Advances in sequencing technology herald a new frontier in cattle genomics and genome-enabled selection

Authors: Bickhart, Derek; McClure, Jennifer; SCHNABEL, R - University Of Missouri; Rosen, Benjamin - Ben; MEDRANO, JUAN - University Of California, Davis; Smith, Timothy - Tim

Submitted to: Journal of Dairy Science
Publication Type: Review Article
Publication Acceptance Date: 12/3/2019
Publication Date: 4/22/2020
Citation: Bickhart, D.M., McClure, J.C., Schnabel, R.D., Rosen, B.D., Medrano, J.F., Smith, T.P.L. 2020. Advances in sequencing technology herald a new frontier in cattle genomics and genome-enabled selection. Journal of Dairy Science. 103(6):5278-5290. https://doi.org/10.3168/jds.2019-17693.
DOI: https://doi.org/10.3168/jds.2019-17693

Interpretive Summary:

Technical Abstract: The cattle reference genome assembly has underpinned major innovations in beef and dairy genetics through genome-enabled selection, including removal of deleterious recessive variants and selection for favorable alleles affecting quantitative production traits. The initial reference assemblies, up to and including UMD3.1 and Btau4.1, were based on a combination of clone-by-clone sequencing of BACs generated from blood DNA of a Hereford bull, and whole genome shotgun (WGS) sequencing of blood DNA from his inbred daughter/granddaughter named L1 Dominette 01449 (Dominette). The approach introduced assembly gaps, misassemblies, and errors, as well as limiting the ability to assemble regions that undergo rearrangement in blood cells such as immune gene clusters. Nonetheless, the reference supported creation of genotyping tools and provided a basis for many studies of gene expression. Recently, long-read sequencing technologies have emerged that facilitated a re-assembly of the reference genome, using lung tissue from Dominette to resolve many of the problems while providing a bridge to place historical studies in common context. The new reference, ARS-UCD1.2, successfully assembled germline immune gene clusters and improved overall continuity (i.e. reduction of gaps and inversions) by over 250-fold. This reference properly places nearly all of the legacy genetic markers used for over a decade in the industry. In the following review, we discuss the improvements made to the cattle reference; remaining issues present in the assembly; tools developed to support genome-based studies in beef and dairy cattle; and the emergence of newer genome assembly methods that are producing even higher quality assemblies for other breeds of cattle at a fraction of the cost. The new frontier for cattle genomics research will likely include a transition from the individual Hereford reference genome, to a “Pan-Genome” reference representing all the DNA segments existing in commonly used cattle breeds, bringing the cattle reference in line with the current direction of human genome research.