1R01 ES-10876 Jeffrey C. Murray, Principal Investigator Craniofacial anomalies, and in particular, clefts of the lip and palate, are important contributors to the morbidity associated with birth defects.
Clefts have a complex etiology that involves both genes and gene-environmental influences.
Their frequency varies across populations of different geographic origins, but averages about 1 in 700 live births and results in the need for surgical, speech, psychological, dental and cosmetic interventions. One hundred of these candidate genes will undergo complete sequence analysis for 200 cases of cleft lip and palate. In parallel analysis, we will work with the Cancer Genome Anatomy Project Genetic Annotation Initiative to validate and confirm 100 additional variants identified through their efforts to study genes that play a role in development and xenobiotic transformations. Variants identified in the sequence analysis and the Genetic Annotation Initiative will then be studied using linkage disequilibrium and gene-environment analytic strategies for the role that they might play in cleft lip and palate. Significant findings can be validated using samples available by collaboration with the CDC National Birth Defects Prevention Programs.