Genetic landscape and functional exploration of kidney cancer predisposition causality in cross-ancestral populations

To functionally explore renal cell carcinoma (RCC) susceptibility variants, we performed CUT&Tag for H3K27ac and ATAC-seq on 786-O cells to assess transcriptional activity. Subsequently, we conducted a CRISPR screen and CRISPR droplet sequencing (CROP-seq), which combines pooled CRISPR screens with single-cell RNA sequencing (scRNA-seq), to identify target genes potentially regulated by likely causal SNPs. Functionally, we established a novel association between rs28684409 and the oncogene RPL4 at the complex genetic locus 15q22.31. As the next step, we performed CRISPRi on rs28684409 and conducted RNA-seq to identify differential gene expression associated with this variant. Overall design: RNA Sequencing (RNA-seq) to analyze gene expression in CRISPRi-targeted rs28684409 and rs179785 cells compared to control cells. This experiment aims to identify differential expression profiles and elucidate the functional consequences of targeting rs28684409 and rs179785, providing insights into its role in cellular pathways and potential implications in disease.