Nsdtr

[shortstep]

http://www.ncbi.nlm.nih.gov/pubmed/20136772

Association of a dog leukocyte antigen class II haplotype with hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers.

Hughes AM, Jokinen P, Bannasch DL, Lohi H, Oberbauer AM.

Department of Animal Science, University of California, Davis, CA 95616, USA.

Abstract

Canine hypoadrenocorticism (Addison's disease) is due to a deficiency of corticosteroids and mineralocorticoids produced by the adrenals. Although this is a relatively uncommon disease in the general dog population, some breeds, including the Nova Scotia Duck Tolling Retriever (NSDTR), are at increased risk for developing hypoadrenocorticism. A prior study has shown that the increased risk is due to a heritable component. This potentially lethal disorder is hypothesized to have an autoimmune etiology, thus the aim of this study was to determine whether genetic susceptibility to hypoadrenocorticism in NSDTRs is associated with genes of the canine major histocompatibility complex [MHC; dog leukocyte antigen system (DLA)]. Samples were collected from NSDTRs diagnosed with hypoadrenocorticism and healthy siblings or country-matched controls. The DLA class II alleles and haplotypes were determined and compared between cases and controls. We found seven different haplotypes of which the haplotype DLA-DRB1*01502/DQA*00601/DQB1*02301 was significantly more prevalent in the diseased dogs (P = 0.044). In addition, these affected dogs also were more likely to be homozygous across the DLA class II region than the control dogs (OR = 6.7, CI = 1.5-29.3, P = 0.011). We also found that homozygous dogs, regardless of their haplotype, tended to have earlier disease onset compared with heterozygous dogs. These data indicate a limited MHC diversity in North American NSDTRs and suggest that the MHC may play a role in the development of hypoadrenocorticism in the NSDTR, supporting the autoimmune origin of the disease.

Would be interested to hear how people think this study (granted it is only one but evidently there are many many more just finishing up or in the works) on what it will mean purebred breeds or all purebred dogs in general, inbreeding, open stud books and so forth.

I guess that from what I have read in NSDTR COI rates (amount of inbreeding) is a minimum of 25% and the effective population world wide is genetically equal to 50. I understand that the German kennel club has requested the FCI to open the stud book for controlled cross breedings in an effort to 'save' the breed and to reduce disease.

I understand our Claire Wade (Sydny Uni) is in opposition to this idea, as is the AKC. However there also seems to be very strong support world wide from most experts in genetics to support the opening of the stud book.

[RallyValley]

I am just trying to find the full text now through online journal access from uni. Seems like a very interesting article... however as only USA tollers were used in the test and they only were an AKC registered breed fairly recently and are in my understanding not too common there it could also be popular sire effect contributing...

ETA- I can't get full text until I am on campus it seems, we only have the article available through the journal that you must be on campus to read.

Edited March 25, 2011 by RallyValley

[shortstep]

I am just trying to find the full text now through online journal access from uni. Seems like a very interesting article... however as only USA tollers were used in the test and they only were an AKC registered breed fairly recently and are in my understanding not too common there it could also be popular sire effect contributing...

ETA- I can't get full text until I am on campus it seems, we only have the article available through the journal that you must be on campus to read.

Canada?? I do not know much about the breed. I am thinking more in terms of all purebred dogs rather than this breed.

I am sure popular sire syndrome is part of what has lead to the high COI even more important the high rate of dogs homozygous in DLA class II region, but also a small population when the stud book was closed and even just closing the stud book on any breed.

Once a stud book is closed there is only one way the COI can go and that is up and there is only one way the diversity of genes can go and that is down.

As I understand it, the 'idea' is that in a breed when this happens, that there is nothing left (genetically) to choose from, so you cannot try to outcross from within the breed to reduce COI or increase the diversity of genes in the offspring. No matter which way you turn to breed you will only be getting the same stuff you already have.

When immune systems are involved, the more diverse the genes in the dog the healthier immune system the dog will have. Immune systems work the same way in populations, the more diverse the gene choices are in the population, the more likely when you breed two dogs you will be getting different genes, and this will make the pups have better immune systems.

What studies like this are showing is that this is more then theory, they are actually starting to do the studies to attempt to prove it as fact.

Edited March 25, 2011 by shortstep

[Ptolomy]

There is a huge debate going on at the moment about outcrossing tollers in Germany for this reason, has all the breeders in the US and Canada up in arms.

[shortstep]

There is a huge debate going on at the moment about outcrossing tollers in Germany for this reason, has all the breeders in the US and Canada up in arms.

