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The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
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 mutati...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830884/ https://www.ncbi.nlm.nih.gov/pubmed/35018888 http://dx.doi.org/10.7554/eLife.73577 |
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author | Bergeron, Lucie A Besenbacher, Søren Turner, Tychele Versoza, Cyril J Wang, Richard J Price, Alivia Lee Armstrong, Ellie Riera, Meritxell Carlson, Jedidiah Chen, Hwei-yen Hahn, Matthew W Harris, Kelley Kleppe, April Snøfrid López-Nandam, Elora H Moorjani, Priya Pfeifer, Susanne P Tiley, George P Yoder, Anne D Zhang, Guojie Schierup, Mikkel H |
author_facet | Bergeron, Lucie A Besenbacher, Søren Turner, Tychele Versoza, Cyril J Wang, Richard J Price, Alivia Lee Armstrong, Ellie Riera, Meritxell Carlson, Jedidiah Chen, Hwei-yen Hahn, Matthew W Harris, Kelley Kleppe, April Snøfrid López-Nandam, Elora H Moorjani, Priya Pfeifer, Susanne P Tiley, George P Yoder, Anne D Zhang, Guojie Schierup, Mikkel H |
author_sort | Bergeron, Lucie A |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8830884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-88308842022-02-14 The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates Bergeron, Lucie A Besenbacher, Søren Turner, Tychele Versoza, Cyril J Wang, Richard J Price, Alivia Lee Armstrong, Ellie Riera, Meritxell Carlson, Jedidiah Chen, Hwei-yen Hahn, Matthew W Harris, Kelley Kleppe, April Snøfrid López-Nandam, Elora H Moorjani, Priya Pfeifer, Susanne P Tiley, George P Yoder, Anne D Zhang, Guojie Schierup, Mikkel H eLife Evolutionary Biology 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. eLife Sciences Publications, Ltd 2022-01-12 /pmc/articles/PMC8830884/ /pubmed/35018888 http://dx.doi.org/10.7554/eLife.73577 Text en © 2022, Bergeron et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Evolutionary Biology Bergeron, Lucie A Besenbacher, Søren Turner, Tychele Versoza, Cyril J Wang, Richard J Price, Alivia Lee Armstrong, Ellie Riera, Meritxell Carlson, Jedidiah Chen, Hwei-yen Hahn, Matthew W Harris, Kelley Kleppe, April Snøfrid López-Nandam, Elora H Moorjani, Priya Pfeifer, Susanne P Tiley, George P Yoder, Anne D Zhang, Guojie Schierup, Mikkel H The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates |
title | The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates |
title_full | The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates |
title_fullStr | The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates |
title_full_unstemmed | The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates |
title_short | The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates |
title_sort | mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates |
topic | Evolutionary Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830884/ https://www.ncbi.nlm.nih.gov/pubmed/35018888 http://dx.doi.org/10.7554/eLife.73577 |
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