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Variant Analyses of Candidate Genes in Orofacial Clefts in Multi‐Ethnic Populations
Author(s) -
Awotoye Waheed,
Li Mary,
Olotu Joy,
BuxoMartinez Carmen,
Mossey Peter,
Anand Deepti,
Busch Tamara,
Alade Azeez,
Gowans Lord,
Eshete Mekonen,
Adeyemo Wasiu,
Naicker Thirona,
Adeleke Chinyere,
Bravo Valeria,
Huang Siyong,
Adamson Olatunbosun,
Toraño Ada,
Bello Carolina,
Soto Mairim,
Soto Marilyn,
Ledesma Ricardo,
Marquez Myrellis,
Cordero Jose,
LopezDel Valle Lydia,
Salcedo Maria,
Debs Natalio,
Petrin Aline,
Malloy Hannah,
Elhadi Khalid,
Olutayo James,
Ogunlewe Mobolanle,
Abate Fekir,
Hailu Taye,
Mohammed Ibrahim,
Gravem Paul,
Deribew Milliard,
Gesses Mulualem,
Hassan Mohaned,
Pape John,
ObiriYeboah Solomon,
Arthur Fareed,
Oti Alexander,
Donkor Peter,
Marazita Mary,
Lachke Salil,
Adeyemo Adebowale,
Murray Jeffrey,
Butali Azeez
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03614
Subject(s) - missense mutation , genetics , biology , gene , in silico , candidate gene , exome sequencing , mutation
Cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) are congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. CL/P and CPO fall under the larger category of orofacial clefts (OFCs), which affect ~1.2/1000 live births world‐wide and imposes significant social and financial burdens on affected individuals and their families. The etiology of orofacial clefts is complex and likely results from a combination of genetic mutations with environmental covariates. Recent genome wide association studies (GWAS) and whole exome sequencing (WES) for orofacial clefting identified significant genetic associations and variants in several genes. Of these genes, we investigated the role of common and rare variants in the SHH , RORA , MRPL53 , ACVR1 , and GDF11 genes. We sequenced these five genes in multi‐ethnic CL/P and CPO samples in order to find mutations that may provide potential explanations for OFCs missing heritability. In total, 19 variants of interest were found, seven of which were in SHH , one in RORA , three in MRPL53 , six in ACVR1 , and two in GDF11 . Types of mutations found included stop‐gained, missense, synonymous, intronic, and splice site variants. Of these 19 variants, 3 novel missense variants were found, one in SHH , one in RORA , and one in GDF11 . Rare and novel variants were further analyzed using in‐silico predictive tools such as SIFT, Polyphen‐2, Provean score, CADD, and HOPE. This study provides evidence that mutations in SHH , RORA , MRPL53 , ACVR1 , and GDF11 may contribute to risk of OFCs in various populations.