Assessment of the gene mosaicism burden in blood and its implications for immune disorders

Abstract There are increasing evidences showing the contribution of somatic genetic variants to non-cancer diseases. However, their detection using massive parallel sequencing methods still has important limitations. In addition, the relative importance and dynamics of somatic variation in healthy t...

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Autores principales:	Manuel Solís-Moruno, Anna Mensa-Vilaró, Laura Batlle-Masó, Irene Lobón, Núria Bonet, Tomàs Marquès-Bonet, Juan I. Aróstegui, Ferran Casals
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71ffda2323b34170856d383b012a8230
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spelling	oai:doaj.org-article:71ffda2323b34170856d383b012a82302021-12-02T16:07:04ZAssessment of the gene mosaicism burden in blood and its implications for immune disorders10.1038/s41598-021-92381-y2045-2322https://doaj.org/article/71ffda2323b34170856d383b012a82302021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92381-yhttps://doaj.org/toc/2045-2322Abstract There are increasing evidences showing the contribution of somatic genetic variants to non-cancer diseases. However, their detection using massive parallel sequencing methods still has important limitations. In addition, the relative importance and dynamics of somatic variation in healthy tissues are not fully understood. We performed high-depth whole-exome sequencing in 16 samples from patients with a previously determined pathogenic somatic variant for a primary immunodeficiency and tested different variant callers detection ability. Subsequently, we explored the load of somatic variants in the whole blood of these individuals and validated it by amplicon-based deep sequencing. Variant callers allowing low frequency read thresholds were able to detect most of the variants, even at very low frequencies in the tissue. The genetic load of somatic coding variants detectable in whole blood is low, ranging from 1 to 2 variants in our dataset, except for one case with 17 variants compatible with clonal haematopoiesis under genetic drift. Because of the ability we demonstrated to detect this type of genetic variation, and its relevant role in disorders such as primary immunodeficiencies, we suggest considering this model of gene mosaicism in future genetic studies and considering revisiting previous massive parallel sequencing data in patients with negative results.Manuel Solís-MorunoAnna Mensa-VilaróLaura Batlle-MasóIrene LobónNúria BonetTomàs Marquès-BonetJuan I. ArósteguiFerran CasalsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manuel Solís-Moruno Anna Mensa-Vilaró Laura Batlle-Masó Irene Lobón Núria Bonet Tomàs Marquès-Bonet Juan I. Aróstegui Ferran Casals Assessment of the gene mosaicism burden in blood and its implications for immune disorders
description	Abstract There are increasing evidences showing the contribution of somatic genetic variants to non-cancer diseases. However, their detection using massive parallel sequencing methods still has important limitations. In addition, the relative importance and dynamics of somatic variation in healthy tissues are not fully understood. We performed high-depth whole-exome sequencing in 16 samples from patients with a previously determined pathogenic somatic variant for a primary immunodeficiency and tested different variant callers detection ability. Subsequently, we explored the load of somatic variants in the whole blood of these individuals and validated it by amplicon-based deep sequencing. Variant callers allowing low frequency read thresholds were able to detect most of the variants, even at very low frequencies in the tissue. The genetic load of somatic coding variants detectable in whole blood is low, ranging from 1 to 2 variants in our dataset, except for one case with 17 variants compatible with clonal haematopoiesis under genetic drift. Because of the ability we demonstrated to detect this type of genetic variation, and its relevant role in disorders such as primary immunodeficiencies, we suggest considering this model of gene mosaicism in future genetic studies and considering revisiting previous massive parallel sequencing data in patients with negative results.
format	article
author	Manuel Solís-Moruno Anna Mensa-Vilaró Laura Batlle-Masó Irene Lobón Núria Bonet Tomàs Marquès-Bonet Juan I. Aróstegui Ferran Casals
author_facet	Manuel Solís-Moruno Anna Mensa-Vilaró Laura Batlle-Masó Irene Lobón Núria Bonet Tomàs Marquès-Bonet Juan I. Aróstegui Ferran Casals
author_sort	Manuel Solís-Moruno
title	Assessment of the gene mosaicism burden in blood and its implications for immune disorders
title_short	Assessment of the gene mosaicism burden in blood and its implications for immune disorders
title_full	Assessment of the gene mosaicism burden in blood and its implications for immune disorders
title_fullStr	Assessment of the gene mosaicism burden in blood and its implications for immune disorders
title_full_unstemmed	Assessment of the gene mosaicism burden in blood and its implications for immune disorders
title_sort	assessment of the gene mosaicism burden in blood and its implications for immune disorders
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/71ffda2323b34170856d383b012a8230
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Assessment of the gene mosaicism burden in blood and its implications for immune disorders

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