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的方法，以高通量产生等基因诱导多能干细胞（iPSC），并使用其分化的后代来了解人类遗传变异对冠状动脉疾病（CAD）风险的影响。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体在缺乏已知基因的chr9p21的延伸中被发现。我们将使用这个基因座作为我们研究的模型，同时专注于9p21，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。