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We can reduce the risk of hip dysplasia NOW!

7/21/2018

By Carol Beuchat PhD

You can't be a dog breeder without worrying about hip dysplasia. It's the single greatest cause of pain and suffering in dogs despite diligent efforts of breeders to reduce risk through selection.

Why have we made so little progress in 50 years? I think there are a number of issues, but one of the most important is that we don't worry as much as we could about environmental (i.e., non-genetic) factors.

For example, these are data for Labrador Retrievers raised from birth under common conditions in a research facility. From each litter of puppies, one puppy of a pair went into the control group and the sibling went into the treatment group. The dogs were raised through adulthood and every year (but one) their hips were evaluated for evidence of dysplasia. The only difference between the control and treatment groups was how much they were fed.

The results of this simple experiment were astonishing. In Labradors that were fed the normal amount of food, more than half had evidence of hip dysplasia by 6 years of age and most by about 12 years. In the treatment group that was fed less, half of the dogs were still free of dysplasia at 12 years old.

The dogs in these two groups were litter mates, so genetics was not responsible for the huge differences in the development of hip dysplasia. The explanation is very simple: dogs that were fed less had a dramatically lower incidence of hip dysplasia.

The food restricted group not only suffered less pain and loss of mobility, they also lived longer. Only about half of the control group lived longer than 11 years and only 30% survived to 12 years. But about 75% of the dogs in the treatment group survived to 11 years and 50% lived to 13.

Think about this. We can make a dramatic difference in the risk of hip dysplasia and quality of life of a dog just by adjusting food intake. If I sold a pill that would make a huge difference like this, I'd be rich and your dog would be much happier.

You have probably heard of many things that are claimed to prevent hip dysplasia. Vitamin C, raw diet, mineral supplements, specific forms of exercise, and on and on. But most of these failed to prove beneficial in careful scientific experiments. Don't waste your time and money on supposed treatments that make no difference. Focus on the things that have been proven to matter and that you can control.

Food just one of the many non-genetic factors that can affect the development of hip dysplasia in dogs. There is much more we can do that will reduce risk and make a real difference in quality of life after the breeding decision is made. You can learn more about the cause and prevention of hip and elbow dysplasia in dog in ICB's online course.

Check out ICB's online course

UNDERSTANDING HIP & ELBOW DYSPLASIA

Learn more about how genes and environment affect the risk of hip and elbow dysplasia, as well as how to use heritability and Estimated Breeding Values (EBVs) to dramatically improve the efficiency of genetic selection.

The 10 week course is online and you can work at your own pace!

Class starts MONDAY, 23 July 2018

Sign up now!

REFERENCES

Smith, GK, ER Paster, MY Powers, DF Lawler, DN Biery, FS Shofer, PJ McKellvie & RD Kealy. 2006. Lifelong diet restriction and radiographic evidence of osteoarthritis of the hip joint in dogs. JAVMA 229: 690-693.

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Is BetterBred Better?

7/12/2018

By Carol Beuchat PhD

If you haven't already, please read my recent post, "Assessing genetic diversity and relatedness in dogs using DNA", about methods of assessing relatedness and genetic diversity in dogs. In it I present a brief summary of the comments from a paper just published by Nicholas et al. (2018). I also provide some information from a paper published in 2006 by Oliehoek et al. that evaluated several different ways of estimating relatedness. If you missed that, you should read it now or you won't understand the rest of my comments here.

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The method under discussion is used by the genetic diversity test available from UC Davis for dog breeds, breeders should be aware of these potential problems with the accuracy of the test.

You will have noticed that I presented direct quotes from the two papers noted above. I also provided a direct quote from published response by the authors of the first paper. It's important to note that the critical comments were not my opinion, scientific or even personal; they were from two groups of very well known canine population geneticists. I did suggest that the issues might be resolved with data validating the usefulness of the test, and until that is available I would view the test as flawed.

At the end of my blog, I made a big point of the fact that scientists have disagreements all the time, and a lot of the progress made in how we understand the world is the product of critical review and the resulting discussions. The concerns are published and the journal allows the other authors to respond. This is a normal and essential part of the scientific process. These are always civil, respectful debates. If you don't take criticism well, a career as a professional scientists is definitely not for you.

