Center of Regenerative Medicine in Barcelona (CMRB), Hospital Duran i Reynals, 3rd Floor, Av. Gran Via 199-203, 08908 Hospitalet de Llobregat (Barcelona), Spain; Institute of Biomedicine (IBUB) of the University of Barcelona (UB), 08028 Barcelona, Spain; Department of Pathology and Experimental Therapeutics, School of Medicine, University of Barcelona, 08908 Barcelona, Spain.
Institute of Biomedicine (IBUB) of the University of Barcelona (UB), 08028 Barcelona, Spain; Department of Pathology and Experimental Therapeutics, School of Medicine, University of Barcelona, 08908 Barcelona, Spain.
Curr Opin Genet Dev. 2017 Oct;46:123-131. doi: 10.1016/j.gde.2017.06.002. Epub 2017 Jul 28.
Patient-specific iPSC are being intensively exploited as experimental disease models. Even for late-onset diseases of complex genetic influence, such as Parkinson's disease (PD), the use of iPSC-based models is beginning to provide important insights into the genetic bases of PD heritability. Here, we present an update on recently reported genetic risk factors associated with PD. We discuss how iPSC technology, combined with targeted edition of the coding or noncoding genome, can be used to address clinical observations such as incomplete penetrance, and variability in phenoconversion or age-at-onset in familial PD. Finally, we also discuss the relevance of advanced iPSC/CRISPR/Cas9 disease models to ascertain causality in genotype-to-phenotype correlation studies of sporadic PD.
患者特异性 iPSC 正在被深入开发为实验性疾病模型。即使是对于遗传影响复杂的迟发性疾病，如帕金森病（PD），基于 iPSC 的模型的使用也开始为 PD 遗传性的遗传基础提供重要的见解。在这里，我们介绍了最近报道的与 PD 相关的遗传风险因素的最新进展。我们讨论了如何将 iPSC 技术与靶向编辑编码或非编码基因组相结合，用于解决临床观察结果，如不完全外显率，以及家族性 PD 中表型转化或发病年龄的可变性。最后，我们还讨论了先进的 iPSC/CRISPR/Cas9 疾病模型与散发性 PD 的基因型-表型相关性研究中确定因果关系的相关性。
