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 23 133 692 single-nucleotide variants (SNVs) and 10 048 038 short indels, including 93% undescribed variants. On average, each individual dog genome carried ∼4.1 million single-nucleotide and ~1.4 million 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 247 141 SNVs and 99 562 short indels having moderate or high impact on 11 267 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.
Bibliographical noteFunding Information:
The authors would like to thank Eva Andrist, Nathalie Besuchet Schmutz, Muriel Fragni?re and Sabrina Schenk for expert technical assistance, the Next Generation Sequencing Platform of the University of Bern for performing many high-throughput sequencing experiments and the Interfaculty Bioinformatics Unit of the University of Bern for providing high-performance computing infrastructure. We also acknowledge all researchers of the canine community who deposited dog or wolf whole genome sequencing data into public databases. Funding information is listed in Appendix S1.
© The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics
- Canis lupus familaris
- animal model
- functional annotation
- genetic diversity
- precision medicine
- rare disease
- variant database
- whole genome sequencing