The current debate on the origin of dogs is a great example of various groups of scientists, each with different ideas, duking it out in the scientific literature, one publication at a time. This note in one of the world's most prestigious journals was published in 2013, and the lively debate still continues. I'm sure that sooner or later, we will figure it out and most scientists will come to a consensus. In the meantime, the critical comments of colleagues focus on details, data, assumptions, and methods. There are no personal attacks. Nobody's credentials are questioned. In fact, the scientists that engage in lively debate all know each other, consider themselves colleagues, and are likely to sit down for coffee when run into each other at meetings.

Science is a community of individuals that are committed to figuring out the truth, even if that means there might be winners and losers in the debate. This is the warp and woof of science, and the debate and process of ferreting out the truth is what I love about it.

https://www.nature.com/news/dog-genetics-spur-scientific-spat-1.13227

I brought all this up in my blog - and emphasize it again here - because I expected that there might be some members of the dog community that would see the papers and even my blog post as some sort of personal attack on the Davis test. Clearly it was not. But yes, unfortunately, that is how some took it.

I posted links to my blog in various relevant groups, one of which was the ICB Facebook page. Sure enough, the trolls came.

This person is associated with BetterBred, a company that is using the Davis test as an online breeding tool. She is known to me, because she has been trolling me for years now, as have a number of people associated with the group at BetterBred. She is not a scientist. She has no comments to make about the substance of my blog post.

I did try to make my post understandable to any breeder, from the lawyer and veterinarian to the dog groomer. But Laura Bernier notes (twice) that she didn't understand it, so her comments are not about the substance of that blog but are persona; her intent is apparently to sully my reputation. I've been a professional scientist for nearly 40 years, I have a long list of publications, a record of more than $1.2M in grant support, and the respect of my peers. Her belittling remarks will have not effect at all on my reputation, and they don't even keep me up at night, but I am concerned that she carries around so much anger. Stress isn't good for your health, and I truly hope she gets the help that she needs.

To be fair, I have to say that nobody has been busier with the personal flogging than the person who runs BetterBred, Natalie Tessier Green. I blocked her long ago, but her posts are sent to me by the people that find them offensive or even appalling. This was posted in one of her private groups for users of the BetterBred website and I was gifted several copies.

Natalie Tessier Green has been trolling me for years. She fosters an environment in her company that normalizes this sort of bad behavior, which is not just unprofessional, but antithetical to the process of science. Comments in Natalie's groups often disparage me; it's very reminiscent of the sort of dialog you would hear between two rival clicks at a junior high school.

I'm especially disappointed that Natalie Tessier Green didn't have a single thing to say about the concerns expressed about the Davis diversity test, but she does note that "it is wrong on nearly every point". Note that I don't sell any DNA tests. For a time about 2 years ago I took orders from breeders who didn't have enough dogs to qualify for the volume discount, but the price was Embark's and I made no money from it. As the test became more well known, breeders have been able to find enough other people to send in a bulk order so I no longer do this. I do however recommend Embark's test if I'm asked and in my professional opinion that is the test that would best suit the breeder's needs. The ICB Breeder Tool is built around the test results from Embark. But I have no affiliation with them. None.

I must note here that I am not the only one being trolled. The Dog Diversity Project as well as Embark (which runs their DNA analyses) receive a good volume of hateful Facebook posts from BetterBred. There could be other organizations that find themselves in the crosshairs of BetterBred.

I'm not bothered at all by the attempts of the folks at BetterBred to affect my reputation, although it does upset people who know me, in both the dog fancy and the scientific community. I am, however, tired of the silly attacks. For each one, I get a flood of copies sent to me from people that spot them and find them offensive enough to bring them to my attention. I have to go delete the post, block the author, and add the comments to my "L&S" folder. Yes, it's gotten tiresome.

