IDENTIFICATION OF THE GENE(S) RESPONSIBLE FOR ALAGILLESYNDROME

阿拉吉尔综合征（AGS）是一种影响多器官系统的发育障碍，包括肝脏、心脏、眼睛、面部和脊椎。我们已经证明，编码Notch受体配体的Jagged1 （JAG1）基因的突变是导致AGS的原因。由于斑马鱼是脊椎动物发育的良好模型，我们从斑马鱼中分离并表征了3个同源基因，称为Jagged 1, 2和3。其独特的表达模式及其异位表达对斑马鱼发育的影响，支持Jagged基因在组织边界和外胚层基板形成中的作用。我们还鉴定并鉴定了另外两个编码Notch配体的人类基因，Jagged2和Delta1。Jagged2基因位于Usher综合征1型A （USH1A）的14q32位点附近，而Delta1基因位于多种肿瘤中经常缺失的6q27位点，这为探索它们在人类疾病中的作用（如果有的话）提供了机会。-肝脏疾病，基因定位（人类），基因定位（非人类）

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)