Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes
Abstract Craniofacial disorders arise in early pregnancy and are one of the most common congenital defects. To fully understand how craniofacial disorders arise, it is essential to characterize gene expression during the patterning of the craniofacial region. To address this, we performed bulk and s...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40363-1 |
| _version_ | 1797752702963286016 |
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| author | Tara N. Yankee Sungryong Oh Emma Wentworth Winchester Andrea Wilderman Kelsey Robinson Tia Gordon Jill A. Rosenfeld Jennifer VanOudenhove Daryl A. Scott Elizabeth J. Leslie Justin Cotney |
| author_facet | Tara N. Yankee Sungryong Oh Emma Wentworth Winchester Andrea Wilderman Kelsey Robinson Tia Gordon Jill A. Rosenfeld Jennifer VanOudenhove Daryl A. Scott Elizabeth J. Leslie Justin Cotney |
| author_sort | Tara N. Yankee |
| collection | DOAJ |
| description | Abstract Craniofacial disorders arise in early pregnancy and are one of the most common congenital defects. To fully understand how craniofacial disorders arise, it is essential to characterize gene expression during the patterning of the craniofacial region. To address this, we performed bulk and single-cell RNA-seq on human craniofacial tissue from 4-8 weeks post conception. Comparisons to dozens of other human tissues revealed 239 genes most strongly expressed during craniofacial development. Craniofacial-biased developmental enhancers were enriched +/− 400 kb surrounding these craniofacial-biased genes. Gene co-expression analysis revealed that regulatory hubs are enriched for known disease causing genes and are resistant to mutation in the normal healthy population. Combining transcriptomic and epigenomic data we identified 539 genes likely to contribute to craniofacial disorders. While most have not been previously implicated in craniofacial disorders, we demonstrate this set of genes has increased levels of de novo mutations in orofacial clefting patients warranting further study. |
| first_indexed | 2024-03-12T17:07:16Z |
| format | Article |
| id | doaj.art-8fb52a1254b34d8ba4d504c9a78dcfc6 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-12T17:07:16Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-8fb52a1254b34d8ba4d504c9a78dcfc62023-08-06T11:19:18ZengNature PortfolioNature Communications2041-17232023-08-0114112310.1038/s41467-023-40363-1Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genesTara N. Yankee0Sungryong Oh1Emma Wentworth Winchester2Andrea Wilderman3Kelsey Robinson4Tia Gordon5Jill A. Rosenfeld6Jennifer VanOudenhove7Daryl A. Scott8Elizabeth J. Leslie9Justin Cotney10Graduate Program in Genetics and Developmental Biology, UConn HealthUniversity of Connecticut School of Medicine, Department of Genetics and Genome SciencesGraduate Program in Genetics and Developmental Biology, UConn HealthGraduate Program in Genetics and Developmental Biology, UConn HealthDepartment of Human Genetics, Emory University School of MedicineDepartment of Molecular and Human Genetics, Baylor College of MedicineDepartment of Molecular and Human Genetics, Baylor College of MedicineUniversity of Connecticut School of Medicine, Department of Genetics and Genome SciencesDepartment of Molecular and Human Genetics, Baylor College of MedicineDepartment of Human Genetics, Emory University School of MedicineUniversity of Connecticut School of Medicine, Department of Genetics and Genome SciencesAbstract Craniofacial disorders arise in early pregnancy and are one of the most common congenital defects. To fully understand how craniofacial disorders arise, it is essential to characterize gene expression during the patterning of the craniofacial region. To address this, we performed bulk and single-cell RNA-seq on human craniofacial tissue from 4-8 weeks post conception. Comparisons to dozens of other human tissues revealed 239 genes most strongly expressed during craniofacial development. Craniofacial-biased developmental enhancers were enriched +/− 400 kb surrounding these craniofacial-biased genes. Gene co-expression analysis revealed that regulatory hubs are enriched for known disease causing genes and are resistant to mutation in the normal healthy population. Combining transcriptomic and epigenomic data we identified 539 genes likely to contribute to craniofacial disorders. While most have not been previously implicated in craniofacial disorders, we demonstrate this set of genes has increased levels of de novo mutations in orofacial clefting patients warranting further study.https://doi.org/10.1038/s41467-023-40363-1 |
| spellingShingle | Tara N. Yankee Sungryong Oh Emma Wentworth Winchester Andrea Wilderman Kelsey Robinson Tia Gordon Jill A. Rosenfeld Jennifer VanOudenhove Daryl A. Scott Elizabeth J. Leslie Justin Cotney Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes Nature Communications |
| title | Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes |
| title_full | Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes |
| title_fullStr | Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes |
| title_full_unstemmed | Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes |
| title_short | Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes |
| title_sort | integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes |
| url | https://doi.org/10.1038/s41467-023-40363-1 |
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