Journal article
Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations
Oral diseases, Vol.28(7), pp.1921-1935
10/2022
DOI: 10.1111/odi.13932
PMCID: PMC9733635
PMID: 34061439
Abstract
Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11.
We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools.
Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11.
This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.
Details
- Title: Subtitle
- Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations
- Creators
- Mary Li - University of IowaJoy Olotu - University of Port HarcourtCarmen J Buxo-Martinez - University of Puerto Rico SystemPeter A Mossey - University of DundeeDeepti Anand - University of DelawareTamara Busch - University of IowaAzeez Alade - University of IowaLord J J Gowans - Kwame Nkrumah University of Science and TechnologyMekonen Eshete - Addis Ababa UniversityWasiu L Adeyemo - University of LagosThirona Naicker - University of KwaZulu-NatalWaheed O Awotoye - University of IowaSagar Gupta - University of IowaChinyere Adeleke - University of IowaValeria Bravo - University of Puerto Rico SystemSiyong Huang - University of IowaOlatunbosun O Adamson - University of LagosAda M Toraño - Manchester Family Dental, Manchester, IA, USA.Carolina A Bello - Montefiore Medical CenterMairim Soto - University of Puerto Rico SystemMarilyn Soto - University of Puerto Rico SystemRicardo Ledesma - University of Puerto Rico SystemMyrellis Marquez - University of Puerto Rico SystemJose F Cordero - University of Puerto Rico SystemLydia M Lopez-Del Valle - University of Puerto Rico SystemMaria I Salcedo - University of Puerto Rico SystemNatalio Debs - University of Puerto Rico SystemAline Petrin - University of IowaHannah Malloy - University of IowaKhalid Elhadi - University of IowaOlutayo James - University of LagosMobolanle O Ogunlewe - University of LagosFekir Abate - Addis Ababa UniversityAbiye Hailu - Addis Ababa UniversityIbrahim Mohammed - Addis Ababa UniversityPaul Gravem - Addis Ababa UniversityMilliard Deribew - Addis Ababa UniversityMulualem Gesses - Addis Ababa UniversityMohaned Hassan - University of IowaJohn Pape - University of IowaSolomon Obiri-Yeboah - Kwame Nkrumah University of Science and TechnologyFareed K N Arthur - Kwame Nkrumah University of Science and TechnologyAlexander A Oti - Kwame Nkrumah University of Science and TechnologyPeter Donkor - Kwame Nkrumah University of Science and TechnologyMary L Marazita - University of PittsburghSalil A Lachke - University of DelawareAdebowale A Adeyemo - University of DundeeJeffrey C Murray - University of IowaAzeez Butali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Oral diseases, Vol.28(7), pp.1921-1935
- DOI
- 10.1111/odi.13932
- PMID
- 34061439
- PMCID
- PMC9733635
- NLM abbreviation
- Oral Dis
- ISSN
- 1354-523X
- eISSN
- 1601-0825
- Grant note
- R01DE028300 / NIDCR NIH HHS R90 DE024296 / NIDCR NIH HHS S21 MD001830 / NIMHD NIH HHS R00 DE024571 / NIDCR NIH HHS R00 DE022378 / NIDCR NIH HHS U54 GM133807 / NIGMS NIH HHS R01 DE028300 / NIDCR NIH HHS R03 DE024776 / NIDCR NIH HHS U54 MD007587 / NIMHD NIH HHS
- Language
- English
- Date published
- 10/2022
- Academic Unit
- Orthodontics; Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984353801002771
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