Genetic Variants Associated with AD/ADRD

在这个项目中，我们计划从已知全基因组序列的捐赠者中产生200个新的诱导多能干细胞(IPSCs)。由于这个项目的规模，我们已经开始引入实验室自动化，以便能够处理和维护大量的细胞系。我们还从适当的临床来源确定了捐赠者，并开始产生IPSC系。在接下来的几个月里，我们将测试生产的品系是否与原始捐赠者具有相同的遗传背景，以防止样品混淆和品系中的遗传漂移，例如，选择可能获得致癌突变的细胞。 截至2020年夏天，第一组品系已经生成并扩展，准备进行基因分型。我们还成功地试验了一种生物信息学去卷积策略，使我们能够在有多个捐赠者的池中分化细胞。我们计划使用这种方法从单细胞RNA-Seq数据中生成我们的初级数据集。

In this project, we plan to generate 200 new induced pluripotent stem cells (IPSCs) from donors whose whole genome sequence is already known. Due to the scale of this project, we have started to introduce laboratory automation in order to be able to handle and maintain a large number of cell lines. We have also identified donors from appropriate clinical sources and started to generate IPSC lines. We will test that the produced lines have the same genetic background as the original donors in the next few months to guard against sample mixups and genetic drift in the lines due to, for example, selection for cells that might have acquired oncogenic mutations. As of summer 2020, the first set of lines are generated and are expanded, ready for genotyping. We have also successfully trialed a bioinformatic deconvolution strategy that enables us to differentiate cells in pools with multiple donors. We plan to use this approach to generate our primary datasets from single cell RNA-Seq data.