So what do you think about it and how it affects your dogs and your breeding program?

BTW have you done COI on yor dogs? I am not sure how many generations they used for that 25% rate, do you know how many generations they area talking about?

[Miranda]

I would also like to know how many generations they use for these studies, I have COI's on all my dogs and I calculate over 20 generations.

[Ptolomy]

There is a huge debate going on at the moment about outcrossing tollers in Germany for this reason, has all the breeders in the US and Canada up in arms.

So what do you think about it and how it affects your dogs and your breeding program?

BTW have you done COI on yor dogs? I am not sure how many generations they used for that 25% rate, do you know how many generations they area talking about?

My non science background and the amount of reading I have done on the subject is poor

Yes I have done breeding COI on all my kids and have to be honest and say most of them are around 24-25% (we do know of breeders in the US and Canada who go as high as 30-31%) - and the program goes back 10 generations. Our gene pool in Oz is very very small and yes there is a high degree of popular sire syndrome - something I am very mindful of with my Norweign import.

Other inbreeding and immune related articles:

http://www.tollertales.nl/download/research%20auto-immune%20Tollers.pdf

http://www.tollertales.nl/download/inbreeding%20def.pdf

[shortstep]

My non science background and the amount of reading I have done on the subject is poor

Yes I have done breeding COI on all my kids and have to be honest and say most of them are around 24-25% (we do know of breeders in the US and Canada who go as high as 30-31%) - and the program goes back 10 generations. Our gene pool in Oz is very very small and yes there is a high degree of popular sire syndrome - something I am very mindful of with my Norweign import.

Other inbreeding and immune related articles:

http://www.tollertales.nl/download/research%20auto-immune%20Tollers.pdf

http://www.tollertales.nl/download/inbreeding%20def.pdf

Thanks for the links will read them this evening.

I was going to guess 10 generations but did not want influence you. I know all the work done with poodles has been on 10 generations and most people I know who work in the area usually talk about 10 generations.

Personally I think that 3-5 generations really only shows the recent history and can hide dogs that have a long history of high COI. 6-10 shows more of what will be effecting the dog today. Total COI (all generations of the breed) shows the long term breeding histories and patterns. All good to know, but I think if you want to know about what is affecting your dog in the here and now the 10 generation is the most valuable with perhaps a 6 generation for a more recent view.

I have ask at Sydney Uni how many generations they used and never heard an answer. I am thinking they used 3 generations, not sure why they would have done that?? Anyone know more about this?

My dogs at 6 generations run usually less than 1%, at 10 generations about 3.5% and total COI back to early 1900s is about 6-7%. They are considered low inbreeding levels, and in fact those numbers would be considered outcross by most systems. However when I showed them the the Uni folks doing the 10 point plan, they sugested that 0% COI at 6 generations should be the goal. I can not do that for more than the one off odd breeding and it would offer no choice in selection of dogs. (but who needs to select for anything else but COI eh?).

I guess this is the point, there is really only one direction one can move over time in a closed stud books and that is to ever higher COIs. How fast will depend on many factors such as popular sire, number of avilable dogs, number of different dogs used, keeping as many dogs as possible in the gene pool and using them. Other factors that can have real effects in a shor t period of time is culling for disease. I noticed in my breed a large culling of carrier dogs once some DNA tests came out. This was not good for the breed and will only hasten an increase COI and a decrease in diversity. Worse is there is nothing that can be done to bring those dogs and their gene back into the gene pool, they are lost forever and lost over a disease which could easily be controlled.

Edited March 25, 2011 by shortstep

[Sayreovi]

There is a huge debate going on at the moment about outcrossing tollers in Germany for this reason, has all the breeders in the US and Canada up in arms.

Yes, it's been an interesting read. I don't believe that an extremely new and inexperience breed club like the Toller club of Germany has the knowledge and necessary research behind it to want to open the stud books and do it correctly. The only two clubs that have that knowledge and experience is the US and Canadian clubs.

Majority of Toller breeders will not send any Tollers to Germany any more for fear that their dogs are used in a cross breeding program. Unfortunately it is now a damned if you do damned if you don't.

I am curious though, for those with linebred dogs in other breeds what is their COI?

[Ptolomy]

and if they do introduce cross breeding in Germany - what other problems will we see crop up in the breed further down the line that we currently don't have??

[Sayreovi]

Exactly right, Tollers have their problems, but they are definately alot more healthier then some breeds going around.

