|   MINI BULL LENS 
    LUXATION RESEARCH PROJECT Recorded, March 
    15, 2002 Louisville, KY Transcribed by: 
    Renges Fabris Guest Speaker: 
    Liz Hanson, Assistant to Dr. 
    Gary Johnson University of 
    Missouri, Department of Pathobiology 
    Speaker: The 
    initial work that we had been doing on the lens luxation project in mini 
    bulls kind of got stymied because of the small gene pool that mini bulls 
    have and many of the markers that we worked with were uninformative. 
    Basically, that means that everyone we tested had the same genotype. We 
    can’t sort out one from the next in terms of effected dogs vs. unaffected 
    dogs. Looking at the genetics we can’t find anything that is linked. We have 
    now added other breeds that also have lens luxation problems. The grant that 
    we just had approved by the AKC Health Foundation is to look not only at 
    lens luxation, but also glaucoma. It seems that often times these run 
    together. As I’m sure we are all aware, lens luxation can cause secondary 
    glaucoma, and sometimes glaucoma can cause the lens to luxate. So not 
    knowing, in some cases, which came first, we decided to study both of these 
    together. Right now we are looking at samples from 14 different breeds and 
    we are hoping that if we can crack this nut in one place, it will help us 
    move along in another. Last fall at the 
    Canine Health Foundation parent club meeting in St Louis, we talked with 
    Matthew Binns from the Animal Health Trust in England. They felt that they 
    had a marker that was looking very promising. It appeared to be linked, but 
    they didn’t have enough dogs to make it statistically significant…to say 
    “yes it is linked”. In order to 
    determine that something is linked, we look at different DNA markers. A 
    marker is just a small piece of DNA. It’s not necessarily a gene; it might 
    be part of a gene; it might be between genes. But we know which chromosome 
    it is on and where it sits on the chromosome, but we don’t necessarily know 
    what it does. If there is a gene known to cause a certain disease in people, 
    we usually try to find that same location on the canine genome and then look 
    for markers that are nearby to see if they link to the disease in the dog as 
    well. So we have a marker in England that they thought was linked. To 
    declare that you actually have it linked, you have to go through a whole 
    statistical analysis. They want to see what they call a load score, which is 
    a log of the odds, which is 3.0 or greater. That simply means that you have 
    load score of 3.0, it means that this would happen by random chance, one in 
    a thousand times. If you had a load score of 2.0, it would happen by random 
    chance one in one hundred times. So you are looking to find the highest load 
    score you can to call the link solid. In the work that they have done in 
    England, they had a load score of 2.7, which is pretty good, but it’s not 
    quite at that level where they can say it is actually linked. They asked if 
    we would be willing to send the DNA we have from the mini bulls here. They 
    have about 40 dogs that they are working with there. We sent them samples 
    from close to 80 dogs that we have samples from here. They ran their marker 
    on all the samples we sent them and they still come up with a load score of 
    2.7. It is almost impossible that you could run that many more samples and 
    come up with the exact same score. It should have moved up or down. We think 
    what is happening is that in a lot of these families that we are working 
    with, we have random members. We might have one effected sibling and maybe a 
    parent, or maybe a parent and a couple of the offspring. It will really help 
    us to move this along if we can get entire families…all of the siblings and 
    both of the parents, which in a lot of cases are missing. So if any of you 
    have family members of effected dogs, or dogs who have luxated, it is really 
    important for us to get these additional dogs sampled so we can try to 
    either say that it’s really not linked or move the load score up and say 
    “yes, we’ve got it!”…and then we will have a marker that you can all use. At this point, I 
    would like to answer any questions you may have: 
    Audience: My 
    partner and I haven’t had anything luxate yet. If we got the people who 
    bought our puppies, and get all the puppies and the parents sampled, would 
    that help your research so far. 
    Speaker: The thing that will tell us the 
    most is whether these dogs are related to dogs that have luxated. The 
    animals that we most want to sample are effected dogs, their full siblings 
    and their half siblings. Also, the parents and the grandparents if they are 
    still alive. Grandparents are useful if we can get them. I know this is not 
    always possible when you have a late onset problem like this. If the dog had 
    been used for breeding prior to luxating, we would like samples from all the 
    puppies and the other parent as well. The lines where there hasn’t really 
    been any problem, and they don’t appear to be related to any dogs that have 
    a problem, they probably are not going to tell us a whole lot, 
    unfortunately. 
