The Health Foundation of the American Lhasa Apso Club wants to welcome you to this new site devoted to health issues of the Lhasa Apso.  Besides articles on various health concerns affecting the breed, we intend to bring you the latest news of current developments and discoveries in the area of canine health.  We hope to offer a breed health survey soon, so that we can better assess the needs for research in this breed.  We also intend to have a write-in Q&A  section as a service to our readers.  All this and more, coming soon!

* IVDD RESEARCH AT THE UNIVERSITY OF CA - DAVIS

 

Hello:
             My name is Linda Stowe and I'm the founder of Dodgerslist, www.dodgerslist.com a group organized to help fight IVDD (back problems) in Dachshunds, a breed where the average of 19%+ have this terrible disease.   I am also a member of the Dachshund Club of America Health and Welfare Committee.  Since your breed is also known to have a higher incidence of this, I am contacting you to ask for your help in getting this information to breeders. 
 
            A few years ago we contacted a researcher, Dr. Mark Neff, at Davis and asked them to do gene research for IVDD.   They agreed and at this time, they have over 1000 Dachshund cheek swabs plus several hundred of other breeds who are also affected by this disease.

            At the present time, they would like other breeds who have a high incidence of IVDD in their breed also.  You can learn more about their research at http://www.vgl.ucdavis.edu/research/canine/projects/ivdd/ .   I would like to ask your help in helping Dr. Neff find an answer for our Dachshunds and other breeds as well.
 
            If you would like to help with our research, please email me at lstowe@insightbb.com or call me at 217/359-7148.    For participants in your breed, I will send 4 cheek swabs with instructions and a short questionnaire along with a postage paid envelope to be sent directly back to Davis.   This is very easy to do.  Also, any verification of surgery or diagnosis would be helpful.

        We are now also starting to do a blood draw on IVDD dogs.   For more information on this http://www.dodgerslist.com/lit/ivddhandout.htm

        Thank you and hope you will help all our dogs in fighting this terrible disease.   Any questions, please let me know.

Linda
 
Help Fight Dachshund Disc Disease
www.dodgerslist.com
Participate in the Univ of CA Davis IVDD gene study
http://www.vgl.ucdavis.edu/research/canine/projects/ivdd/

News Flash!!! From Geneticist Dr. Mary Whitely, who is working to identify the mutation(s) responsible for Hereditary Renal Disease in Lhasa Apsos and Shih-Tzus:

March 7, 2007

Good news from Dr. Whitely!  She has results coming out now on the test for the “C” mutation.  The previously seen sequence mutations “A” and “B” that affected the same gene seem now to have represented alterations in the nucleotides of the gene,  peculiar to Lhasas and Shih-Tzus, that may only represent a “weak spot” in the DNA which is susceptible to mutation.  The real culprit seems to be “C”,  also a mutated sequence in the same gene.  

Mary has found a 100% correspondence between the disease and the presence of “C”.  She has also found that “C” prevents the formation of any protein by the gene.  All active genes are templates for proteins.  These proteins are the enzymes and messengers that control development and all chemical functions of the body.  Whatever the critical protein is, that controls some aspect of development of the renal system, IT IS NOT MADE by the chromosome with the “C” mutation.  The implication of this is that if there are two “C” mutations the protein is completely missing.  And if the animal has only one “C”, the animal may have some deficiency or delay in the manufacture of the essential protein which governs development of the kidney.  The former would totally prevent differentiation of the renal system, while the latter would present itself as a variable degree of incomplete development of the kidney - which is exactly what we see in HKD/JRD.

The further implications of this fit very well with what Mary has discovered.  NONE of her DNA specimens so far, taken from living animals, have contained two copies of the “C” mutation.   Since the heterozygous state (one mutation, one normal) is fairly common, it is statistically possible to have NO homozygotes ONLY if all of the homozygotes fail to develop in utero.  If the protein in question is one that induces the embryonic mesenchyme to develop a kidney, and possibly other mesenchymal structures, then the embryo which lacks that very early induction protein most likely will not develop past an early stage. 

