A pangenome graph reference of 30 chicken genomes allows genotyping of large and complex structural variants
Edward S. Rice,
Antton Alberdi,
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,
M. Thomas P. Gilbert,
Cari J. Hearn,
Erich D. Jarvis,
Christophe Klopp,
Sofia Marcos,
Andrew S. Mason,
Deborah Velez-Irizarry,
Luohao Xu,
Wesley C. Warren
Affiliations
Edward S. Rice
Bond Life Sciences Center, University of Missouri
Antton Alberdi
Center for Evolutionary Hologenomics, Globe Institute, University of Copenhagen (UCPH)
James Alfieri
Department of Ecology & Evolutionary Biology, Texas A&M University
Giridhar Athrey
Department of Poultry Science, Texas A&M University
Jennifer R. Balacco
Vertebrate Genome Laboratory, The Rockefeller University
Philippe Bardou
Sigenae, GenPhySE, Université de Toulouse, INRAE, ENVT
Heath Blackmon
Department of Biology, Texas A&M University
Mathieu Charles
University Paris-Saclay, INRAE, AgroParisTech, GABI, Sigenae
Hans H. Cheng
Avian Disease and Oncology Laboratory, USDA, ARS, USNPRC
Olivier Fedrigo
Vertebrate Genome Laboratory, The Rockefeller University
Steven R. Fiddaman
Department of Biology, University of Oxford
Giulio Formenti
Vertebrate Genome Laboratory, The Rockefeller University
Laurent A. F. Frantz
Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität
M. Thomas P. Gilbert
Center for Evolutionary Hologenomics, Globe Institute, University of Copenhagen (UCPH)
Cari J. Hearn
Avian Disease and Oncology Laboratory, USDA, ARS, USNPRC
Erich D. Jarvis
Vertebrate Genome Laboratory, The Rockefeller University
Christophe Klopp
Sigenae, Genotoul Bioinfo, MIAT UR875, INRAE
Sofia Marcos
Center for Evolutionary Hologenomics, Globe Institute, University of Copenhagen (UCPH)
Andrew S. Mason
Department of Biology, The University of York
Deborah Velez-Irizarry
Avian Disease and Oncology Laboratory, USDA, ARS, USNPRC
Luohao Xu
Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University
Wesley C. Warren
Department of Animal Sciences, University of Missouri
Abstract 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.
