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A common inversion under selection in Europeans

Nature Genetics 37, 129–137 (2005) | Download Citation

Abstract

A refined physical map of chromosome 17q21.31 uncovered a 900-kb inversion polymorphism. Chromosomes with the inverted segment in different orientations represent two distinct lineages, H1 and H2, that have diverged for as much as 3 million years and show no evidence of having recombined. The H2 lineage is rare in Africans, almost absent in East Asians but found at a frequency of 20% in Europeans, in whom the haplotype structure is indicative of a history of positive selection. Here we show that the H2 lineage is undergoing positive selection in the Icelandic population, such that carrier females have more children and have higher recombination rates than noncarriers.

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Acknowledgements

We thank D. Reich, N. Patterson and D. Donnelly for constructive comments regarding this work.

Author information

    • Hreinn Stefansson
    • , Agnar Helgason
    • , Augustine Kong
    •  & Kari Stefansson

    These authors contributed equally to this work.

Affiliations

  1. deCODE Genetics, Sturlugata 8, 101 Reykjavík, Iceland.

    • Hreinn Stefansson
    • , Agnar Helgason
    • , Gudmar Thorleifsson
    • , Valgerdur Steinthorsdottir
    • , Gisli Masson
    • , Adam Baker
    • , Aslaug Jonasdottir
    • , Andres Ingason
    • , Vala G Gudnadottir
    • , Natasa Desnica
    • , Andrew Hicks
    • , Arnaldur Gylfason
    • , Daniel F Gudbjartsson
    • , Gudrun M Jonsdottir
    • , Jesus Sainz
    • , Kari Agnarsson
    • , Birgitta Birgisdottir
    • , Shyamali Ghosh
    • , Adalheidur Olafsdottir
    • , Jean-Baptiste Cazier
    • , Kristleifur Kristjansson
    • , Michael L Frigge
    • , Thorgeir E Thorgeirsson
    • , Jeffrey R Gulcher
    • , Augustine Kong
    •  & Kari Stefansson

  2. Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

    • John Barnard

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Competing interests

H. Stefansson, A. Helgason, G. Thorleifsson, V. Steinthorsdottir, G. Masson, A. Baker, A. Jonasdottir, A. Ingason, V. G. Gudnadottir, N. Desnica, A. Hicks, A. Gylfason, D. F. Gudbjartsson, G. M. Jonsdottir, J. Sainz, K. Agnarsson, B. Birgisdottir, S. Ghosh, A. Olafsdottir, J.-B. Cazier, K. Kristjansson, M. L. Frigge, T. E. Thorgeirsson, J. R. Gulcher, A. Kong & K. Stefansson own stock or stock options in deCODE Genetics.

Corresponding authors

Correspondence to Augustine Kong or Kari Stefansson.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Genotype analysis on homozygous samples sharing (identical-by-descent) over the 17q21.31 locus.

  2. 2.

    Supplementary Fig. 2

    The relative copy number for H1D1 and H1D3 variants compared to H2 variants estimated by gene dose analysis at three loci.

  3. 3.

    Supplementary Fig. 3

    Five chromosomal variants with considerable variation in size at the inverted locus on 17q21.31.

  4. 4.

    Supplementary Fig. 4

    Positive correlation is found between copy numbers of the 5′ end of the NSF gene per sample.

  5. 5.

    Supplementary Fig. 5

    A sliding window analysis of sequence divergence in 5 kb sequence segments inside the inverted region of a 77 kb fragment that spans much of intron 1 and 2 from the MAPT gene from 44.444005-44.520949 Mb in the H1 orientation in Build 34.

  6. 6.

    Supplementary Fig. 6

    LD between SNP markers spanning the inversion at 17q21.31.

  7. 7.

    Supplementary Fig. 7

    The estimate frequency of H2 for females and males who have 0, 1, 2, 3, 4 and 5 or more children.

  8. 8.

    Supplementary Table 1

    Available sequences and contigs from the RP11 library mapping to 17q21.31.

  9. 9.

    Supplementary Table 2

    Test for the impact of selection of H2 chromosomes in the Utah sample using the mutational diversity of five microsatellites.

  10. 10.

    Supplementary Table 3

    The distribution of the number of children for 82,992 Icelandic males and for 79,811 Icelandic females born between 1925 and 1965.

  11. 11.

    Supplementary Table 4

    Results from multiple regression analyses for a cohort of 16959 females and 12178 males born between 1925 and 1965.

  12. 12.

    Supplementary Table 5

    Primer sequences for markers shown in Figures 1 and 3.

  13. 13.

    Supplementary Table 6

    Difference in mutation rate for microsatellites on H1 and H2 backgrounds.

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DOI

https://doi.org/10.1038/ng1508

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