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Sequence variants affecting the genome-wide rate of germline microsatellite mutations

Author

Listed:
  • Snaedis Kristmundsdottir

    (deCODE genetics / Amgen Inc.
    Reykjavik University)

  • Hakon Jonsson

    (deCODE genetics / Amgen Inc.)

  • Marteinn T. Hardarson

    (deCODE genetics / Amgen Inc.
    Reykjavik University)

  • Gunnar Palsson

    (deCODE genetics / Amgen Inc.)

  • Doruk Beyter

    (deCODE genetics / Amgen Inc.)

  • Hannes P. Eggertsson

    (deCODE genetics / Amgen Inc.)

  • Arnaldur Gylfason

    (deCODE genetics / Amgen Inc.)

  • Gardar Sveinbjornsson

    (deCODE genetics / Amgen Inc.)

  • Guillaume Holley

    (deCODE genetics / Amgen Inc.)

  • Olafur A. Stefansson

    (deCODE genetics / Amgen Inc.)

  • Gisli H. Halldorsson

    (deCODE genetics / Amgen Inc.
    University of Iceland)

  • Sigurgeir Olafsson

    (deCODE genetics / Amgen Inc.)

  • Gudny. A. Arnadottir

    (deCODE genetics / Amgen Inc.
    University of Iceland)

  • Pall I. Olason

    (deCODE genetics / Amgen Inc.)

  • Ogmundur Eiriksson

    (deCODE genetics / Amgen Inc.)

  • Gisli Masson

    (deCODE genetics / Amgen Inc.)

  • Unnur Thorsteinsdottir

    (deCODE genetics / Amgen Inc.
    University of Iceland)

  • Thorunn Rafnar

    (deCODE genetics / Amgen Inc.)

  • Patrick Sulem

    (deCODE genetics / Amgen Inc.)

  • Agnar Helgason

    (deCODE genetics / Amgen Inc.
    University of Iceland)

  • Daniel F. Gudbjartsson

    (deCODE genetics / Amgen Inc.
    University of Iceland)

  • Bjarni V. Halldorsson

    (deCODE genetics / Amgen Inc.
    Reykjavik University)

  • Kari Stefansson

    (deCODE genetics / Amgen Inc.)

Abstract

Microsatellites are polymorphic tracts of short tandem repeats with one to six base-pair (bp) motifs and are some of the most polymorphic variants in the genome. Using 6084 Icelandic parent-offspring trios we estimate 63.7 (95% CI: 61.9–65.4) microsatellite de novo mutations (mDNMs) per offspring per generation, excluding one bp repeats motifs (homopolymers) the estimate is 48.2 mDNMs (95% CI: 46.7–49.6). Paternal mDNMs occur at longer repeats than maternal ones, which are in turn larger with a mean size of 3.4 bp vs 3.1 bp for paternal ones. mDNMs increase by 0.97 (95% CI: 0.90–1.04) and 0.31 (95% CI: 0.25–0.37) per year of father’s and mother’s age at conception, respectively. Here, we find two independent coding variants that associate with the number of mDNMs transmitted to offspring; The minor allele of a missense variant (allele frequency (AF) = 1.9%) in MSH2, a mismatch repair gene, increases transmitted mDNMs from both parents (effect: 13.1 paternal and 7.8 maternal mDNMs). A synonymous variant (AF = 20.3%) in NEIL2, a DNA damage repair gene, increases paternally transmitted mDNMs (effect: 4.4 mDNMs). Thus, the microsatellite mutation rate in humans is in part under genetic control.

Suggested Citation

  • Snaedis Kristmundsdottir & Hakon Jonsson & Marteinn T. Hardarson & Gunnar Palsson & Doruk Beyter & Hannes P. Eggertsson & Arnaldur Gylfason & Gardar Sveinbjornsson & Guillaume Holley & Olafur A. Stefa, 2023. "Sequence variants affecting the genome-wide rate of germline microsatellite mutations," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39547-6
    DOI: 10.1038/s41467-023-39547-6
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    References listed on IDEAS

    as
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