TY - JOUR

T1 - A pangenome graph reference of 30 chicken genomes allows genotyping of large and complex structural variants

AU - Rice, Edward S.

AU - Alberdi, Antton

AU - Alfieri, James

AU - Athrey, Giridhar

AU - Balacco, Jennifer R.

AU - Bardou, Philippe

AU - Blackmon, Heath

AU - Charles, Mathieu

AU - Cheng, Hans H.

AU - Fedrigo, Olivier

AU - Fiddaman, Steven R.

AU - Formenti, Giulio

AU - Frantz, Laurent A. F.

AU - Gilbert, M. Thomas P.

AU - Hearn, Cari J.

AU - Jarvis, Erich D.

AU - Klopp, Christophe

AU - Marcos, Sofia

AU - Mason, Andrew S.

AU - Velez-Irizarry, Deborah

AU - Xu, Luohao

AU - Warren, Wesley C.

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - ev21

KW - Gallus gallus

KW - IGLL1

KW - K locus

U2 - 10.1186/s12915-023-01758-0

DO - 10.1186/s12915-023-01758-0

M3 - Journal article

C2 - 37993882

AN - SCOPUS:85177605780

VL - 21

JO - B M C Biology

JF - B M C Biology

SN - 1741-7007

M1 - 267

ER -