Canine Genetic Engineering

[Gary M]

MSN

 

While I can see many benefits, I can see as many or more pitfalls.

Particularly in the ACK world of breeding

[sweet_ceana]

when it come to genetics it is so hard to have an absolutue on anything except.... no cloning of whole people or whole animals! I think genetic reasearch is incredibly important in unlocking the proteins that can harm and help everything and everyone live a better life, but everyone's idea of better is different. Call me a downer but I think that people have shown themselves, over time and with virtually everything, corruptable. With that said I do however think that allowing pain and suffering to go on without trying to stop it is worse than the corruption of discoveries made to prevent/heal such pains and sufferings. A slow dog, as in the case with the bully whippets/whippets gene, is not suffering in my book. I have never seen a dog mortified when it sees a faster dog run by. I guess my view of Border Collies reflects my view of Canine genetic engineering: the more natural the better. We can manipulate dogs through breeding for the rights reasons (ie BCs working & intelligence) Why do we need to go in and physically reassemble and select their genes? If we can cure hip dysplacia, lets do it. If people just want a specific coat or pricked ears because it tickles their fancy I see it pretty level with animal abuse, especially when it risks a dogs health and quality of life for the amusement/ pleasure of people. There are an assortment of genes for a reason, not because some dogs are genetically superior to others. (IE.... flexibility of hips and how different breeds need different levels of flexibility to accomplish their jobs).

 

I'll get off my soap box now, I could go on forever. Genetics is an amazing tool (but so is fire and we have strict rules against arsony...sp?,,)

[bexie]

But can't hip displaysia be cured by reliably breeding from dogs that don't have it? I thought that defect was primarily caused by a history of poor breeding when AKC breeders went after weird appearance traits.

 

But I didn't see the link the orig poster referred to. It requires software not supported by my operating system.

[Pipedream Farm]

But can't hip displaysia be cured by reliably breeding from dogs that don't have it?

 

Not quite, dogs can and do carry the gene(s) that cause HD without having the disease themselves. Breeding these dogs will not eliminate HD from the gene pool.

 

Despite what some may claim, data from numerous scientific studies provide overwhelming evidence that HD is an inherited disease. It is thought to be caused by at least three and possibly as many as six primary genes. The number of genes involved, combined with the high incidence, means it's probable that most Border Collies are at least carriers of one or more of the genes that can contribute to the development of HD, even if they don't have the disease themselves. To confuse matters more, the expression of the disease is affected by environmental conditions such as the type and amount of food a dog gets at critical growth stages, as well as the type and amount of exercise and activity it gets. It must be remembered, however, that these environmental factors do not cause HD. They merely affect whether the HD genes present in that individual will be expressed to the fullest. Even if the expression of HD in a certain individual is suppressed by careful control of environmental factors, you have not changed the dog's genetic makeup. That dog will still pass on the genetic tendency for HD just as if it actually had the disease. Conversely, if a dog does not have the genes for HD, it won't develop the disease no matter how it's raised.

 

Source: ABCA Health & Genetics

 

Mark

[bexie]

Thanks for the explanation. That makes sense. So basically genetic testing to at least determine who carries what recessive gene could help prevent HD? And with that many genes involved and them now being so prevalent in so many breeds, I can imagine that it could take generations and risk some nasty inbreeding to try to breed it back out. And who knows what the consequences could be with all that.

[Pipedream Farm]

So basically genetic testing to at least determine who carries what recessive gene could help prevent HD?

Yes, except that the gene(s) have not been identified yet.

 

Mark

[Pearse]

To confuse matters more, the expression of the disease is affected by environmental conditions such as the type and amount of food a dog gets at critical growth stages, as well as the type and amount of exercise and activity it gets. It must be remembered, however, that these environmental factors do not cause HD. They merely affect whether the HD genes present in that individual will be expressed to the fullest. Even if the expression of HD in a certain individual is suppressed by careful control of environmental factors, you have not changed the dog's genetic makeup. That dog will still pass on the genetic tendency for HD just as if it actually had the disease. Conversely, if a dog does not have the genes for HD, it won't develop the disease no matter how it's raised.

 

I would take issue with this statement.

 

First of all, while most researchers in the field agree that there is a heritable component to susceptibility to hip dysplasia, the best estimates of heritability range from 0.11 to 0.5 (the higher numbers are generally for hip score and not incidence of disease). That means that between 10% and 50% of the variability in hip score or the incidence of hip dysplasia is genetic. The remaining 50% to 90% is something else.

 

Second, based on available evidence, one cannot say that environmental factors do not cause hip dysplasia. Nor can one say that an animal without the "genes for hip dysplasia" cannot get hip dysplasia. I would make that argument based on several lines of evidence.

 

No one knows which genes, or how many genes, contribute to hip dysplasia. Greg Acland's group (Todhunter RJ et. al. Mamm Genome 2005 16(9): 720-30), did microsatellite marker analysis across a 3 generation pedigree and identified loci on 12 different chromosomes (at p<0.05, 3 of which p<0.01) which could be contributing. That's a possible minimum of 12 genes but possibly more. Now in all likelihood, a few of those contribute in a big way and others in minor ways but we are still a long way from understanding the genetic component so it would be incorrect to say that genetics is the most important contributing factor at this time.

