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Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias
The hereditary anemias are a relatively heterogeneous set of disorders that can show wide clinical and genetic heterogeneity, which often hampers correct clinical diagnosis. The classical diagnostic workflow for these conditions generally used to start with analysis of the family and personal histor...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783452/ https://www.ncbi.nlm.nih.gov/pubmed/33414725 http://dx.doi.org/10.3389/fphys.2020.613559 |
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author | Russo, Roberta Marra, Roberta Rosato, Barbara Eleni Iolascon, Achille Andolfo, Immacolata |
author_facet | Russo, Roberta Marra, Roberta Rosato, Barbara Eleni Iolascon, Achille Andolfo, Immacolata |
author_sort | Russo, Roberta |
collection | PubMed |
description | The hereditary anemias are a relatively heterogeneous set of disorders that can show wide clinical and genetic heterogeneity, which often hampers correct clinical diagnosis. The classical diagnostic workflow for these conditions generally used to start with analysis of the family and personal histories, followed by biochemical and morphological evaluations, and ending with genetic testing. However, the diagnostic framework has changed more recently, and genetic testing is now a suitable approach for differential diagnosis of these patients. There are several approaches to this genetic testing, the choice of which depends on phenotyping, genetic heterogeneity, and gene size. For patients who show complete phenotyping, single-gene testing remains recommended. However, genetic analysis now includes next-generation sequencing, which is generally based on custom-designed targeting panels and whole-exome sequencing. The use of next-generation sequencing also allows the identification of new causative genes, and of polygenic conditions and genetic factors that modify disease severity of hereditary anemias. In the research field, whole-genome sequencing is useful for the identification of non-coding causative mutations, which might account for the disruption of transcriptional factor occupancy sites and cis-regulatory elements. Moreover, advances in high-throughput sequencing techniques have now resulted in the identification of genome-wide profiling of the chromatin structures known as the topologically associating domains. These represent a recurrent disease mechanism that exposes genes to inappropriate regulatory elements, causing errors in gene expression. This review focuses on the challenges of diagnosis and research into hereditary anemias, with indications of both the advantages and disadvantages. Finally, we consider the future perspectives for the use of next-generation sequencing technologies in this era of precision medicine. |
format | Online Article Text |
id | pubmed-7783452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77834522021-01-06 Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias Russo, Roberta Marra, Roberta Rosato, Barbara Eleni Iolascon, Achille Andolfo, Immacolata Front Physiol Physiology The hereditary anemias are a relatively heterogeneous set of disorders that can show wide clinical and genetic heterogeneity, which often hampers correct clinical diagnosis. The classical diagnostic workflow for these conditions generally used to start with analysis of the family and personal histories, followed by biochemical and morphological evaluations, and ending with genetic testing. However, the diagnostic framework has changed more recently, and genetic testing is now a suitable approach for differential diagnosis of these patients. There are several approaches to this genetic testing, the choice of which depends on phenotyping, genetic heterogeneity, and gene size. For patients who show complete phenotyping, single-gene testing remains recommended. However, genetic analysis now includes next-generation sequencing, which is generally based on custom-designed targeting panels and whole-exome sequencing. The use of next-generation sequencing also allows the identification of new causative genes, and of polygenic conditions and genetic factors that modify disease severity of hereditary anemias. In the research field, whole-genome sequencing is useful for the identification of non-coding causative mutations, which might account for the disruption of transcriptional factor occupancy sites and cis-regulatory elements. Moreover, advances in high-throughput sequencing techniques have now resulted in the identification of genome-wide profiling of the chromatin structures known as the topologically associating domains. These represent a recurrent disease mechanism that exposes genes to inappropriate regulatory elements, causing errors in gene expression. This review focuses on the challenges of diagnosis and research into hereditary anemias, with indications of both the advantages and disadvantages. Finally, we consider the future perspectives for the use of next-generation sequencing technologies in this era of precision medicine. Frontiers Media S.A. 2020-12-22 /pmc/articles/PMC7783452/ /pubmed/33414725 http://dx.doi.org/10.3389/fphys.2020.613559 Text en Copyright © 2020 Russo, Marra, Rosato, Iolascon and Andolfo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Russo, Roberta Marra, Roberta Rosato, Barbara Eleni Iolascon, Achille Andolfo, Immacolata Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias |
title | Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias |
title_full | Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias |
title_fullStr | Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias |
title_full_unstemmed | Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias |
title_short | Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias |
title_sort | genetics and genomics approaches for diagnosis and research into hereditary anemias |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783452/ https://www.ncbi.nlm.nih.gov/pubmed/33414725 http://dx.doi.org/10.3389/fphys.2020.613559 |
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