{"doi":"10.1101/2025.08.15.670618","title":"Recurrent structural variation and recent turnover at the 17q21.31 locus in humans and great apes","abstract":"ABSTRACT The 17q21.31 locus in humans harbors several complex structural haplotypes including a ∼970kb inversion. Different inversion haplotypes have been associated with susceptibility to microdeletions causing Koolen-de Vries syndrome and variation in fecundity and recombination rates. Here, using 210 haplotype-resolved human genome assemblies and pangenome graph-based approaches we characterize 11 distinct structural haplotypes, several of which have not been previously described. Extending our analyses to a set of haplotype-resolved great-ape genomes, we characterize the structure of an independent inversion in chimpanzees which extends an additional 650kb, encompasses 5 additional genes, and is ∼2 million years younger than the human inversion. We further determine that gorillas exhibit an independent duplication of the KANSL1 gene which may predispose them to Koolen-de Vries syndrome causing microdeletions. Using short read sequencing data we characterize 17q21.31 haplotype diversity worldwide in ∼5174 individuals from 107 populations finding increased frequencies of KANSL1 duplication-containing haplotypes in both European and South Asian populations as well as 8 double recombination events between inverted and non-inverted haplotypes ranging in size from 20-180kb. Finally, using 626 ancient Eurasian human genomes we show the frequency of haplotypes containing KANSL1 duplications has increased ∼6-fold over the past 12 thousand years in Europe. Together, our results highlight the dynamics, complexity, and recurrent, independent evolution of a medically relevant locus across humans and great apes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":555717,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9383,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1240381,"name":"Runyang Nicolas Lou","orcid":"0000-0002-1568-0024","position":1,"is_corresponding":false},{"id":1454551,"name":"Scott Ferguson","orcid":"0000-0002-4821-7490","position":2,"is_corresponding":false},{"id":51357,"name":"Joana L. Rocha","orcid":"0000-0003-3266-6328","position":3,"is_corresponding":false},{"id":1454988,"name":"Rishi De-Kayne","orcid":null,"position":4,"is_corresponding":false},{"id":24512,"name":"Matthew W. Mitchell","orcid":"0000-0002-6947-0495","position":5,"is_corresponding":false},{"id":1454989,"name":"Alison N Killilia","orcid":null,"position":6,"is_corresponding":false},{"id":304235,"name":"Víctor Borda","orcid":"0000-0003-3209-3961","position":7,"is_corresponding":false},{"id":644166,"name":"Santiago Gerardo Medina-Muñoz","orcid":"0000-0001-8448-3561","position":8,"is_corresponding":false},{"id":574151,"name":"Simon Gravel","orcid":null,"position":9,"is_corresponding":false},{"id":1454990,"name":"CAAPA2 PopGen Working Group","orcid":null,"position":10,"is_corresponding":false},{"id":62191,"name":"Brenna M. Henn","orcid":"0000-0003-4998-287X","position":11,"is_corresponding":false},{"id":40404,"name":"Peter H. Sudmant","orcid":"0000-0002-9573-8248","position":12,"is_corresponding":false},{"id":1454987,"name":"S. SRIDHARAN","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:03.976486Z","pmid":"41040191","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":[]}