 

It is entirely possible that some dogs develop hip dysplasia due to environmental or developmental causes. The only way to rule this would would be a large scale study that showed that no dogs diagnosed with clinical hip dysplasia were without ancestors who had bad hips. It would be a difficult study to do but until it is done and confirmed, one cannot say that only dogs genetically predisposed to hip dysplasia will get it.

 

Even if you could do that study, and even if it showed that only dogs genetically predisposed to getting hip dysplasia can get it, that in no way means that every dog genetically predisposed to hip dysplasia (or every dog with a bad hip score) will develop CHD. If the best heritability estimates are all <0.5, that means that 50% of the contributing factors are non-genetic. It's easier to look for genetic factors but it would be wrong to neglect research into the other contributing factors. It is entirely possible that many or most dogs with genetic predisposition to CHD never get clinical disease unless some other non-genetic risk factors are present.

 

There are lines of dogs with bad hips and a high incidence of CHD. That pretty much proves the point that heritability can be important especially if hip structure predisposed to CHD is accidentally selected for while deliberately selecting for other traits (extreme angulation in German Shepherd dogs comes to mind).

 

One more note of caution. We don't know what collection of genetic factors contributes to working ability in Border Collies ( I won't say causes there either). Genes don't exist in isolation. They exist on chromosomes with other genes and with other DNA that affects how, when, and if they are expressed. You can't "eliminate" one form of a gene from a population without affecting nearby genes (at least not yet, and not in the forseeable future on a population basis), so before people went hying off to get rid of the "CHD genes" (or any other complex quantitative trait), you'd want to be really really sure you weren't throwing the baby (eye, stock sense, prey drive, biddability etc etc) out with the bath water.

 

It's tough to simplify these issues to make them comprehensible. It's really easy to oversimplify them. Scientists occasionally, and the media as a matter of course, do oversimplify and often overhype discovery to make news (how many times have you heard a cure for x, y, or z has been found?), so treat new data as sceptically as most scientists do.

 

Pearse

[Pipedream Farm]

......the best estimates of heritability range from 0.11 to 0.5 (the higher numbers are generally for hip score and not incidence of disease).

 

 

Pearse,

 

Please define "incidence of disease". Doesn't part of the diagnosis often include a hip score (formal or informal) and without the score the diagnosis might not be made. As I see it, the disease does not have a clear-cut diagnosis (like a serological test for an analyte) and this is part of the problem addressing the disease (in terms of diminishing the rate of incidence).

 

Mark

[jackspack]

when it come to genetics it is so hard to have an absolutue on anything except.... no cloning of whole people or whole animals!

 

I'm not sure I understood that statement, but scientists clone whole animals all the time. In particular cattle.

 

I couldn't see the video, but I am always interested in the GM debate. If my response is completely off topic my apologies, it is more in regards to sweet_ceana's comment.

 

There are many genetic techniques that can be applied to breeding that aren't "genetic engineering". In other words, not directly modifying an organism. Dog breeding is a classic example of how human manipulation of an animals genetics has been taken to the extreme (I say as I think of my Mother's pug). So the comment "the more natural the better" with regards to dogs is, in my opinion, contradictory. Even border collies, bless their hearts, have been, and continue to be, deliberately manipulated with respect to heritable traits. Should the methods be the focus of concern, or the outcome? In other words, is a traditionally bred species bred to be prone to chronic health problems less wrong then the same dog obtained with a different approach. It is clear that the potential applications of the technology are enormous, but I agree that regulations are critical and that ethics must be taken into consideration in guiding the decision making process. However, fears of new technology based on a lack of understanding and trust should not stand in the way of carefully considered, researched and balanced evaluations of how to apply knowledge.

[Pearse]

Pearse,

 

Please define "incidence of disease". Doesn't part of the diagnosis often include a hip score (formal or informal) and without the score the diagnosis might not be made. As I see it, the disease does not have a clear-cut diagnosis (like a serological test for an analyte) and this is part of the problem addressing the disease (in terms of diminishing the rate of incidence).

 

Mark

 

 

I can't answer that Mark not being a veterinarian. The papers I was reading made a clear distinction between clinical hip dysplasia, where the animal was experiencing discomfort or loss of function and/or had pathology in the joint (arthritis etc), and animals who had no pathology or morbidity yet but had been evaluated solely for hip scores at a fairly young age.

 

Pearse

[HighDesertSpice]

MSN

 

While I can see many benefits, I can see as many or more pitfalls.

Particularly in the ACK world of breeding

 

 

Gary, do you mind describing the video? (I don't run flash on this system). Thanks.

