Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms.
Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms.
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DOI：
10.1016/j.brainres.2015.11.009
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发表时间：
2017-01-15
期刊：
影响因子：
2.9
通讯作者：
Brennand KJ
中科院分区：
文献类型：
--
作者：
Flaherty EK;Brennand KJ
精神分裂症是一种具有很强遗传成分的神经心理疾病；精神分裂症的遗传风险既有影响相对较小的常见变异，也有影响较高的罕见变异。基因工程小鼠模型可以概括罕见的变异，显示出与精神分裂症有关的一些行为缺陷；然而，这些小鼠模型不能概括这种疾病背后的完整遗传结构。患者来源的人类诱导多能干细胞(HiPSCs)为研究罕见变异提供了一种替代方法，在所有其他风险等位基因的背景下。基因组编辑技术，如CRISPR-Cas9，能够产生等基因的hiPSC系，用来检查任何遗传背景中单个变异体的功能贡献。使用HiPSCs对这些罕见变异的研究有可能识别精神分裂症中常见的被干扰的通路，并允许识别新的治疗靶点。
Schizophrenia is a neuropsychological disorder with a strong heritable component; genetic risk for schizophrenia is conferred by both common variants of relatively small effect and rare variants with high penetrance. Genetically engineered mouse models can recapitulate rare variants, displaying some behavioral defects associated with schizophrenia; however, these mouse models cannot recapitulate the full genetic architecture underlying the disorder. Patient-derived human induced pluripotent stem cells (hiPSCs) present an alternative approach for studying rare variants, in the context of all other risk alleles. Genome editing technologies, such as CRISPR-Cas9, enable the generation of isogenic hiPSC lines with which to examine the functional contribution of single variants within any genetic background. Studies of these rare variants using hiPSCs have the potential to identify commonly disrupted pathways in schizophrenia and allow for the identification of new therapeutic targets.