    Audience: How 
    do you get a DNA sample? 
    Speaker: We 
    prefer to use a blood sample. I know it’s much quicker and easier to use a 
    cheek swab, but it doesn’t give use much DNA to work with. The last thing we 
    want to do is get halfway there and run out of DNA. So we ask for a blood 
    sample. If the dog is having surgery, we’ll take whatever “spare parts” 
    there are (laughter) because that’s a mountain of DNA if we can get a tissue 
    sample. If a dog is being euthanized, we would like to get a tissue sample, 
    preferably from the spleen. We don’t need the whole thing…just about a thumb 
    size chunk. That would be more DNA than all the researchers in the world 
    could use. We at least need blood samples in a purple top tube. Right now, 
    when you’re getting ready to go in for a heartworm test, this is an ideal 
    time to be sampling these dogs. Just get a little bit more blood and send it 
    in. Contact puppy buyers and other people that you know and advise them when 
    they go in for heartworm testing on their dogs that they should also get the 
    dog sampled for this project. 
    Audience: I understand that glaucoma and 
    lens luxation are two separate diseases. But if your dog starts luxating, it 
    can shift the lens and that can interfere with drainage… 
    Speaker: Right. A luxated lens can 
    interfere with drainage. 
    Audience: But then that’s not actually 
    glaucoma? 
    Speaker: That 
    would be secondary glaucoma. 
    Audience: If a dog has glaucoma and it 
    is predisposed to lens luxation, the pressure of glaucoma can cause the 
    zonules to weaken further and further along to lens luxation. Is that 
    common? 
    Speaker: Yes. 
    That is why we are looking at these two diseases together, because one can 
    predispose the dog to the other. Initially, when we started on this, we 
    thought that you guys with the mini bulls were experiencing strictly lens 
    luxation, and we went merrily along our way with that assumption. And then 
    we found out that you’ve also got glaucoma. We thought we kind of had a 
    spectrum here with Basset Hounds having only glaucoma and you guys only 
    having lens luxation and a lot of breeds that were experiencing different 
    levels of these diseases in between. However, now we have a few Bassett 
    Hounds that have luxated. 
    Audience: But 
    a dog that has glaucoma won’t necessarily get lens luxation. And a dog that 
    has lens luxation won’t necessarily get glaucoma. Right? 
    Speaker: 
    Right. That’s why it is important to keep us updated as you send samples in. 
    We really need to know what’s going on as the dogs age. We’ve had people 
    whose dogs were sampled two or three years ago that have contacted us and 
    told us that the dog luxated or it’s being treated for elevated pressure. If 
    we think we’ve got a link marker, but we don’t have the right phenotype (if 
    we don’t know that your dog has luxated) we might pass up a marker by saying 
    that these are all normal dogs so this can’t be the correct marker. So it is 
    very important that we are updated as to what is going on with the dogs as 
    you have them checked every year. We have to have those updates, or we are 
    going to pass up the correct marker. 
    Audience: I guess you are really 
    familiar with glaucoma? 
    Speaker: I’m 
    not an ophthalmologist. My role is to be a liaison between the scientists 
    and the breeders. I have Standard Schnauzers. I started in this with some 
    epilepsy research. I’ve had Standard Schnauzers for 26 years and another 
    breeder and I got hit with epilepsy. Not wanting to give up all that work, 
    we looked for someone to help us. After about a year of bringing samples to 
    Doctor Johnson, he said “You know, you just need come work for me”. The 
    epilepsy research is the other big project we are working on. We have a lot 
    of other smaller dog projects. I fit into this because I’m a dog breeder; 
    I’m an exhibitor. I’m here showing this weekend. I know what all you folks 
    are going through when something like this hits. Any one of these inherited 
    diseases can devastate a breeding program. I also have a background in 
    science and veterinary medicine, although I am not a vet. I can work between 
    in trying to help get the samples that we need into the researchers and get 
    the results of the research back to you. Dr. Johnson is the gene jockey. He 
    is the molecular geneticist and works on that end of it. But whatever 
    project we are working on, we collaborate with an expert in that field. So, 
    we have several neurologists that we work with in the epilepsy research; we 
    have the opt homology staff at Missouri, and we are hoping to get a research 
    consortium going there as well. In the epilepsy research, we have four 
    universities working together and we are hoping to get something similar to 
    that going with the eye research. 
