Resources for Teleost Gene Duplicates and Human Disease

描述（由申请人提供）：硬骨鱼为了解人类健康和疾病提供了重要的模型。这些包括癌症和肿瘤发生、人类发育和婴儿健康、心血管疾病、眼病、骨病、环境毒理学、衰老以及基因组结构和调控的模型。由于硬骨鱼有着基因组扩增的历史，可能是由于基因组复制，它们通常有两个单拷贝人类基因。在重复的硬骨鱼基因拷贝之间划分祖先基因子功能有助于分析与人类共享的祖先基因功能。拟议工作的长期目标是提供与复制硬骨鱼基因相关的资源，以大大扩展现有硬骨鱼模型在人类发育、器官功能、健康和疾病方面的效用。目的1是开发TelGen软件资源，用于硬骨鱼基因组测序中重复基因的自动识别和系统发育分析。目的2是使用新软件来识别，调查，并在TelGen2数据库中公开访问，在拟议的射线鳍基因组重复事件中出现的基因重复集。目的3是确定最近的分歧，复制前的射线鳍谱系，并提供有形的基因组资源，包括大型插入基因组克隆和cDNA文库，和OldFish，这些序列的数据库。最后，目标4是创建TelExDB，一个用于人类疾病基因的硬骨鱼重复拷贝的基因表达数据的资源，并研究硬骨鱼基因重复拷贝中功能进化的一般原则。这些资源和研究将提高连接性和实用性的硬骨鱼类模型提供了一个普遍的理解重复基因分歧的硬骨鱼类。此外，它们有助于分析单拷贝哺乳动物基因的早期基本功能掩盖了后期功能的情况。分析重复的硬骨鱼基因可以容易地发现候选组织特异性调控元件和蛋白质结构基序，这些元件和蛋白质结构基序可能是副作用较少的药物的靶点。

DESCRIPTION (provided by applicant): Teleost fish provide important models for understanding human health and disease. These include models for cancer and tumorigenesis, human development and infant health, cardiovascular disease, eye disease, bone disease, environmental toxicology, aging, and genome structure and regulation. Because teleost fish share a history of genome expansion, likely due to genome duplication, they often have 2 copies of single copy human genes. The partitioning of ancestral gene subfunctions between duplicated teleost gene copies facilitates analysis of ancestral gene functions shared with humans. The long-term objective of the proposed work is to provide resources related to duplicated teleost genes to greatly expand the utility of existing teleost models for human development, organ function, health, and disease. Aim 1 is to develop TelGen, software resources to automate the identification and phylogenetic analysis of duplicated genes in the sequenced genomes of teleost fish. Aim 2 is to use the new software to identify, investigate, and make publicly accessible in the TelGen2 database, the set of gene duplicates that arose in the proposed ray-fin genome duplication event. Aim 3 is to identify the most recently diverging, pre-duplication ray-fin lineage, and make available tangible genomic resources, including large insert genomic clones and cDNA libraries, and OldFish, a database for these sequences. Finally, Aim 4 is to create TelExDB, a resource of gene expression data for both copies of teleost duplicates of human disease genes, and to investigate general principles for the evolution of function in teleost gene duplicates. These resources and studies will improve connectivities and utility of teleost models by providing a general understanding of duplicate gene divergence across teleosts. In addition, they facilitate analysis in cases where the early essential function of a single copy mammalian gene obscures a later function. Analysis of duplicated teleost genes can ease discovery of candidate tissue-specific regulatory elements and protein structural motifs that may be targets for drugs with fewer side effects.