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

• Published in: Nature communications Vol. 13; no. 1; pp. 3012 - 13
• Main Authors: Leonard, Alexander S., Crysnanto, Danang, Fang, Zih-Hua, Heaton, Michael P., Vander Ley, Brian L., Herrera, Carolina, Bollwein, Heinrich, Bickhart, Derek M., Kuhn, Kristen L., Smith, Timothy P. L., Rosen, Benjamin D., Pausch, Hubert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31-05-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114/2785/2302; 631/208/726; 631/208/8; Algorithms; Animals; Assemblies; Bos taurus; Cattle; Conserved sequence; Diploids; Diploidy; Genome - genetics; Genomes; Haplotypes; Heterozygosity; High-Throughput Nucleotide Sequencing; Humanities and Social Sciences; multidisciplinary; Nucleotide sequence; Offspring; Phenotypes; Science; Science (multidisciplinary); Sequence Analysis, DNA; Topology; Vertebrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30680-2

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.
Pangenomes have a number of advantages over linear reference assemblies. Here the authors use bovine haplotype-resolved assemblies to show that structural variant-based pangenomes are consistent regardless of sequence platform, assembler, or coverage, suggesting that rigid protocols may not be required.