Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Mutation frequency is not increased in CRISPR–Cas9-edited mice

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Parent–progeny study.

Data Availability

The data are available at SRA under project number PRJNA470569.


  1. Schaefer, K. A. et al. Nat. Methods 14, 547–548 (2017).

    Article  CAS  Google Scholar 

  2. Anonymous. Nat. Methods 15, 229 (2018).

  3. McKenna, A. et al. Genome Res. 20, 1297–1303 (2010).

    Article  CAS  Google Scholar 

  4. Van der Auwera, G. A. et al. Curr. Protoc. Bioinformatics 43, 11.10.1–11.10. 33 (2013).

    Google Scholar 

  5. DePristo, M. A. et al. Nat. Genet. 43, 491–498 (2011).

    Article  CAS  Google Scholar 

  6. Layer, R. M., Chiang, C., Quinlan, A. R. & Hall, I. M. Genome Biol. 15, R84 (2014).

    Article  Google Scholar 

  7. Shin, H. Y. et al. Nat. Commun. 8, 15464 (2017).

    Article  CAS  Google Scholar 

  8. Iyer, V. et al. PLoS Genet. 14, e1007503 (2018).

    Article  Google Scholar 

  9. Luo, X. et al. bioRxiv Preprint at (2018).

Download references


This study was funded through the IRPs of NIDDK and NHLBI. Research support was received from the NIH Director’s Challenge Innovation Award program (to L.H.). We also thank the team of the NIH HPC Biowulf cluster, especially W. Resch, for their advice, as well as their continued maintenance of hardware and software. We acknowledge the Genomics Platform at The Broad Institute for their support and services provided for the generation of the WGS data.

Author information

Authors and Affiliations



M.W., H.E.S., C.L., C.W. and L.H. designed the study. C.L. and C.W. conducted mouse experiments. M.W. and H.E.S. carried out computational analyses. M.W., H.E.S. and L.H. wrote the manuscript.

Corresponding authors

Correspondence to Michaela Willi or Lothar Hennighausen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Integrated supplementary information

Supplementary Figure 1 Equivalence test.

(a) The equivalence test for the de novo SNPs is significant, which verifies that the number of de novo SNPs is equivalent. (CRISPR and control group: n = 6; δ = +/- 1.35) (b) The equivalence test for the de novo indels is inconclusive, as the 90% CI reaches over zero and the lower boundary (CRISPR and control group: n = 6; δ = +/- 0.82).

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1, Supplementary Methods, Supplementary Notes 1–4 and Supplementary Tables 1–7

Reporting Summary

Supplementary Data

De novo mutations in CRISPR–Cas9-edited and control mice

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Willi, M., Smith, H.E., Wang, C. et al. Mutation frequency is not increased in CRISPR–Cas9-edited mice. Nat Methods 15, 756–758 (2018).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research