ABCA Health & Genetics Committee Annual Report

[Mark Billadeau]

For those of you, like me, who could not attend the annual meeting here is the committee's report.

Mark

 

 

 

 

2014 ABCA Health & Genetics Committee Summary

Mark Billadeau, PhD, ABCA Health & Genetics Committee Chair

 

Over the past few years the ABCA has supported or funded studies on three health issues in our breed (Epilepsy, Border Collie Collapse, and Early Onset Deafness). The Health & Genetics Committee monitors progress in these studies and the scientific literature for studies on Border Collies.

 

The Epilepsy project, in which a Genome Wide Association study was conducted looking for genetic differences between 100 epileptic and 100 normal Border Collies, was completed in 2013. The study results indicated selective breeding away from epilepsy is unlikely to substantially reduce the likelihood of producing a pup with epilepsy. No additional information has come forth to alter the conclusions drawn by Dr Mark Neff and his associates. Dr Neff had proposed a few additional studies followed by a possible publication of their results. This work may be delayed due to personal changes for Dr Neff; he has moved from the Van Andel Institute when his wife received an appointment to Yale University. In other developments in the literature on epilepsy, there was a recently published study from Japan on a possible genetic cause for the ineffectiveness of phenobarbital in the treatment of epilepsy in some dogs in Japan; the committee is reviewing the study to see how it may apply to Border Collies in North America. The publication can be found here: http://downloads.hindawi.com/journals/dm/2013/695918.pdf.

 

 

The clinical study part of the ABCA funded project on Border Collie Collapse (BCC) had been completed by the 2013 annual meeting, and a Genome Wide Association study was initiated by Dr Jim Mickelson at no additional costs to the ABCA. The clinical study provided a means to clinically identify affected dogs. In the 2014 project report Dr Mickelson has summarized the clinical findings.

 

As a result of these studies it has become clear that the extreme hyperthermia and laboratory abnormalities identified after exercise in dogs with BCC are not different from what is seen in normal exercise tolerant Border Collies performing the same exercise. It is also clear that collapsing Border Collies from sheep-herding and ball-chasing lines have similar clinical signs and laboratory findings, suggesting the same underlying basis for collapse in both populations. Further, the same, or highly similar, condition exists in many Australian Shepherds, which may not be surprising given their close genetic relationship with Border Collies. A number of other breeds may also have a similar condition.

 

Dr Mickelson added that the study determined that Border Collies with BCC do not have the gene mutations identified as the cause of Exercise Induced Collapse in Labrador Retrievers and other related breeds. Additionally, Border Collies with BCC do not have a mutation known to cause a canine form of malignant hyperthermia." A more sophisticated technique, a Genome Wide Association study (the same type of technique used for the Epilepsy study), was initiated to determine if there were genetic differences between normal dogs and dogs affected with BCC.

 

The study results summarized by Dr Mickelson indicate that while there is evidence of BCC being inherited, the Genome Wide Association study was unable to locate any genetic differences between normal and affected dogs. Dr Mickelson suggests this indicates that BCC is likely polygenic rather than a simple Mendelian trait (such as Autosomal Recessive). He also indicates that based upon their past experiences with these types of studies they expect that with more dogs than the 55 affected and 50 normal used in the initial study, they will be able to identify likely locations of gene mutations associated with BCC. This project has a website where they communicate to the public the results and by which samples can be submitted: http://www.cvm.umn.edu/vbs/faculty/Mickelson/lab/EIC/bordercollieEIC/home.html.

 

There have been no new developments in the Early Onset Deafness (EOD) study by Dr Neff. The results of his Genome Wide Association study strongly suggested an Autosomal Recessive inheritance for EOD but the exact location of the gene could not be identified. The published study can be found here: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002898. During the year another study on EOD was published which included data collected by Dr Teresa Chu at several sheepdog trials. The committee reviewed the article in which an inheritance pattern was proposed; however, the scientists on the committee found the provided family trees (only three with limited number of family members) did not support drawing any conclusion about the inheritance pattern for EOD.

 

The committee has been receiving increasing reports of EOD in our breed. Due to this, the ABCA has decided to fund a BAER clinic at the 2014 Finals. In addition to the clinic, the committee has prepared a confidential survey on deafness. The purpose of the survey is to gather information on the status of deafness in our breed, to collect information regarding those willing to submit samples for future EOD studies together with the current hearing status of their dog(s), and to gather sufficient pedigree information to evaluate the proposed Autosomal Recessive inheritance pattern from the genetic study. This information will be very useful in identifying key dogs for future genetic studies aimed at developing and then validating a genetic test for EOD. Knowing the dogs hearing status at several ages well before any genetic study is carried out speeds up the time to completing studies on a disease that takes years to be manifested. The committee wants to be very clear to the community that the personal information and pedigree information provided on the surveys will be held confidential. The committee will share only general information obtained from the survey, such as number of respondents, percentage of EOD in respondents, ages of onset, and so forth. From the surveys, the committee will gather more information to help provide guidance to breeders on EOD.

