Genome resources for model amphibians

描述（由申请人提供）：蝾螈是人类健康和疾病研究的几个领域中重要的脊椎动物模式生物，包括脊髓和肢体再生、胚胎后发育、毒理学、视觉、嗅觉、心脏发育、肾功能和神经传递。我们启动了蝾螈基因组计划（SGP），以开发第一个基因组和生物信息资源，用于使用钝口蝾螈的研究。在上一个资助期间，我们创建了第一个全面的两栖动物遗传图谱，几个注释的分子数据库，一个社区门户网站（www.ambystoma.org），并确定了大量对应于Ambystoma基因组中不同基因的独特序列。我们提出了三个具体目标，以进一步提高蝾螈在生物医学研究中的效用。首先，我们将增加从墨西哥钝口鱼中鉴定出的基因的数量，这些基因的功能在人类中是已知的。这将增加用于分子研究、微阵列分析和基因定位的探针的数量。更一般地，它将允许从蝾螈到其他脊椎动物模式生物（斑马鱼、爪蟾、小鸡、小鼠、大鼠、人等）的更大量的遗传和基因组信息被交叉引用。第二，我们将设计一个微阵列基因芯片，并使用它来鉴定在自然脊髓再生和甲状腺激素诱导的变态过程中差异表达的基因。为了更好地使研究社区，我们将使微阵列设计免费提供。这一目标将为蝾螈研究人员提供一个强大的新工具，并为非蝾螈研究人员提供一种快速筛选蝾螈候选基因和基因网络的手段。第三，我们将建立一个大的种间作图组，并利用它来鉴定重要的A. mexicanum突变体和性别决定位点。基因标记将提高管理联邦资助的实验室库存的效率，该库存为来自世界各地的研究人员提供蝾螈材料。关于较长期的目标，拟议的项目将促进开发更多的资源，以促进确定具有生物医学意义的蝾螈基因。

DESCRIPTION (provided by applicant): Salamanders are important vertebrate model organisms in several areas of human health and disease research, including spinal cord and limb regeneration, post-embryonic development, toxicology, vision, olfaction, heart development, renal function, and neural transmission. We initiated the Salamander Genome Project (SGP) to develop the first genomic and bioinformatic resources for research using ambystomatid salamanders. During the last grant period, we created the first comprehensive amphibian genetic map, several annotated molecular databases, a community web-portal (www.ambystoma.org), and identified a large number of unique sequences that correspond to different genes in the Ambystoma genome. We propose three Specific Aims to further increase the utility of salamanders in biomedical research. First, we will increase the number of genes identified from Ambystoma mexicanum whose functions are known in humans. This will increase the number of probes for molecular studies, microarray analysis, and gene mapping. More generally, it will allow a greater amount of genetic and genomic information to be cross- referenced from salamander to other vertebrate model organisms (Zebrafish, Xenopus, Chick, Mouse, Rat, Human, etc). Second, we will design a microarray gene chip and use it to identify genes that are differentially expressed during natural spinal cord regeneration and thyroid hormone induced metamorphosis. To better enable the research community, we will make the microarray design freely available. This aim will provide a powerful new tool for salamander researchers and a means for non-salamander researchers to rapidly screen the salamander for candidate genes and gene networks. Third, we will develop a large interspecific mapping panel and use it to identify markers and candidate genes for important A. mexicanum mutants and the sex- determining locus. Gene markers will increase the efficiency of managing a federally funded laboratory stock that provides salamander material to researchers from around the world. With respect to longer-term goals, the proposed project will spur development of additional resources that will facilitate identification of salamander genes of biomedical significance.