Systematic Vertebrate Functional Genomics

描述（由申请人提供）：脊椎动物基因组包含预测的30，000+个基因，大多数功能未知。基因注释是理解脊椎动物基因组的主要步骤之一。斑马鱼中基于吗啉代的基因“敲低”技术的最新发展为在模式脊椎动物中基于序列的全基因组功能分配打开了大门。在这次竞争性更新中，我们将重点关注300种假定分泌蛋白的生物学功能的系统分配，以确定这些临床相关过程中的新参与者。 我们将通过以下具体目标实现这一目标： 艾姆岛分泌性蛋白质吗啉核心数据库的建立。将产生靶向这些基因的吗啉代，并检查其在以下生物过程中的功能：目的II。胚胎发育和器官形成所需的分泌蛋白的分离。 Aim III.心血管和感觉器官形成所需的分泌蛋白的分离。目标四。消化器官形成和功能所需的分泌蛋白的分离。 目的V.注释鉴定的表型并将该基因集信息并入ZFIN的国际斑马鱼数据库。 脊椎动物模式化和器官功能所需的分子的鉴定对于理解这些过程中的遗传缺陷具有重要意义。此外，被鉴定为对体内发育至关重要的分子将作为潜在小分子药物靶向干预和建立干细胞操作条件（如体外器官形成）的关键底物分子。斑马鱼提供了第一个机会，全面分析这些过程使用作为模板的整个脊椎动物基因组。

DESCRIPTION (provided by applicant): The vertebrate genome contains a predicted 30,000+ genes, most of unknown function. The annotation of genes is one of the major next steps in understanding the vertebrate genome. The recent development of morpholino-based gene 'knockdown' technology in zebrafish has opened the door to the genome-wide assignment of function based on sequence in a model vertebrate. In this competitive renewal, we will focus on the systematic assignment of biological function to 300 putative secreted proteins to identify new players in these clinically relevant processes. We will accomplish this goal through the following specific aims: Aim I. Development of a secreted protein morpholino core database. Morpholinos targeted to these genes will be generated and examined for function in the following biological processes: Aim II. Isolation of secreted proteins required for embryonic patterning and organogenesis. Aim III. Isolation of secreted proteins required for cardiovascular and sensory organ formation. Aim IV. Isolation of secreted proteins required for digestive organ formation and function. Aim V. Annotation of the identified phenotypes and incorporation of this gene set information into the international zebrafish database at ZFIN. The identification of molecules required for vertebrate patterning and organ function has critical implications for the understanding of genetic deficiencies in these processes. In addition, the molecules identified as crucial for development in vivo will serve as key substrate molecules for potential small molecule drug target intervention and for the establishment of conditions for stem cell manipulation such as in vitro organ formation. The zebrafish offers the first opportunity for a comprehensive analysis of these processes using as template an entire vertebrate genome.