GENOMIC RESOURCE DEVELOPMENT IN THE LABORATORY OPOSSUM

实验室负鼠基因组资源开发

• 批准号: 6285896
• 负责人: PAUL B SAMOLLOW
• 金额: $ 34.52万
• 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/6285896
• 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)：灰尾短尾 负鼠，家蝇，已被确立为模式生物 在广泛的相关主题上进行比较生物医学研究 对人类发育、生理和疾病易感性的影响。然而，一个缺乏 关于基本遗传特征的基本信息限制了它的 可能涉及正常基因调控的调查 发育和生理过程以及遗传因素的影响 与健康相关的生理特征的变异。 为了缓解这种情况，家蝇基因组图谱将被 构建了可用于检测、映射并最终隔离和克隆的 影响正常和异常表型变异的基因。整体而言 目标是构建一个具有200个或更多多态标记的连锁图谱 利用物理作图研究将连锁图谱锚定在 物理基因组，并使用地图来确定一个或多个 影响饮食中胆固醇和脂肪的可变反应性的基因。 具体的目标是：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谱上进行基因标记 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将其用于作图的CM连锁作图 该小组旨在最大限度地增加检测和测绘 功能基因座的多态；3)开发一个物理图谱，显示 家蝇已知连锁群的位置和方向 染色体；以及4)检测和定位一个或多个负责 饮食诱导的高胆固醇血症反应的高度遗传性变异 出现在这个物种中。 该连锁图谱由多态遗传标记基因座组成，包括 匿名小卫星基因座和功能基因，将由 由基因分析确定的基因间重组率的分析 来自两个大型回交家系的后代。原位荧光 杂交(FISH)将被用来定位 个体染色体上已知的连锁群。参数LOD-Score链接 将使用基于分析和谱系的方差分量方法来寻找 连锁图谱上的标记基因与影响基因的连锁 家族性心脏病患者的血浆脂蛋白表型 饮食挑战养生法。