So, I have now decided to address this problem another way. I will post noxious comments made by anybody affiliated with BetterBred, including their clients, on my website. I will be liberal with links to the BetterBred site, so the curious can see for themselves the vitriol directed by BetterBred and their fans towards members of the canine scientific community. If the posts continue, I'll even set up a separate section on the ICB website where they can be catalogued and searched so that they show up in Google searches for BetterBred.

If anybody at BetterBred has comments about the two papers I blogged about, they should direct them to the authors of those papers, not me; I was not involved with either of them.

Finally -

"Not enough people call you out, because you just block them because you truly don't have the ability to have a decent debate."

No, Laura Bernier, we are not going to have a "debate" this time either. And you now join the others from BetterBred who are blocked and banned for bad behavior.

The Fallout

Oh dear. I didn't even have time to get a cup of coffee after posting this before comments from BetterBred started appearing in my In box.

I actually find this one humorous under the circumstances. Considering.

Then a bit later, a dig about mental illness.
Again, they've been trolling me for years. Yet here I am. Still.

Updated 12 July 1:07 pm to include additional comments.

13 July 2018 - Spammed by BetterBred

Today I get an email from BetterBred, this one some sort of "announcement", for which they have used a DISPOSABLE, TEMPORARY email address. You know, to avoid spam.

Assessing genetic diversity and relatedness in dogs using DNA

7/7/2018

By Carol Beuchat PhD

There are a variety of commercial options available to breeders for assessing the genetic diversity and inbreeding of individual dogs as well as breeds. UC Davis Veterinary Genetics Laboratory offers a test based on microsatellite markers (STRs), and MyDogDNA and Embark Vet offer tests using single nucleotide polymorphisms (SNPs). Microsatellites have been around for decades, while SNP technology has developed rapidly over the last 15 years or so and is increasingly used in genomic studies of animals and plants. Which test is most appropriate for you to use for your own dog will depend on the type of information you need, how you want to use it, and cost effectiveness.

Xoloitzcuintli (Photo: (c) Beuchat)

A paper just published (Nicholas et al. 2018) has expressed some reservations about the microsatellite test being used by Davis. The authors are highly qualified and well known canine geneticists, and their comments are specific and significant. Since they question the validity and appropriateness of the test to estimate relatedness and genetic variation in dogs, it is important for breeders that might use this test to understand the issues.

Below I will summarize the concerns expressed in the paper by Nicholas et al., but first I will also review some information from a paper published in 2006 that also bears on the reliability of the test (Oliehoek et al., 2006). I have excerpted material directly from both papers so you can read the comments from these papers directly.

If you get bored reading about the first issue, don't skip reading about the second one. It is just as important.

Paper by Oliehoek et al, 2006

The effectiveness of methods for estimating relatedness, including the method used by Davis, was examined in a paper by Oliehoek et al (2006). They looked at eight different algorithms, including the one used in the Davis test by Queller & Goodnight (1989), which they refer to as "Q&G". The Q&G estimator was originally designed to estimate relatedness between populations, but with a modification it can be used for pairwise comparisons of individuals.

To do their assessments of the various computation methods, Oliehoek et al. worked with a simulated pedigree so that they could assume that all of the pedigree information was "true" (which wouldn't be the case with real pedigree data). This also allowed them to test the performance of the estimators under various conditions such as random breeding or inbreeding.

After reviewing the information in these two tables, Oliehoek et al. say this:

Oliehoek et al. concluded that two of the algorithms they tested, UCS and Q&G (the one used by Davis), performed so poorly as to not merit further consideration. What is meant by "poorest results"? It means that their estimators of relationship deviated significantly from the true relationships, which were known because they used a simulated pedigree database. They felt that the errors were so consequential that they didn't proceed with further testing of these two algorithms.

Paper by Nicholas et al., 2018

A paper has just been published that is critical of the Davis diversity test (Nicholas et al. 2018) as used in a study of Samoyeds (Pedersen et al. 2017).

Their complaints:

1) "using a small number (33) of microsatellite markers that cover only 66% (25/38) of autosomes is suboptimal for determining genetic variation occurring across the genome"; and

2) "the sample of dogs from which "breed-wide genetic diversity" was estimated contained a substantial but undisclosed number of close relatives (and so was not a random sample nor representative of the wider breed, meaning that the findings pertaining to genetic variation cannot safely be extrapolated without qualification."

