GENOMIC RESOURCE DEVELOPMENT IN THE LABORATORY OPOSSUM

实验室负鼠基因组资源开发

• 批准号: 6499496
• 负责人: PAUL B SAMOLLOW
• 金额: $ 33.87万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6499496
• 关键词: animal genetic material tag; blood lipoprotein metabolism; cholesterol; chromosomes; developmental genetics; dietary lipid; family genetics; fluorescent in situ hybridization; genetic mapping; genetic markers; genetic models; genetic polymorphism; genetic recombination; genetic regulation; genome; genotype; hypercholesterolemia; linkage mapping; model design /development; nucleic acid sequence; nutrition related tag; opossums; polymerase chain reaction; quantitative trait loci; tissue /cell culture

DESCRIPTION (Adapted from the applicant's abstract): The gray-short-tailed opossum, M. domestica, has been established as a model organism for comparative biomedical research on a broad range of topics that are relevant to human development, physiology, and disease susceptibility. However, a lack of basic information on fundamental genetic characteristics limits its potential for inquiries involving the genetic regulation of normal developmental and physiologic processes, and the influences of genetic variation on health-related physiologic characteristics. To mitigate this situation, a map of the M. domestica genome will be constructed that can be used to detect, map, and ultimately isolate and clone genes that influence normal and abnormal phenotypic variation. The overall objectives are to construct a linkage map of 200 or more polymorphic marker loci, to use physical mapping studies to anchor the linkage map on the physical genome, and to use the map to determine the locations of one or more genes that influence variable responsiveness of dietary cholesterol and fat. The Specific Aims are to: 1) expand the number of anonymous and functional gene markers on the existing, sparsely-filled linkage map through continuing linkage studies utilizing an existing backcross mapping panel; 2) complete a 5 cM linkage map by creating, and utilizing for mapping, a new backcross mapping panel designed to maximize opportunities for the detection and mapping of polymorphisms at functional gene loci; 3) develop a physical map showing the locations and orientations of known linkage groups on M. domestica chromosomes; and 4) detect and map one or more of the genes responsible for highly heritable variation in diet-induced hypercholesterolemic responsiveness that occurs in this species. The linkage map, comprised of polymorphic genetic marker loci including anonymous micosatellite loci and functional genes, will be developed by analysis of intergenic recombination rates determined from genotype analyses of offspring from two large backcross family panels. Fluorescence in situ hybridization (FISH) will be used to locate the physical positions of the known linkage groups on individual chromosomes. Parametric LOD-score linkage analyses and pedigree based variance components methods will be used to seek linkage between marker genes on the linkage map and genes that influence plasma lipoprotein phenotypes in a family panel that has been subjected to a dietary challenge regimen.

描述（改编自申请人的摘要）：灰短尾 负鼠（M. Domestica）已被确立为模式生物 广泛相关主题的比较生物医学研究 人类发育、生理和疾病易感性。 然而，缺乏 基本遗传特征的基本信息限制了其 涉及正常基因调控的研究潜力 发育和生理过程以及遗传的影响 与健康相关的生理特征的变化。 为了缓解这种情况，将绘制 M. Domestica 基因组图谱 构建可用于检测、绘制图谱并最终分离和克隆 影响正常和异常表型变异的基因。 整体 目标是构建 200 个或更多多态性标记的连锁图 位点，使用物理作图研究将连锁图锚定在 物理基因组，并使用图谱来确定一个或多个 影响膳食胆固醇和脂肪的可变反应性的基因。 具体目标是： 1）扩大匿名和功能性的数量 通过继续在现有的、稀疏填充的连锁图上添加基因标记 利用现有回交作图小组进行连锁研究； 2）完成5 通过创建新的回交作图并利用其进行作图，进行 cM 连锁图谱 面板旨在最大限度地增加检测和绘图的机会 功能基因位点的多态性； 3) 绘制物理图来显示 家蝇已知连锁群的位置和方向 染色体； 4) 检测并绘制一个或多个负责的基因图谱 饮食引起的高胆固醇血症反应性的高度遗传变异 发生在这个物种中。 连锁图谱由多态性遗传标记位点组成，包括 匿名微卫星位点和功能基因，将由 对基因型分析确定的基因间重组率进行分析 来自两个大型回交家族小组的后代。 原位荧光 杂交（FISH）将用于定位 单个染色体上已知的连锁群。 参数化 LOD-分数联动 将使用分析和基于谱系的方差分量方法来寻求 连锁图上标记基因与影响基因之间的连锁 已进行家族检测的血浆脂蛋白表型 饮食挑战方案。