Normally,  breeding of two carriers (heterozygotes) produces 25% clears, 50 % heterozygotes, and 25% homozygotes. Our previous understanding of the breeding statistics was that 75% of the offspring of two carriers were at risk of having and transmitting HKD/JRD.  The "C" mutation improves the odds that an individual in one of our litters is a "clear" since  homozygotes are all lost at conception or shortly thereafter.  What we will actually see in our litters from two heterozygous animals, is 33% clears, and 67% heterozygotes.   Of course, because some embryos are lost, litters might be smaller. 

Mary should have some results soon for all you Apso owners and breeders who sent in specimens.  Some of the results may be disappointing to those who originally had the good news that their animals were free of the “A” and “B” mutations,  But the advice remains the same because the facts are still the same.  Very few of the animals with the “C” mutation are clinically affected by HKD/JRD, though they are able to transmit the disease to offspring.  Our breeding programs will need to continue to use the heterozygotes so as not to cause another “genetic bottleneck”  like the original founder effect.  If we do this, we can, through testing, gradually eliminate the gene, while preserving the diversity of the breed. 

CM

Jan. 2007: From Dr. Mary Whiteley: 

 

To all Lhasa Apso and Shih Tzu Breeders:

Research involving pedigree studies and analysis of the gene for JRD in three other breeds has uncovered another mutation in the same gene that was studied in the Shih Tzu and Lhasa Apso breeds.  Within the other three breeds alleles A and B were present, but there were some dogs with JRD that did not have either mutation but still had JRD.  This meant that there appeared to be another mutation either in the current gene, or another gene that participates in the renal dysplasia disease process. 

DNA sequencing from these new breeds revealed another mutation in the same gene as the one that has alleles A & B for Shih Tzu and Lhasas. Upon further investigation, we have also located this mutation in the Shih Tzu and Lhasas. This new mutation is much stronger and has serious consequences to the gene’s ability to function correctly.  Because this mutation appears on the same chromosome (and the same gene) as the mutations that we have been testing for, but was not picked up earlier in the research, we are re-testing all of the dogs that were submitted in the research study and those dogs that have been tested for A & B earlier this year.

The high frequency of A and B in Shih Tzu and Lhasas appeared to be the defect we had been looking for with JRD. However, by researching the other breeds that have entered into the study that also have JRD, it was discovered that these dogs had a lower frequency of A & B and in fact only one of those breeds had mutation B.

It appears that this new mutation is inherited with the A and B alleles most of the time, and therefore the overall frequency of the disease causing mutation and the genotype (diagnosis) should not change significantly. However because of the work in all the breeds we believe that the new mutation is the actual defect.

We have developed a screening test for this mutation, and are in the process of validating this assay.

What does this mean to you:

1.  All of the animals tested so far will be screened for this mutation at no cost, and the results will be reported to the owners.

2.  In the future only a single genetic test will be required for the inherited defect for JRD. From this test, breeding strategies can be determined to eliminate the chromosome with the mutant allele.

3. Those people who have paid for A & B will get a credit of one test to use in the future.

Please allow us a few weeks to re-test and report results to the breeders. Those people waiting for results should get theirs within four weeks of the test being validated. We appreciate your patience and understanding. We will continue to strive to do the best research we can for the breeders. 

 

Information on the JRD test can be found at the Dogenes website:  www.dogenes.com

 

Ed. note:
For those of you who may be confused at this point, allow me to interpret.  It seems from the further research, that the initial mutations found (A & B) were not the real culprits, but another mutation is the actual mutation which causes the disease.  Mary is going to re-test all of the previously tested samples for the newly discovered sequence.  Hereafter, animals will not need to be tested for A and B,  but only for the "C" gene ("c" for culprit?).  Now we know what has caused the delay in getting back results.  Thank you Mary, for your diligence and persistence in tracking down this killer!

Cathy Marley M.D., Editor