    Audience: I 
    had my dog tested at an eye clinic held in conjunction with the Montgomery 
    County all-terrier show. When I took her in, I took her directly from the 
    show to the clinic. I took her on a choke lead. She was playing with 
    everything. When he did the testing on her eyes, her pressure was up. I 
    don’t remember who the ophthalmologist was…it was in Pennsylvania. I 
    immediately panicked because I was told that glaucoma and lens luxation were 
    one-in-the-same disease. I immediately went out and got Xalatan because that 
    is what he recommended. When I got home, I went immediately the University 
    of Florida, to Dr. Galett and Dr. Biros. I wouldn’t take her off Xalatan 
    even though they kept telling me to do it for almost a year because I was 
    afraid my dog would have a glaucoma attack and that she would be in terrible 
    pain. Finally, after almost a year the doctor told me to take her off. I 
    did, and she never developed glaucoma. He told me don’t ever go in and have 
    your dog tested under those conditions. It’s like being strangled or 
    hanged…your eye pressure goes up. That’s what happened in this case. 
    Speaker: When 
    you run into a problem, it never hurts to get a second opinion. 
    Audience: So…when you take your dog to 
    be tested, take them in a crate, or carry them in? (No response 
    from Speaker) 
    Audience: I 
    was asked by Roz Clamper, who is a bull terrier breeder-judge, to mention 
    that her standard bull terrier developed glaucoma and has sub-luxated. Would 
    this be of interest to your studies? 
    Speaker: Yes. 
    Definitely. With this new grant that is looking at both lens luxation and 
    glaucoma, it is fully funded, and I think your club contributed to that. We 
    had several clubs that did contribute to the grant, and it is open to any 
    breed that has the problem. So, we are definitely interested in other 
    breeds. 
    Audience: Of 
    course, standard and miniature bull terriers are very closely related. It’s 
    almost a shame to call them a different breed. They’re not really a 
    different breed. Only in the United States. 
    Speaker: Are 
    there any other reports of standard bull terriers that have luxated first? 
    Audience: I don’t know about luxated 
    first, but I talked to Dr. Vainisi about standard bull terriers that he has 
    seen with glaucoma. 
    Speaker: Yes. 
    We would definitely be interested in this data. Wednesday, before I drove 
    here, I interviewed an ophthalmology candidate coming from Missouri who is 
    one of Dr. Galett's post doc students. He is either going to NIH to study 
    glaucoma using animal models for human glaucoma, or come to Missouri. I 
    tried to lay out all the things that we are doing in Missouri and the 
    reasons why it would be best to come to Missouri. He seemed pretty excited 
    about the things we are doing. So we hope he will come because it will help 
    us out quite a bit. 
    Audience: I 
    was under the impression that the miniature bull terrier picked up the lens 
    luxation when the standards were crossed to the Jack Russell Terrier in 
    order to get the size down, although we don’t know this for sure. Are Jack 
    Russell's taking part in this study? 
    Speaker: Yes. 
    We are just starting. And, it is the non-AKC Jack Russell people that are 
    more excited about it than the AKC people…there is such a split in that 
    club. But they got past the idea that the AKC was involved and decided they 
    could work with the Canine Health Foundation. We are getting quite a few 
    Jack Russell Terrier samples in the last few months. Because lens luxation 
    seems to be primarily in a lot of the true terrier breeds, it is possible 
    that there is a founding mutation that is behind the luxation that is behind 
    most, if not all, of these breeds. We have quite a few samples from the 
    Tibetan Terriers, which are not true terriers, but they have luxation. They 
    believe that it came from one individual dog in England. In the 40s or 50s, 
    if you got two or three British judges to say that is was…then it was. They 
    found this dog on a wharf. It looked like a Tibetan Terrier. These judges 
    said that if it walked and talked like a Tibetan Terrier, then it’s a 
    Tibetan Terrier. And all of the Tibetan Terriers with lens luxation can be 
    traced back to this one animal. The club sort of did the outcross that is 
    useful to use. We don’t have as many samples as we would like to from the 
    families. But it’s getting better. We get little spurts of Tibetan Terrier 
    luxation families. 
