Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations
| Autor: | Alexander Acheampong Oti, Olatunbosun O Adamson, Lydia M. López del Valle, Aline Petrin, Valeria Bravo, Fekir Abate, Mary Li, Ada M. Toraño, Chinyere Adeleke, John Pape, Adebowale A. Adeyemo, Jeffrey C. Murray, Peter Donkor, Sagar Gupta, Abiye Hailu, Carmen J. Buxo‐Martinez, Mulualem Gesses, Tamara Busch, Peter A. Mossey, Ibrahim Mohammed, Lord J.J. Gowans, Hannah Malloy, Siyong Huang, Fareed K. N. Arthur, Salil A. Lachke, Wasiu Lanre Adeyemo, Mary L. Marazita, Ricardo Ledesma, Thirona Naicker, Paul Gravem, Azeez Alade, Solomon Obiri-Yeboah, Maria I. Salcedo, Mekonen Eshete, Mohaned Hassan, Carolina A. Bello, Marilyn Soto, Joy Olotu, Azeez Butali, Olutayo James, Khalid Elhadi, Waheed O Awotoye, Deepti Anand, Mobolanle O. Ogunlewe, Myrellis Marquez, Mairim Soto, José F. Cordero, Natalio Debs, Milliard Deribew |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genetics Candidate gene Cleft Lip Genome-wide association study 030206 dentistry ACVR1 Biology Cleft Palate Growth Differentiation Factors 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Otorhinolaryngology Missing heritability problem Bone Morphogenetic Proteins Etiology Missense mutation Humans General Dentistry Exome sequencing Genetic association Genome-Wide Association Study |
| Zdroj: | Oral diseases. 28(7) |
| ISSN: | 1601-0825 |
| Popis: | Objectives Cleft lip with/without cleft palate and cleft palate only are congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births world-wide, 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. Materials and methods 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. Results 19 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. Conclusion This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations. |
| Databáze: | OpenAIRE |
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