More than 700 inherited disorders and traits have been described in the domestic dog.1 Approximately 300 of these are estimated to have a genetically simple (Mendelian) mode of inheritance with the causal mutations for over 240 Mendelian disorders and traits (such as coat colour) having been identified to date.1 The precise number of globally available canine DNA tests that are based on specific disease-associated mutations is unknown but is likely to be well in excess of 150. The appropriate use of DNA tests has long been anecdotally described as an effective means to control the spread of recessive mutations within populations/breeds. This is because carriers of recessive disease-associated mutations are healthy with respect to the disease they carry, and can only be identified retrospectively, once they have produced clinically affected offspring and as such DNA testing for autosomal recessive disease mutations in many dog breeds is now relatively commonplace. There have, however, been few efforts made to determine changes in the frequency of disease causing mutations as a result of selection based on the results of DNA testing, in other words, to answer the question ‘Does DNA testing lead to a reduction in the frequency of disease mutations within breeds?’. A recent study uniquely analysed genotype data from two sources i) dogs who had been DNA tested themselves and whose test results had been reported to the UK Kennel Club and ii) dogs with a known hereditary status, for whom a definitive genotype could be inferred and ascribed based on known parental genotypes, to address this question.3
Eight disease-specific mutations that segregate in eight different breeds were selected for investigation. The breeds and disorders were chosen to reflect differences in numerical breed size and frequency of the disease-causing mutation at the time of publication; all eight mutations had been published, and thus formed the basis of a commercially available DNA test, at least five years prior to the study. For each disorder/breed mutation frequencies were calculated within pre- and post-test periods, for the population of dogs that had been DNA tested themselves (test results) and for the larger population of dogs with known genotypes (DNA tested dogs plus those with a known hereditary status).
The results, using known genotype data, indicated a general and sizeable decline in disease-mutation frequency across eight diseases in eight breeds (by between 12–86% in dogs born 2–4 years after publication of the mutation, and by nearly 90% or more in those born 8–10 years after). In contrast, data from test results only, while revealing an almost complete and immediate end to the production of affected individuals, show little general decline in either the derived mutation frequency or the proportion of heterozygote carriers. The data also showed that the numerical size of the breed is an important determinant on the rate of uptake of a DNA test (as judged by the proportion of a breed born four years after publication of the disease-causing mutation with a known genotype).
These findings, which will be presented and discussed in detail, show that dog breeders appear to be incorporating the results of DNA testing into their selection strategies to successfully decrease the frequency of mutations within breeds, which presumably is also leading to a reduced prevalence of the same diseases.
1. Faculty of Veterinary Science, University of Sydney. Online Mendelian Inheritance in Animals, OMIA. http://omia.angis. org.au/. Accessed 28 September, 2018.
2. Donner J, Anderson H, Davison S, Hughes AM, Bouirmane J, Lindqvist J, Lytle KM, Ganesan B, Ottka C, Ruotanen P, Kaukonen M, Forman OP, Fretwell N, Cole CA, Lohi H. Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs. PLoS Genet. 2018;14(4):e1007361.
3. Lewis TW, Mellersh CS. Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. PLoS One. 2019;14(1):e0209864.