Genetic models and approaches to study orofacial clefts

Orofacial clefts (OFCs) are common craniofacial birth defects with heterogeneous phenotype and etiology. Geneticists have applied nearly every available method and technology for further understanding of the genetic architectures of OFCs.

This review describes the evidence for a genetic etiology in OFCs, statistical genetic approaches employed to identify genetic causes, and how the results have shaped our current understanding of the genetic architectures of syndromic and nonsyndromic OFCs.

There has been rapid progress toward elucidating the genetic architectures of OFCs due to the availability of large collections of DNA samples from cases, controls, and families with OFCs and the consistent adoption of new methodologies and novel statistical approaches as they are developed. Genetic studies have identified rare and common variants influencing risk of OFCs in both Mendelian and complex forms of OFCs, blurring the distinction traditional categories used in genetic studies and clinical medicine.