CORE--GENOTYPING

基因分型核心将提供用于该计划项目各个方面的UM-HET3雌性小鼠的遗传信息。在Animal Oore生产的600只1号种群动物将在150个基因座上进行基因分型，每个基因座能够区分四个祖父母等位基因。对于每种动物，基因扫描将提供大约15到20 cM的基因组覆盖率。将对其他UM-HET3女性进行基因分型，以筛选少量与寿命相关的候选基因座。被识别为在该基因座上具有所需等位基因组合的动物将保留为种群2(最终总数为180只)。这些群体将在个别项目中进行表型检查，并由数据分析核心公司评估基因型与表型的关联。具体目标：目标1.建立一个高通量的基因分型服务，每年能够处理大约30,000个基于聚合酶链式反应的基因分析。目的2.从所有项目动物中提取基因组DNA并对其进行定量。目的3.鉴定、发展和质量评估150个多态标记反应。在该项目的最后两年，将在GNOME的候选区域确定更多的标记反应。目的4.从600个种群1的150个标记中产生高质量的基因分型数据。最终的数据集将包括大约90,000个基因类型，遗漏数据不到3%，误差不超过1%。数据将被传输到Data Animal Core进行分析。目的5.在大约1500只UM-HET3候选动物的6个多态座位上产生高质量的基因型数据。将在8周龄时确定基因类型，并根据基因类型选择180只动物。用于筛选的基因座将包含三个被建议为寿命候选的数量性状基因座(QTL)。对于这项筛查，将在两年内获得大约9000个基因型值，误差百分比和缺失数据水平可与第一群体相当。目标6.开发一个实验室信息管理系统(LIMS)，用于有效的基因数据处理、资源管理和成本控制。

The Genotyping Core will provide genetic information on the UM-HET3 female mice used for all aspects of the Program Project. The 600 Population 1 animals produced in Animal ore will be genotyped at 150 loci, with each locus able to distinguish the four grandparental alleles. For each animal the genotype scan will provide approximately 15 to 20 cM coverage across the genome. Genotyping will be performed on additional UM-HET3 females to screen for a small number of candidate lifespan-associated loci. Animals identified as having the desired combination of alleles at the loci will be retained as Population 2 (180 animals final total). The Populations will be examined for phenotypes in the individual Projects and assessed for genotype by-phenotype associations by Data Analysis Core. The Specific Aims: Aim 1. Establish a high-throughput genotyping service capable of handling approximately 30,000 PCR-based genotype assays per year. Aim 2. Prepare and quantify genomic DNA from all project animals. Aim 3. Identify, develop, and quality assess 150 polymorphic marker reactions. Additional marker reactions will be identified in candidate regions of the gnome in the final two years of the Project. Aim 4. Generate high-quality genotype data from 150 marker on 600 Population 1 animals. The final dataset will include approximately 90,000 genotypes with less than 3% missing data and less than 1% error. The data will be transferred to Data Animal Core for analysis. Aim 5. Generate high-quality genotype data at six polymorphic loci on approximately 1500 UM-HET3 candidate animals for Population 2. Genotypes will be determined at 8 weeks of age and 180 animals will be selected based on the genotypes. The loci used for the screen will bracket three quantitative trait loci (QTL) proposed as candidates for lifespan. For this screen, approximately 9000 genotype values will be obtained over two years, with percent error and missing data levels comparable to Population I. Aim 6. Develop a laboratory information management system (LIMS) for efficient genotype data handling, resource management, and cost control.