Abstract
The 17q21.31 locus in humans harbors several complex structural haplotypes including a ~ 970 kb 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 650 kb, encompasses 5 additional genes, and is ~2 million years younger than the human inversion. 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 20-180 kb. 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.
Acknowledgments
We thank R Nielsen, P Moorjani, CT Miller, JM Vazquez and J Chin for helpful discussion. This work was supported by NIH National Institute of General Medicine award R35GM142916 to PHS and NIH National Human Genome Research Institute award R01HG013017 to PHS and a Leakey Foundation award to SS. NIH 5R01HL104608 was awarded to BM Henn and used to generate the CAAPA data that has been used in this study. This manuscript is the result of funding in whole or in part by the National Institutes of Health (NIH). It is subject to the NIH Public Access Policy. Through acceptance of this federal funding, NIH has been given the right to make this manuscript publicly available in PubMed Central upon the Official Date of Publication, as defined by NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Sridharan, S., Lou, R.N., Ferguson, S. et al. Recurrent structural variation and recent turnover at the 17q21.31 locus in humans and great apes. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73174-1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41467-026-73174-1
