The domestic dog, inherited disease, and DNA testingIntense selection, high levels of inbreeding, the extensive use of a limited number of sires, and genetic isolation are all hallmarks of modern breeds of domestic dog. It is widely agreed that part of the collateral damage from these practices is that purebred dogs have a greater risk of suffering from genetically simple inherited disorders than their cross-breed cousins. Intense media interest continues to apply pressure on both dog breeders and the veterinary profession to improve the health of purebred dogs, the result being that these stakeholders are turning increasingly to DNA tests to assist with both breeding decisions and also the diagnostic process. Some dog breeders are exceptionally well informed when it comes to genetics and possess a very good understanding of the inherited disorders that affect their breed(s). But many are not, and they rely on their general practice veterinarian for information, who also may not have a good knowledge of the majority of inherited conditions that affect all the different breeds they encounter.
It is, therefore, ultimately the responsibility of the scientists who identify genetic variants associated with canine inherited disorders to exercise prudence when they make DNA tests available. Purebred dog populations, by definition, are genetically compromised, with many having an unequivocal need to maximise diversity. Breeders are increasingly using DNA tests to shape their breeding decisions, with the need to reduce the frequency of deleterious mutations being balanced with the need to maintain genetic diversity. There is a critical need, therefore, for full and transparent information, written in lay terms, explaining (1) the mode of inheritance and penetrance of specific mutations, (2) the risk of disease associated with specific genotypes, (3) the frequency of each mutation within different breed populations, and (4) the breeds that are genuinely at risk, so that dogs are not unnecessarily eliminated from the breeding population. The existence of phenocopies within the breed, if known, should also be documented.
DNA testing of companion animals is unregulated, and so one of the few ways in which potential “customers” can judge the merit of any DNA test is if a description of the mutation on which the test is based has been accepted by a peer-reviewed scientific publication. However, the data that establish a genetic variant as a provocative candidate for downstream, comparative studies (and therefore worthy of publication) is not always the same information that a dog owner needs to discern whether they should use the DNA test and what decisions to make in light of the results. It is therefore not sufficient for a DNA test provider merely to provide a hyperlink to a peer-reviewed publication without backing it up with some layman-friendly explanation.
It is worth noting that once a mutation has been reported in the scientific literature there is little stopping private, for-profit organisations from offering a genetic test based on a published finding, irrespective of the opinion of the scientists who made the discovery. Therefore, suggesting that researchers have absolute control over which DNA tests are offered might be an oversimplification in some cases. Nevertheless, scientists should certainly be encouraged to offer “user-friendly” advice on how to use genetic tests and to work with dog breed clubs and organisations to disseminate this advice. Perhaps they should also be willing to suggest when consideration of a particular disease-associated variant to shape breeding decisions is inappropriate.
DNA tests for recessive mutationsThe vast majority of DNA tests currently available are for autosomal recessive mutations associated with Mendelian or single-gene traits. Some of these traits are morphological, such as coat colour, but most are for disease mutations, many of which are severe and debilitating. Providing advice to breeders for these tests is generally very straightforward; essentially all dogs can be safely bred, regardless of their genotype, provided both the sire and the dam have been tested and carriers and genetically affected dogs are mated only to dogs that are clear of the mutation. Often, the initial reaction of breeders is to avoid breeding with all but homozygous wild-type (+/+) dogs, and indeed many members of the veterinary community who were indoctrinated to never breed affected dogs condone this view. However, if a mutation is frequent within a breed, breeders should be counselled to include carriers in the breeding population, for at least a generation, to avoid reducing diversity unnecessarily. Recent data from the 1,000 genomes project revealed that humans carry, on average, between 250 and 300 recessive mutations and at least 50 mutations previously associated with inherited disorders, and it seems reasonable to assume the average dog will carry the same burden of disease-associated variants (Durbin et al. 2010). Expecting breeding dogs to be clear of all risk alleles, therefore, is unrealistic and will severely jeopardise breed diversity.
You may find the videos below interesting the first is from the TV Program Pedigree Dogs Exposed 2. it features our first LUA import.. The Famous Fiona. The second video is the Kennel Clubs respons... interestingly...it also features Fiona!
It is, therefore, ultimately the responsibility of the scientists who identify genetic variants associated with canine inherited disorders to exercise prudence when they make DNA tests available. Purebred dog populations, by definition, are genetically compromised, with many having an unequivocal need to maximise diversity. Breeders are increasingly using DNA tests to shape their breeding decisions, with the need to reduce the frequency of deleterious mutations being balanced with the need to maintain genetic diversity. There is a critical need, therefore, for full and transparent information, written in lay terms, explaining (1) the mode of inheritance and penetrance of specific mutations, (2) the risk of disease associated with specific genotypes, (3) the frequency of each mutation within different breed populations, and (4) the breeds that are genuinely at risk, so that dogs are not unnecessarily eliminated from the breeding population. The existence of phenocopies within the breed, if known, should also be documented.
DNA testing of companion animals is unregulated, and so one of the few ways in which potential “customers” can judge the merit of any DNA test is if a description of the mutation on which the test is based has been accepted by a peer-reviewed scientific publication. However, the data that establish a genetic variant as a provocative candidate for downstream, comparative studies (and therefore worthy of publication) is not always the same information that a dog owner needs to discern whether they should use the DNA test and what decisions to make in light of the results. It is therefore not sufficient for a DNA test provider merely to provide a hyperlink to a peer-reviewed publication without backing it up with some layman-friendly explanation.
It is worth noting that once a mutation has been reported in the scientific literature there is little stopping private, for-profit organisations from offering a genetic test based on a published finding, irrespective of the opinion of the scientists who made the discovery. Therefore, suggesting that researchers have absolute control over which DNA tests are offered might be an oversimplification in some cases. Nevertheless, scientists should certainly be encouraged to offer “user-friendly” advice on how to use genetic tests and to work with dog breed clubs and organisations to disseminate this advice. Perhaps they should also be willing to suggest when consideration of a particular disease-associated variant to shape breeding decisions is inappropriate.
DNA tests for recessive mutationsThe vast majority of DNA tests currently available are for autosomal recessive mutations associated with Mendelian or single-gene traits. Some of these traits are morphological, such as coat colour, but most are for disease mutations, many of which are severe and debilitating. Providing advice to breeders for these tests is generally very straightforward; essentially all dogs can be safely bred, regardless of their genotype, provided both the sire and the dam have been tested and carriers and genetically affected dogs are mated only to dogs that are clear of the mutation. Often, the initial reaction of breeders is to avoid breeding with all but homozygous wild-type (+/+) dogs, and indeed many members of the veterinary community who were indoctrinated to never breed affected dogs condone this view. However, if a mutation is frequent within a breed, breeders should be counselled to include carriers in the breeding population, for at least a generation, to avoid reducing diversity unnecessarily. Recent data from the 1,000 genomes project revealed that humans carry, on average, between 250 and 300 recessive mutations and at least 50 mutations previously associated with inherited disorders, and it seems reasonable to assume the average dog will carry the same burden of disease-associated variants (Durbin et al. 2010). Expecting breeding dogs to be clear of all risk alleles, therefore, is unrealistic and will severely jeopardise breed diversity.
You may find the videos below interesting the first is from the TV Program Pedigree Dogs Exposed 2. it features our first LUA import.. The Famous Fiona. The second video is the Kennel Clubs respons... interestingly...it also features Fiona!
