Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs

Abstract

Knowledge on the genetic epidemiology of disorders in the dog population has implications for both veterinary medicine and sustainable breeding. Limited data on frequencies of genetic disease variants across breeds exists, and the disease heritage of mixed breed dogs remains poorly explored to date. Advances in genetic screening technologies now enable comprehensive investigations of the canine disease heritage, and generate health-related big data that can be turned into action. We pursued population screening of genetic variants implicated in Mendelian disorders in the largest canine study sample examined to date by examining over 83,000 mixed breed and 18,000 purebred dogs representing 330 breeds for 152 known variants using a custom-designed beadchip microarray. We further announce the creation of MyBreedData (www.mybreeddata.com), an online updated inherited disorder prevalence resource with its foundation in the generated data. We identified the most prevalent, and rare, disease susceptibility variants across the general dog population while providing the first extensive snapshot of the mixed breed disease heritage. Approximately two in five dogs carried at least one copy of a tested disease variant. Most disease variants are shared by both mixed breeds and purebreds, while breed- or line-specificity of others is strongly suggested. Mixed breed dogs were more likely to carry a common recessive disease, whereas purebreds were more likely to be genetically affected with one, providing DNA-based evidence for hybrid vigor. We discovered genetic presence of 22 disease variants in at least one additional breed in which they were previously undescribed. Some mutations likely manifest similarly independently of breed background; however, we emphasize the need for follow up investigations in each case and provide a suggested validation protocol for broader consideration. In conclusion, our study provides unique insight into genetic epidemiology of canine disease risk variants, and their relevance for veterinary medicine, breeding programs and animal welfare.

Two mixed breed dogs with sensory neuropathy are homozygous for an inversion disrupting FAM134B previously identified in Border Collies

“…Also as previously reported, hereditary genetic diseases can affect mixed‐breed dogs and characterizing them also may help other breeds . In 2 recently published studies, it was found that a large number of mixed‐breed dogs carried autosomal recessive mutations .…”

“…In 2 recently published studies, it was found that a large number of mixed‐breed dogs carried autosomal recessive mutations . In these studies, the same commercially available canine breed ancestry test (Wisdom Panel, Mars Veterinary) was used, and it was found that many of the mixed‐breed dogs carrying the alternate or mutant allele had the specific breed, in which the mutation initially was identified, in their ancestry …”

True Colors: commercially-acquired morphological genotypes reveal hidden allele variation among dog breeds, informing both trait ancestry and breed potential

“…Most publications to date that assess allele frequency within dog breeds have been conducted on a relatively small scale, limited to select sets of breeds and/or variants of known relevance to specific breeds (36–42). A recent publication focused on a very large set of purebred and mixed-breed dogs and a panel of 152 disease markers (43), but did not evaluate morphological or pigmentation gene variants. Here, we have leveraged an expansive number of DNA samples, both in terms of dog numbers and breed representation for which 12 genes impacting coat color and morphological variation have been genotyped on a commercial genotyping platform (Table 1).…”

“…Genotype data from 11,790 canids, representing 212 pure dog breeds and 4 wild canine populations, was compiled during the development and implementation of the Mars WISDOM PANEL platform (Wisdom Health, Vancouver, WA, USA). DNA collections herein represent a subset of those initially reported in Donner, et al (43). Dog DNA samples were obtained by Wisdom Health (formerly Mars Veterinary) and Genoscoper Laboratories (Helsinki, Finland), between January 2005 and October 2016, as owner-submitted, non-invasive cheek swab collections.…”

“…Genotyping of seven coat color and five morphological trait variants (Table 1) was conducted on a custom-designed Illumina Infinium HD bead chip using manufacturer-recommended protocols ((81); Illumina, San Diego, CA, USA). The validation and genotyping quality control measures for this platform were previously described in detail (43,81). Trait variant assays specifically were valideated through extensive correlation of genotypes with established breed phenotypes and owner-submitted pictures of individual dogs.…”