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OCD Bullyologist
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  • [FONT=&quot](Permission is given to reprint this document in its entirety as submitted for educational purposes)[/FONT]

    When a gene is referred to as an "autosomal recessive," it means:
    (a) That the gene is NOT on the X or Y chromosome, but one of the "normal" ones. This is important in that "X-linked" diseases inherit in a different pattern than autosomal ones.
    (b) That the gene must be present in TWO COPIES for disease to appear. This is important for several reasons. First off it means that if you have one copy of the disease gene, then you have one copy of the normal gene, and so you will be safe, you will not get the disease. But it also means that you will then be a "silent carrier" in that you *can* pass on the gene, sight unseen, to your offspring.
    It also means that for any animal to have any trait that is inherited as an autosomal recessive, that individual has to have TWO parents who were BOTH (at least) "silent carriers" of the disease. (Geneticists call them "obligate carriers" as they are "obligated" to have the gene being a producer of a diseased offspring.) It's a case of where "it takes two to tango" when it comes to autosomal recessives. The gene ALWAYS comes from BOTH sides of the pedigree.
    Carriers won't meet carriers very often when a gene is rare, so people will not (cannot) always realize their animals are carriers (without a gene test). It takes the unfortuitous meeting of two carriers, often a complete surprise to all, to produce a dog with an autosomal recessive disease.
    What is important from that point on is for all breeders (and owners I suppose) to understand, given what is currently known, is that any pup who has, for example, Addison's has to be dealt with as having:

  • Two parents, both of whom are carriers, if neither is also afflicted with Addison's.
  • Normal appearing (i.e. non-diseased) littermates that mostly are also all carriers. Each littermate of an afflicted dog has a 2 in 3 chance of being a carrier just like both the parents are.
  • Anytime a dog with the disease is used for breeding, then ALL of that dog's offspring will be carriers (assuming they are bred to a normal, non-carrier, mate).
  • Anytime a carrier is used for breeding, 1/2 (50%) of their offspring will also be carriers (assuming they are bred to a normal, non-carrier mate).

Naturally in applying this to Addison's in Danes, we are assuming that the evidence for it being an autosomal recessive is correct. But the evidence to date, as far as I know, is strong. And the fact that the disease "came out of nowhere" (i.e. parents were normal, breeder hadn't seen the disease before) all suggests a recessive mode of inheritance is very likely. Plus, geneticists like Padgett always advise breeders to treat diseases with an unknown or even potentially complex inheritance, as they would a case where the disease is thought to be autosomal recessive. As practically, this gives the breeder some control over how to minimize the disease expression and manage the spread of the disease genes. That's why knowing the gene is inherited as an autosomal recessive means we have some better control, via our breeding decisions, over the incidence of disease. It's a "good thing" for a disease to be thought to be strongly and directly heritable; these sorts of diseases, once recognized and explored, can be controlled then largely by the breeding decisions made.

  • In the case of canine Addison's disease we are just at the beginning of understanding. Addison's is a disease that has often been misdiagnosed or missed entirely. I'm fairly confident a certain number of Addison's dogs, for example, have been written off as heart deaths when in an Addisonian crisis. And many a sudden death, kidney problems, etc. may be underlying adrenal issues that did not get addressed, so went unrecognized. (Addison's is not called "the great imitator" for nothing!) Plus there is always a certain resistance in some breeding quarters to accepting that a disease has a strongly heritable component. Disease is not sin, but there is that feeling at times amongst dog owners and breeders. This misconception therefore provides another reason for a failure to recognize the pattern of disease in a pedigree. Plus many breeders are uncomfortable with genetics and have a hard time working through a pedigree analysis to discern relative risk as a result. Add to this the idea that prevails in many immunological circles: that these diseases like Addison's and thyroiditis are different manifestations (not really separate diseases) of a central defect in the immune system's ability to tell "friend from foe" so come from the same gene, and you can see how complicated it can get to track the true incidence of the actual genetic defect.
    Until we have a test that can identify the carriers and/or more specific information, we are going to have to use a formula like the one outlined above to define relative risk in a pedigree, so to breed conservatively and therefore work to avoid breeding carrier to carrier to reduce the number of actual Addison's Danes we produce.
    JP Yousha, Chair, Health & Welfare
    Great Dane Club of America
    [email protected]
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