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。因为硬骨鱼有基因组扩张的历史，可能是由于基因组复制，它们通常有两个拷贝的单拷贝人类基因。在重复的硬骨鱼基因拷贝之间划分祖先基因亚功能有助于分析与人类共享的祖先基因功能。这项工作的长期目标是提供与硬骨鱼复制基因相关的资源，以极大地扩展现有硬骨鱼模型在人类发育、器官功能、健康和疾病方面的应用。目标1是开发TelGen软件资源，用于硬骨鱼基因组序列中重复基因的自动鉴定和系统发育分析。目标2是使用新软件来识别、调查并在TelGen2数据库中公开获取在拟议的鳍基因组复制事件中产生的一组基因复制。目标3是确定最近分化的、复制前的鳐鳍谱系，并提供切实的基因组资源，包括大型插入基因组克隆和cDNA文库，以及这些序列的OldFish数据库。最后，目标4是创建TelExDB，这是一个关于人类疾病基因的硬骨鱼副本的基因表达数据资源，并研究硬骨鱼基因副本功能进化的一般原理。这些资源和研究将通过提供对硬骨鱼重复基因分化的一般理解，提高硬骨鱼模型的连通性和实用性。此外，它们还有助于在单个复制哺乳动物基因的早期基本功能掩盖了后来功能的情况下进行分析。对复制硬骨鱼基因的分析有助于发现候选的组织特异性调控元件和蛋白质结构基元，这些结构基元可能是副作用较小的药物的靶点。

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.