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

Authors: RICE, EDWARD - University Of Missouri; ALBERDI, ANTTON - University Of Copenhagen; ALFIERI, JAMES - Texas A&M University; ATHERY, GIRIDHAR - Texas A&M University; BALACCO, JENNIFER - Rockefeller University; BARDOU, PHILIPPE - Institut National De La Recherche Agronomique (INRA); BLACKMON, HEATH - Texas A&M University; CHARLES, MATHIEU - Institut National De La Recherche Agronomique (INRA); Cheng, Hans; FEDRIGO, OLIVIER - Rockefeller University; FIDDAMAN, STEVEN - University Of Oxford; FORMENTI, GIULIO - Rockefeller University; FRANTZ, LAURENT - Queen Mary University Of London; M. THOMAS, GILBERT - University Of Copenhagen; Hearn, Cari; JARVIS, ERICH - Rockefeller University; KLOPP, CHRISTOPHE - Institut National De La Recherche Agronomique (INRA); MARCOS, SOFIA - University Of Copenhagen; VELEZ-IRIZARRY, DEBORAH - Orise Fellow; XU, LUOHAO - School Of Life Sciences And Bioengineering; WARREN, WESLEY - University Of Missouri; MASON, ANDREW - University Of York

Submitted to: BMC Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2023
Publication Date: 11/22/2023
Citation: Rice, E.S., Alberdi, A., Alfieri, J., Athery, G., Balacco, J.R., Bardou, P., Blackmon, H., Charles, M., Cheng, H.H., Fedrigo, O., Fiddaman, S., Formenti, G., Frantz, L., M. Thomas, G.P., Hearn, C.J., Jarvis, E.D., Klopp, C., Marcos, S., Velez-Irizarry, D., Xu, L., Warren, W.C., Mason, A.S. 2023. A pangenome graph reference of 30 chicken genomes allows genotyping of large and complex structural variants. BMC Biology. 21(267). https://doi.org/10.1186/s12915-023-01758-0.
DOI: https://doi.org/10.1186/s12915-023-01758-0

Interpretive Summary: In chicken, like most other species, the genome assembly is the basis for much of fundamental biology especially for associating genetic (DNA) variation with phenotypic (trait) variation. Since 2004, the chicken genome assembly was based on a single bird. However, this lone individual does not capture all of the variation found in other types of chickens. To address this shortcoming, what is known as a pangenome was developed from 30 different bird genome assemblies. By aligning DNA sequence reads to this new tool, much more genetic variation can be identified. This is particularly important for complex regions, which are often associated with immune response genes. Ultimately, both basic and applied scientists will benefit greatly by having a better reference tool to compare sequences from their individual of interest.

Technical Abstract: Background. The red junglefowl, the wild origin of modern domestic chickens, has historically served as a reference for genotype to phenotype studies in domestic chickens and their genetic origins. These studies have provided insight into the etiology of many traits of commercial importance. However, this reference of a single mixed-origin individual does not capture the diversity present among all modern breeds, including the relevant commercial lines many of which are highly divergent due to their artificial selection histories. Further, while reference-based resequencing studies are well-suited to cataloging simple variants such as single nucleotide changes and short insertions and deletions, they are for the most part incapable of confidently calling more complex structural variation in the genome. Results. We present a pangenome reference for the domestic chicken consisting of 30 assemblies of chickens from different breeds or research lines. 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 a panel of 100 diverse chickens to the pangenome improves mapping and genotyping. Finally, we genotype a large and complex pair of structural variants at the K ‘feathering’ locus in 100 chickens with only short reads, which would not be possible using a linear reference. Conclusions. We expect that this new paradigm of genomic reference will contribute to a better understanding of the diversity present at complex immune-related loci, which will in turn be necessary for breeding chickens resilient to quickly evolving pathogen threats.