Deep Genome Sequencing Uncovers Extensive Genetic Heterogeneity in Early Human Placentas

Deep Genome Sequencing Uncovers Extensive Genetic Heterogeneity in Early Human Placentas | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Deep Genome Sequencing Uncovers Extensive Genetic Heterogeneity in Early Human Placentas Ieva Miceikaite, Christina Fagerberg, Charlotte Brasch-Andersen, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5140201/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Aug, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Placental biopsy in early pregnancy is widely used in prenatal genetic diagnostics as a surrogate for fetal tissue. Confined placental chromosomal mosaicism is a well-documented phenomenon causing genetic discrepancies between the fetus and placenta. Although comprehensive sequencing methods are becoming popular for prenatal screening of monogenic disorders, knowledge of concordance between the fetus and early placenta at the sequence level remains limited. By deep genome sequencing, we mapped the mutational landscape across multiple sites and stages of placental development. We revealed profound mutations, with distinct clusters of postzygotic non-fetal small sequence variants, indicating extensive clonal evolution in all early placenta samples, including first-trimester CVS. Our study illuminates spatial and temporal genetic heterogeneity of the developing placenta. These findings underscore the need for awareness and caution when using placental biopsies as fetal proxy for diagnostics and emphasize the importance of confirmatory testing using amniotic fluid when placenta mosaicism is suspected. Health sciences/Medical research/Genetics research Biological sciences/Genetics/Genome/Genetic variation Biological sciences/Genetics/Clinical genetics/Genetic testing Health sciences/Health care/Diagnosis/Genetic testing Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryFigure1.pptx SupplementaryFigure2.pptx SupplementaryTable1.xlsx SupplementaryTable2.xlsx Cite Share Download PDF Status: Published Journal Publication published 23 Aug, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5140201","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":360363972,"identity":"d74d10f0-2ce0-4043-ae74-5ca947b31f54","order_by":0,"name":"Ieva 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