Academic Journal
Investigating gene functions and single-cell expression profiles of de novo variants in orofacial clefts.
| Τίτλος: | Investigating gene functions and single-cell expression profiles of de novo variants in orofacial clefts. |
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| Συγγραφείς: | Itai T; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Yan F; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Liu A; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, Houston, TX 77030, USA., Dai Y; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Iwaya C; Department of Diagnostic & Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA; Center for Craniofacial Research, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA., Curtis SW; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA., Leslie EJ; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA., Simon LM; Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA., Jia P; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Chen X; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Iwata J; Department of Diagnostic & Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA; Center for Craniofacial Research, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA; Pediatric Research Center, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA., Zhao Z; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: zhongming.zhao@uth.tmc.edu. |
| Πηγή: | HGG advances [HGG Adv] 2024 Jul 18; Vol. 5 (3), pp. 100313. Date of Electronic Publication: 2024 May 27. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101772885 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-2477 (Electronic) Linking ISSN: 26662477 NLM ISO Abbreviation: HGG Adv Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York : Elsevier Inc., [2020]- |
| Ιατρικοί όροι (MeSH): | Cleft Lip*/genetics , Cleft Palate*/genetics , Single-Cell Analysis*, Genetic Variation/genetics ; Humans ; Mice ; Animals ; Transcriptome ; Gene Expression Profiling |
| Περίληψη: | Orofacial clefts (OFCs) are common congenital birth defects with various etiologies, including genetic variants. Online Mendelian Inheritance in Man (OMIM) annotated several hundred genes involving OFCs. Furthermore, several hundreds of de novo variants (DNVs) have been identified from individuals with OFCs. Some DNVs are related to known OFC genes or pathways, but there are still many DNVs whose relevance to OFC development is unknown. To explore novel gene functions and their cellular expression profiles, we focused on DNVs in genes that were not listed in OMIM. We collected 960 DNVs in 853 genes from published studies and curated these genes, based on the DNVs' deleteriousness, into 230 and 23 genes related to cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), respectively. For comparison, we curated 178 CL/P and 277 CPO genes from OMIM. In CL/P, the pathways enriched in DNV and OMIM genes were significantly overlapped (p = 0.002). Single-cell RNA sequencing (scRNA-seq) analysis of mouse lip development revealed that both gene sets had abundant expression in the ectoderm (DNV genes: adjusted p = 0.032, OMIM genes: adjusted p < 0.0002), while only DNV genes were enriched in the endothelium (adjusted p = 0.032). Although we did not achieve significant findings using CPO gene sets, which was mainly due to the limited number of DNV genes, scRNA-seq analysis implicated various expression patterns among DNV and OMIM genes. Our results suggest that combinatory pathway and scRNA-seq data analyses are helpful for contextualizing genes in OFC development. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| References: | Development. 2019 Jun 17;146(12):. (PMID: 31118233) Sci Rep. 2022 Jul 11;12(1):11743. (PMID: 35817949) Hum Mol Genet. 2023 Jan 13;32(3):473-488. (PMID: 36018820) Nucleic Acids Res. 2010 Sep;38(16):e164. (PMID: 20601685) Nat Genet. 2021 Aug;53(8):1143-1155. (PMID: 34239132) Genome Res. 2003 Nov;13(11):2498-504. (PMID: 14597658) BMC Genomics. 2019 Nov 14;20(1):852. (PMID: 31727022) Hum Genet. 2017 Mar;136(3):275-286. (PMID: 28054174) Clin Genet. 2022 Jul;102(1):3-11. (PMID: 35342932) Am J Hum Genet. 2020 Jul 2;107(1):124-136. (PMID: 32574564) Am J Hum Genet. 2015 Mar 5;96(3):397-411. (PMID: 25704602) Mol Genet Genomic Med. 2023 Mar;11(3):e2109. (PMID: 36468602) Am J Hum Genet. 2018 Jun 7;102(6):1143-1157. (PMID: 29805042) Innovation (Camb). 2021 Jul 01;2(3):100141. (PMID: 34557778) Fam Cancer. 2014 Sep;13(3):415-21. (PMID: 24838934) Sci Bull (Beijing). 2021 Dec 15;66(23):2340-2342. (PMID: 36654117) Cell Tissue Res. 2015 Sep;361(3):711-22. (PMID: 25759071) Oral Dis. 2022 Jul;28(5):1327-1338. (PMID: 34923716) Cell. 2021 Jun 24;184(13):3573-3587.e29. (PMID: 34062119) Bioengineered. 2021 Dec;12(1):1471-1483. (PMID: 33947308) Front Bioeng Biotechnol. 2022 Aug 29;10:962040. (PMID: 36105604) Bioinformatics. 2019 Oct 1;35(19):3842-3845. (PMID: 30824912) J Clin Med. 2023 Mar 04;12(5):. (PMID: 36902838) Nat Commun. 2024 Jan 27;15(1):821. (PMID: 38280850) Gene. 2018 Jun 5;658:123-128. (PMID: 29524576) Elife. 2021 Jan 22;10:. (PMID: 33482080) Nat Rev Cardiol. 2023 Mar;20(3):197-210. (PMID: 36198871) Hum Mol Genet. 2018 Apr 15;27(8):1421-1433. (PMID: 29432562) Nucleic Acids Res. 2022 Jul 5;50(W1):W782-W790. (PMID: 35610053) Lancet. 2009 Nov 21;374(9703):1773-85. (PMID: 19747722) |
| Grant Information: | R03 DE027103 United States DE NIDCR NIH HHS; R01 DE030342 United States DE NIDCR NIH HHS; R01 LM012806 United States LM NLM NIH HHS; R01 DE030122 United States DE NIDCR NIH HHS; R01 DE029818 United States DE NIDCR NIH HHS |
| Contributed Indexing: | Keywords: cleft lip with or without palate; de novo variant; endothelium; nonsyndromic orofacial clefts; single-cell RNA sequencing |
| Entry Date(s): | Date Created: 20240529 Date Completed: 20240719 Latest Revision: 20250307 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11318074 |
| DOI: | 10.1016/j.xhgg.2024.100313 |
| PMID: | 38807368 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2666-2477 |
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| DOI: | 10.1016/j.xhgg.2024.100313 |