Journal article
Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate
Scientific reports, Vol.12(1), pp.1-14
07/01/2022
DOI: 10.1038/s41598-022-15885-1
PMCID: PMC9273634
PMID: 35817949
Abstract
Abstract The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.
Details
- Title: Subtitle
- Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate
- Creators
- Waheed Awotoye - University of IowaPeter A. Mossey - University of DundeeJacqueline B. Hetmanski - Johns Hopkins UniversityLord J. J. Gowans - Kwame Nkrumah University of Science and TechnologyMekonen A. Eshete - Addis Ababa UniversityWasiu L. Adeyemo - University of LagosAzeez Alade - Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of IowaErliang Zeng - University of IowaOlawale Adamson - University of LagosThirona Naicker - University of KwaZulu-NatalDeepti Anand - University of DelawareChinyere Adeleke - Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of IowaTamara Busch - University of IowaMary Li - University of IowaAline Petrin - University of IowaBabatunde S. Aregbesola - Department of Oral and Maxillofacial Surgery, Obafemi Awolowo UniversityRamat O. Braimah - Department of Oral and Maxillofacial Surgery, Obafemi Awolowo UniversityFadekemi O. Oginni - Department of Oral and Maxillofacial Surgery, Obafemi Awolowo UniversityAyodeji O. Oladele - Department of Oral and Maxillofacial Surgery, Obafemi Awolowo UniversityAbimbola Oladayo - University of IowaSami Kayali - Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of IowaJoy Olotu - University of Port HarcourtMohaned Hassan - Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of IowaJohn Pape - Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of IowaPeter Donkor - Kwame Nkrumah University of Science and TechnologyFareed K. N. Arthur - Kwame Nkrumah University of Science and TechnologySolomon Obiri-Yeboah - Kwame Nkrumah University of Science and TechnologyDaniel K. Sabbah - Kwame Nkrumah University of Science and TechnologyPius Agbenorku - Kwame Nkrumah University of Science and TechnologyGyikua Plange-Rhule - Kwame Nkrumah University of Science and TechnologyAlexander Acheampong Oti - Kwame Nkrumah University of Science and TechnologyRose A. Gogal - University of IowaTerri H. Beaty - Johns Hopkins UniversityMargaret Taub - Johns Hopkins UniversityMary L. Marazita - University of PittsburghMichael J. Schnieders - University of IowaSalil A. Lachke - University of DelawareAdebowale A. AdeyemoJeffrey C. Murray - University of IowaAzeez Butali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.12(1), pp.1-14
- DOI
- 10.1038/s41598-022-15885-1
- PMID
- 35817949
- PMCID
- PMC9273634
- NLM abbreviation
- Sci Rep
- eISSN
- 2045-2322
- Publisher
- Nature Portfolio
- Grant note
- DOI: 10.13039/100000072, name: National Institute of Dental and Craniofacial Research, award: DE024296, DE024776, DE022378, DE28300; DOI: 10.13039/100000002, name: National Institutes of Health, award: DK110023, DC012049; DOI: 10.13039/100000001, name: National Science Foundation, award: CHE-1751688
- Language
- English
- Date published
- 07/01/2022
- Academic Unit
- Preventive and Community Dentistry; Oral Pathology, Radiology and Medicine; Biostatistics; Pediatric Dentistry; Craniofacial Anomalies Research Center; Biochemistry and Molecular Biology; Chemical and Biochemical Engineering; Roy J. Carver Department of Biomedical Engineering; Orthodontics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Iowa Neuroscience Institute; Dental Research
- Record Identifier
- 9984274855402771
Metrics
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