Recurrent structural variation and recent turnover at the 17q21.31 locus in humans and great apes
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.
Authors
- Peter H. Sudmant (ORCID: https://orcid.org/0000-0002-9573-8248)
- Matthew W. Mitchell (ORCID: https://orcid.org/0000-0002-6947-0495)
- Caitlin Uren (ORCID: https://orcid.org/0000-0003-2358-0135)
- Scott Ferguson (ORCID: https://orcid.org/0000-0002-4821-7490)
- Joana L. Rocha (ORCID: https://orcid.org/0000-0003-3266-6328)
- Rishi De‐Kayne (ORCID: https://orcid.org/0000-0001-5569-8061)
- S. SRIDHARAN
- Runyang Nicolas Lou (ORCID: https://orcid.org/0000-0002-1568-0024)
- Marlo Möller (ORCID: https://orcid.org/0000-0002-0805-6741)
- Daniel Ansong
- Brooke Scelza
- Simon Gravel
- Brenna Henn (ORCID: https://orcid.org/0000-0003-4998-287X)
- Kathleen Barnes
- Andre Garcia
- CAAPA PopGen Working Group
- Akmel Negash
- Alison N. Killilia (ORCID: https://orcid.org/0000-0002-8308-8196)
- Sandra Kwarteng Owusu
Institutions
- South African Medical Research Council (ZA)
- University of California, Los Angeles (US)
- Hawassa University (ET)
- Stellenbosch University (ZA)
- Komfo Anokye Teaching Hospital (GH)
- Coriell Institute For Medical Research (US)
- Kwame Nkrumah University of Science and Technology (GH)
- National Institute for Theoretical Physics (ZA)
- Galena Biopharma (United States) (US)
- Africa Health Research Institute (ZA)
- Institut de Recherche pour le Développement (FR)
- McGill University (CA)
- University of California, Davis (US)
- University of California, Berkeley (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-19
- DOI
- https://doi.org/10.1038/s41467-026-73174-1
- Primary Topic
- Genomic variations and chromosomal abnormalities
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Leakey Foundation
- National Institutes of Health
- National Human Genome Research Institute
- National Institute of General Medical Sciences