Renal Dysplasia DNA Test Now Available
Posted: June 9, 2007 Filed under: Lotsa Lhasa Info Leave a commentFrom Dr. Catherine Marley:
RENAL DYSPLASIA UPDATE:
March 2007
Good news from Dr. Whiteley! 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 alteration 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 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.
Learn more about Renal Dysplasia
American Lhasa Apso Club’s 2007 National
Posted: June 9, 2007 Filed under: Lotsa Lhasa Info Leave a commentGrab your cowboy hat and spurs! We’re off to Houston, Texas next year. The dates for the 2007 National Specialty will be October 22 through 26. ALAC Judges are Keke Kahn for the Regional, Barbara Schwartz for the National and Ron Crowder for the Futurity. Greater Houston Lhasa Apso Club Specialty Judge will be Darby McSorley.
An “Above all, do no harm” Approach
Posted: June 9, 2007 Filed under: Lotsa Lhasa Info Leave a commentWritten by Leslie Baumann to the apsobreeders list.
In my opinion, when we had more clears in the breeding population, the breed actually had a greater chance of bottlenecking on those dogs. If we all started out with plenty of clears, our human tendency would be to ditch the carriers, removing all sorts of worthwhile strains from the breed, and only breed the clears. Having a high rate of carriers makes a breeder’s job harder but I would argue that the fact that more of us are forced to continue to breed our healthy carriers may end up protecting genetic diversity rather than limiting it. At best, we can remove the mutation from the breed. At worst, we may find we have to live with it in a certain percentage of the breed population. But at least we’ll know which dogs are which!!!! As Kathy R. points out, we may be in something of the same boat as folks with breeds that carry for the merle gene or the hairless gene…they have to “zig/zag” to get the color/hair type they want without producing the defects that those genes, in their homozygous form, can produce. For the next two or three generations, we may have to do a similar “zig zag” to get what we want. But just because it’s hard, seems to me is no reason to give up!!!!
I will say that we are all learning something about science…that is, the more we know, the more questions remain! And, of course, if this were an easy disease, we wouldn’t need a genetic test! I believe we will find that testing full litters can provide some valuable insights for us, particularly if we all feel free to share our results without being “judged.”
Why does our carrier rate seem so high right now? Is there, as Cathy suggests, another piece of the genetic puzzle that we need to know? As we’ve discussed before, seeking the component that modifies the penetrance of the mutation, is problematic. It might or might not even be genetic. However, without knowing where and when we have the mutation, we certainly can’t begin to find the modifier. In addition, as Kathy R. asks, is there a trait that we’ve been selecting for (or selecting against) that is the reason we seem to have a higher than anticipated carrier rate in the breeding population overall? Frankly, if even a few of us feel able to share puppy quality evaluations vis a vis RD test results, it shouldn’t take many litters to figure that one out! With luck, all we have to do is keep some typey clear puppies and move forward. At the very worst, we “zig zag” just as Chinese Crested people do between hairless and powderpuff…or as folks “zig zag” between tri and merle in Collies. Because of the test, we’ll know what sort of “zig zags” we need to do.
We know this mutation has 100% correlation with the disease in other breeds as well as in our own. So, over time, removing the mutation from our breeding population will eliminate the rarest but most heartbreaking manifestation of the disease…early death from renal failure in puppies and adult dogs. The fact that the worst of the disease is also the rarest means we have the TIME to select for the betterment of the breed’s future and do it well and wisely. In addtion, right now the mutation appears to be homozygous lethal…thus giving us one explanation (but obviously not the only explanation) for small litter size and/or missed breedings in our otherwise healthy carrier population. For me, that is plenty of impact on my own breeding program as well as on the long term health and well-being of the breed…incentive enough to test my dogs and my puppies and then “soldier” on.
Nativ
Posted: June 9, 2007 Filed under: Lotsa Lhasa Info | Tags: Gompa Lhasa Apso Leave a comment
Excerpt from an article written by Passang Norbu, originally published on Kuenselonline, Bhutan’s Daily News Site… “What are the possibilities of coming across a pure bred Apsoo with its extra shaggy coat or a Damchi in Bhutan? A very rare chance.”
Rabies Challenge Fund
Posted: June 9, 2007 Filed under: Lotsa Lhasa Info Leave a commentFrom Zeke’s people: Ken and I have donated to this fund in Mychal’s name, to honor his memory, to make his loss count for something, and to help all future dogs and their people confront this state-mandated health horror inflicted on our beloved pets. Even if you can’t donate, please follow the links at the end of the article to educate yourself on this issue of over-vaccination and it’s terrible health consequences in our pets.KatyTo learn more
Kunza at FleetFire Timbers 