Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies

Authors

Alexander S. Leonard, Animal Genomics, ETH ZurichFollow
Danang Crysnanto, Animal Genomics, ETH Zurich
Zih-Hua Fang, Animal Genomics, ETH Zurich
Michael P. Heaton, USDA, ARS, U.S. Meat Animal Research CenterFollow
Brian L. Vander Ley, University of Nebraska-LincolnFollow
Carolina Herrera, University of ZurichFollow
Heinrich Bollwein, University of ZurichFollow
Derek M. Bickhart, USDA-ARS, Madison, WIFollow
Benjamin D. Rosen, USDA ARS Beltsville Agricultural Research CenterFollow
Hubert Pausch, Animal Genomics, ETH ZurichFollow

ORCID IDs

Alexander S. Leonard http://orcid.org/0000-0001-8425-5630

Danang Crysnanto http://orcid.org/0000-0003-4444-9371

Zih-Hua Fang http://orcid.org/0000-0002-0225-8772

Michael P. Heaton http://orcid.org/0000-0003-1386-1208

Brian L. Vander Ley http://orcid.org/0000-0003-0732-2590

Timothy P. L. Smith http://orcid.org/0000-0003-1611-6828

Benjamin D. Rosen http://orcid.org/0000-0001-9395-8346

Hubert Pausch 1✉ http://orcid.org/0000-0002-0501-6760

Date of this Version

2022

Citation

NATURE COMMUNICATIONS (2022) 13:3012

https://doi.org/10.1038/s41467-022-30680-2

Comments

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License

Abstract

Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrate significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identifies 90 thousand structural variants including 931 overlapping with coding sequences; this approach reveals variants affecting QRICH2, PRDM9, HSPA1A, TAS2R46, and GC that have potential to affect phenotype.