Behjati, S. et al. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513, 422–425 (2014). This study is one of the first to use colony sequencing from a multicellular organism to reconstruct phylogenies based on shared variants.
Article CAS PubMed PubMed Central Google Scholar
Ju, Y. S. et al. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo. Nature 543, 714–718 (2017).
Article CAS PubMed PubMed Central Google Scholar
Ye, A. Y. et al. A model for postzygotic mosaicisms quantifies the allele fraction drift, mutation rate, and contribution to de novo mutations. Genome Res. 28, 943–951 (2018).
Article CAS PubMed PubMed Central Google Scholar
Spencer Chapman, M. et al. Lineage tracing of human development through somatic mutations. Nature 595, 85–90 (2021).
Article CAS PubMed Google Scholar
Coorens, T. H. H. et al. Extensive phylogenies of human development inferred from somatic mutations. Nature 597, 387–392 (2021).
Article CAS PubMed Google Scholar
Rockweiler, N. B. et al. The origins and functional effects of postzygotic mutations throughout the human life span. Science 380, eabn7113 (2023). This study demonstrates the potential to use widely available bulk RNA-seq databases for mosaic variant discovery and to reveal insights about embryonic variant acquisition.
Article CAS PubMed Google Scholar
Jaiswal, S. et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498 (2014). In this study, the authors provide one of the first demonstrations of the ubiquity of somatic mosaicism in the blood of aged individuals and link it to adverse health outcomes.
Article PubMed PubMed Central Google Scholar
Genovese, G. et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N. Engl. J. Med. 371, 2477–2487 (2014).
Article PubMed PubMed Central Google Scholar
Coombs, C. C. et al. Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes. Cell Stem Cell 21, 374–382.e4 (2017).
Article CAS PubMed PubMed Central Google Scholar
Martincorena, I. et al. Somatic mutant clones colonize the human esophagus with age. Science 362, 911–917 (2018).
Article CAS PubMed PubMed Central Google Scholar
Watson, C. J. et al. The evolutionary dynamics and fitness landscape of clonal hematopoiesis. Science 367, 1449–1454 (2020).
Article CAS PubMed Google Scholar
Moore, L. et al. The mutational landscape of human somatic and germline cells. Nature 597, 381–386 (2021).
Article CAS PubMed Google Scholar
Aluri, J. & Cooper, M. A. Genetic mosaicism as a cause of inborn errors of immunity. J. Clin. Immunol. 41, 718–728 (2021).
Article PubMed PubMed Central Google Scholar
Campbell, I. M., Shaw, C. A., Stankiewicz, P. & Lupski, J. R. Somatic mosaicism: implications for disease and transmission genetics. Trends Genet. 31, 382–392 (2015).
Article CAS PubMed PubMed Central Google Scholar
Martinez-Glez, V. et al. A six-attribute classification of genetic mosaicism. Genet. Med. 22, 1743–1757 (2020).
Article PubMed PubMed Central Google Scholar
Park, S. et al. Clonal dynamics in early human embryogenesis inferred from somatic mutation. Nature 597, 393–397 (2021).
Article CAS PubMed Google Scholar
Acuna-Hidalgo, R. et al. Post-zygotic point mutations are an underrecognized source of de novo genomic variation. Am. J. Hum. Genet. 97, 67–74 (2015). This study is one of the earliest to use trio sequencing to demonstrate that a substantial portion of variants presumed to be germline are in fact mosaic.
Article CAS PubMed PubMed Central Google Scholar
Cook, C. B. et al. Somatic mosaicism detected by genome-wide sequencing in 500 parent–child trios with suspected genetic disease: clinical and genetic counseling implications. Cold Spring Harb. Mol. Case Stud. 7, a006125 (2021).
Article PubMed PubMed Central Google Scholar
Wright, C. F. et al. Clinically-relevant postzygotic mosaicism in parents and children with developmental disorders in trio exome sequencing data. Nat. Commun. 10, 2985 (2019).
Article CAS PubMed PubMed Central Google Scholar
Gambin, T. et al. Low-level parental somatic mosaic SNVs in exomes from a large cohort of trios with diverse suspected Mendelian conditions. Genet. Med. 22, 1768–1776 (2020).
Article CAS PubMed PubMed Central Google Scholar
Domogala, D. D. et al. Detection of low-level parental somatic mosaicism for clinically relevant SNVs and indels identified in a large exome sequencing dataset. Hum. Genomics 15, 72 (2021).
Article CAS PubMed PubMed Central Google Scholar
Sasani, T. A. et al. Large, three-generation human families reveal post-zygotic mosaicism and variability in germline mutation accumulation. eLife 8, e46922 (2019).
Article PubMed PubMed Central Google Scholar
Lee, H. et al. Characterization of early postzygotic somatic mutations through multi-organ analysis. J. Hum. Genet. 66, 777–784 (2021).
Rodin, R. E. et al. The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing. Nat. Neurosci. 24, 176–185 (2021).
Article CAS PubMed PubMed Central Google Scholar
Gallini, S. et al. Injury prevents Ras mutant cell expansion in mosaic skin. Nature 619, 167–175 (2023).
Article CAS PubMed PubMed Central Google Scholar
Thorpe, J., Osei-Owusu, I. A., Avigdor, B. E., Tupler, R. & Pevsner, J. Mosaicism in human health and disease. Annu. Rev. Genet. 54, 487–510 (2020). In this review, the authors discuss the genetic mechanisms of mosaic variant acquisition and details about various detection techniques.
Article CAS PubMed PubMed Central Google Scholar
van Echten-Arends, J. et al. Chromosomal mosaicism in human preimplantation embryos: a systematic review. Hum. Reprod. Update 17, 620–627 (2011).
Taylor, T. H. et al. The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans. Hum. Reprod. Update 20, 571–581 (2014).
Article CAS PubMed Google Scholar
Levy, B., Hoffmann, E. R., McCoy, R. C. & Grati, F. R. Chromosomal mosaicism: origins and clinical implications in preimplantation and prenatal diagnosis. Prenat. Diagn. 41, 631–641 (2021).
Article PubMed PubMed Central Google Scholar
Vorsanova, S. G., Yurov, Y. B. & Iourov, I. Y. Dynamic nature of somatic chromosomal mosaicism, genetic–environmental interactions and therapeutic opportunities in disease and aging. Mol. Cytogenet. 13, 16 (2020).
Article CAS PubMed PubMed Central Google Scholar
Campbell, I. M. et al. Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders. Am. J. Hum. Genet. 95, 173–182 (2014).
Article CAS PubMed PubMed Central Google Scholar
Hatton, I. A. et al. The human cell count and size distribution. Proc. Natl Acad. Sci. USA 120, e2303077120 (2023).
Article CAS PubMed PubMed Central Google Scholar
Munisha, M. & Schimenti, J. C. Genome maintenance during embryogenesis. DNA Repair. 106, 103195 (2021).
Article CAS PubMed Google Scholar
Kermi, C., Aze, A. & Maiorano, D. Preserving genome integrity during the early embryonic DNA replication cycles. Genes 10, 398 (2019).
Article CAS PubMed PubMed Central Google Scholar
Bae, T. et al. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 359, 550–555 (2018).
Article CAS PubMed Google Scholar
Fasching, L. et al. Early developmental asymmetries in cell lineage trees in living individuals. Science 371, 1245–1248 (2021).
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