Poodle Diversity Project - Blog

  • Outcrossing - what is it really?

    A topic that's come up recently in a few situations is the concept of what makes an inbred dog and what makes an outcross. Some of you have a sense of this from the Standard Poodle Project list - some of you have the more common idea of an outcross thought of in most breeding circles. (I am helping a number of other breeds and this is similar in those too.)

    In an outbred population, one with lots of the original diversity left, like Miniature Poodles, if you were to look at the 15th or the 20th generation you would see some repeats, but mostly different families. For most Standard Poodles, if you go to PHR and look at the 15th generation, start at the top and scroll down, you will see the same names hundreds of times. If you don't in that generation, check it for each of your dog's grandparents.

    It's so far back you'd think it wouldn't matter, but what breeders don't know (because they aren't geneticists) is that genes DO NOT CHANGE IN 20 GENERATIONS. There are about 19,000 genes in a dog and a few might mutate along the way, but what are 10 genes out of 19,000? What are 100? Not enough to make for completely different dogs. The only thing that changes the genetic make-up of a population in that period of time is SELECTION: which dogs are bred to which dogs. So because in the 50s, 60s, 70s, 80s, and 90s everyone linebred on the same dogs, who were linebred on the same dogs, who were linebred on the same dogs, the dogs that exist now are genetically extremely similar to one another. This is simply fact, proven five ways to Sunday through pedigrees AND genetic data. Arguing about that is like saying just because we don't perceive the earth to be round in our daily lives, perhaps it's not.

    So at this point, the question of what makes an outcross is relative. For most breeders, an outcross is a dog with different dogs in oh, the first eight generations or so. Technically this SHOULD be an outcross, so it's not like people are wrong to assume it. They just don't realize that the legacy of the Mid Century Bottleneck means that most likely it doesn't matter AT ALL that your pedigree is different from that other pedigree in the last 8 generations - these dogs are likely as close genetically as siblings would be in a normal population.

    Now most breeders understand that full sibling breedings are risky and won't do them. They would expect to turn up problems, and would be prepared to cull whatever issues came up. In Standard Poodles, we can make what we think is an outcross and run into the kind of problems that wouldn't surprise us in a full sibling breeding. When we see these problems in what should be an outcross, it seems likely that it was "outcrossing" that caused the problem. This is only because of the faulty premise that if your dog has different recent ancestors than those of the dog it was bred to, it means these dogs have different genes.

    One of the problems with our perception is that Standard Poodles have been highly similar genetically for the last 20 years. Yes there were some odd ball lines that were different, but these were never taken seriously, or were considered lower quality. Of course they looked different - there were genetically different. They were no less poodles though. It's tempting to think - and I've heard many people say or imply this - that the other lines weren't pure poodle. I can understand that because they look different from the typical Standard lines - but there's no reason to believe they aren't pure. Miniatures have a ton of variety in type AND a ton of variety genetically. Based on photographic evidence, Standards used to have the same wide range of type. Look at Nunsoe the Duc, or Bibelot's Tall, Dark and Handsome, both huge, show-winning, important dogs, and they'd be considered not typey enough for the ring now. Some consider that improvement, but it's improvement based on historical inbreeding, which is dangerous for a population. (Also a simple proven fact - can be discussed further if necessary.)

    I heard someone say recently that obviously your COI will be low if you cross to a Golden Retriever, so what difference does that make? First, that person was absolutely right. Low COI for low COI's sake is kind of silly. This is still selective breeding, right? We want poodles that look like poodles and are actual poodles. Certainly there are still plenty of examples of the breed that don't look much like poodles at all. I would still bet that unless someone lied and bred in another breed, as has obviously happened with merles, most of those ugly poodles are as influenced by the Mid Century Bottleneck as the most elegant show dog, as many of them have the SAME breed-specific diseases well bred dogs have.

    Here's another concept that's important: because genes don't change, but can be selected for: a singular outcross 8 generations back, with descendants bred back into a population without any backcrossing will be imperceptible in its descendents. The only way you might notice is would be if it has a single trait that's been selected for in each generation. No one wants a poodle with some cross breed, obviously, but a single cross will not make a dent in an historically inbred breed unless it is used more than once and there's more than one outcross. So shocking as it may be to some, from a scientific standpoint, such an ancestor doesn't make any real genetic difference at all. The ONLY way for dogs to be genetically different is for them to have many distinctly different ancestors.

