IDENTIFICATION OF THE GENE(S) RESPONSIBLE FOR ALAGILLESYNDROME

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Alagille syndrome (AGS) is a developmental disorder affecting multiple organ systems including liver, heart, eye, face and vertebrae. We have shown that mutations in the Jagged1 (JAG1) gene, which encodes a ligand for a Notch receptor, are responsible for AGS. Since zebrafish is a well-studied model for vertebrate development, we have isolated and characterized 3 homologous genes termed Jagged 1, 2 and 3 from zebrafish. Their distinct expression pattern, and the effect of their ectopic expression on zebrafish development, supports a role for the Jagged genes in the formation of tissue boundaries and ectodermal placodes. We also have identified and characterized two other human genes encoding Notch ligands, Jagged2 and Delta1. The Jagged2 gene maps close to the Usher syndrome type 1 A (USH1A) locus at 14q32, and Delta1 maps to the region of 6q27 deleted often in many kinds of tumors, offering an opportunity to explore their role, if any, in human diseases. - Liver Disease, Gene Mapping (HUMAN), Gene Mapping (NON- HUMAN)