A Genetic Mapping Resource for Zebrafish

描述（由申请人提供）：斑马鱼突变筛选有望识别与发育和疾病相关的表型基础基因。将表型和基因型相关联需要开发与这些筛选规模相匹配的基因分型工具。该提案针对“斑马鱼遗传研究工具”计划公告解决了这一差距。我们建议运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。首席研究员开发了最先进的基因分型技术和信息学工具，目前可用于斑马鱼制图并直接适用。我们已经完成了大约100万个基因型，开发了bbbb75荧光简单串联重复（STR）标记面板（包括一套强大的人类遗传图谱），在大规模人类研究中发现了跨候选基因的综合单核苷酸多态性（SNP）图谱并进行了基因分型，目前正在进行全基因组小鼠SNP扫描。在这里，我们建议开发共享的斑马鱼定位资源：用于高通量遗传筛选的健壮的全基因组标记集，以及用于组织和设计定制分析的公共生物信息学系统，以进行后续的精细定位。

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.