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An explanation of the RTR system, evolved by Dick Koster
Background (by Marjukka Mäkinen)
According to the Mendelian rules of genetic transmission, when a dog tests positive for PLL, both its parents and all its first generation issue automatically become carriers of genetic material encoded for PLL. This applies to a recessive mode of transmission, in a dominant mode you only have affected and unaffected individuals. With high probability, looking at the pattern so far with whole generations skipped, the mode of transmission in PLL is an autosomal recessive one. I would venture as far as suggesting that it is definitely not dominant. Of course, it could be polygenic, but when a population is saturated with genetic material, it tends to mimick autosomal recessive transmission. Certainly, there will always be carriers that can never be identified, for example in the second generation.
Everything follows the Mendelian rules. However, with polygenic features (including modifying genes) it seems different, but still remains Mendelian. We are all pinning our hopes on finding a DNA test for PLL. DNA research is most productive in diverse populations, i.e. not heavily inbred populations, since it searches for differences. That might prove to be a major stumbling block for the Heeler, the very close inter-relations in the breed frustrating the identification of the responsible gene. Until the gene is actually isolated, it is all rather speculative.
If PLL were transmitted in an autosomal recessive mode (as I have already pointed out above, and, looking at the information available so far, this would seem to be the case) the breeding results according to the Mendelian rules would be:
* Carrier x Unaffected dog, result: 50% clears, 50% carriers
* Carrier x Affected dog, result: 50% carriers, 50% affected
* Carrier x Carrier dog, result: 50% carriers, 25% clears, 25% affected.
Of course, everything is a chance, some matings are luckier than others, and some breeders just seem to have very bad luck. So the absence of affected dogs in, let's say, a litter of four, doesn't mean that everything gets altered because of that. This would also seem to go a long way towards explaining the "mysterious" things that have happened with matings, with a bitch producing three healthy litters with three different males, and then with the fourth: BANG. This indicates the problem of identifying a particular type of carrier. However, based on the ancestry of the dog, one should be able to identify a certain risk of carriership.
Recently there is a risk assessment scheme developed to give some lead on the relative chance of a particular dog transmitting PLL, based on the cases known in the dog's background. Admittedly, it is not perfect, but until there is a DNA test, we have to use the best guess method available to us. This risk assessment scheme has been introduced to Finnish Heeler breeders, and I believe something similar is also used in Sweden, as part of the sophisticated Lathund/Genetica programme their Club has. The demand for neutral, anonymous indexes seems to be growing, since e.g. several major Finnish Breed Clubs (Rottweilers, German Shepherds, Golden Retrievers) have started using the so-called BLUP Index to determine the breeding value of a particular individual or mating combination, with view to elbows and hips. (Doctor's thesis by Katariina Mäki, kamaki@animal.helsinki.fi ). The Hovawarts in Gemany, along with many other breeds of German origin, use the Breeding Value Estimate, targeted at improving certain features of the breed.
All these methods are aimed at offering breeders an easy-to-use tool for making their breeding decisions as balanced and safe as possible. However, the BLUP Index and the Breeding Value Estimate are used for clearly different situations from the one the Heeler is facing. What we have to deal with is a late-onset, difficult to diagnose condition, whereas the two methods mentioned above are for early-onset and/or clearly visible conditions/features. The RTR© system is intended to tackle that problem. RTR stands for Relative Transmission Risk.
Starting points for the RTR© system
It must be emphasized that no one can be blamed for PLL in a dog. However, the dogs in the past form an important genetic burden for the dogs at present. It was the intention to construct a formula which objectifies this burden, and hence objectifies the risk that a dog has for one or two PLL-genes. Basis for this calculation was that known affected dogs have two affected genes, and parents and offspring automatically one. It must also be emphasized that in the following system potential carriers are NOT included. For example: offspring from a combination of a carrier and a clear dog have a 50% chance of having the gene. However, as none of the offspring can be identified for sure for being a carrier, this is NOT taken into account. All these offspring dogs are considered to be clear as long as there is no other proof (i.e. affected offspring from themselves). Please note that the resulting value only says something about the burden from the ancestry, and nothing whether the dog is actually a carrier or even affected. If there is enough data, there might in the end emerge a correlation between the RTR© value and the genotype.
The calculation
Having said that, it will be clear that a great great grandparent as carrier (in the 4th generation) has a completely different impact on the genetic constitution than the direct parents. In the formula every generation is corrected for this effect, the highest weight being applied on the first, the lowest on the 4th generation. With these parameters, a database can calculate a value for the dog in consideration. This is expressed as a percentage of the maximum genetic burden from 4 generations. So a value 30 means 30% of the maximum burden. The maximum burden consists of all dogs in 4 generations ancestry being affected.
Limitations and possibilities
The resulting value has been named Relative Transmission Risk© or RTR©. It says exactly what it is: It is a risk, a chance, without certainty or guarantee. In addition, it is relative so you can only compare dogs to each other. It means that a dog with an RTR© of 5 is at a lower risk than a dog with an RTR© 50; however, with bad luck this RTR© 5 dog can still be a carrier or appear to be an affected dog in the end.
One limitation is that it only takes into account known carriers and known affected dogs but as the importance of the information in preserving the breed becomes widely understood, more and more submissions will be made to the register. Another limitation is that it doesn’t say anything about the distribution in a pedigree. A value of 50% can mean for example that all affected dogs are cumulated in one branch of the pedigrees.
However, the advantages of the system compensate for the limitations.
It offers an objectified value.
It takes away all emotions one can feel about a certain dog (or owner/breeder).
It is anonymous. It is not important which dogs in the pedigree produce the resulting value.
A major advantage is that with this tool a breeder can try to find a low risk dog for, for example, a high risk bitch. Or, if you are considering two otherwise equivalent studs for your bitch, this value can help you to decide in a rational way. You can also take the resulting RTR© value of the intended litter as a guideline by setting limits to the resulting value. Or you try not to exceed a certain value of the RTR© sum of the parents.
It should be understood that focussing on one feature almost automatically leads to a certain loss in other aspects. If a breeder focuses on PLL, they could lose a bit on show quality, or on another health issue like CEA. This illustrates the enormous responsibility the breeders have for the survival of the breed. However, this system might buy us time, until there is a DNA test.
In conclusion, the system uses every piece of information available and projects the risk forwardly. It is dynamic, which means that one affected dog can change the RTR© values of a whole series of dogs and every value is therefore time dependent. In fact, the data that the LHC and the SKK are offering are extremely important but relatively static and not easy to interpret for the individual breeder.
Essential preconditions
If the RTR© system is going to be used more widely, it is essential that the formula is applied to a single database in order to ensure reliability and consistency of the generated values. The data from the LHC and Swedish Kennel Club should form the backbone of it.
Information
If you want more information about the system, you can contact Dick Koster at sukelyas@wxs.nl . However the liability with regard to use of RTR values is limited by the following disclaimer.
Disclaimer
The data has been compiled to the best of my ability and knowledge, based on information received from numerous sources. However, one should bear in mind that although checked and cross-checked, this information could be incomplete, outdated or untrue. No rights or claims should ever be based on RTR values: a low RTR value gives absolutely no guarantee against PLL, nor, in reverse, does a high RTR value indicate a certain onset of PLL. The application of RTR values is subject to one's own risk alone, and consequently no claims pertaining to RTR can be made against the author.
Please note: Never use an RTR value without simultaneously giving the date when it was generated.
RTR and Relative Transmission Risk system are copyright Dick Koster sukelyas@wxs.nl
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