Oral-facial clefts, particularly cleft lip with or without cleft palate (CL/P), are a major public health problem, affecting one in every 500- 1000 births worldwide. Therefore, many research groups have attempted to identify genetic loci contributing to the etiology of CL/P, with limited success to date. There have been several allelic associations identified in European Caucasian populations, a few potentially linked markers; however, these results have not been consistent across study populations. It appears that the genetic contribution to the etiology of oral-facial clefting is complex, possibly heterogeneous, or possibly due to interacting effects of multiple loci. A possible impediment to identifying loci for clefting is that the cleft itself is unlikely to be the proximate phenotype coded by the etiologic gene or genes. There is increasing evidence that developmental asymmetry effects may contribute to the etiology of oral-facial clefts. If we can more accurately identify the phenotype that is segregating at a genetic level in these families, then gene mapping and association studies will be more successful. Furthermore, it we can identify unaffected individuals who are likely to carrying cleft genes (e.g. individuals with sub-clinical phenotypic expression), then recurrence risk calculation and genetic counseling for this common birth defect will be vastly improved. The goal of this project is to investigate phenotypic features in multiplex kindreds (i.e. with 2 or more affecteds) ascertained through CL/P individuals served by the University of Pittsburgh Cleft Palate- Craniofacial Center. The specific features that will be investigated included: handedness, craniofacial measurements, asymmetry (based on dermatoglyphic patterns and craniofacial measurements), and anatomy of the orbicularis oris muscle. These features will be evaluated in each member of the multiplex kindreds. Each individual feature will be analyzed, as well as composite traits composed of two or more features. Statistical genetic methods will be used to investigate the segregation patterns of each trait in the sample of kindreds. In addition, a sample of controls with no known family history of clefting will be evaluated for the same phenotypic features in order to compare to the unaffected relatives (of cleft individuals). DNA will be obtained from all study participants in order to investigate a number of loci that have shown linkage and/or association with CL/P in other studies. These loci are located in specific regions of chromosomes 1, 2, 4, 6, 17 and 19.