Hip dysplasia remains one of the most significant causes of pain and disability in dogs despite decades of research into the causes and diligent efforts by breeders to reduce risk through selective breeding. A new review article aimed at veterinarians provides a useful summary of the current state of our understanding of its causes (Witte 2019). The comments here are detailed in that review.

A number of non-genetic (environmental) factors are known to affect the risk of developing hip dysplasia, and some of these appear to be especially critical to manage properly in the puppy. Housing on a slippery floor, access to stairs, and some types of exercise can significantly increase risk in puppies. Higher weight at birth and while growing elevates risk. On the other hand, dogs raised on farms and those born in spring and summer are less likely to develop hip dysplasia. Aside from nutritional deficiencies, or overconsumption that leads to overweight, there is no evidence that the type of the diet plays a role in development of dysplasia. Although exercise in the adult might lead to clinical signs of pain or lameness, there is little evidence that the amount of exercise alters the progression of development of osteoarthritis once the dog matures. Dogs neutered before 6 months have a higher risk of developing hip dysplasia.

Managing the risk of hip dysplasia remains a challenge for breeders and dog owners. Breeders must consider both genetics in mate selection and environmental factors, especially when the puppies are young. When puppies go to their new homes, owners must be educated about the factors that elevate the risk of developing hip dysplasia, especially weight, stairs, and unsuitable exercise and activities.
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REFERENCES
Witte PG, 2019. Hip dysplasia - understanding the disease. Companion Animal 24:77-81.

The adrenal cortex is the outer layer of the adrenal gland, which is a small organ near the kidneys. It secretes hormones that are part of the stress response (e.g., cortisol), and it also produces aldosterone, a hormone essential for maintaining normal levels of minerals involved in the regulation of blood pressure.

In some dogs (and in humans), the immune system fails to recognize the tissue of the adrenal cortex as "self" and destroys it. The result is Addison's disease, which can be fatal. Addision's is especially common in some breeds, including Standard Poodles, Portuguese Water Dogs, Cocker Spaniels, Nova Scotia Duck Tolling Retrievers, and Bearded Collies. The frequency in Poodles is relatively high, estimated at 5-10% (Famula et al. 2003).

Studies looking for a genetic basis for Addison's have identified SNPs that might be associated with the disease, but causative genes have not been found. Because Addison's is an auto-immune disease, we might expect to find relationships between risk and the genes of the immune system. In dogs, these genes are called the dog leukocyte antigens (DLA), and they come in combinations called haplotypes. There has been some success in identifying DLA haplotypes that confer risk of disease in several breeds (Hughes et al. 2010, Massey et al. 2013, Pedersen et al. 2015). 

A study just out takes a closer look at the association between DLA haplotypes and Addison's Disease in Poodles, using a larger sample size than previous studies and also looking for potential associations related to sex of the dog (Treeful et al. 2019). The results are both interesting and sobering. While the data are for Poodles, the implications are relevant for every breed, so you should read this even if you don't have Poodles.

​Furthermore, haplotypes 2-8 and "other" are uncommon in the breed, which means that the options for "breeding away" from haplotype 1 to reduce the incidence of Addison's in male dogs will be limited by the paucity of dogs to breed to.  Haplotype 5 is a risk for females, presenting similar problems.

The problem here is that we know very little about the DLA genes and how they work. In mammals, the immune system genes have the highest diversity because the individuals with the most diversity also have the highest rates of survival. This tells us that high diversity is important, and we can surmise that low diversity will compromise the function of the immune system. In dogs, limited diversity from a small number of founder dogs, together with inbreeding and loss of diversity through selection and genetic drift, has resulted in both reduced diversity and uneven representation of haplotypes as seen in the Poodle, where haplotype 1 is overrepresented.

Breeders are likely to be strongly tempted to use information about DLA haplotypes to inform breeding decisions, based on the perception that the frequencies of some allele should be increased and others decreased. Dr Lorna Kennedy, who has studied the canine DLA genes for many years, cautions against this. (Note that Kennedy uses the term MHC, which stands for "major histocompatibility complex,"  the broad class of immune system genes to which DLA belong.)

The one recommendation Kennedy makes is to avoid producing puppies that will be homozygous for DLA haplotypes. Otherwise, as she notes, because the interactions among genes are complex and the workings of the immune system poorly understood, breeders should not attempt to alter haplotype frequencies through selective breeding. At the very least, if there is a serious problem in a breed, breeders could consult with experts that can advise on the best course of action.
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Perhaps the best strategy, once again, is to protect the existing genetic diversity in your breed and avoid producing homozygosity by inbreeding.