Dr. Vicki Meyers-Wallen is Associate Professor in the Department Biomedical Sciences at the J.A. Baker Institute for Animal Health, College of Veterinary Medicine at Cornell University. For a number of years she has been researching inherited disorders of sexual development in animals and is currently searching for the gene causing XX sex reversal in the American Cocker Spaniel. A number of other dog breeds are also affected by XX sex reversal, including the Kerry Blue Terrier. After learning of a number of Kerries affected with XXSR in 1997, I contacted Dr. Meyers-Wallen for information about the disorder. At the time, she was conducting a survey which the Kerry Blue Terrier Club of Canada assisted through distribution to its membership. I recently contacted Dr. Meyers-Wallen for an update on her research on XXSR, in particular for Kerry information, such a frequency in the breed, if the genetic defect is the same as in other breeds, and how close a genetic test might be. My questions are in italics and her responses are in normal type face. If you would like more information about XXSR or would like to consult with Dr. Meyers-Wallen about a potentially affected dog, her e-mail is <[email protected]>.
Health & Genetics Director
Kerry Blue Terrier Foundation
I do not know the gene that is causing this. Right now we are concentrating on this condition in the American cocker spaniel because I have the pedigree information, DNA etc, on enough animals to get a good analysis. That study is now in the genome wide screen phase and the data is being analyzed. We hope to find an area in one or two chromosomes to pursue further meaning an area in which we can find the causative gene. Then of course, we will be examine the same gene in all the breeds having this problem to see if they are all mutations in the same gene.
I would rather not say how many I have evaluated, just because I do not want to panic anyone. I do not know the frequency in the breed because I am pretty sure that some affecteds are never referred to us. But all those that I have received as “suspects” based on evaluation by their vets have been affected (diagnosis of Sry-negative XX sex reversal) when I finished evaluating their gonadal histology and PCR test for the Sry gene. There have been XX males and XX true hermaphrodites, as was previously reported.
I personally think this is inherited as an autosomal recessive trait in the Kerry, as was suggested by previous literature. (We know this is the mode of inheritance in a few other breeds.) To my knowledge no one has confirmed this with breeding experiments. It is most likely that all affected Kerrys are caused to the same mutation but we will not know that until the gene responsible is isolated and we can examine the mutation(s).
The thing that seems to be more of a health problem in the Kerry blue than in other breeds is that there can be a very narrow vaginal opening in some of those that look more female externally. This narrowing can lead to pooling of urine behind the narrow area. It also is a great place for bacteria to grow- that is, infection and irritation can follow. When the dog lies down or changes position the urine leaks out so it looks like urinary incontinence with or without infection. This may require surgical correction in the vaginal area (rather than giving only antibiotics or performing surgery on the urinary bladder). So it is important to determine that the narrowing is the cause of the problem.
Do you have enough to put together some [genetic] pedigrees? I was looking at the 1979 paper by Williamson [Williamson JH. 1979. J. Heredity 70: 138-139] on intersexuality in Kerries and wondering if you had been able to get any information about those pedigrees and if there was any relationship to the current cases.
I do not have any of the Williamson information. I have pedigrees on some of the affected dogs that we have evaluated. However, I only have DNA on the affected animals for most of these. A pedigree for the purpose of a genetic study would be a 3-5 generation pedigree with several affecteds at the bottom AND DNA samples on all parents, grandparents, great grand parents, etc of the affecteds. (It is difficult to get DNA samples from nonaffected parents, etc. as you might imagine.)
Is the survey still running? Is there anything we can do to assist you in your research?
The survey is not really running now as the funding to support the survey has been used. If this gene in the Kerry blue is turns out to be different from the one causing the problem in the Am Cocker Spaniel, then I will really need to build a pedigree for the purpose of a genetic study (as above, a 3-5 generation pedigree with several affecteds at the bottom AND DNA samples on all parents, grandparents, great grand parents, etc of the affecteds.) If the gene is the same as in the American Cocker, then DNA I [already have] from affecteds and a few normals will be sufficient. However, I have to be the one to evaluate the affecteds in order to be sure that I am dealing with the same disorder. (eg. the microscopic evaluation of both gonads and the PCR for Sry.)
If you can help with any of this, that would be great.
The copyright on this material is held by Vicki Meyers-Wallen DVM, PhD, and is printed with permission. If you would like to reprint this material, please contact Dr. Meyers-Wallen at <[email protected]>.