The first sheep graph pan-genome reveals the spectrum of structural variations and their effects on different tail phenotypes

Li, R.; Gong, M.; Zhang, X.; Wang, F.; Liu, Z.; Zhang, L.; Xu, M.; Zhang, Y.; Dai, X.; Zhang, Z.; Fang, W.; Yang, Y.; Zhang, H.; Fu, W.; Cao, C.; Yang, P.; Ghanatsaman, Z. A.; Negari, N. J.; Nanaei, H. A.; Yue, X.; Song, Y.; Lan, X.; Deng, W.; Wang, X.; Xiang, R.; Ibeagha-Awemu, E. M.; Heslop-Harrison, P.; Lenstra, J. A.; Gan, S.; Jiang, Y.

doi:10.1101/2021.12.22.472709

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bioRxiv · 10.1101/2021.12.22.472709

The first sheep graph pan-genome reveals the spectrum of structural variations and their effects on different tail phenotypes

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Abstract

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here, we assembled 26 haplotype-resolved genome assemblies from 13 genetically diverse sheep using PacBio HiFi sequencing. We constructed a graph-based ovine pan-genome and discovered 142,422 biallelic insertions and deletions, 7,028 divergent alleles and 13,419 multiallelic variations. We then used a graph-based approach to genotype the biallelic SVs in 684 individuals from 45 domestic breeds and two wild species. Integration with RNA-seq data allows to identify candidate expression-associated SVs. We demonstrate a direct link of SVs and phenotypes by localizing the putative causative insertion in HOXB13 gene responsible for the long-tail trait and identifying multiple large SVs associated with the fat-tail. Beyond generating a benchmark resource for ovine structural variants, our study highlights that animal genetic research will greatly benefit from using a pan-genome graph rather than a single reference genome.

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Li, R., Gong, M., Zhang, X., Wang, F., Liu, Z., Zhang, L., Xu, M., Zhang, Y., Dai, X., Zhang, Z., Fang, W., Yang, Y., Zhang, H., Fu, W., Cao, C., Yang, P., Ghanatsaman, Z. A., Negari, N. J., Nanaei, H. A., Yue, X., Song, Y., Lan, X., Deng, W., Wang, X., Xiang, R., Ibeagha-Awemu, E. M., Heslop-Harrison, P., Lenstra, J. A., Gan, S., Jiang, Y.. 2021-12-23. The first sheep graph pan-genome reveals the spectrum of structural variations and their effects on different tail phenotypes. https://doi.org/10.1101/2021.12.22.472709

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