The second criticism is specific to the population of Samoyed used in that particular study. The first, however, is about the method itself and would apply to all breeds using the test. Specifically, they are suggesting that it cannot be assumed that the genetic variation determined from a small number of markers on only 25 of 38 autosomes is representative of whole genome diversity.

They go on to say:

"The study used microsatellite markers to estimate the genetic diversity of the Samoyed breed. While microsatellites have previously been used to this, they have largely been superseded by dense SNP chips, where the quantity of bi-allelic marker data provides more precise information on the extent of genetic variation via homozygosity.

The study used 33 short tandem repeats (STRs) on 25 autosomes, which is an average of 1.32 STRs per autosome included. However, since Canis familiaris has 38 autosomes, there was no means in this study to determine genetic variation across 1/3 of the genome. It is highly likely that there is genetic variation present within the Samoyed breed on these 13 autosomes, but this study is simply unable to detect its extent.

Furthermore, genetic variation at genomic regions on the 25 included autosomes not in linkage disequilibrium with the STRs also cannot be detected.

Thus, while this number of STRs may be sufficient for their stated purpose (parentage verification and forensic testing) and an acceptable "broad brush" means of estimating diversity in a population where there is no alternative (such as wild populations), they are unable adequately to describe the extent of genetic variation across the canine genome, including regions of depleted variation due to selection."

This figure represents the 38 autosomal chromosomes of a dog (from Embark). The blue stripes are regions of homozygosity. The small red vertical lines are the positions of the STR markers used in the Davis test. Nicholas et al. are questioning how reliably a test with so few markers - only 25 for 38 autosomes - quantifies the actual genome-wide degree of genetic variability. The critical question here is whether these markers, placed as they are, will accurately assess the true genetic variation across the entire genome of a dog.

These are the relevant parts of the response to Nicholas et al. from Pedersen et a. (2018):

"Professors Nicholas and Mellersh and Dr Lewis were concerned about the methodology that led us to conclude that Samoyed lack genetic diversity...

Their first criticism involved the use of 33 microsatellites markers across only 25/38 autosomes. This was linked to another question pertaining to why microsatellites were even being used at all, given modern SNP technology. The microsatellites chosen for this study were vigorously selected for their ability to discern genetic differences by the International Society for Animal Genetics, with addition of several new markers from our Veterinary Genetics Laboratory. The microsatellites are known to be highly polymorphic and have been used successfully for many studies concerning parentage and genetic diversity.

Some of the added markers were for the DLA class I and II regions, which contains genes concerned with immune responses. This region is in strong linkage disequilibrium, with one copy inherited by descent from each parent. It is extremely difficult to define the DLA region using SNPs due to the numerous polymorphisms, but it is very efficient and accurate to track this region using microsatellites. DLA haplotypes are powerful identifiers of breed founders.

We were also concerned about the fact that our markers did not cover every chromosome and added 25 more microsatellites to cover missing chromosomes. We found that the additional microsatellites, although carefully selected, did not add anything to the power of the current 33 markers to study breed-wide genetic diversity and relatedness. We also compared genetic diversity in Standard Poodles by both microsatellites and 170K SNPs and found no major differences...

We are confident, therefore, that the genetic diversity we were measuring in Samoyed was accurate as described and that employing large panels of SNPs would not significantly alter the conclusions."

The problem I suspect Nicholas et al. will have with this is that there is no information provided that directly addresses their concerns about the measurement of genetic variation. Much of the response was about the markers for DLA and was not relevant to the estimation of autosomal genetic variation. Assurances were offered that, in unpublished experiments they did, the addition of 25 microsatellites "did not add anything to the power of the current 33 markers". Further, a comparison of diversity measured with the microsatellite panel and 170K SNPs "found no major differences". However, no data are provided to support either of these statements. It would have been appropriate and useful for them to provide the data and analyses behind these statements, but unfortunately they do not.

