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- Title
The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates.
- Authors
Bergeron, Lucie A.; Besenbacher, Søren; Turner, Tychele; Versoza, Cyril J.; Wang, Richard J.; Price, Alivia Lee; Armstrong, Ellie; Riera, Meritxell; Carlson, Jedidiah; Hwei-yen Chen; Hahn, Matthew W.; Harris, Kelley; Kleppe, April Snøfrid; López-Nandam, Elora H.; Moorjani, Priya; Pfeifer, Susanne P.; Tiley, George P.; Yoder, Anne D.; Guojie Zhang; Schierup, Mikkel H.
- Abstract
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.
- Subjects
GERM cells; MACAQUES; GENETIC mutation; RHESUS monkeys; STANDARDIZATION
- Publication
eLife, 2022, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.73577