Elucidating the genetic control of morphogenesis and cell differentiation during tooth development is crucial to our understanding of the pathogenesis of genetic and acquired diseases that involve dentition. Hypodontia constitutes the most commonly encountered dental defect. The lack of teeth, primary or permanent, is an important public health concern predisposing to malnutrition and secondary infections, and is of high clinical relevance. Our goal is to elucidate factors important for tooth development in humans and to understand how mutations within genes encoding these factors contribute to hypodontia. We have previously identified a mutation in PAX9 in a family with hypodontia involving molars. We propose to identify (i) additional families and sample these and previously identified families segregating non-syndromic hypodontia of unknown etiology and (ii) the gene(s) underlying hypodontia by genome-wide linkage analysis, candidate gene identification and mutation analysis. Linkage analysis will be conducted by parametric and non-parametric approaches. Candidate genes will be prioritized by bioinformatics and molecular approaches including a microarray approach. Mutation analysis of selected candidate genes and validation in families will identify the hypodontia gene(s). Our studies will map and identify genes underlying hypodontia. This information will add to our knowledge of human tooth development and enable design of better diagnostic and treatment strategies for hypodontia patients in the future.
