Functional Genetics Approaches to Investigate Human Evolution

对人类和黑猩猩基因组的分析已经对单核苷酸和结构变异进行了编目， 自从人类从非人类灵长类动物中分化出来后就出现了。几乎所有这些基因变异都保留了下来 功能上没有特征。这些遗传变异体中包含顺式调节元件的改变， 蛋白质编码基因、非编码RNA、基因拷贝数、重复元件和其他基因组特征 人类和非人类灵长类之间的表型差异。因为难以预测 人类谱系内的基因组差异如何导致表型差异， 高通量，系统的方法来询问功能性遗传变异。因此，我寻求 开发一个定量基因组规模的平台，用于确定人类特异性 细胞和分子水平的进化突变。为了实现这一目标，我将把联合收割机的进展 在黑猩猩多能干细胞衍生模型中，使用CRISPR干扰（CRISPRi）、单细胞RNA测序（scRNA-seq）和单细胞ATAC测序（scATAC-seq）。这个项目是伟大的

Analyses of human and chimpanzee genomes have catalogued the single-nucleotide and structural variants that have emerged since humans diverged from nonhuman primates. Nearly all of these genetic variants remain functionally uncharacterized. Contained within these genetic variants are alterations to cis-regulatory elements, protein-coding genes, noncoding RNAs, gene copy number, repetitive elements, and other genomic features that underlie phenotypic differences between humans and nonhuman primates. Because it is difficult to predict how genomic differences within the hominid lineage contribute to phenotypic differences, there is a critical need for high-throughput, systematic approaches to interrogate functional genetic variation. Therefore, I seek to develop a quantitative genome-scale platform for identifying the phenotypic consequences of human-specific evolutionary mutations at a cellular and molecular level. To accomplish this objective, I will combine advances in chimpanzee pluripotent stem cell-derived models with CRISPR interference (CRISPRi), single-cell RNAsequencing (scRNA-seq), and single-cell ATAC-sequencing (scATAC-seq). This project is of great