    Thus any suggestion that parti dogs were at some point crossbred for the various colors - while possible I suppose - such mythical outcrosses don't mean that their genetics are really going to be any different - except for the three or four genes (out of 19,000) that control color. Those are retained only because they would have been selected for and all other traits selected for would have been poodle traits. We also know parti poodles from pure lines existed from historical evidence so no one would HAVE to outcross to another breed to produce partis anyway. The genetic data so far also indicates that they are pure Standard Poodles, and just as influenced by the MCB as most others. I know there were those hoping they would be outcrosses, and while one or two proved to be outliers, most aren't.

    So going back to outcrosses, there are a few lines that are genuine outcrosses -as in different at the 20th generation - and they come from different places. These few lines consistently look different in their genetic data. Some also look different in type, but truly, many of these are better looking than some poor quality high MCB dogs. They also tend to be quite different from one another. There are brown lines that are different from apricot lines that are different from silver lines that are different from black lines. And all of these are different from the mainstream lines. (And by the way, "mainstream" is not meant as an insult. I do not mean they are ordinary or bad - some are and some aren't. What they are is genetically similar.)

    So try to remember that most breedings still being done today are MCB cluster to MCB cluster breedings. True outcrosses are few and far between. I am not saying they are inherently better in quality - I am saying they are actually, effectively, genetically different while still being Standard Poodles. Quality is a rating breeders have to make for themselves.

    From a genetic, scientific and medical standpoint, finding true outcrosses and using them if you have typical lines is an excellent idea, because most of the dogs you think are different most likely aren't.

    From a breed culture standpoint, using a true outcross takes a lot of guts, will likely be unpopular among your peers, will give you a broader range of type in your litter with fewer to choose from to show, and the development will not necessarily be as you are used to now.

    I'm well aware of how tempting that sounds!! It's not for the faint of heart. But keep in mind that neither is breeding genetic siblings. It's a matter of picking your poison. This is why I have no judgment about people not jumping on the bandwagon. There are no silver bullets. If someone doesn't perceive a health issue, why would they outcross? To be fair, most people interested in diversity have either experienced some autoimmune or other diseases in their line or have seen so much in others they can't find a stud dog. So there are many who know there's a problem. PCAF wouldn't have funded the study if they didn't perceive a problem. It should be addressed and outcrossing is one way worth exploring.

    (This is Gaston de Grenier, a true blue outcross, and pure Standard Poodle. Shown expertly by Rebekah Zurbrugg.)

  • Genetic Markers? Pedigrees? What should we believe?

    With recent progress  on genetic marker analyses for pure bred dogs, breeders get told a lot of different, conflicting information. There are those enthusiastically for the idea, and those staunchly against it. That's very normal for new things - it happens with all significant progress. In this case, here are those who have invested heavily in inbred lines who don't want to be told they've been doing it wrong.

    For all of those who aren't sure what to think about the conflicting information about microsatellite data vs. pedigrees, and about the value of genetic markers to assess diversity, and various other related rumors that continue to float about, this is for you.

    Some say pedigrees are most important, some say genetic markers are what matters, some say using genetic diversity tests is brand new and untested. While these discussions may be new to the purebred dog world, they have long been hotly debated by researchers in population genetics, conservation and ecology. The pedigree based calculation of coefficient of inbreeding (COI) has been around since the 1922, throughout the period of time when inbreeding in dogs became considered normal and even preferred. In 1989 Queller and Goodnight published their method in a paper called "Estimating Relatedness using Genetic Markers." Since then various other mathematical ways of using genetic markers to estimate the heterozygosity in both an individual and a population were discovered. These have been in use and have improved significantly over the last 15 years, as has the ability and cost to genotype and analyze vast amounts of genetic data.

    The experts in the field are way ahead of the dog world on these discussions, and have already asked and answered a lot of the questions, comments, and opinions now passed around among us. Since a lot of those discussions have happened among population geneticists, dog breeders don't know about them. Here are some you might have had:

