Solís Moruno, Manuel, 1993-Mensa Vilaró, AnnaBatlle Masó, Laura, 1993-Lobon Garcia, IreneBonet, NúriaMarquès i Bonet, Tomàs, 1975-Aróstegui Gorospe, Juan IgnacioCasals López, Ferran2021-08-042021-08-042021Solís-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-y2045-2322http://hdl.handle.net/10230/48309There 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.application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-021-92381-yBioinformaticsDiseasesGeneticsGenomic analysisImmunologyMedical researchinfo:eu-repo/semantics/openAccess