A., Steinberg, Martin H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517356/
https://www.ncbi.nlm.nih.gov/pubmed/26215470
http://dx.doi.org/10.1186/s12920-015-0120-2
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author Ngo, Duyen A.
Steinberg, Martin H.
author_facet Ngo, Duyen A.
Steinberg, Martin H.
author_sort Ngo, Duyen A.
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description Sickle cell disease and β thalassemia are common severe diseases with little effective pathophysiologically-based treatment. Their phenotypic heterogeneity prompted genomic approaches to identify modifiers that ultimately might be exploited therapeutically. Fetal hemoglobin (HbF) is the major modulator of the phenotype of the β hemoglobinopathies. HbF inhibits deoxyHbS polymerization and in β thalassemia compensates for the reduction of HbA. The major success of genomics has been a better understanding the genetic regulation of HbF by identifying the major quantitative trait loci for this trait. If the targets identified can lead to means of increasing HbF to therapeutic levels in sufficient numbers of sickle or β-thalassemia erythrocytes, the pathophysiology of these diseases would be reversed. The availability of new target loci, high-throughput drug screening, and recent advances in genome editing provide the opportunity for new approaches to therapeutically increasing HbF production.
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spelling pubmed-45173562015-07-29 Genomic approaches to identifying targets for treating β hemoglobinopathies Ngo, Duyen A. Steinberg, Martin H. BMC Med Genomics Review Sickle cell disease and β thalassemia are common severe diseases with little effective pathophysiologically-based treatment. Their phenotypic heterogeneity prompted genomic approaches to identify modifiers that ultimately might be exploited therapeutically. Fetal hemoglobin (HbF) is the major modulator of the phenotype of the β hemoglobinopathies. HbF inhibits deoxyHbS polymerization and in β thalassemia compensates for the reduction of HbA. The major success of genomics has been a better understanding the genetic regulation of HbF by identifying the major quantitative trait loci for this trait. If the targets identified can lead to means of increasing HbF to therapeutic levels in sufficient numbers of sickle or β-thalassemia erythrocytes, the pathophysiology of these diseases would be reversed. The availability of new target loci, high-throughput drug screening, and recent advances in genome editing provide the opportunity for new approaches to therapeutically increasing HbF production. BioMed Central 2015-07-29 /pmc/articles/PMC4517356/ /pubmed/26215470 http://dx.doi.org/10.1186/s12920-015-0120-2 Text en © Ngo and Steinberg. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Ngo, Duyen A.
Steinberg, Martin H.
Genomic approaches to identifying targets for treating β hemoglobinopathies
title Genomic approaches to identifying targets for treating β hemoglobinopathies
title_full Genomic approaches to identifying targets for treating β hemoglobinopathies
title_fullStr Genomic approaches to identifying targets for treating β hemoglobinopathies
title_full_unstemmed Genomic approaches to identifying targets for treating β hemoglobinopathies
title_short Genomic approaches to identifying targets for treating β hemoglobinopathies
title_sort genomic approaches to identifying targets for treating β hemoglobinopathies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517356/
https://www.ncbi.nlm.nih.gov/pubmed/26215470
http://dx.doi.org/10.1186/s12920-015-0120-2
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