| Title: | Sequence variants affecting the genome-wide rate of germline microsatellite mutations |
| Journal: | Nature Communications |
| Published: | 29 Jun 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37386006/ |
| DOI: | https://doi.org/10.1038/s41467-023-39547-6 |
| URL: | https://www.nature.com/articles/s41467-023-39547-6.pdf |
Publication 11604
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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.</p>
23 Authors
- Snaedis Kristmundsdottir
- Hakon Jonsson
- Marteinn T. Hardarson
- Gunnar Palsson
- Doruk Beyter
- Hannes P. Eggertsson
- Arnaldur Gylfason
- Gardar Sveinbjornsson
- Guillaume Holley
- Olafur A. Stefansson
- Gisli H. Halldorsson
- Sigurgeir Olafsson
- Gudny. A. Arnadottir
- Pall I. Olason
- Ogmundur Eiriksson
- Gisli Masson
- Unnur Thorsteinsdottir
- Thorunn Rafnar
- Patrick Sulem
- Agnar Helgason
- Daniel F. Gudbjartsson
- Bjarni V. Halldorsson
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 68574 | WGS Sample Identification and Access |
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