The reason the methods and results of research are provided in such detail when published is to support the claims made about the data to the satisfaction of other scientists. Here, we're supposed to just "take their word for it". I think many scientists would be concerned about doing this.

Now what?

Where does that leave us? Breeders have to assume that information provided to them by science professionals is "true". Davis is arguably the best vet school in the country, and they have a stellar group of veterinary and population geneticists with much expertise and sound reputations. I would go to them for advice or information and I have. But on this one thing, I have to agree with my scientific colleagues: the information provided by the Davis test is likely flawed and should not be used by breeders unless it can be proven otherwise.

The fix for the problems with the method used to calculate internal relatedness could be simple. Redo the calculations using the equation that performed best in the simulations by Oliehoek et al. Davis could do this, or the dog owners could provide their data to somebody carefully chosen to have the appropriate expertise for reanalysis, preferably one of the authors (e.g., Pieter Oliehoek).

The issue with the reliability of the test because it uses too few markers is more difficult to remedy and just as serious. This test is the basis for several published studies, and there is a growing list of breeds that are using it for assessment of genetic variation and relatedness in making breeding decisions.

Breeders need to be aware of these issues. There is no more serious concern about a method than that the data produced are not reliable. There are other test options available that use SNPs, and for breeders that must also do trait or mutation testing those are probably more cost effective. SNPs are rapidly replacing STRs in many applications, and there is considerable value in having data from today's dogs that will be compatible with data for future generations. Breeders should carefully assess what information they need, now and in the future, and select the test option that best suits these requirements.

______________________________________

POSTSCRIPT

The layperson might be horrified to read the critical comments about a scientific study from other scientists. Be assured that this is the normal process of science. A scientist can expect every word that comes out of their mouth for their entire career to be scrutinized, assessed, and criticized by their colleagues. The criticism will be direct but never personal. In fact, it could be said that scientists sit around picking away at the work of their colleagues for mental sport. It is interesting, stimulating, even fun, and it often results in useful insights that advance a project or field. It is not "bashing", "slamming", or any of the other many terms I have heard used by dog breeders in these contexts. Indeed, I have never heard these terms used by scientists about each other; they simply are not appropriate because they imply that the comments are unfair, inappropriate, and personal, when they are not. Scientists disagree with each other all the time. It's the normal warp and woof of science.

By way of an example, my own favorite criticism was directed to me by the editor of a journal to which I had sent a manuscript for review very early in my career. Although the reviews were favorable, the editor (whom I knew) told me that he didn't like the statistics I had used and suggested that were he to publish the paper, I would "come to find it an embarrassment" later in my career. I sent the paper to another (better!) journal, which published it. It was well-received, and I have never been embarrassed about it. The editor and I remained friends and colleagues.

REFERENCES

Nicholas FW, C Mellersh, & T Lewis 2018. Letter to the editor regarding an autosomal recessive mutation in SCL24A4 causing enamel hypoplasia in Samoyed and its relationship to breed-wide genetic diversity. Canine Genetics and Epidemiology 5: 4. DOI 10.1186/s40575-018-0059-7

Oliehoek PA, JJ Windig, JAM van Arendonk, & P Bijma. 2006. Estimating relatedness between individuals in general populations wiht a focus on their use in conservation programs. Genetics 173: 483-496.

Pedersen NC, B Shope, and H Liu. 2017. An autosomal recessive mutation in SCL24A4 causing enamel hypoplasia in Samoyed and its relationship to breed-wide genetic diversity. Canine Genetics and Epidemiology 4:11. DOI 10.1186/s40575-017-0049-1

Pedersen NC, B Shope, and H Liu. 2018. Letter to the editor regarding an autosomal recessive mutation in SCL24A5 causing enamel hypoplasia in Samoyed and its relationship to breed-wide genetic diversity. Authors' response. Canine Genetics and Epidemiology 5: 4. DOI 10.1186/s40575-018-0059-7

We can reduce the risk of hip dysplasia NOW!

Is BetterBred Better?

Assessing genetic diversity and relatedness in dogs using DNA

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