Maas. Rapid Identification and Validation of Human Craniofacial Development Genes

The advent of new genomic sequencing technologies has made the task of gene discovery in human developmental disorders highly efficient. Simultaneously, advances in gene targeting in model organisms, specifically in zebrafish, have made semi-high throughput validation and analysis of human candidate genes feasible, including those responsible for craniofacial disorders. This project will take advantage of this convergence of new technologies to identify and functionally validate approximately two dozen genes involved in novel aspects of human craniofacial development. Specifically, we will take advantage of already ascertained collections of craniofacial dysmorphoses from Boston Children’s Hospital (BCH) and from King Faisal Specialist Hospital and Research Center (KFSHRC) in Saudi Arabia, where the high incidence of consanguinity makes autozygosity mapping and the identification of recessive causal loci highly feasible. We will extend the work of FaceBase beyond its current focus on disorders of palatal development by including a relatively wide range of craniofacial disorders that involve other components of the craniofacial complex. In addition, use of resources already compiled by FaceBase, including detailed gene expression data in mouse and zebrafish, enhancer analyses, and genome wide association studies, in combination with the present data and publicly available datasets, will further facilitate the functional annotation of these newly validated genes.