A pangenome graph reference of 30 chicken genomes allows genotyping of large and complex structural variants

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  • Edward S. Rice
  • James Alfieri
  • Giridhar Athrey
  • Jennifer R. Balacco
  • Philippe Bardou
  • Heath Blackmon
  • Mathieu Charles
  • Hans H. Cheng
  • Olivier Fedrigo
  • Steven R. Fiddaman
  • Giulio Formenti
  • Laurent A. F. Frantz
  • Cari J. Hearn
  • Erich D. Jarvis
  • Christophe Klopp
  • Sofia Marcos
  • Andrew S. Mason
  • Deborah Velez-Irizarry
  • Luohao Xu
  • Wesley C. Warren

Background: The red junglefowl, the wild outgroup of domestic chickens, has historically served as a reference for genomic studies of domestic chickens. These studies have provided insight into the etiology of traits of commercial importance. However, the use of a single reference genome does not capture diversity present among modern breeds, many of which have accumulated molecular changes due to drift and selection. While reference-based resequencing is well-suited to cataloging simple variants such as single-nucleotide changes and short insertions and deletions, it is mostly inadequate to discover more complex structural variation in the genome. Methods: We present a pangenome for the domestic chicken consisting of thirty assemblies of chickens from different breeds and research lines. Results: We demonstrate how this pangenome can be used to catalog structural variants present in modern breeds and untangle complex nested variation. We show that alignment of short reads from 100 diverse wild and domestic chickens to this pangenome reduces reference bias by 38%, which affects downstream genotyping results. This approach also allows for the accurate genotyping of a large and complex pair of structural variants at the K feathering locus using short reads, which would not be possible using a linear reference. Conclusions: We expect that this new paradigm of genomic reference will allow better pinpointing of exact mutations responsible for specific phenotypes, which will in turn be necessary for breeding chickens that meet new sustainability criteria and are resilient to quickly evolving pathogen threats.

OriginalsprogEngelsk
Artikelnummer267
TidsskriftBMC Biology
Vol/bind21
Antal sider17
ISSN1741-7007
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by USDA NIFA grants 2020-67015-31574 and 2022-67015-36218 and the European Union’s Horizon Research and Innovation Programme under grant agreement No. 817729 (Project HoloFood). Computation for this work was performed on the high performance computing infrastructure provided by Research Computing Support Services and in part by the National Science Foundation under grant number CNS-1429294 at the University of Missouri, Columbia MO. The authors gratefully acknowledge the Gauss Centre for Supercomputing e.V. ( www.gauss-centre.eu ) for funding this project by providing computing time on the GCS Supercomputer SuperMUC-NG at Leibniz Supercomputing Centre ( www.lrz.de ).

Funding Information:
We thank Adam Novak and Jordan Eizenga (UC Santa Cruz) for discussion and bug fixes related to our usage of the VG toolkit for this project and Laurie Molitor and Melanie Flesberg (USDA-ARS) for assistance with animal care and DNA isolation.

Publisher Copyright:
© 2023, The Author(s).

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