A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves. (5th September 2019)

• Record Type: Journal Article
• Authors: Jagannathan, V.; Drögemüller, C.; Leeb, T.
• Other Names: Aguirre Gustavo investigator.; André Catherine investigator.; Bannasch Danika investigator.; Becker Doreen investigator.; Davis Brian investigator.; Ekenstedt Kari investigator.; Faller Kiterie investigator.; Forman Oliver investigator.; Friedenberg Steve investigator.; Furrow Eva investigator.; Giger Urs investigator.; Hitte Christophe investigator.; Hytönen Marjo investigator.; Lohi Hannes investigator.; Mellersh Cathryn investigator.; Mickelson James R. investigator.; Murgiano Leonardo investigator.; Oberbauer Anita investigator.; Schmutz Sheila investigator.; Schoenebeck Jeffrey investigator.; Summers Kim investigator.; van Steenbeek Frank investigator.; Wade Claire investigator.
• Is Part Of: Animal genetics. Volume 50:Number 6(2019)
• Page Start: 695
• Page End: 704
• Publication Date: 2019-09-05
• Subjects: animal model -- bioinformatics -- Canis lupus familaris -- functional annotation -- genetic diversity -- Mendelian -- precision medicine -- rare disease -- variant database -- whole genome sequencing; Animal genetics -- Periodicals; 572.8
• DOI: 10.1111/age.12834
• Languages: English
• ISSNs: 0268-9146

Abstract

Summary: 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.