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Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups

Findings resulting from whole-genome sequencing (WGS) have markedly increased due to the massive evolvement of sequencing methods and have led to further investigations such as clinical actionability of genes, as documented by the American College of Medical Genetics and Genomics (ACMG). ACMG’s acti...

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Autores principales: Chimusa, Emile R., Alosaimi, Shatha, Bope, Christian D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263835/
https://www.ncbi.nlm.nih.gov/pubmed/35812734
http://dx.doi.org/10.3389/fgene.2022.835713
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author Chimusa, Emile R.
Alosaimi, Shatha
Bope, Christian D.
author_facet Chimusa, Emile R.
Alosaimi, Shatha
Bope, Christian D.
author_sort Chimusa, Emile R.
collection PubMed
description Findings resulting from whole-genome sequencing (WGS) have markedly increased due to the massive evolvement of sequencing methods and have led to further investigations such as clinical actionability of genes, as documented by the American College of Medical Genetics and Genomics (ACMG). ACMG’s actionable genes (ACGs) may not necessarily be clinically actionable across all populations worldwide. It is critical to examine the actionability of these genes in different populations. Here, we have leveraged a combined WES from the African Genome Variation and 1000 Genomes Project to examine the generalizability of ACG and potential actionable genes from four diseases: high-burden malaria, TB, HIV/AIDS, and sickle cell disease. Our results suggest that ethnolinguistic cultural groups from Africa, particularly Bantu and Khoesan, have high genetic diversity, high proportion of derived alleles at low minor allele frequency (0.0–0.1), and the highest proportion of pathogenic variants within HIV, TB, malaria, and sickle cell diseases. In contrast, ethnolinguistic cultural groups from the non-Africa continent, including Latin American, Afro-related, and European-related groups, have a high proportion of pathogenic variants within ACG than most of the ethnolinguistic cultural groups from Africa. Overall, our results show high genetic diversity in the present actionable and known disease-associated genes of four African high-burden diseases, suggesting the limitation of transferability or generalizability of ACG. This supports the use of personalized medicine as beneficial to the worldwide population as well as actionable gene list recommendation to further foster equitable global healthcare. The results point out the bias in the knowledge about the frequency distribution of these phenotypes and genetic variants associated with some diseases, especially in African and African ancestry populations.
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spelling pubmed-92638352022-07-09 Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups Chimusa, Emile R. Alosaimi, Shatha Bope, Christian D. Front Genet Genetics Findings resulting from whole-genome sequencing (WGS) have markedly increased due to the massive evolvement of sequencing methods and have led to further investigations such as clinical actionability of genes, as documented by the American College of Medical Genetics and Genomics (ACMG). ACMG’s actionable genes (ACGs) may not necessarily be clinically actionable across all populations worldwide. It is critical to examine the actionability of these genes in different populations. Here, we have leveraged a combined WES from the African Genome Variation and 1000 Genomes Project to examine the generalizability of ACG and potential actionable genes from four diseases: high-burden malaria, TB, HIV/AIDS, and sickle cell disease. Our results suggest that ethnolinguistic cultural groups from Africa, particularly Bantu and Khoesan, have high genetic diversity, high proportion of derived alleles at low minor allele frequency (0.0–0.1), and the highest proportion of pathogenic variants within HIV, TB, malaria, and sickle cell diseases. In contrast, ethnolinguistic cultural groups from the non-Africa continent, including Latin American, Afro-related, and European-related groups, have a high proportion of pathogenic variants within ACG than most of the ethnolinguistic cultural groups from Africa. Overall, our results show high genetic diversity in the present actionable and known disease-associated genes of four African high-burden diseases, suggesting the limitation of transferability or generalizability of ACG. This supports the use of personalized medicine as beneficial to the worldwide population as well as actionable gene list recommendation to further foster equitable global healthcare. The results point out the bias in the knowledge about the frequency distribution of these phenotypes and genetic variants associated with some diseases, especially in African and African ancestry populations. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9263835/ /pubmed/35812734 http://dx.doi.org/10.3389/fgene.2022.835713 Text en Copyright © 2022 Chimusa, Alosaimi and Bope. https://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 Genetics
Chimusa, Emile R.
Alosaimi, Shatha
Bope, Christian D.
Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups
title Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups
title_full Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups
title_fullStr Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups
title_full_unstemmed Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups
title_short Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups
title_sort dissecting generalizability and actionability of disease-associated genes from 20 worldwide ethnolinguistic cultural groups
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263835/
https://www.ncbi.nlm.nih.gov/pubmed/35812734
http://dx.doi.org/10.3389/fgene.2022.835713
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