    • What markers are chosen and why? What do those markers do? What traits do they control? 
    • What's the difference in quality of information between different kinds of tests? Why do some tests say they have thousands or hundreds of thousands of markers and some of them have only 21 or 33 or 58? How many is enough?
    • How can a tiny sample of DNA possibly tell us about the rest of the DNA in a dog? 
    • How can a few hundred dogs from a single breed represent the whole breed? Don't you have to get DNA from all dogs for it to be accurate?
    • What about COI and other pedigree-based information? When genetic results are so different from the COI, how can you trust either?
    You can rest assured that people whose careers are based on studying these precise questions, i.e. actual population geneticists, have already hotly debated these. In fact, a definitive paper came out 6 years ago that answered many of these questions, and there have been hundreds of studies since that have built up a body of research, replication of results, and more comparisons. Some things became clear - like that inbreeding estimates derived from genetic markers are most accurate with inbred populations, and that more markers make for more accurate results. There are also studies that have shown that not all positive fitness traits are caused by more heterozygosity - some are due to specific genes. But many traits, often generalized ones like body weight or the ability to adapt to environmental stressors are strongly connected to heterozygosity.
    I strongly suggest that readers NOT automatically believe those on Facebook who spout off theories, because many (and there are many) only sound like they understand and don't. If someone doesn't answer your questions, or can't or won't, there are many ways of finding out for yourself. Ask for documentation and don't take "because it's true" for an answer - not even from me. The truth is out there and it's not all so scientific that you need someone to translate it.
    First, to answer the questions above:
    • What markers are chosen and why? What do those markers do? What traits do they control?

    Genetic diversity tests do not look for causative markers for specific traits, nor do they track what traits those markers control. Breeders are used to DNA tests for specific genes or markers - ones that cause disease or don't cause disease. These diversity tests use loci, or specific places on the DNA, that have a number of different alleles found at them, not just a normal one or a mutation, like in the DNA tests for diseases.  These genetic diversity tests look for markers that, when viewed as a group, are most informative about the overall genetic diversity in a population or an animal. In the case of UC Davis and Genoscoper, both of which offer genetic marker tests for genetic diversity, they have confirmed that their methods offer reasonable estimates of DNA heterozygosity across the genome. Not only have hundreds of studies used this method with success to show levels of inbreeding in populations of various species, but more studies on dogs are replicating recent results.

    • What's the difference in quality of information between different kinds of tests? Why do some tests say they have thousands or hundreds of thousands of markers and some of them have only 21 or 33 or 58? How many is enough?

    STRs and SNPs are different ways to genotype (record) DNA. STRs identify larger markers often are a group of genes, while SNPs identify the tiny pairs of chemicals (purine bases to be precise) that are the building blocks of DNA - called base pairs. When you see pictures of DNA that look like a twirling ladder, each base pair makes up one rung on that ladder. There are about 2.8 billion base pairs in a single dog's DNA, which comprise about 19,000 genes in total. That means about 147 million base pairs make up each gene! The use of tens of STRs, 21 or 33 or 58, offers about as much information as using tens of thousands of SNPs, say 170,000 or 220,000. Either way, it's a fraction of all the DNA. 

    The UC Davis method uses only STRs  because they are cost effective, don't require blood draws, and can be turned around very quickly. However, they have compared their panels to extensive SNP panels, as well as larger STR panels, to see if they get as much necessary information with them, and they do.  Genoscoper uses a combination of SNPs and STRs to assess dogs. While some breeders have discussed whole genome testing as being what's "really" going to matter, the computational requirements for the analysis of 2.8 billion pieces of data are expensive,  time consuming and impractical at the moment. Most importantly, it's not necessary for the purposes of genetic diversity testing. Samples like the panels used by UC Davis and Genoscoper are effective, just as sampling data is effective in many, many areas of science. 

    • How can a tiny sample of DNA possibly tell us about the rest of the DNA in a dog? 
    DNA samples have been able to identify individual humans and animals with certainty for decades, and they've been able to find obvious single locus disease genes. Every test should be appropriate for its purpose, and as discussed above, these estimates do an excellent job of assessing diversity. While there have been some debates on how well markers can accurately estimate overall diversity, an ever growing body of research has proven that genetic markers and the methods of assessing them work very well under varied circumstances to estimate heterozygosity in both individuals and populations. Researchers now regularly use them to assess how these different levels of heterozygosity affect certain "fitness" traits in a population. Usually they find that more heterozygous populations are better able to survive under certain circumstances. For some traits, heterozygosity has no effect.

    There have of course been improvements made in response to some early criticism, such as selecting which loci to use, as well as how many is necessary. The mathematical methods to estimate overall heterozygosity have also improved. There are still a few researchers who advise caution, but more and more, researchers have simply changed their main focus from pedigree based assessments to genomic assessments. 

