Genetic Determinants of Orofacial Shape and Relationship to

Genetic Determinants of Orofacial Shape and Relationship to Cleft Lip/Palate Richard Spritz University of Colorado School of Medicine Fernando Pardo-Manuel de Villena University of North Carolina Benedikt Hallgrimsson University of Calgary Ophir Klein HMGP University of California San Francisco

Specific Aims 1. 2. 3. Determination of heritable midfacial morphometric variation among mouse strains Fine-map major quantitative trait loci (QTLs) responsible for those major heritable orofacial morphometric parameters using the mouse Collaborative Cross Test genetic association of candidate genes for mouse orofacial QTLs with human orofacial morphometric parameters

Collaborative Cross Analyses A. Micro-CT Scans of Adult Craniofacial Morphology C. Progress – Completed Scans by Strain (N=300 adult) (Plan N=7200, 360 RIX Strains) Typical scan quality at 35 microns B. Neonatal and Embryo Scans (Plan N= approx. 360; N=200 completed) Typical scan quality at 6. 25 microns Typical scan quality at 10 microns

Human Facial 3 D Morphometric Data Sex and Age Distribution of Sample to date (N=979)

Human Facial 3 D Morphometric Data Regression of Total Shape Variation on Face Size

Summary of Human Scans/Collections l Calgary (Tanzania): Opened 1/10: 979 African l Denver: Opened 5/19/10: 1 Caucasian, 2 Hispanic l UCSF: Not yet opened