 

Independent of the ABCA and the committee, a new genetic study on EOD in Border Collies will be starting. The study is being run by an associate of Dr Neff, Dr Alison Ruhe, through the non-profit organization projectDOG (https://projectdog.org/). This study is Dr Neffs proposed risk test discussed at last years annual meeting. The proposed test would evaluate the genetic status of dogs at multiple narrow locations where the genetic mutation(s) responsible for EOD may reside; these locations were not specifically tested during the Genome Wide Association study. A similar study for EOD in Rhodesian Ridgebacks is ongoing with projectDOG and the study for Border Collies is likely to be run the same way. While the researchers hope to be able to give those who contribute samples some evaluation of the "risk" that the dog is affected, normal, or a carrier of EOD, it is likely only a small percentage of the dogs tested will yield results where a definitive assignment can be made. Most dogs will yield results where no assignment can be made. There will be a few key dogs where the test results, along with the dogs hearing status (or future hearing status) will allow elimination of one or more of these locations as the site of the genetic mutation for EOD. This risk test may prove beneficial in narrowing the search for the mutation(s) responsible for EOD.

[NCStarkey]

Thank you for the update, Mark.

 

Regards,

nancy

[Alchemist]

Thanks, Mark, for the recap - and for what you and the rest of the Committee has taken on. The entire working Border collie community is greatly in your debt!

[DeltaBluez Tess]

Love ya, Cousin for the update

[ShoresDog]

Me too! I'm very appreciative of the work that you and the committee are doing. Thanks, Mark.

[Maja]

"For those of you, like me," I read it at first "For those who like me" and I thought, "Of course I like you"

 

Thank you for the update. But this is depressing:

 

"The Epilepsy project, in which a Genome Wide Association study was conducted looking for genetic differences between 100 epileptic and 100 normal Border Collies, was completed in 2013. The study results indicated selective breeding away from epilepsy is unlikely to substantially reduce the likelihood of producing a pup with epilepsy. No additional information has come forth to alter the conclusions drawn by Dr Mark Neff and his associates."

 

Basically, I am not breeding my terrific, healthy bitch because of, well, nothing. A peace of mind I guess. Not at all directed at the research of course, just a general thought)

[Donald McCaig]

Dear Fellow Border Collie Owners,

 

The Health and Genetics Committee has been uncommonly useful to our breed. Thanks to Mark and his hard working predecessors.

 

Donald McCaig

[CMP]

It's wonderful that this breed has so many dedicated, capable and willing advocates. On behalf of my dogs, past, present and future, I thank you.

[GentleLake]

Thanks for all the great work you and the committee do, Mark.

 

And for the updates.

[Sue R]

Mark - We and the dogs are very fortunate to have dedicated people who are making sure that research into these problems is being carried out.

 

Thank you for the updates. Thank all of you on the committee for this work. And thank the ABCA for the funding and pursuit of answers to issues that affect the working dog.

[juliepoudrier]

I find this part of the report rather depressing (in addition to what Maja posted above about epilepsy):

 

 

The committee reviewed the article in which an inheritance pattern was proposed; however, the scientists on the committee found the provided family trees (only three with limited number of family members) did not support drawing any conclusion about the inheritance pattern for EOD.

 

Why so few families and family members? Given all the discussion of the presence of EOD in the working border collie, which would imply much larger numbers in the general population, and the fact that EOD can send a lot of training time and effort right down the drain, I had really hoped that people would put the importance of the overall health of the working population ahead of their own personal concerns about being labeled as a breeder of deaf dogs. Why else so few contributors? It's very disappointing.

 

Thanks for the update, Mark.

 

J.

[Liz P]

Julie, I tried to contribute samples, pedigrees and data (including serial BAER tests) to that study but was turned away. No interest was shown in adding more dogs/families by the researchers.

[workindogs]

In support of continuing EOD study, ProjectDog is still soliciting DNA samples of affected as well as DNA of closely related family members…..also samples of older unaffected dogs. You can contact ProjectDog directly to request a kit if you wish to support their study.

