Lawson, A. R. J. et al. Somatic mutation and selection at population scale. Nature https://doi.org/10.1038/s41586-025-09584-w (2025).
Maeda, H. & Kakiuchi, N. Clonal expansion in normal tissues. Cancer Sci. 115, 2117–2124 (2024).
Bernstein, N. et al. Analysis of somatic mutations in whole blood from 200,618 individuals identifies pervasive positive selection and novel drivers of clonal hematopoiesis. Nat. Genet. 56, 1147–1155 (2024).
Fowler, J. C. & Jones, P. H. Somatic mutation: what shapes the mutational landscape of normal epithelia? Cancer Discov. 12, 1642–1655 (2022).
Goriely, A., McVean, G. A. T., Röjmyr, M., Ingemarsson, B. & Wilkie, A. O. M. Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science 301, 643–646 (2003).
Tiemann-Boege, I. et al. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. Proc. Natl Acad. Sci. USA 99, 14952–14957 (2002).
Maher, G. J. et al. Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes. Genome Res. 28, 1779–1790 (2018).
Wood, K. A. et al. SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline. Am. J. Hum. Genet. 111, 1953–1969 (2024).
Kaplanis, J. et al. Evidence for 28 genetic disorders discovered by combining healthcare and research data. Nature 586, 757–762 (2020).
Hamdan, F. F. et al. High rate of recurrent de novo mutations in developmental and epileptic encephalopathies. Am. J. Hum. Genet. 101, 664–685 (2017).
Jin, S. C. et al. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat. Genet. 49, 1593–1601 (2017).
Zhou, X. et al. Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes. Nat. Genet. 54, 1305–1319 (2022).
Richter, F. et al. Genomic analyses implicate noncoding de novo variants in congenital heart disease. Nat. Genet. 52, 769–777 (2020).
Francioli, L. C. et al. Genome-wide patterns and properties of de novo mutations in humans. Nat. Genet. 47, 822–826 (2015).
Iossifov, I. et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515, 216–221 (2014).
Genome of the Netherlands Consortium. Whole-genome sequence variation, population structure and demographic history of the Dutch population. Nat. Genet. 46, 818–825 (2014).
An, J.-Y. et al. Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder. Science 362, eaat6576 (2018).
Gulsuner, S. et al. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell 154, 518–529 (2013).
Zhao, G. et al. Gene4Denovo: an integrated database and analytic platform for de novo mutations in humans. Nucleic Acids Res. 48, D913–D926 (2020).
Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434–443 (2020).
Neville, M. D. C. et al. Sperm sequencing reveals extensive positive selection in the male germline. Nature https://doi.org/10.1038/s41586-025-09448-3 (2025).
Amberger, J. S., Bocchini, C. A., Scott, A. F. & Hamosh, A. OMIM.org: leveraging knowledge across phenotype–gene relationships. Nucleic Acids Res. 47, D1038–D1043 (2019).
Halldorsson, B. V. et al. Characterizing mutagenic effects of recombination through a sequence-level genetic map. Science 363, eaau1043 (2019).
Seplyarskiy, V. B. & Sunyaev, S. The origin of human mutation in light of genomic data. Nat. Rev. Genet. 22, 672–686 (2021).
Seplyarskiy, V. et al. A mutation rate model at the basepair resolution identifies the mutagenic effect of polymerase III transcription. Nat. Genet. 55, 2235–2242 (2023).
Totsika, V., Liew, A., Absoud, M., Adnams, C. & Emerson, E. Mental health problems in children with intellectual disability. Lancet Child Adolesc. Health 6, 432–444 (2022).
Raudvere, U. et al. g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res. 47, W191–W198 (2019).
Tate, J. G. et al. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res. 47, D941–D947 (2019).
Boßelmann, C. M. et al. Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR. Nat. Commun. 15, 10429 (2024).
Gogate, A. et al. The genetic landscape of autism spectrum disorder in an ancestrally diverse cohort. NPJ Genomic Med. 9, 62 (2024).
Gallego-Martinez, A. et al. Using coding and non-coding rare variants to target candidate genes in patients with severe tinnitus. NPJ Genomic Med. 7, 70 (2022).