I just checked my guys COI and were around the same 24%, I only just added Jovi so won't know for another 1-2 weeks but it will be slightly higher as there is a common great grandparent.

[shortstep]

There is a huge debate going on at the moment about outcrossing tollers in Germany for this reason, has all the breeders in the US and Canada up in arms.

Yes, it's been an interesting read. I don't believe that an extremely new and inexperience breed club like the Toller club of Germany has the knowledge and necessary research behind it to want to open the stud books and do it correctly. The only two clubs that have that knowledge and experience is the US and Canadian clubs.

Majority of Toller breeders will not send any Tollers to Germany any more for fear that their dogs are used in a cross breeding program. Unfortunately it is now a damned if you do damned if you don't.

I am curious though, for those with linebred dogs in other breeds what is their COI?

The COI is of interest in the Toller because the minimun inbreeding level in the breed is around 25%, not that any dog is 25%. Another words there are not any dogs with less than that number left in the breed, but there will many at that number of higher. this off course means at the number of generations they are using, which I think would be 10 perhaps or maybe the total number back to when the stud book closed.

The Germans feel that no matter which dog they use, even if they import, they will still only be getting the same genetics they already have.

I was doing some reading this morning and found a lot of interesting things and have a lot of questions.

Firstly that they have north american farm collie type dogs in them and this is further proven by the presence of CEA. I think they also show border collie type dog in their looks very strongly. What was interesting about the CEA is that in most of the population the carrier rate is very low at 5%, but in some distinct and seperate lines (they did not say what made them seperate or distinct) it is almost 40% carrier rate. Are most people DNA testing for CEA and would most people avoid using any CEA carrier in their breeding programs?

The prcd-PRA carrier rate is thought to 40% or higher. So I assume most people are testing for this. Are you using affected dogs for breeding? I assume you are not breeding carrier to carrier? So this would eliminate 40% of the population from the selection process for any litter bred from a carrier. Will owners of clear dogs normally pick another clear dog for breeding, so would avoid using a carrier? From Carrier to Clear litters, are the breeders selecting only the clear pups to breed forward from? Is the breeding goal to clear the lines as soon as possible? Can you already see a drop in the number of carriers in the breed?

Edited March 25, 2011 by shortstep

[Ptolomy]

The COI is of interest in the Toller because the minimun inbreeding level in the breed is around 25%, not that any dog is 25%. Another words there are not any dogs with less than that number left in the breed, but there will many at that number of higher. this off course means at the number of generations they are using, which I think would be 10 perhaps or maybe the total number back to when the stud book closed.

The Germans feel that no matter which dog they use, even if they import, they will still only be getting the same genetics they already have.

I was doing some reading this morning and found a lot of interesting things and have a lot of questions.

Firstly that they have north american farm collie type dogs in them and this is further proven by the presence of CEA. I think they also show border collie type dog in their looks very strongly. What was interesting about the CEA is that in most of the population the carrier rate is very low at 5%, but in some distinct and seperate lines (they did not say what made them seperate or distinct) it is almost 40% carrier rate. Are most people DNA testing for CEA and would most people avoid using any CEA carrier in their breeding programs?

The prcd-PRA carrier rate is thought to 40% or higher. So I assume most people are testing for this. Are you using affected dogs for breeding? I assume you are not breeding carrier to carrier? So this would eliminate 40% of the population from the selection process for any litter bred from a carrier. Will owners of clear dogs normally pick another clear dog for breeding, so would avoid using a carrier? From Carrier to Clear litters, are the breeders selecting only the clear pups to breed forward from? Is the breeding goal to clear the lines as soon as possible? Can you already see a drop in the number of carriers in the breed?

Yes farm collie type dogs are in their background. I am relatively new in the breed (10 years) and initially breeders were testing only for PRA. The CEA test came later and most people are testing for both now. Interesting that in Europe a large majority of breedings are PRA clear to carrier. Intrigued, I asked why and was told that by breeding clear to clear they were limiting themselves with the choice of dogs and were perhaps passing on or doubling up on faults that may only show themselves further down the line. They felt that by discounting carriers they were throwing away some good quality dogs. I do know of a couple of carrier to carrier breedings for which he breeders coped a lot of flack. So in answer to your question, breeders are selecting carriers to breed from.

In June last year I imported a 12 week old pup from Norway - he was from a carrier to clear breeding, both parents were CEA clear. I have tested him for PRA and he is clear (so is worth his weight in gold!) Interesting that none of his sibblings have yet been tested. I also have a PRA carrier (from a carrier to clear breeding), she has been steralised due to other health issues. My 4 other kids are all clear for PRA and CEA.

