The genetic architecture of normal facial variation in relation to orofacial clefting

Orofacial clefting is the most frequent facial congenital malformation, but its etiology remains poorly understood. To unravel the genetic architecture of nonsyndromic cleft lip +/- cleft palate (NSCL/P), it can be useful to focus on the phenotype of non-affected first-degree relatives of these patients since they have a high chance to carry susceptibility genes for the condition. Recently, we confirmed the presence of specific facial characteristics in non-affected relatives of patients with NSCL/P (Roosenboom et al. 2015). In this project, we will use innovative 3D morphometric analytic techniques and large databases of 3D facial images with corresponding DNA to raise insight into the genetic architecture of both NSCL/P and normal facial variation. After fine-tuning the definition of endophenotypic facial characteristics for NSCL/P in a larger cohort of relatives, we will associate these endophenotypic features to genes with known involvement in CL/P. Next, we will study if genes that are associated with the endophenotype also play a role in normal facial variation in the general population. In a final stage, the presence of facial endophenotypic features in the large datasets of normal facial variation will serve as input for a GWAS on the corresponding DNA, which may lead to the identification of new candidate genes for NSCL/P. Subsequently, we will verify these newly identified SNPs in a CL/P patient cohort in order to test their true involvement. Roosenboom, J., Saey, I., Peeters, H., Devriendt, K., Claes, P. & Hens, G. (2015), 'Facial Characteristics and Olfactory Dysfunction: Two Endophenotypes Related to Nonsyndromic Cleft Lip and/or Palate.'. BioMed Research International, vol. 2015, Chapter 10, pp. 1-8.status: publishe