Variant Analyses of Candidate Genes in Orofacial Clefts in Multi‐Ethnic Populations

Cleft lip with or without cleft palate (CL/P) and only (CPO) are congenital birth defects where the upper and/or fail to fuse properly during embryonic facial development. CL/P CPO fall under larger category of orofacial clefts (OFCs), which affect ~1.2/1000 live births world-wide imposes significant social financial burdens on affected individuals their families. The etiology is complex likely results from a combination genetic mutations environmental covariates. Recent genome wide association studies (GWAS) whole exome sequencing (WES) for clefting identified associations variants in several genes. Of these genes, we investigated role common rare SHH, RORA, MRPL53, ACVR1, GDF11 We sequenced five genes multi-ethnic samples order find that may provide potential explanations OFCs missing heritability. In total, 19 interest were found, seven one three six two GDF11. Types found included stop-gained, missense, synonymous, intronic, splice site variants. variants, 3 novel missense Rare further analyzed using in-silico predictive tools such as SIFT, Polyphen-2, Provean score, CADD, HOPE. This study provides evidence contribute risk various populations.