Elucidating cardiovascular phenotaypes employing genome editing of iPS cells

描述(由申请人提供)： 我们的目标是开发一种创新的方法来高通量地产生等基因诱导的多能干细胞(IPSCs)，并使用它们分化的后代来了解人类基因变异对发展成冠状动脉疾病(CAD)风险的影响。在一段缺乏已知基因的chr9p21中发现了一个与冠心病、心肌梗死、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，我们的总体方法将广泛适用于复杂遗传结构的HLBS疾病的研究。

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.