    • How can a few hundred dogs from a single breed represent the whole breed? Don't you have to get DNA from all dogs for it to be accurate?

     Depending on the size of a population and its species, it typically only takes a relatively small number of individuals to have a full set of all possible genes. In dogs, that amount can vary depending on how popular a breed is (rare breeds might take fewer dogs) and how inbred that breed is. A very varied breed that is popular around the world would require more individuals, where as less well known, highly inbred breed would require fewer.  

    This is because there is a variety of possible genes at each locus on the DNA, and each breed has a limited number of versions of these genes. For the first few dozen dogs, for instance, more and more new alleles are identified at each locus. Inbred breeds, - ones with few founders, or ones that have had a significant genetic bottleneck sometime after the founders - have many fewer alleles, and the more diverse populations have more. Most breeds have some of the same markers or haplotypes at the same locus, but this doesn't mean they have been crossed to one another. Often they simply have the same ancestors from before breed development- which for many breeds was a very long time ago. No matter the make up of the breed, once new alleles are no longer or only very rarely being found at each locus as new samples come in, then the population structure is well known. From that point on, the changes are mostly in the frequencies of each allele (how often they appear in the population) and more samples will only change frequencies very slightly. 

    • What about COI and other pedigree-based information? When genetic results are so different from the COI, how can you trust either?

    Pedigree analysis is still helpful for its historical data, none of which can be had by reading a sample of DNA. Knowing the actual qualities of the dogs in the recent pedigree will always be extremely important, therefore.  However, simply knowing names of distant ancestors with no attached data is of little value, as are COIs for individuals or those based on fewer than 10 generations. Before there was available genetic marker based assessment, COI was better than guessing, but there have often been wild populations where no pedigrees were available, and some breeds have abysmal pedigree records or very closely guarded ones. In such circumstances, genetic marker assessments are excellent methods of showing relatedness. Without any pedigree information, modern assessment methods can quickly and easily identify close genetic relationships and accurately describe populations structure.

    Pedigree-based inbreeding estimates are not only dependent on the quality and depth of the pedigrees, but also on how related the founders were. Every pedigree calculation method assumes founders were unrelated and this is often untrue. However, there's more and more evidence that genetic marker data matches high quality pedigree data when looking at whole populations. This is great news for both populations that have good pedigree databases (only some do) and populations who don't (most wild populations and even many domesticated species and breeds.) 

    Below are some excerpts from only some of the research on which I based the statements above. Reading even the summaries of these papers (called abstracts) will help you decide what to think about all the new advancements being made right now. If you still have questions, do some searches on pubmed.gov. You will be surprised at how much information is available!


    When considering the methods used to correlate marker data and inbreeding, the authors of this somewhat older but comprehensive paper Heterozygosity-Fitness Correlations: Time for a Reappraisal   (Szulkin M, Bierne N, David P., Evolution. 2010 May;64(5):1202-17. doi: 10.1111/j.1558-5646.2010.00966.x. Epub 2010 Feb 9.
    https://web.natur.cuni.cz/~muncling/Szulkin2010Heterozygosity.pdf) from 2010 say,

    These theoretical expectations are highly concordant with observed correlations between heterozygosity and f(population inbreeding) when the latter can be estimated independently using pedigree data.

    I was very interested to see that, just like the studies coming out of UC Davis that have pedigree data, this recent study on Bullmastiffs, which used microsatellite data and pedigrees came to highly similar mean inbreeding coefficients in the genotyped population using genetic markers (0.35.) and the larger pedigree database of 16,739 dogs (0.39.) (They cited the recent Standard Poodle paper, along with many other recent studies.)  
    Comparative Analysis of Genome Diversity in Bullmastiff  Dogs
    (Sally-Anne Mortlock, Mehar S. Khatkar, Peter Williamson, Published: January 29, 2016, DOI: 10.1371/journal.pone.0147941 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147941)

    The molecular analysis overcomes limitations in calculations based on pedigree data, and takes into account recent breeding events plus the effects of past inbreeding, selection and genetic drift. Molecular data has the advantage of accurately measuring genetic heterogeneity between individuals used for breeding.

