Genes and regulation of eye development

Abstract

SummaryDevelopmental ocular disorders have a strong genetic component. Our laboratory has been applying whole exome sequencing (WES) to identify novel human genes associated with abnormal eye development for many years. WES provides the opportunity to simultaneously screen coding regions of all genes in order to identify causative mutations. While this comprehensive examination greatly improves the chances of mutation detection, interpretation of the large volume of data is complicated. Since many developmental processes are conserved in vertebrates, studies of zebrafish orthologs of human disease genes can provide critical information about their embryonic function and determine other genes involved in the same pathway. With this, studies of zebrafish mutants help to identify an additional pool of relevant gene candidates for corresponding human phenotypes. Moreover, zebrafish model allows for rapid in vivo testing of promising human variants by overexpression and/or rescue experiments. Our utilization of this approach in studies of zebrafish orthologs of several transcription factors, such as PITX2, PITX3 and FOXE3 associated with Axenfeld‐Rieger syndrome, anterior segment dysgenesis, cataracts and microphthalmia, will be presented.