Elucidating cardiovascular phenotaypes employing genome editing of iPS cells

利用 iPS 细胞基因组编辑阐明心血管表型

• 批准号: 8689147
• 负责人: Kristin Kay Baldwin
• 金额: $ 210.18万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-05 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8689147
• 关键词: 9p21; Abdominal Aortic Aneurysm; Affect; Architecture; Blood Vessels; Cardiovascular system; Cells; Chromatin; Collection; Complex; Coronary Arteriosclerosis; DNA; Data; Disease; Elderly; Endothelium; Generations; Genes; Genetic; Genetic Transcription; Genetic Variation; Genome; Genomics; Genotype; Haplotypes; Human Genetics; Individual; Intracranial Aneurysm; Measures; Modeling; Molecular; Myocardial Infarction; Open Reading Frames; Patients; Phase; Phenotype; Principal Investigator; Risk; Smooth Muscle; Smooth Muscle Myocytes; Stretching; Technology; Variant; cohort; epigenome; evidence base; genome wide association study; induced pluripotent stem cell; innovation; protective effect; small molecule; tool

DESCRIPTION (provided by applicant): We aim to develop an innovative approach to generate, at high-throughput, isogenic induced pluripotent stem cells (iPSCs), and use their differentiated progeny to understand the impact of human genetic variation on the risk of developing coronary artery disease (CAD). A genomic variant associated with CAD, myocardial infarction (Ml), abdominal aortic aneurysm, and intracranial aneurysm is found in a stretch of chr9p21 devoid of known genes. We will use this locus as a model for our study; while focusing on 9p21, our overall approach will be broadly applicable to the study of HLBS diseases of complex genetic architecture.

描述（由申请人提供）： 我们的目标是开发一种创新方法，以高通量生成同基因诱导多能干细胞 (iPSC)，并利用其分化后代来了解人类遗传变异对患冠状动脉疾病 (CAD) 风险的影响。在缺乏已知基因的 chr9p21 片段中发现了与 CAD、心肌梗塞 (MI)、腹主动脉瘤和颅内动脉瘤相关的基因组变异。我们将使用这个基因座作为我们研究的模型；在关注 9p21 的同时，我们的整体方法将广泛适用于复杂遗传结构的 HLBS 疾病的研究。