Non-syndromic cleft lip and palate are common complex traits resulting from genetic and environmental risk factors. The genetic model that best explain non-syndromic clefting (NSC) is a multiplicative model under which a few genes (i.e. less than or equal to 3) with moderate effect operate against a multifactorial background to produce the clefting. Most genetic studies on NSC treat the clefting phenotype as a dichotomous trait. Recent evidence suggested that family members of NSC patients are more likely to have various craniofacial dysmorphology. In this proposal, we will define the craniofacial abnormalities in NSC patients and families by imaging and measurement of their craniofacial skeleton, and evaluate the mode of inheritance of specific dysmorhologic features in NSC families using complex segregation analysis. We will also determine if the transmission of specific genetic alleles is associated with the transmission of specific craniofacial dysmorphologic features in NSC families using the transmission disequilibrium test. This is a novel approach to the mapping of a complex structural trait and the genetic information will help future identification of environmental factors that contribute to these common birth defects.
