Parent Project - Main Theme (MAIN)

父项目 - 主题 (MAIN)

• 批准号: 7909451
• 负责人: MARK J RATAIN
• 金额: $ 106.22万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7909451
• 关键词: Alternative Splicing; Amish; Asthma; Biological Models; Cell Line; Cells; Computer software; Confounding Factors (Epidemiology); Data; Databases; Disease; Educational workshop; Electronics; Evaluation; Gene Expression; Generations; Genetic; Genetic Markers; Genetic Polymorphism; Genotype; Growth; Human; Hypertension; Individual; Institutes; International; Learning; Location; Medical Research; Methylation; MicroRNAs; Modeling; Pear; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Phenotype; Research; Research Personnel; Resources; Sampling; Scanning; Serum; System; Testing; Validation; Variant; base; data sharing; falls; healthy volunteer; improved; lymphoblastoid cell line; member; programs; response; statistics

Interindividual variation in response to drug administration is multi-factorial, with genetic factors often contributing significantly. Because of the difficulfies in studying drug response in humans, cell-based models are being developed as a means to identify and characterize genetic markers associated with drug response. Particulariy with the availability of extensive genotypic (e.g. SNPs and copy number variants) and phenotypic (e.g., gene expression) data for the International HapMap cell lines, investigators have begun to analyze pharmacological endpoints within these lines in efforts to identify clinically important genotype-phenotype relafionships. Over the past 5 years, there has been significant growth in the number of PGRN investigators employing cell-based models as a component of their pharmacogenomic research program (Figure 1). Some PGRN groups (PAAR, CREATE, PPII) have utilized the International HapMap and or the Polymorphism Discovery lymphoblastoid cell lines (LCLs) that are commercially available from the Coriell Institute for Medical Research (http://www.coriell.org/). Other groups have created their own cell lines from individuals with a specific disease such as asthma (PHAT) or hypertension (PEAR), or they have generated cell lines from key individuals in deeply-phenotyped populafions such as the Amish (PAPI) or SOPHIE (healthy volunteers) study (PMT). Therefore, providing a resource for the exchange of information generated via the use of cell lines would be highly beneficial to the majority of existing PGRN groups (8 out of 11). This resource will also be of great benefit to PGRN invesfigators who currently do not use cell-based models, because it will provide them with opportunities to learn about the applications for cell-based research and invesfigate results of pharmacogenomic studies within this model system.

响应药物给药的个体差异是多因素的，遗传因素通常 贡献很大。由于研究人类的药物反应困难，基于细胞的模型 正在开发作为识别和表征与药物反应相关的遗传标记的一种手段。 特别具有广泛的基因型（例如SNP和拷贝数变体）和表型的可用性 （例如，基因表达）国际HAPMAP细胞系的数据，研究人员已经开始分析 这些线中的药理学终点，以识别临床上重要的基因型 - 表型 遗产。在过去的5年中，PGRN研究人员的数量已显着增长 采用基于细胞的模型作为其药物基因组研究计划的组成部分（图1）。一些 PGRN组（PAAR，CREATE，PPII）使用了国际HAPMAP和 /或多态性 Coriell医学研究所可获得市售的发现淋巴细胞细胞系（LCLS） 研究（http://www.coriell.org/）。其他小组也从一个人那里创建了自己的细胞系 特定疾病，例如哮喘（PHAT）或高血压（梨），或者它们已经从钥匙中产生了细胞系 深层型人口中的个人，例如阿米什（Papi）或索菲（Sophie）（健康志愿者）研究 （PMT）。因此，为通过使用单元线的使用提供了用于交换信息的资源 对大多数现有PGRN组非常有益（11分中的8个）。此资源也将是 对于当前不使用基于单元的模型的PGRN InvesFigators的巨大好处，因为它将为其提供 有机会了解基于细胞的研究的应用，并提出结果 该模型系统中的药物基因组学研究。