Deep genome sequencing reveals extensive genetic heterogeneity in early human placentas
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 method...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-63296-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849226154523754496 |
|---|---|
| author | Ieva Miceikaite Christina Fagerberg Charlotte Brasch-Andersen Pernille M. Torring Britta Schlott Kristiansen Qin Hao Lene Sperling Martin J. Larsen |
| author_facet | Ieva Miceikaite Christina Fagerberg Charlotte Brasch-Andersen Pernille M. Torring Britta Schlott Kristiansen Qin Hao Lene Sperling Martin J. Larsen |
| author_sort | Ieva Miceikaite |
| collection | DOAJ |
| description | 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 have mapped the mutational landscape across multiple sites and stages of placental development. We have revealed wide-spread mutations, with distinct clusters of postzygotic non-fetal small sequence variants, indicating extensive clonal evolution in all early placental biopsies, including first-trimester chorionic villus samples. Our study illuminates spatial and temporal genetic heterogeneity of the developing placenta. While most clonal sequence variants in placental biopsies exhibit low variant allele frequency, their presence underscores the need for caution when using placental tissue as a fetal proxy for diagnostics. These findings highlight the importance of confirmatory testing using AF in cases where placental mosaicism is suspected to avoid misinterpretation and unnecessary interventions. |
| format | Article |
| id | doaj-art-a7a15821668e47b69e8c724f214d1a08 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a7a15821668e47b69e8c724f214d1a082025-08-24T11:37:12ZengNature PortfolioNature Communications2041-17232025-08-0116111210.1038/s41467-025-63296-3Deep genome sequencing reveals extensive genetic heterogeneity in early human placentasIeva Miceikaite0Christina Fagerberg1Charlotte Brasch-Andersen2Pernille M. Torring3Britta Schlott Kristiansen4Qin Hao5Lene Sperling6Martin J. Larsen7Human Genetics Unit, Department of Clinical Research, Faculty of Health Sciences, University of Southern DenmarkHuman Genetics Unit, Department of Clinical Research, Faculty of Health Sciences, University of Southern DenmarkHuman Genetics Unit, Department of Clinical Research, Faculty of Health Sciences, University of Southern DenmarkDepartment of Clinical Genetics, Odense University HospitalDepartment of Clinical Genetics, Odense University HospitalDepartment of Clinical Genetics, Odense University HospitalCenter for Fetal Genetics, Odense University HospitalHuman Genetics Unit, Department of Clinical Research, Faculty of Health Sciences, University of Southern DenmarkAbstract 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 have mapped the mutational landscape across multiple sites and stages of placental development. We have revealed wide-spread mutations, with distinct clusters of postzygotic non-fetal small sequence variants, indicating extensive clonal evolution in all early placental biopsies, including first-trimester chorionic villus samples. Our study illuminates spatial and temporal genetic heterogeneity of the developing placenta. While most clonal sequence variants in placental biopsies exhibit low variant allele frequency, their presence underscores the need for caution when using placental tissue as a fetal proxy for diagnostics. These findings highlight the importance of confirmatory testing using AF in cases where placental mosaicism is suspected to avoid misinterpretation and unnecessary interventions.https://doi.org/10.1038/s41467-025-63296-3 |
| spellingShingle | Ieva Miceikaite Christina Fagerberg Charlotte Brasch-Andersen Pernille M. Torring Britta Schlott Kristiansen Qin Hao Lene Sperling Martin J. Larsen Deep genome sequencing reveals extensive genetic heterogeneity in early human placentas Nature Communications |
| title | Deep genome sequencing reveals extensive genetic heterogeneity in early human placentas |
| title_full | Deep genome sequencing reveals extensive genetic heterogeneity in early human placentas |
| title_fullStr | Deep genome sequencing reveals extensive genetic heterogeneity in early human placentas |
| title_full_unstemmed | Deep genome sequencing reveals extensive genetic heterogeneity in early human placentas |
| title_short | Deep genome sequencing reveals extensive genetic heterogeneity in early human placentas |
| title_sort | deep genome sequencing reveals extensive genetic heterogeneity in early human placentas |
| url | https://doi.org/10.1038/s41467-025-63296-3 |
| work_keys_str_mv | AT ievamiceikaite deepgenomesequencingrevealsextensivegeneticheterogeneityinearlyhumanplacentas AT christinafagerberg deepgenomesequencingrevealsextensivegeneticheterogeneityinearlyhumanplacentas AT charlottebraschandersen deepgenomesequencingrevealsextensivegeneticheterogeneityinearlyhumanplacentas AT pernillemtorring deepgenomesequencingrevealsextensivegeneticheterogeneityinearlyhumanplacentas AT brittaschlottkristiansen deepgenomesequencingrevealsextensivegeneticheterogeneityinearlyhumanplacentas AT qinhao deepgenomesequencingrevealsextensivegeneticheterogeneityinearlyhumanplacentas AT lenesperling deepgenomesequencingrevealsextensivegeneticheterogeneityinearlyhumanplacentas AT martinjlarsen deepgenomesequencingrevealsextensivegeneticheterogeneityinearlyhumanplacentas |