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The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates.

Publication ,  Journal Article
Bergeron, LA; Besenbacher, S; Turner, T; Versoza, CJ; Wang, RJ; Price, AL; Armstrong, E; Riera, M; Carlson, J; Chen, H-Y; Hahn, MW; Harris, K ...
Published in: eLife
January 2022

In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a 'Mutationathon,' a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a twofold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria, and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees.

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Published In

eLife

DOI

EISSN

2050-084X

ISSN

2050-084X

Publication Date

January 2022

Volume

11

Start / End Page

e73577

Related Subject Headings

  • Reference Standards
  • Pedigree
  • Mutation Rate
  • Macaca mulatta
  • Laboratories
  • Germ-Line Mutation
  • Germ Cells
  • Genetic Techniques
  • Animals
  • 42 Health sciences
 

Citation

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Bergeron, L. A., Besenbacher, S., Turner, T., Versoza, C. J., Wang, R. J., Price, A. L., … Schierup, M. H. (2022). The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates. ELife, 11, e73577. https://doi.org/10.7554/elife.73577
Bergeron, Lucie A., Søren Besenbacher, Tychele Turner, Cyril J. Versoza, Richard J. Wang, Alivia Lee Price, Ellie Armstrong, et al. “The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates.ELife 11 (January 2022): e73577. https://doi.org/10.7554/elife.73577.
Bergeron LA, Besenbacher S, Turner T, Versoza CJ, Wang RJ, Price AL, et al. The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates. eLife. 2022 Jan;11:e73577.
Bergeron, Lucie A., et al. “The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates.ELife, vol. 11, Jan. 2022, p. e73577. Epmc, doi:10.7554/elife.73577.
Bergeron LA, Besenbacher S, Turner T, Versoza CJ, Wang RJ, Price AL, Armstrong E, Riera M, Carlson J, Chen H-Y, Hahn MW, Harris K, Kleppe AS, López-Nandam EH, Moorjani P, Pfeifer SP, Tiley GP, Yoder AD, Zhang G, Schierup MH. The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates. eLife. 2022 Jan;11:e73577.

Published In

eLife

DOI

EISSN

2050-084X

ISSN

2050-084X

Publication Date

January 2022

Volume

11

Start / End Page

e73577

Related Subject Headings

  • Reference Standards
  • Pedigree
  • Mutation Rate
  • Macaca mulatta
  • Laboratories
  • Germ-Line Mutation
  • Germ Cells
  • Genetic Techniques
  • Animals
  • 42 Health sciences