A Genetic Mapping Resource for Zebrafish

描述(申请人提供)：斑马鱼突变筛选有望识别与发育和疾病相关的表型基因。将表型和基因型联系起来将需要开发出与这些筛查的规模相匹配的基因分型工具。这项建议是对“斑马鱼遗传研究工具”项目公告的回应，旨在解决这一差距。我们建议应用我们在高通量基因分型方面的丰富经验，为斑马鱼群落创建一个共享的全基因组图谱资源。首席调查员开发了最先进的基因分型技术和信息学工具，目前可操作并直接适用于斑马鱼地图绘制。我们已经完成了大约一百万种基因类型，开发了&gt；75荧光简单串联重复序列(STR)标记板(包括用于人类遗传图谱的强大的全基因组集)，在大规模的人类研究中发现了候选基因的全面单核苷酸多态(SNP)图谱并进行了基因分型，目前正在进行全基因组的小鼠SNP扫描。在这里，我们建议开发共享的斑马鱼作图资源：用于高通量遗传筛选的强大的全基因组标记集，以及为随后的精细作图组织和设计定制分析的公共生物信息学系统。

DESCRIPTION (provided by applicant): Zebrafish mutagenesis screens hold promise for identifying genes underlying phenotypes relevant to development and to disease. Associating phenotype and genotype will require development of genotyping tools matched in throughput to the scale of these screens. This proposal addresses this gap in response to the program announcement "Tools for Genetic Studies in Zebrafish." We propose to apply our extensive experience in high-throughput genotyping to create a shared genome-wide mapping resource for the zebrafish community. The Principal Investigator has developed state-of-the-art genotyping technologies and informatics tools that are currently operational and directly applicable in zebrafish mapping. We have completed approximately one million genotypes, developed >75 fluorescent simple tandem repeat (STR) marker panels (including a robust genome-wide set for human genetic mapping), discovered and genotyped comprehensive single nucleotide polymorphisms (SNP) maps across candidate genes in large-scale human studies, and are now performing a genome-wide mouse SNP scan. Here we propose development of shared zebrafish mapping resources: robust genome-wide marker sets for high-throughput genetic screens, and a public bioinformatics system to organize and design custom assays for subsequent fine mapping.