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.

个体间对给药反应的差异是多因素的，遗传因素通常 做出了重大贡献。由于研究人类药物反应的困难，基于细胞的模型 正在被开发为鉴定和表征与药物反应相关的遗传标记的手段。 特别是随着广泛的基因型（例如SNP和拷贝数变体）和表型（例如表型）的可用性， (e.g.,基因表达）数据，研究人员已经开始分析 这些品系中的药理学终点，以确定临床重要的基因型-表型 相对论在过去的5年里，PGRN调查人员的数量有了显着增长 采用基于细胞的模型作为其药物基因组学研究计划的组成部分（图1）。一些 PGRN研究组（帕尔，CREATE，PPII）已经利用了国际单体型图和/或多态性 可从Coriell医学研究所商购获得的发现类淋巴母细胞系（LCL） 研究（http：//www.coriell.org/）。其他研究小组已经从具有以下特征的个体中创建了自己的细胞系： 特定疾病，如哮喘（PHAT）或高血压（PEAR），或者他们已经从关键的 表型确定人群中的个体，如Amish（PAPI）或SOPHIE（健康志愿者）研究 （PMT）。因此，为通过使用细胞系产生的信息交换提供资源 将对大多数现有PGRN组（11个中的8个）非常有益。这一资源也将是 对于目前不使用基于单元的模型的PGRN投资者来说，这是一个很大的好处，因为它将为他们提供 有机会了解基于细胞的研究的应用和研究结果， 在该模型系统中进行药物基因组学研究。