دورية أكاديمية
Rare variants analyses suggest novel cleft genes in the African population.
| العنوان: | Rare variants analyses suggest novel cleft genes in the African population. |
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| المؤلفون: | Alade A; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA. Azeez-alade@uiowa.edu.; Department of Epidemiology, College of Public Health, University of Iowa, Butali Laboratory, ML2198, 500 Newton Road, Iowa City, IA, 52242, USA. Azeez-alade@uiowa.edu., Mossey P; Department of Orthodontics, University of Dundee, Dundee, UK., Awotoye W; Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA., Busch T; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Oladayo AM; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Aladenika E; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Olujitan M; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Wentworth E; Department of Genetics and Genome Sciences, University of Connecticut, Farmington, CT, USA.; Graduate Program in Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, CT, USA., Anand D; Department of Biological Sciences, University of Delaware, Newark, DE, USA., Naicker T; Department of Paediatrics, Clinical Genetics, University of KwaZulu-Natal and Inkosi Albert Luthuli Central Hospital, Durban, South Africa., Gowans LJJ; Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Eshete MA; Department of Surgery, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia., Adeyemo WL; Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Idi-araba, Lagos, Nigeria., Zeng E; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Van Otterloo E; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA.; Department of Periodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA., O'Rorke M; Department of Epidemiology, College of Public Health, University of Iowa, Butali Laboratory, ML2198, 500 Newton Road, Iowa City, IA, 52242, USA., Adeyemo A; National Human Genomic Research Institute, Bethesda, MD, USA., Murray JC; Department of Pediatrics, University of Iowa, Iowa City, IA, USA., Cotney J; Department of Genetics and Genome Sciences, University of Connecticut, Farmington, CT, USA., Lachke SA; Department of Biological Sciences, University of Delaware, Newark, DE, USA.; Center for Bioinformatics and Computational Biology, University of Delaware, Newark, DE, USA., Romitti P; Department of Epidemiology, College of Public Health, University of Iowa, Butali Laboratory, ML2198, 500 Newton Road, Iowa City, IA, 52242, USA., Butali A; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA. azeez-butali@uiowa.edu.; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Butali Laboratory, ML2198, 500 Newton Road, Iowa City, IA, 52242, USA. azeez-butali@uiowa.edu. |
| المصدر: | Scientific reports [Sci Rep] 2024 Jun 20; Vol. 14 (1), pp. 14279. Date of Electronic Publication: 2024 Jun 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
| مواضيع طبية MeSH: | Cleft Lip*/genetics , Cleft Palate*/genetics, Animals ; Child ; Female ; Humans ; Male ; Mice ; Black People/genetics ; Ethiopia ; Genetic Predisposition to Disease ; Ghana ; Nigeria ; Sub-Saharan African People/genetics |
| مستخلص: | Non-syndromic orofacial clefts (NSOFCs) are common birth defects with a complex etiology. While over 60 common risk loci have been identified, they explain only a small proportion of the heritability for NSOFCs. Rare variants have been implicated in the missing heritability. Thus, our study aimed to identify genes enriched with nonsynonymous rare coding variants associated with NSOFCs. Our sample included 814 non-syndromic cleft lip with or without palate (NSCL/P), 205 non-syndromic cleft palate only (NSCPO), and 2150 unrelated control children from Nigeria, Ghana, and Ethiopia. We conducted a gene-based analysis separately for each phenotype using three rare-variants collapsing models: (1) protein-altering (PA), (2) missense variants only (MO); and (3) loss of function variants only (LOFO). Subsequently, we utilized relevant transcriptomics data to evaluate associated gene expression and examined their mutation constraint using the gnomeAD database. In total, 13 genes showed suggestive associations (p = E-04). Among them, eight genes (ABCB1, ALKBH8, CENPF, CSAD, EXPH5, PDZD8, SLC16A9, and TTC28) were consistently expressed in relevant mouse and human craniofacial tissues during the formation of the face, and three genes (ABCB1, TTC28, and PDZD8) showed statistically significant mutation constraint. These findings underscore the role of rare variants in identifying candidate genes for NSOFCs. (© 2024. The Author(s).) |
| التعليقات: | Update of: Res Sq. 2024 Feb 27:rs.3.rs-3921355. doi: 10.21203/rs.3.rs-3921355/v1. (PMID: 38464065) |
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| معلومات مُعتمدة: | Cleft Research Grant 2022 IADR/Smile Train; DE022378 NIH/NIDCR; DE28300 NIH/NIDCR; DEO24776 NIH/NIDCR |
| فهرسة مساهمة: | Keywords: Craniofacial; Genetics; Nonsyndromic; Orofacial clefts; Rare variants; Transcriptomics |
| تواريخ الأحداث: | Date Created: 20240620 Date Completed: 20240620 Latest Revision: 20240924 |
| رمز التحديث: | 20240924 |
| مُعرف محوري في PubMed: | PMC11189897 |
| DOI: | 10.1038/s41598-024-65151-9 |
| PMID: | 38902479 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2045-2322 |
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| DOI: | 10.1038/s41598-024-65151-9 |