    From the Jan 2015 paper entitled  Relatedness in the post-genomic era: is it still useful?
    (Speed D, Balding DJ, Nat Rev Genet. 2015 Jan;16(1):33-44. doi: 10.1038/nrg3821. Epub 2014 Nov 18.  http://www.ncbi.nlm.nih.gov/pubmed/25404112)

    The classical theory of kinship coefficients based on lineage paths in pedigrees provides a mathematically beautiful structure that has historically been useful, but its weaknesses are apparent. Pedigree founders are typically assumed to be unrelated, but this is only realistic in certain settings, such as some designed breeding programmes or an isolated population created by a specific founding event. All pairs of individuals with no common ancestor in the pedigree have coancestry (θ) of zero, but in practice they can have important differences in genome similarity.

    In this paper, the researchers tested the accuracy of using over 35,000 SNPs compared to pedigree inbreeding coefficients:   Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees  (Kardos M, Luikart G, Allendorf FW.,Heredity (Edinb). 2015 Jul;115(1):63-72. doi: 10.1038/hdy.2015.17. Epub 2015 Mar 18.  http://www.ncbi.nlm.nih.gov/pubmed/26059970)

    We used computer simulations to test whether the realized proportion of the genome that is identical by descent (IBDG) is predicted better by the pedigree inbreeding coefficient (FP) or by genomic (marker-based) measures of inbreeding...  Our results demonstrate that IBDG can be more precisely estimated with large numbers of genetic markers than with pedigrees. We encourage researchers to adopt genomic marker-based measures of IBDG as thousands of loci can now be genotyped in any species.

    This next recent paper from New Zealand rightly urges caution and careful analysis of the methods used to assess heterozygosity in a population. It is possible to test methods by matching known relationships to genetic estimates to the genetic marker based relatedness estimates. I was able to use the method studied to assess the Standard Poodle population from the recent study and confirm the usefulness of the method as suggested in the paper.  The use and abuse of genetic marker-based estimates of relatedness and inbreeding  (Helen R. Taylor,  Ecol Evol. 2015 Aug; 5(15): 3140–3150.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559056)

    Genetic marker-based estimators remain a popular tool for measuring relatedness (r xy) and inbreeding (F) coefficients at both the population and individual level. The performance of these estimators fluctuates with the number and variability of markers available, and the relatedness composition and demographic history of a population.

    Finally, there is this recent and important synopsis, entitled Pedigrees or markers: Which are better in estimating relatedness and inbreeding coefficient? 

    ( Wang, J., Theor Popul Biol. 2016 Feb;107:4-13. doi: 10.1016/j.tpb.2015.08.006. Epub 2015 Sep 3.
    http://www.ncbi.nlm.nih.gov/pubmed/26344786 )  Dr. Jinliang Wang is a leading researcher who also writes computer programs that assess inbreeding and relatedness in various ways. He wrote the program discussed in the paper above, and he sums it all up rather nicely in the abstract:

    Individual inbreeding coefficient (F) and pairwise relatedness (r) are fundamental parameters in population genetics and have important applications in diverse fields such as human medicine, forensics, plant and animal breeding, conservation and evolutionary biology. Traditionally, both parameters are calculated from pedigrees, but are now increasingly estimated from genetic marker data. Conceptually, a pedigree gives the expected F and r values, FP and rP, with the expectations being taken (hypothetically) over an infinite number of individuals with the same pedigree. In contrast, markers give the realised (actual) F and r values at the particular marker loci of the particular individuals, FM and rM. Both pedigree (FP, rP) and marker (FM, rM) estimates can be used as inferences of genomic inbreeding coefficients FG and genomic relatedness rG, which are the underlying quantities relevant to most applications (such as estimating inbreeding depression and heritability) of F and r. In the pre-genomic era, it was widely accepted that pedigrees are much better than markers in delineating FG and rG, and markers should better be used to validate, amend and construct pedigrees rather than to replace them. Is this still true in the genomic era when genome-wide dense SNPs are available? In this simulation study, I showed that genomic markers can yield much better estimates of FG and rG than pedigrees when they are numerous (say, 10(4) SNPs) under realistic situations (e.g. genome and population sizes). Pedigree estimates are especially poor for species with a small genome, where FG and rG are determined to a large extent by Mendelian segregations and may thus deviate substantially from their expectations (FP and rP). Simulations also confirmed that FM, when estimated from many SNPs, can be much more powerful than FP for detecting inbreeding depression in viability. However, I argue that pedigrees cannot be replaced completely by genomic SNPs, because the former allows for the calculation of more complicated IBD coefficients (involving more than 2 individuals, more than one locus, and more than 2 genes at a locus) for which the latter may have reduced capacity or limited power, and because the former has social and other significance for remote relationships which have little genetic significance and cannot be inferred reliably from markers.

