Section: Genomics
Topic: Genetics/Genomics, Evolution, Population biology

Performance and limitations of linkage-disequilibrium-based methods for inferring the genomic landscape of recombination and detecting hotspots: a simulation study

10.24072/pcjournal.254 - Peer Community Journal, Volume 3 (2023), article no. e27.

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Knowledge of recombination rate variation along the genome provides important insights into genome and phenotypic evolution. Population genomic approaches offer an attractive way to infer the population-scaled recombination rate ρ=4Ner using the linkage disequilibrium information contained in DNA sequence polymorphism data. Such methods have been used in a broad range of plant and animal species to build genome-wide recombination maps. However, the reliability of these inferences has only been assessed under a restrictive set of conditions. Here, we evaluate the ability of one of the most widely used coalescent-based programs, LDhelmet, to infer a genomic landscape of recombination with the biological characteristics of a human-like landscape including hotspots. Using simulations, we specifically assessed the impact of methodological (sample size, phasing errors, block penalty) and evolutionary parameters (effective population size (Ne),  demographic history, mutation to recombination rate ratio) on inferred map quality. We report reasonably good correlations between simulated and inferred landscapes, but point to limitations when it comes to detecting recombination hotspots. False positive and false negative hotspots considerably confound fine-scale patterns of inferred recombination under a wide range of conditions, particularly when Ne is small and the mutation/recombination rate ratio is low, to the extent that maps inferred from populations sharing the same recombination landscape appear uncorrelated. We thus address a message of caution for the users of these approaches, at least for genomes with complex recombination landscapes such as in humans.

Published online:
DOI: 10.24072/pcjournal.254
Type: Research article
Keywords: Population-scaled recombination rate, LDhelmet, simulations, linkage disequilibrium, recombination hotspots
Keywords: Population-scaled recombination rate, LDhelmet, simulations, linkage disequilibrium, recombination hotspots
Raynaud, Marie 1; Gagnaire, Pierre-Alexandre 1; Galtier, Nicolas 1

1 ISEM, Univ Montpellier, CNRS, IRD, Montpellier, France
License: CC-BY 4.0
Copyrights: The authors retain unrestricted copyrights and publishing rights
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     title = {Performance and limitations of linkage-disequilibrium-based methods for inferring the genomic landscape of recombination and detecting hotspots: a simulation study},
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Raynaud, Marie; Gagnaire, Pierre-Alexandre; Galtier, Nicolas. Performance and limitations of linkage-disequilibrium-based methods for inferring the genomic landscape of recombination and detecting hotspots: a simulation study. Peer Community Journal, Volume 3 (2023), article  no. e27. doi : 10.24072/pcjournal.254. https://peercommunityjournal.org/articles/10.24072/pcjournal.254/

PCI peer reviews and recommendation, and links to data, scripts, code and supplementary information: 10.24072/pci.genomics.100161

Conflict of interest of the recommender and peer reviewers:
The recommender in charge of the evaluation of the article and the reviewers declared that they have no conflict of interest (as defined in the code of conduct of PCI) with the authors or with the content of the article.

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