[shortstep]

Interesting that in Europe a large majority of breedings are PRA clear to carrier. Intrigued, I asked why and was told that by breeding clear to clear they were limiting themselves with the choice of dogs and were perhaps passing on or doubling up on faults that may only show themselves further down the line. They felt that by discounting carriers they were throwing away some good quality dogs. I do know of a couple of carrier to carrier breedings for which he breeders coped a lot of flack. So in answer to your question, breeders are selecting carriers to breed from.

In June last year I imported a 12 week old pup from Norway - he was from a carrier to clear breeding, both parents were CEA clear. I have tested him for PRA and he is clear (so is worth his weight in gold!) Interesting that none of his sibblings have yet been tested.

Norway has a very high level of education and guidance for it's breeders. They would have a panel of experts, both in the breed and in science who would be reviewing trends in the breed and helping to decide what needs to be addressed. I would guess that there is a guideline or limit on COI for this breed. I would love to know what it is is if you speak to the breeder some time about it. I would also think there has been a lot of education on keeping every dog possible in the breeding pool, and the use of carriers and even possibly affected would be encouraged. Also not promoting limited registration or placing most pups on breeders terms so they can have at least one litter to help protect the future of the breed. Getting as many dogs as possible contributing to the next generation would be very important.

I would guess the reason the other siblings have not been tested yet is that they don't really care, they do not base any decisions on if the dog is a carrier or normal. Another words they will not choose the dog to breed because it is normal, nor will they cull the dog from breeding because it is a carrier. When all of the other things they are looking at to make the decisions to breed have been decided, and they are preparing to breed the dog, only then would they look so they can use that information as needed in the mate selection. Doing this prevents breeders from selecting normal dogs over carriers. As they do not have the information so it cannot shade their opinion one way or the other. The dog really will get picked because it was a good dog to breed, not because it would make their kennel or the litter all PRA clear.

Have you ever seen this on web site. 'All our dogs are DNA Normal on X Y and Z diseases!" On the surface to the uneducated it might sound very good. But over the life of a the breed, if this desire to have all DNA normal dogs and kennels is a breeding priority, then this is very bad news for the breed.

Take your breed, over 40% are carriers of PRA and 5% carriers of CEA. if you remove all these dogs from breeding, you can in one generation clear the 2 diseases from the breed. But you also lost 45% of your total breeding population and 45% of your possible genetic diversity. When it is already know that the total effective population is around 50 dogs, that would have been cut by 45%, leaving an effective population of only 23 dogs to maintain your breed.

I know of some breeds where this culling of carriers has happened and they have lost up to 30% of the population in less than 2 generations. Just think what we would be saying if we lost 30% of breeding dogs to say parvo, but we willingly toss them out only because they are carrier a disease we can fully control.

Glad to hear in Norway they are getting it right. I am sure that is the case here in Oz too.

Edited March 26, 2011 by shortstep

[Sayreovi]

Norway has a very high level of education and guidance for it's breeders. They would have a panel of experts, both in the breed and in science who would be reviewing trends in the breed and helping to decide what needs to be addressed. I would guess that there is a guideline or limit on COI for this breed. I would love to know what it is is if you speak to the breeder some time about it. I would also think there has been a lot of education on keeping every dog possible in the breeding pool, and the use of carriers and even possibly affected would be encouraged. Also not promoting limited registration or placing most pups on breeders terms so they can have at least one litter to help protect the future of the breed. Getting as many dogs as possible contributing to the next generation would be very important.

The Scandinavian countries had a different approach to Tollers when they were first imported to their country, much like what you are saying, nearly every dog had a litter so they contributed to widening the gene pool. I am not sure what COI dogs from those countries are and if they are getting lower as a result.

I guess the thing to remember is they are still a new breed, and as such will obviously have a higher than normal COI as the breed was only started by a handful of dogs less then a hundred years ago. Just checking my guys and they only have about 12 generations before they are back to the original dogs.

Carriers are widely used and acceptable as breeding dogs and all breeding dogs are tested for PRA and CEA (unless clear by parentage). I am sure that affected dogs are bred to clears as well on occasion overseas when the affected dog has something too offer the breed. With Tollers there has been no need to remove carriers as we now have tests to show which is a carrier and which is clear, and as said, removing that much of the breeds genepool just to rid of a disease that is easily controlled would be disasterous and the end of the breed.