[Mark Billadeau]

Why so few families and family members? Given all the discussion of the presence of EOD in the working border collie, which would imply much larger numbers in the general population, and the fact that EOD can send a lot of training time and effort right down the drain, I had really hoped that people would put the importance of the overall health of the working population ahead of their own personal concerns about being labeled as a breeder of deaf dogs. Why else so few contributors? It's very disappointing.

I don't know why the author did not include more families when preparing the published article. Perhaps they did not have enough longitudinal data (littermates) for most of the samples collected during their study.

 

 

The ABCA Health & Genetics committee has prepared a confidential deafness survey that will allow us to collect info on our dogs. With this information we hope to determine the inheritance pattern for EOD. We will be providing a means for this survey to be submitted by all those willing.

[Mark Billadeau]

"The Epilepsy project, in which a Genome Wide Association study was conducted looking for genetic differences between 100 epileptic and 100 normal Border Collies, was completed in 2013. The study results indicated selective breeding away from epilepsy is unlikely to substantially reduce the likelihood of producing a pup with epilepsy. No additional information has come forth to alter the conclusions drawn by Dr Mark Neff and his associates."

 

Basically, I am not breeding my terrific, healthy bitch because of, well, nothing. A peace of mind I guess. Not at all directed at the research of course, just a general thought)

We continue to recommend against breeding affected dogs or repeat crosses that produce epilepsy.

[Maja]

We continue to recommend against breeding affected dogs or repeat crosses that produce epilepsy.

Yes, I do remember it and this is what I repeat to many people who write to me about epilepsy. Bonnie is a healthy 5yo with two siblings that died from very severe epilepsy (within about 9 a 4 months from the onset). When it happened I was really hoping for a DNA test. But looks like we are running out of time.

[workindogs]

The ABCA funded BAER Clinic at the 2014 USBCHA Finals had overwhelming response from the handlers. Our plan to test 56 dogs over two days, ended up testing 61 dogs, all of breeding age 2-8 years.and we could have easily filled a 3rd day with this segment of dogs. Under 2 yrs and over 8 yrs were excluded due to demand and priority toward breeding age dogs. The BAER veterinarian was Dr. Greg Burns of South Mesa Veterinary Hospital of Fort Collins, CO. Dr. Burns noted that the majority of dogs tested had higher amplitude peaks than other breeds of similar age. This could be interpreted as more acute hearing but would need further confirmation by research.

 

Of the 61 dogs tested, there were 5 abnormal results. All abnormal result dogs could hear (and were not deaf) but tested at a lower amplitude than the rest of the dogs tested. The abnormal tests were both unilateral and bilateral. Owners of these dogs are advised to follow up with a comprehensive ear exam with their veterinarian to check for infection, injury or other malformation that might be affecting hearing. The owners are advised to re-test annually to monitor change in test results.

[Liz P]

I just wish kennels would stop line breeding on known epilepsy producers.

[Crawford Dogs]

Wow, thanks for all the great updates. I look forward to learning more.

[Astrasheepdogs]

The publication can be found here: http://downloads.hindawi.com/journals/dm/2013/695918.pdf.

 

There have been no new developments in the Early Onset Deafness (EOD) study by Dr Neff. The results of his Genome Wide Association study strongly suggested an Autosomal Recessive inheritance for EOD but the exact location of the gene could not be identified. The published study can be found here: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002898.

 

These links are not working (page cannot be found)

[Mark Billadeau]

Variation in Genes Related to Cochlear Biology Is Strongly Associated with Adult-Onset Deafness in Border Collies

 

High Frequency of a Single Nucleotide Substitution (c.-6-180T>G) of the Canine MDR1/ABCB1 Gene Associated with Phenobarbital-Resistant Idiopathic Epilepsy in Border Collie Dogs

[Astrasheepdogs]

Thank you very much Mark

[Eileen Stein]

I find this part of the report rather depressing (in addition to what Maja posted above about epilepsy):

 

 

The committee reviewed the article in which an inheritance pattern was proposed; however, the scientists on the committee found the provided family trees (only three with limited number of family members) did not support drawing any conclusion about the inheritance pattern for EOD.

Why so few families and family members? Given all the discussion of the presence of EOD in the working border collie, which would imply much larger numbers in the general population, and the fact that EOD can send a lot of training time and effort right down the drain, I had really hoped that people would put the importance of the overall health of the working population ahead of their own personal concerns about being labeled as a breeder of deaf dogs. Why else so few contributors? It's very disappointing.

 

Thanks for the update, Mark.

 

J.

Just want to make it clear that the study referred to here as having few families explicated is a different study from the work done by Neff, et al.