Dog10K_Boxer_Tasha_1.0: A Long-Read Assembly of the Dog Reference Genome

Abstract

The domestic dog has evolved to be an important biomedical model for studies regarding the genetic basis of disease, morphology and behavior. Genetic studies in the dog have relied on a draft reference genome of a purebred female boxer dog named “Tasha” initially published in 2005. Derived from a Sanger whole genome shotgun sequencing approach coupled with limited clone-based sequencing, the initial assembly and subsequent updates have served as the predominant resource for canine genetics for 15 years. While the initial assembly produced a good-quality draft, as with all assemblies produced at the time, it contained gaps, assembly errors and missing sequences, particularly in GC-rich regions, which are found at many promoters and in the first exons of protein-coding genes. Here, we present Dog10K_Boxer_Tasha_1.0, an improved chromosome-level highly contiguous genome assembly of Tasha created with long-read technologies that increases sequence contiguity >100-fold, closes >23,000 gaps of the CanFam3.1 reference assembly and improves gene annotation by identifying >1200 new protein-coding transcripts. The assembly and annotation are available at NCBI under the accession GCF_000002285.5.

Domestic dog lineages reveal genetic drivers of behavioral diversification

“…While our study establishes that canine breed diversification is principally driven by non-coding variation, we did not perform structural variant analysis and therefore do not detect potentially consequential copy number variants (Serres-Armero et al, 2021), which play significant roles in mammalian brain evolution and human neurodevelopmental disorder risk (Dennis et al, 2012; Zarrei et al, 2019). Newly available long-read reference annotated genomes (Edwards et al, 2021; Field et al, 2020; Halo et al, 2021; Jagannathan et al, 2021; Wang et al, 2021) will improve accuracy in identification of CNVs and indels, as well as variant identification in GC-rich promoter regions (Kim et al, 2021; Rhie et al, 2021).…”

“…In addition to the above, this study relied on human annotations as part of a broad approach to characterizing loci. Identification of canine-specific regulatory elements within associated loci and topological associations will be done in future studies using newly available long-read canine reference genomes with improved annotations (Halo et al, 2021; Jagannathan et al, 2021; Wang et al, 2021). Finally, our identification of behavioral shifts among domestic dog breeds, though robust, are based on a questionnaire designed to measure broad aspects of temperament in dogs rather than expressly targeting breed-typical behavioral functions (e.g., pointing, herding, scent-trailing, etc.).…”

The Australasian dingo archetype:De novochromosome-length genome assembly, DNA methylome, and cranial morphology

“…Next, we compared single-copy "Complete" BUSCO genes in Alpine dingo Cooinda and nine canid genomes [6,27,28,36,[38][39][40][41]). Of the 13,722 genes, 13,711 were found in the assembly using BUSCOMP v1.0.1.…”

“…Great Dane [38], Labrador [39], Dog10K Boxer [40], and Greenland Wolf [41]) using BUSCOMP v1.0.1. Additional kmer-based assembly completeness and quality evaluations were performed using Merqury v21.3 [42] from the 10x reads.…”

Canine reference genome accuracy impacts variant calling: Lessons learned from investigating embryonic lethal variants

“…Several other dog genome assemblies (Table S2) have been recently reported that might mitigate the shortcomings of a single alignment (i.e. CanFam3.1), including ROS_Cfam_1.0, UNSW_CanFamBas_1.0, Basenji_breed‐1.1, Dog10K_Boxer_Tasha, UU_Cfam_GSD_1.0 and UMICH_Zoey_3.1 (Edwards et al, 2021; Halo et al, 2021; Jagannathan et al, 2021; The Roslin Institute, 2020; Wang et al, 2021). The present findings demonstrate the importance of confirming putative variants across multiple assemblies, as a single reference genome may be insufficient for accurately identifying variants.…”