Structurally complex genomic regions are not yet well understood. One such locus, human chromosome 17q21.31, contains a megabase-long inversion polymorphism1, many uncharacterized copy-number variations (CNVs) and markers that associate with female fertility1, female meiotic recombination1,2,3 and neurological disease4,5. Additionally, the inverted H2 form of 17q21.31 seems to be positively selected in Europeans1. We developed a population genetics approach to analyze complex genome structures and identified nine segregating structural forms of 17q21.31. Both the H1 and H2 forms of the 17q21.31 inversion polymorphism contain independently derived, partial duplications of the KANSL1 gene; these duplications, which produce novel KANSL1 transcripts, have both recently risen to high allele frequencies (26% and 19%) in Europeans. An older H2 form lacking such a duplication is present at low frequency in European and central African hunter-gatherer populations. We further show that complex genome structures can be analyzed by imputation from SNPs.
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J. Korn provided an early version of software for visualizing haplotype diversity. N. Rohland and T. Mullen contributed expertise on laboratory experiments. We thank N. Patterson, D. Reich, D. Altshuler, E. Lander, B. Browning, J. Korn, J. Gray, C. Patil, G. Genovese, A. Sekar and S. Grossman for helpful conversations and/or comments on the manuscript. This work was supported by a Smith Family Award for Excellence in Biomedical Research to S.A.M., by the National Human Genome Research Institute (U01HG005208) and by startup resources from the Harvard Medical School Department of Genetics.
The authors declare no competing financial interests.
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Boettger, L., Handsaker, R., Zody, M. et al. Structural haplotypes and recent evolution of the human 17q21.31 region. Nat Genet 44, 881–885 (2012). https://doi.org/10.1038/ng.2334
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