{"doi":"10.1101/2023.12.27.573461","title":"Mapping <i>cis</i> - and <i>trans</i> -regulatory target genes of human-specific deletions","abstract":"Abstract Deletion of functional sequence is predicted to represent a fundamental mechanism of molecular evolution 1,2 . Comparative genetic studies of primates 2,3 have identified thousands of human-specific deletions (hDels), and the cis -regulatory potential of short (≤31 base pairs) hDels has been assessed using reporter assays 4 . However, how structural variant-sized (≥50 base pairs) hDels influence molecular and cellular processes in their native genomic contexts remains unexplored. Here, we design genome-scale libraries of single-guide RNAs targeting 7.2 megabases of sequence in 6,358 hDels and present a systematic CRISPR interference (CRISPRi) screening approach to identify hDels that modify cellular proliferation in chimpanzee pluripotent stem cells. By intersecting hDels with chromatin state features and performing single-cell CRISPRi (Perturb-seq) to identify their cis - and trans -regulatory target genes, we discovered 20 hDels controlling gene expression. We highlight two hDels, hDel_2247 and hDel_585, with tissue-specific activity in the brain. Our findings reveal a molecular and cellular role for sequences lost in the human lineage and establish a framework for functionally interrogating human-specific genetic variants.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393978,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.945,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":96211,"name":"Bryan J. Pavlovic","orcid":"0000-0002-7751-5315","position":1,"is_corresponding":false},{"id":1168775,"name":"Dani Swope","orcid":null,"position":2,"is_corresponding":false},{"id":1168776,"name":"Octavio E. Castillo","orcid":null,"position":3,"is_corresponding":false},{"id":374699,"name":"Nathan K. Schaefer","orcid":"0000-0001-5881-7329","position":4,"is_corresponding":false},{"id":254660,"name":"Alex A. Pollen","orcid":"0000-0003-3263-8634","position":5,"is_corresponding":false},{"id":984940,"name":"Tyler Fair","orcid":null,"position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T01:19:10.334330Z","pmid":"38234800","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}