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Why we need a more wholistic approach to managing canine genetic disorders

Discussion in 'Dog Discussion' started by Institute of Canine Biology, Dec 9, 2016.

  1. By Carol Beuchat PhD
    The last decade has seen a dramatic shift in the way we approach dealing with genetic disorders in dogs. Modern genetic technology now allows us to identify single mutations that cause disorders relatively easily. A DNA test is made available, added to the list of routine genetic screens run by the responsible breeders, and the dog is declared to be "health tested".
    As I have pointed out elsewhere, DNA tests screen for mutations, not health. We know with certainty that in every dog and every breed there are many more mutations we don't know about yet, simply because they haven't been manifested as a disease in a dog. A dog can be quite healthy, but we can be sure it carries in its genes dozens of genetic errors that are benign as singletons, but inherited as a pair can produce a serious problem.
    A very interesting paper just out argues that the "one gene, phenotype or disease concept" approach to our genetic testing programs is overly-simplistic.

    In fact, we are finding that a mutation in a single gene can cause multiple disorders, depending not only on environmental factors but also on the "genetic environment" - the other genes in that individual.

    A disease-causing mutation might result in a problem only in a subset of individuals that also carry some other modifying genes that interact in ways that alter expression of the trait. The label we have for this is "penetrance", which is really a polite way of saying that a mutation is not the single cause and we don't know what other environmental or genetic factors might also be in play.

    The author argues for a shift in perspective that has profound implications for how we approach the genetic basis of disease in humans, and certainly also in dogs. Our approach to genetic testing is based on the presumption that we can produce healthy dogs by eliminating the specific genes that cause them, at least for monogenic disorders. The author suggests otherwise.
    "Critically, it might be important to re-evaluate the usage of deterministic language, such as the terms “causes” or “solved”, as such terms simply and inaccurately imply that monogenic disorders are penetrant and minimally
    variable and that alleles at Mendelian loci cannot be influenced by the surrounding genome."
    (Katsanis 2016)
    Untangling complex relationships affecting expression of mutations thought to be Mendelian is going to be difficult at best. There are futher problems when flawed test protocols turn out to be the source of discordent findings, as was recently shown to be the case for the testing for a mutation associated with degenerative myelopathy (Turba et al 2016). (A primer mis-match was found to be the cause of incorrect genotyping for the SOD1 genes.)

    The notion that we can solve the problems of canine genetic diseases, even those thought to be caused by simple monogenic mutations, is misguided. The health status of a dog is not the sum of its known mutations. The physiological and biochemical process behind every trait and function are complex, and the genes and other factors that influence their expression are even more so.

    Breeding against specific disorders is not the path to achieving healthy dogs. We must take a larger, more wholistic view, recognizing that we don't understand all of the genetic and environmental factors that might interact in extremely complex ways. If we want to achieve health, we need to breed for the health of the whole dog.

    Take a few minutes and read this thought-provoking paper. It might make you see the path towards truly healthy dogs in a very different way. You can download a copy below.


    Download File
    Katsanis N. 2016. The continuum of causality in human genetic disorders. Genome Biology 17:233. DOI: 10.1186/s13059-016-1107-9

    Turba ME, R Loechel, E Rombola, GGandini, & F Gentilini. 2016. Evidence of a genomic insertion in intron of SOD1 causing allelic drop-out during routine diagnostic testing for canine degenerative myelopathy. Anim Gen; doi: 10.1111/age.12525
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  2. Has Dr Beuchat been living under a rock for the past 60 yrs or so? BTW, "wholistic" is not academically recognized.

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