The CCDG has established a rich phenotyping paradigm that has been developed over the last decade in order to help define mechanisms that lead to OFCs and more precisely predict individual risks for these defects. Subclinical expressions of OFC (e.g., subtle speech abnormalities) that are distributed within affected families can reveal clues about etiology. Numerous genes/loci have now been identified for overt OFC, based largely on genome-wide association studies resulting from our research group and others. This project is genotyping of the Illumina HumanOmni5Exome SNP panel in 12,000 study subjects from approximately 2,500 families. The overarching goal of this proposal is to investigate the genetics of OFCs in this study population, and importantly, to incorporate subclinical phenotypic features into those studies. The inclusion of this rich phenotyping approach will potentially allow translation of the findings into strategies that can be eventually assessed through robust clinical studies, with the ultimate goal of improving the standard of care of individuals with OFCs.