[sweet_ceana]

jackspack..... I should have made that quote more clear, sorry about that. I believe that cloning an entire person or an entire animal is not the course that genetics should be going. The non-random combination of gametes concerns me (especially when it comes to genetic variety) I am a big fan of the idea that nature selects genes through breeding naturally. I think it is more appropriate in the case of canines that genetic alterations be done through breeding. I ment to clarify that I believe that breeding of dogs should be done for traits that are specific for their "jobs." I do not believe, as most people here feel, that breeding for looks and show is appropriate. The modern dog became a dog by changing into a human assitant, and to deny our influence on a dogs genetics would be naive and not what I intended to impliy. There is an example (somewhere I believe in Russia) where a scientist bread foxes that were the most tolerant of people and their coat color and appearence changed to similar thing that we have seen with dogs. (thus why dogs are not wolves, not my point but really cool study). I especially am concerned about our growing ability to simply use enzymes (I believe the one that I have used is ligase) to open up DNA and then implant things such as plasmids that carry other traits and genes etc... can lead to the selfish missuse of this technology. i am a huge supporter of genetic reaserch, I just feel strongly about its ability to be abused. Selective breeding at least gives the chance for many sperm to go after the egg... not just one that holds specific traits. I do not mean to sound as if I am scared of research. I spent two years in college following this as a passion, which has now become a hobby . I spliced the DNA of Ecoli, implanted the gene of a jelly fish and made it glow when I was 17. Sister chromatids, crossing over, the whole thing intrigues me. I hope one day we can understand it all and I support our quest for knowledge. People just tend to do things until someone says that what they did was bad. I am premptive with genetics because if I don't say be careful and others don't say be careful the thought might not cross someone's mind once, and accidents can create huge problems.

 

Sorry if I simplified HD too much, I was just reaching for an example and it was the first in the doggy realm that came to mind.

[jackspack]

I especially am concerned about our growing ability to simply use enzymes (I believe the one that I have used is ligase) to open up DNA and then implant things such as plasmids that carry other traits and genes etc... can lead to the selfish missuse of this technology.

Usually we use restriction enzymes to cut and ligase to seal.

 

i am a huge supporter of genetic reaserch, I just feel strongly about its ability to be abused .

I agree, but any technology is subject to abuse and I don't agree that a technology can be condemned simply because some person might abuse it at some time one day possibly, despite the potential benefits.

 

I am premptive with genetics because if I don't say be careful and others don't say be careful the thought might not cross someone's mind once, and accidents can create huge problems..

I think it is terrific that you show an interest and are interested in the potential good and bad of a technology! Too many people are apathetic to what is going on around them and it is refreshing when people make an effort to get informed. At the same time, I think the regulation of a technology must be predicated on a thorough understanding of the technology.

 

I have a PhD in molecular genetics, and I find that it is a difficult subject to discuss because there is such a poor understanding out there of what the technology entails and the nature of genetic change in general. I spent along time in university and there are still many many things that I don't understand That is nobody's fault more than scientists, who are often poor communicators and allow the media to inform people, or misinform, about the technology and its applications, without making the effort to educate, preferring instead to lock themselves away in their laboratories avoiding the public at large

 

Anyway, my first years do that experiment (the glow in the dark E.coli), it is always a hit with them. I remember doing it the first time myself and being amazed. It is nice to know there is someone else out there with an interest in science and border collies, lol.

[sweet_ceana]

LOL in knew I used ligase for something Did you by any chance read "The language of God" ( I think that's the title) by one of the scientists on the human genome prodject? It's next on my list.... after I finish my book on Hawian leprosy in the 1800s.... wow I a m a dork.

[HighDesertSpice]

You all seem like good references....Can you recommend a good book on the development of the BC? I'm interested in the development of the breed, and it's lines. I'm not nearly as smart as you, but am interested in a book that brings in discussions of the genetics.

 

Another question: have there been any attempts to continue breeds "from scratch", ie, meaning repeating the same original combinations of dogs/breeds vs. getting an established dog and procreating from it, as if the "ingredients" are established in that dog or small group of dogs? Now you know how much I don't know....

[Gary M]

The video itself was for the most part the usual MSM fluff, although there was a brief part of the segment that should a "bully whippet" which they described as a genetic abnormality that caused an extra set of muscles near the hindquarters.

It (the video) did not pay as much attention to the potential health benefits of genetic engineering (i.e. CHD, CEA, canine epilepsy or other genetic induced inflictions that dogs suffer) as much as it did on "designer dogs".

I certainly would applaud any work done towards isolating and potentially removing what are considered "genetic defects" such as I mentioned above.

My concerns, as stated by others, are that in altering the genetic code to remove one or more "bad" genes may alter "good" genes as well, or create new, heretofore unknown defects.

The down side that is my other concern is that the unethical breeders will use "genetically improved" or "genetically superior" as an advertising tool to foster even more dogs on our (IMHO) oversaturated society.

Mark, Pearce, Solo River and others know infinitely more than I would even presume to know about genetics and the mechanics of genetic manipultion.

I was just curious as to what others thought about the moral and ethical implications and ramifications.