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Clinical genomics and precision medicine
Precision Medicine emerges from the genomic paradigm of health and disease. For precise molecular diagnoses of genetic diseases, we must analyze the Whole Exome (WES) or the Whole Genome (WGS). By not needing exon capture, WGS is more powerful to detect single nucleotide variants and copy number var...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Sociedade Brasileira de Genética
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555143/ https://www.ncbi.nlm.nih.gov/pubmed/36218382 http://dx.doi.org/10.1590/1678-4685-GMB-2022-0150 |
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author | Pena, Sérgio D. J. Tarazona-Santos, Eduardo |
author_facet | Pena, Sérgio D. J. Tarazona-Santos, Eduardo |
author_sort | Pena, Sérgio D. J. |
collection | PubMed |
description | Precision Medicine emerges from the genomic paradigm of health and disease. For precise molecular diagnoses of genetic diseases, we must analyze the Whole Exome (WES) or the Whole Genome (WGS). By not needing exon capture, WGS is more powerful to detect single nucleotide variants and copy number variants. In healthy individuals, we can observe monogenic highly penetrant variants, which may be causally responsible for diseases, and also susceptibility variants, associated with common polygenic diseases. But there is the major problem of penetrance. Thus, there is the question of whether it is worthwhile to perform WGS in all healthy individuals as a step towards Precision Medicine. The genetic architecture of disease is consistent with the fact that they are all polygenic. Moreover, ancestry adds another layer of complexity. We are now capable of obtaining Polygenic Risk Scores for all complex diseases using only data from new generation sequencing. Yet, review of available evidence does not at present favor the idea that WGS analyses are sufficiently developed to allow reliable predictions of the risk components for monogenic and polygenic hereditary diseases in healthy individuals. Probably, it is still better for WGS to remain reserved for the diagnosis of pathogenic variants of Mendelian diseases. |
format | Online Article Text |
id | pubmed-9555143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Sociedade Brasileira de Genética |
record_format | MEDLINE/PubMed |
spelling | pubmed-95551432022-10-17 Clinical genomics and precision medicine Pena, Sérgio D. J. Tarazona-Santos, Eduardo Genet Mol Biol Human and Medical Genetics Precision Medicine emerges from the genomic paradigm of health and disease. For precise molecular diagnoses of genetic diseases, we must analyze the Whole Exome (WES) or the Whole Genome (WGS). By not needing exon capture, WGS is more powerful to detect single nucleotide variants and copy number variants. In healthy individuals, we can observe monogenic highly penetrant variants, which may be causally responsible for diseases, and also susceptibility variants, associated with common polygenic diseases. But there is the major problem of penetrance. Thus, there is the question of whether it is worthwhile to perform WGS in all healthy individuals as a step towards Precision Medicine. The genetic architecture of disease is consistent with the fact that they are all polygenic. Moreover, ancestry adds another layer of complexity. We are now capable of obtaining Polygenic Risk Scores for all complex diseases using only data from new generation sequencing. Yet, review of available evidence does not at present favor the idea that WGS analyses are sufficiently developed to allow reliable predictions of the risk components for monogenic and polygenic hereditary diseases in healthy individuals. Probably, it is still better for WGS to remain reserved for the diagnosis of pathogenic variants of Mendelian diseases. Sociedade Brasileira de Genética 2022-10-10 /pmc/articles/PMC9555143/ /pubmed/36218382 http://dx.doi.org/10.1590/1678-4685-GMB-2022-0150 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (type CC-BY), which permits unrestricted use, istribution and reproduction in any medium, provided the original article is properly cited. |
spellingShingle | Human and Medical Genetics Pena, Sérgio D. J. Tarazona-Santos, Eduardo Clinical genomics and precision medicine |
title | Clinical genomics and precision medicine |
title_full | Clinical genomics and precision medicine |
title_fullStr | Clinical genomics and precision medicine |
title_full_unstemmed | Clinical genomics and precision medicine |
title_short | Clinical genomics and precision medicine |
title_sort | clinical genomics and precision medicine |
topic | Human and Medical Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555143/ https://www.ncbi.nlm.nih.gov/pubmed/36218382 http://dx.doi.org/10.1590/1678-4685-GMB-2022-0150 |
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