IDENTIFICATION OF THE GENE(S) RESPONSIBLE FOR ALAGILLE SYNDROME

Alagille综合征(AGS)是一种影响肝脏、心脏、眼睛、面部和脊椎等多个器官系统的发育障碍。我们已经证明Jagged1(JAG1)基因的突变是导致AGS的原因，JAG1基因编码Notch受体的配体。由于斑马鱼是研究脊椎动物发育的一个很好的模型，我们从斑马鱼中分离并鉴定了3个同源基因，分别命名为Jag1，2和3。它们独特的表达模式，以及它们异位表达对斑马鱼发育的影响，支持锯齿状基因在组织边界和外胚层安慰剂的形成中发挥作用。我们还鉴定了另外两个编码Notch配体的人类基因Jagged2和Delta1。Jagged2基因定位于Usher综合征1A型(USH1A)基因14q32，而Delta1定位于6q27缺失区域，这为探索它们在人类疾病中的作用提供了机会。-肝病，基因图谱(人)，基因图谱(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)