Wainberg, M. et al. Deletion of loss-of-function-intolerant genes and risk of 5 psychiatric disorders. JAMA Psychiatry 79, 78–81 (2022).
Rodan, L. H. et al. Gain-of-function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities. Am. J. Med. Genet. A. 176, 2554–2560 (2018).
Jansen, S. et al. De novo truncating mutations in the last and penultimate exons of PPM1D cause an intellectual disability syndrome. Am. J. Hum. Genet. 100, 650–658 (2017).
Harpak, A., Bhaskar, A. & Pritchard, J. K. Mutation rate variation is a primary determinant of the distribution of allele frequencies in humans. PLoS Genet. 12, e1006489 (2016).
Schraiber, J. G., Spence, J. P. & Edge, M. D. Estimation of demography and mutation rates from one million haploid genomes. Am. J. Hum. Genet. 112, 2152–2166 (2025).
Wakeley, J., Fan, W.-T. L., Koch, E. & Sunyaev, S. Recurrent mutation in the ancestry of a rare variant. Genetics 224, iyad049 (2023).
Nei, M. The frequency distribution of lethal chromosomes in finite populations. Proc. Natl Acad. Sci. USA 60, 517–524 (1968).
Zeng, T., Spence, J. P., Mostafavi, H. & Pritchard, J. K. Bayesian estimation of gene constraint from an evolutionary model with gene features. Nat. Genet. 56, 1632–1643 (2024).
Szklarczyk, D. et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49, D605–D612 (2021).
Schuurs-Hoeijmakers, J. H. M. et al. Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome. Am. J. Hum. Genet. 91, 1122–1127 (2012).
Olson, H. E. et al. A recurrent de novo PACS2 heterozygous missense variant causes neonatal-onset developmental epileptic encephalopathy, facial dysmorphism, and cerebellar dysgenesis. Am. J. Hum. Genet. 102, 995–1007 (2018).
Goriely, A. et al. Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors. Nat. Genet. 41, 1247–1252 (2009).
Ichimura, K. et al. Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy. Acta Neuropathol. 131, 889–901 (2016).
Kimura, T. et al. Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production. Development 130, 1691–1700 (2003).
Sommerer, F. et al. Mutations of BRAF and RAS are rare events in germ cell tumours. Int. J. Cancer 113, 329–335 (2005).
Knudson Hypothesis—an overview. ScienceDirect Topics https://www.sciencedirect.com/topics/medicine-and-dentistry/knudson-hypothesis (2002).
Goriely, A. & Wilkie, A. O. M. Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. Am. J. Hum. Genet. 90, 175–200 (2012).
Penrose, L. S. Parental age and mutation. Lancet 269, 312–313 (1955).
EuroEPINOMICS-RES Consortium, Epilepsy Phenome/Genome Project, & Epi4K Consortium. De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. Am. J. Hum. Genet. 95, 360–370 (2014).
Helbig, K. L. et al. Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. Genet. Med. 18, 898–905 (2016).
Heyne, H. O. et al. De novo variants in neurodevelopmental disorders with epilepsy. Nat. Genet. 50, 1048–1053 (2018).
Klöckner, C. et al. De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy. Genet. Med. 23, 653–660 (2021).
Allen, A. S. et al. De novo mutations in epileptic encephalopathies. Nature 501, 217–221 (2013).
Perez, G. et al. The UCSC Genome Browser database: 2025 update. Nucleic Acids Res. 53, D1243–D1249 (2025).
Karlsson, M. et al. A single–cell type transcriptomics map of human tissues. Sci. Adv. 7, eabh2169 (2021).
Xu, Y. et al. A single-cell transcriptome atlas profiles early organogenesis in human embryos. Nat. Cell Biol. 25, 604–615 (2023).
Agrawal, A. et al. WikiPathways 2024: next generation pathway database. Nucleic Acids Res. 52, D679–D689 (2023).
McLaren, W. et al. The Ensembl variant effect predictor. Genome Biol. 17, 122 (2016).
Cheng, J. et al. Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science 381, eadg7492 (2023).
Moldovan, M. Reproducibility data for the paper ‘Cohort-level analysis of human de novo mutations points to drivers of clonal expansion in spermatogonia’. Zenodo https://doi.org/10.5281/zenodo.15660433 (2025).
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