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