    Audience: Is 
    lens luxation on the increase? 
    Speaker: It’s hard to tell if it is on 
    the increase or if there is better awareness and better openness about it. 
    Audience: I 
    recently had a lens luxation case; my husband is a former Welsh Terrier 
    breeder. Up until recently, I had never heard of lens luxation in Welsh 
    Terriers. 
    Speaker: All 
    of the Welsh Terrier samples we have are glaucoma. I don’t think we have any 
    that have lens luxation cases in Welsh Terriers. 
    Audience: If 
    you go to there website, there is mention of lens luxation in Welsh 
    Terriers. I find this interesting, because I have never heard of it in Welsh 
    Terriers. 
    Speaker: It is 
    very hard to know how much of this is because it is occurring more, or if 
    its because people are more willing to talk about it. Dog people thump each 
    other over the head with any little bit of dirt they can find. I think a lot 
    of things have been hidden and not talked about, so you just stop with that 
    part of the line and move on to something else and just don’t mention it. I 
    think we are getting better about talking to each other about these things. 
    None of us can make informed decisions without information. We have to talk 
    to each other. No one plans to produce a problem…but it happens. We are 
    dealing with living things, and things go wrong. 
    Audience: Is 
    there any feeling about whether lens luxation is a recessive? 
    Speaker: We 
    haven’t run the statistics on that. Ned Patterson, who is working with us on 
    epilepsy research from the University of Minnesota…he is a wiz at 
    statistical modeling. He is going to take a look and see if he can come up 
    with numbers. Just looking at pedigrees without analyzing the numbers, it 
    looks like a simple recessive, but we haven’t proven that. 
    Audience: From 
    a conversation with Dr. Gallant, I understood, that it was recessive. 
    Speaker: Like 
    I said, at-a-glance, looking at it, it seems to be recessive. There are a 
    lot of things that can effect this. We don’t know for sure yet. 
    Audience: We 
    have two dogs that are about 8 and 9 years and are both clear but have 
    produced five puppies, four of which have sub-luxed. So, you think you have 
    a clear dog…they are both clear…no lens luxation, no glaucoma, but out of 
    five puppies from two breedings, two have luxated and two have sub-luxated. 
    This really destroys your comfort level. You’re so careful. You wait so long 
    to breed them…. 
    Speaker: We really encourage people to 
    get samples from their puppies before they are placed, and then get a larger 
    sample later. Do the puppies before they leave so you have the whole family. 
    We are also doing a general DNA bank for several breeds. We charge $10.00 
    per sample and it is stored forever. If we ever decided to close up shop, we 
    would give plenty of notice so that your sample could be moved to another 
    organization. If there is DNA needed at another university or organization, 
    we could send samples elsewhere. So it might be a good idea just to sample 
    everyone and get it stored. We may never use it, but we’ll have the ones 
    that are really important, even if they have died since, it will help us to 
    close up the holes in these pedigrees and move this project along. 
    Eventually, when we do have markers from DNA tests and you can genetically 
    clear both the parents and the grandparents, then you won’t have to test all 
    the puppies, you will already know what the genotype is. I will leave 
    some blood sampling packets here for you and a copy of the poster that we 
    distributed at the Canine Health Foundation Conference. It has general 
    information on the Research Project. If people want dogs sampled, I have 
    needles and tubes with me. I will be here until the end of the day. Well, 
    that depends…if we get the breed, I’ll be here until the end of the day. If 
    we don’t, I’ll be leaving around 1 o’clock. 
    2nd Speaker: 
    As you may know, the entire human genome has now been mapped. There are a 
    lot of grand expectations to come out of that, but one of the first things 
    we expect to come down from that is the identification of markers. It is 
    nice to see that technology spilling over into the canine genome as well. 
    This is particularly good for late onset hereditary problems. It is the only 
    real hope of eliminating these problems. When you have a really small gene 
    pool, as in miniature bull terriers, it is a particularly difficult problem 
    for breeders to avoid these tragic pitfalls. (End of tape) |