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) |