A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves.

• Published in: Animal Genetics
• Main Authors: Jagannathan, V, Drögemüller, C, Leeb, T, Dog Biomedical Variant Database Consortium (DBVDC)
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: eScholarship, University of California 2019
• Subjects: Dog Biomedical Variant Database Consortium; Animals; Dogs; Wolves; Disease Models; Animal; Phylogeny; Genes; Lethal; Whole Genome Sequencing; Canis lupus familaris; Mendelian; animal model; bioinformatics; functional annotation; genetic diversity; precision medicine; rare disease; variant database; Human Genome; Genetics; 2.1 Biological and endogenous factors; Aetiology; Zoology; Veterinary Sciences; Dairy & Animal Science; Canis lupus
• Online Access: https://escholarship.org/uc/item/0hf68790; https://escholarship.org/content/qt0hf68790/qt0hf68790.pdf; https://doi.org/10.1111/age.12834

The domestic dog serves as an excellent model to investigate the genetic basis of disease. More than 400 heritable traits analogous to human diseases have been described in dogs. To further canine medical genetics research, we established the Dog Biomedical Variant Database Consortium (DBVDC) and present a comprehensive list of functionally annotated genome variants that were identified with whole genome sequencing of 582 dogs from 126 breeds and eight wolves. The genomes used in the study have a minimum coverage of 10× and an average coverage of ~24×. In total, we identified 23133692 single-nucleotide variants (SNVs) and 10048038 short indels, including 93% undescribed variants. On average, each individual dog genome carried ∼4.1million single-nucleotide and ~1.4million short-indel variants with respect to the reference genome assembly. About 2% of the variants were located in coding regions of annotated genes and loci. Variant effect classification showed 247141 SNVs and 99562 short indels having moderate or high impact on 11267 protein-coding genes. On average, each genome contained heterozygous loss-of-function variants in 30 potentially embryonic lethal genes and 97 genes associated with developmental disorders. More than 50 inherited disorders and traits have been unravelled using the DBVDC variant catalogue, enabling genetic testing for breeding and diagnostics. This resource of annotated variants and their corresponding genotype frequencies constitutes a highly useful tool for the identification of potential variants causative for rare inherited disorders in dogs.