The focus of this study is to identify meaningful genetic and genomic factors that predict cleft outcomes in families in the African population, translate findings to other populations in order to design strategies towards reducing the outcome and prevention of CLP. We plan to replicate African GWAS significant loci in 1000 CL/P cases, 400 CP and 2000 controls by genotyping 172 single nucleotide polymorphisms. We also plan to conduct whole genome sequencing of 300 triads (proband with bilateral complete cleft lip and palate) and analyses whole genome sequencing (WGS) data of 150 CL/P triads. Finally, we plan to determine the functional consequences of GWAS non-coding variants by systematically testing SNPs with strongest disease association. This study will be led by Dr Butali at the University of Iowa in collaboration with Dr Cornell, Dr Murray and Dr Cao at the University of Iowa, Dr Adeyemo at the NHGRI and Dr Taub at the John Hopkins University.
TITLE: Refining the Genetic and Genomic Architecture of Non?syndromic Orofacial Clefts The long term goal of this study is to identify novel risk loci for orofacial clefts (OFCs) in the African population. This project is inherently transformative and has the potential for far- reaching impact not only in the African population, but also in populations in the United States, Canada, Europe and other societies with multiracial immigration and distributions with persons of African descents. The successful completion of this project will have significant positive impact on strategies designed towards understanding the biological role of identified variants and modification of genetic risk that will reduce the outcome of OFCs.