Data for: Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs

Hundreds of genetic variants implicated in Mendelian disease have been
characterized in dogs and commercial screening is being offered for most
of them worldwide. There is typically limited information available
regarding the broader population frequency of variants and uncertainty
regarding their functional and clinical impact in ancestry backgrounds
beyond the discovery breed. Genetic panel screening of disease variants,
commercially offered directly to the consumer or via a veterinary
clinician, provides an opportunity to establish large-scale cohorts with
phenotype data available to address open questions related to variant
prevalence and relevance. We screened the largest canine cohort examined
in a single study to date (1,054,293 representative dogs from our existing
cohort of 3.5 million; a total of 811,628 mixed breed dogs and 242,665
purebreds from more than 150 countries) to examine the prevalence and
distribution of a total of 250 genetic disease-associated variants in the
general population. Electronic medical records from veterinary clinics
were available for 43.5% of the genotyped dogs, enabling the clinical
impact of variants to be investigated. We provide detailed frequencies for
all tested variants across breeds and find that 57% of dogs carry at least
one copy of a studied Mendelian disease-associated variant. Focusing on a
subset of variants, we provide evidence of full penetrance for 10
variants, and at minimum plausible evidence for clinical significance of
22 variants, on diverse breed backgrounds. Specifically, we report that
inherited hypocatalasia is a notable oral health condition, confirm that
factor VII deficiency presents as subclinical bleeding propensity and
verify two genetic causes of reduced leg length. We further assess
genome-wide heterozygosity levels in over 100 breeds and show that a
reduction in genome-wide heterozygosity is associated with an increased
Mendelian disease load. The accumulated knowledge represents a resource to
guide discussions on genetic test relevance by breed.