A cattle graph genome incorporating global breed diversity

Abstract

Despite only 8% of cattle being found in Europe, European breeds dominate current genetic resources. This adversely impacts cattle research in other important global cattle breeds. To mitigate this issue, we have generated the first assemblies of African breeds, which have been integrated with genomic data for 294 diverse cattle into the first graph genome that incorporates global cattle diversity. We illustrate how this more representative reference assembly contains an extra 116.1Mb (4.2%) of sequence absent from the current Hereford sequence and consequently inaccessible to current studies. We further demonstrate how using this graph genome increases read mapping rates, reduces allelic biases and improves the agreement of structural variant calling with independent optical mapping data. Consequently, we present an improved, more representative, reference assembly that will improve global cattle research.

Optical mapping compendium of structural variants across global cattle breeds

“…No duplications, inverted duplications and translocations passed the quality filtering. Consistent with results from previous studies 28 , most of the post-filtering insertions and deletions identified fell into the smaller classes, though 1,796 SVs (403 deletions, 1,389 insertions and 4 inversions) of over 50kb in length were identified (Figure 1).…”

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

“…Sequencing technologies and assemblers evolve rapidly, and so even recently generated bovine assemblies, including the ones reported here, have been produced under non-uniform conditions (e.g., (Crysnanto et al, 2021; Talenti et al, 2021)). Given the differences we observed between HiFi- and ONT-based assemblies, especially in comparison to the CLR-based ARS-UCD1.2 reference, it was crucial to examine how pangenome construction responded to different assembly inputs.…”

“…Larger structural variants (SVs) and variation located in repetitive or challenging regions have rarely been studied across Bovinae due to the inherent limitations of short sequencing reads and incomplete reference genomes. Moreover, no reference assembly of a single individual can reflect the immense genomic diversity present in global breeds of domestic cattle (Crysnanto et al, 2019(Crysnanto et al, , 2021Crysnanto & Pausch, 2020;Talenti et al, 2021).…”

“…SVs may be involved in expression quantitative trait loci more often than previously estimated, and can impact gene expression more than shorter variants (Chiang et al, 2017). However, previous studies suffer from potential reference bias, because the use of a single taurine cattle reference assembly fails to reflect the immense genomic diversity present in global breeds of domestic cattle (Crysnanto et al, 2019(Crysnanto et al, , 2021Crysnanto & Pausch, 2020;Talenti et al, 2021). Pangenomes have long been proposed (Tettelin et al, 2005) as a way to better reflect variation present in a group of individuals (e.g., breed, species, clade, etc.).…”

ODGI: understanding pangenome graphs

“…This progression is already afoot, particularly for targets that involve complex variation, such as cancer (The Computational Pan-Genomics Consortium, 2016), plant pangenomics (Bayer et al ., 2020; Liu et al ., 2020; Qin et al ., 2021; Li et al ., 2022; Bayer et al ., 2022), and metagenomics (Zhong et al ., 2021). Also, when studying animals like bovines (Leonard et al ., 2021; Talenti et al ., 2022; Bovine Pan-Genome Consortium, 2022).…”