Comparison of the Elisa Essay test and DNA testing for vWD Type I

Doberman breeders have used the Elisa test for a number of years, only to find that it was inadequate to say the least, and found it useless for making breeding decisions.  The Elisa test is not capable of determining the genetic status of Clear (does not carry the mutant gene), can not pass on the disease to it's progeny, Carrier (carries one copy of the mutant gene), is not likely to bleed from cause of vWD, but is capable of passing on the mutation to its progeny, no matter what the vWf % level is at any given time, or, Affected (carries 2 copies of the mutant gene) does always have a potential to bleed given the right circumstance, and will always pass on the disease (mutation) to it's progeny.  The Elisa test capability is to determine the vWf (von Willebrand's factor) on the day of testing and is variable to a large degree, yielding mostly different results on the same dog subject to conditions on the day.    Therefore the Elisa test has no value in determining if a dog is an affected, carrier or clear.

The only test that can provide this information definitively is the genetic DNA test, (a once a lifetime test).  There are no variables, no grades and no percentages.  A carrier for instance is simply a carrier and not less or more a carrier (no matter what the vWf is at any given time), a clear is simply genetically clear and not more or less clear (simply does not have the mutations).  The Elisa test on the other hand is so variable that even in the higher percentages a clear definitive status cannot be determined. I would like to point to a Correlation Graph between Elisa and DNA tested dogs.  Correlation Graph

The information for this graph was voluntarily provided to VetGen by Doberman owners, from various Doberman e-mail lists, who had tested their dogs with the Elisa test and then as the DNA test became available tested their dogs with the DNA test.  It is easy to see the great overlap between the Elisa and DNA test, particularly in the carrier region.

In the event of a pending surgery for a vWD DNA tested genetically affected dog, the test of value is a bleeding time test immediately prior to the surgery, thus enabling the owner and veterinarian to be prepared and make arrangements to combat any possible bleeding episode.

A DNA tested Carrier or Clear dog does not require this precaution regarding concerns of bleeding from vWD.

Blood Clotting & vWD

Type I vWD is a splice site mutation, a characteristic of a mutation at a splice site, which in this case is such that the protein vWf (von Willebrand's factor) is produced some of the time, but not all of the time. vWD affected dogs have two copies of the mutated gene. Each one of these genes is capable of producing 5-10% of normal vWf, because the mutated splice site works correctly just some of the time. For 90-95% of the time when the mutated splice site is used, no useful vWf is produced. Since each of the two mutated genes is producing 5-10% of normal vWf the affected Doberman ends up with twice that amount, or 10-20% of normal vWf in their blood. This means that these dogs are able to produce enough protein (clotting factor) to get by, even through surgery or whelping until such time that the small amount of vWf is used up through stress or trauma, may this be surgical or injury, at which time a dog can becomes a bleeder. For further information please read Dr. G. Brewer's article at:  Dr. G. Brewer vWD Report  

Also a very explanatory article is the 
Temporal Variation and Factors affecting measurement of Canine von Willebrand Factor

Here is another very interesting link. See:  Concept of DNA Sequence The picture on the web page says it all... The loops are the introns which are left out of the coding regions (in green) when RNA is produced (in red) which goes on to produce the protein of interest, relating to vWD, in this case vWf. The places where the gene is reconnected, leaving out the loops, is called the splice site. When it is mutated and doesn't work, it leaves one of the loops in the coding portion and a meaningless protein is produced.

Further, the question of clotting time and bleeding time tests was raised and I might add comments regarding this subject here as well.  There are 2 specific tests used by veterinarians to evaluate bleeding time and clotting time.

This test is performed under anesthesia where a section of the lip is restricted and is a calibrated (done to exact specifications) test and the bleeding time is measured. For reference see: PubMed Abstract
Buccal mucosa bleeding times of healthy dogs and of dogs in various pathologic states, including thrombocytopenia, uremia, and von Willebrand's Disease.  Jergens AE, Turrentine MA, Kraus KH, Johnson GS. Comparative Hemostasis Laboratory, College of Veterinary Medicine, University of Missouri, Columbia 65211.

Inge Craik, 
GenTest
Australian Representative for VetGen
Saturday, April, 6, 2002

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