Welcome to the UPF Digital Repository

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

Show simple item record

dc.contributor.author Solís Moruno, Manuel, 1993-
dc.contributor.author Mensa Vilaró, Anna
dc.contributor.author Batlle Masó, Laura, 1993-
dc.contributor.author Lobón, Irene
dc.contributor.author Bonet, Núria
dc.contributor.author Marquès i Bonet, Tomàs, 1975-
dc.contributor.author Aróstegui Gorospe, Juan Ignacio
dc.contributor.author Casals López, Ferran
dc.date.accessioned 2021-08-04T05:58:09Z
dc.date.available 2021-08-04T05:58:09Z
dc.date.issued 2021
dc.identifier.citation Solís-Moruno M, Mensa-Vilaró A, Batlle-Masó L, Lobón I, Bonet N, Marquès-Bonet T, Aróstegui JI, Casals F. Assessment of the gene mosaicism burden in blood and its implications for immune disorders. Sci Rep. 2021;11(1):12940. DOI: 10.1038/s41598-021-92381-y
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/48309
dc.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.
dc.description.sponsorship This study was funded by grants SAF2015-68472-C2-2-R from the Ministerio de Economía y Competitividad (Spain), RTI2018-096824-B-C22 grant from the Spanish Ministry of Science, Innovation and Universities co-financed by FEDER and by Direcció General de Recerca, Generalitat de Catalunya (2017SGR-702) to F.C. M.S.-M. is supported by the Ministerio de Economía y Competitividad, Spain (Maria de Maetzu grant MDM-2014-0370-16-3). L.B.-M. is supported by a Formació de personal Investigador fellowship from Generalitat de Catalunya (2018_FI_B00072). T.M-B. is supported by BFU2017-86471-P (MINECO/FEDER, UE), U01 MH106874 grant, Howard Hughes International Early Career, Obra Social "La Caixa" and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). Supported in part by CERCA Programme/Generalitat de Catalunya (JI.A.), SAF2015-68472-C2-1-R grant from the Ministerio de Economía y Competitividad (Spain) co-financed by European Regional Development Fund (ERDF) (JI.A.), RTI2018-096824-B-C21 grant from the Ministerio de Ciencia, Innovación y Universidades (Spain) co-financed by ERDF (JI.A.), AC15/00027 grant from the Instituto de Salud Carlos III / Transnational Research Projects on Rare Diseases (JI.A.).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Sci Rep. 2021;11(1):12940
dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Assessment of the gene mosaicism burden in blood and its implications for immune disorders
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41598-021-92381-y
dc.subject.keyword Bioinformatics
dc.subject.keyword Diseases
dc.subject.keyword Genetics
dc.subject.keyword Genomic analysis
dc.subject.keyword Immunology
dc.subject.keyword Medical research
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-68472-C2-2-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096824-B-C22
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86471-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-68472-C2-1-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096824-B-C21
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account


Compliant to Partaking