    And here are lots more to read, if you are so inclined:

    A comparison of approaches to estimate the inbreeding coefficient and pairwise relatedness using genomic and pedigree data in a sheep population.
    Li MH, Strandén I, Tiirikka T, Sevón-Aimonen ML, Kantanen J.
    PLoS One. 2011;6(11):e26256. doi: 10.1371/journal.pone.0026256. Epub 2011 Nov 9.
    Improved estimation of inbreeding and kinship in pigs using optimized SNP panels.
    Lopes MS, Silva FF, Harlizius B, Duijvesteijn N, Lopes PS, Guimarães SE, Knol EF.
    BMC Genet. 2013 Sep 25;14:92. doi: 10.1186/1471-2156-14-92.

    The effect of rare alleles on estimated genomic relationships from whole genome sequence data.
    Eynard SE, Windig JJ, Leroy G, van Binsbergen R,  Calus MP
    BMC Genet. 2015 Mar 12;16:24. doi: 10.1186/s12863-015-0185-0.
    How many SNPs are enough?
    Smouse PE
    Mol Ecol. 2010 Apr;19(7):1265-6. doi: 10.1111/j.1365-294X.2010.04555.x.

    On the use of large marker panels to estimate inbreeding and relatedness: empirical and simulation studies of a pedigreed zebra finch population typed at 771 SNPs.
    Santure AW, Stapley J, Ball AD, Birkhead TR, Burke T, Slate J.
    Mol Ecol. 2010 Apr;19(7):1439-51. doi: 10.1111/j.1365-294X.2010.04554.x. Epub 2010 Feb 10.

    Heterozygosity-fitness correlations in zebra finches: microsatellite markers can be better than their reputation.
    Forstmeier W, Schielzeth H, Mueller JC, Ellegren H, Kempenaers B.
    Mol Ecol. 2012 Jul;21(13):3237-49. doi: 10.1111/j.1365-294X.2012.05593.x. Epub 2012 May 3.

    Heterozygosity-fitness correlations and inbreeding depression in two critically endangered mammals.
    Ruiz-López MJ, Gañan N, Godoy JA, Del Olmo A, Garde J, Espeso G, Vargas A, Martinez F, Roldán ER, Gomendio M.
    Conserv Biol. 2012 Dec;26(6):1121-9. doi: 10.1111/j.1523-1739.2012.01916.x. Epub 2012 Aug 16.

    The imprecision of heterozygosity-fitness correlations hinders the detection of inbreeding and inbreeding depression in a threatened species.
    Grueber CE, Waters JM, Jamieson IG.
    Mol Ecol. 2011 Jan;20(1):67-79. doi: 10.1111/j.1365-294X.2010.04930.x. Epub 2010 Nov 19.

    Context-dependent associations between heterozygosity and immune variation in a wild carnivore.
    Brock PM, Goodman SJ, Hall AJ, Cruz M, Acevedo-Whitehouse K.
    BMC Evol Biol. 2015 Nov 4;15:242. doi: 10.1186/s12862-015-0519-6.

    Direct and indirect causal effects of heterozygosity on fitness-related traits in Alpine ibex.
    Brambilla A, Biebach I, Bassano B, Bogliani G, von Hardenberg A.
    Proc Biol Sci. 2015 Jan 7;282(1798):20141873. doi: 10.1098/rspb.2014.1873.

    Heterozygosity at a single locus explains a large proportion of variation in two fitness-related traits in great tits: a general or a local effect?
    García-Navas V1, Cáliz-Campal C, Ferrer ES, Sanz JJ, Ortego J.
    J Evol Biol. 2014 Dec;27(12):2807-19. doi: 10.1111/jeb.12539. Epub 2014 Nov 23.

    Heterozygosity-fitness correlations in a wild mammal population: accounting for parental and environmental effects.
    Annavi G, Newman C, Buesching CD, Macdonald DW, Burke T, Dugdale HL.
    Ecol Evol. 2014 Jun;4(12):2594-609. doi: 10.1002/ece3.1112. Epub 2014 May 27.

    Effects of inbreeding on fitness-related traits in a small isolated moose population.
    Haanes H, Markussen SS, Herfindal I, Røed KH, Solberg EJ, Heim M, Midthjell L, Sæther BE.
    Ecol Evol. 2013 Oct;3(12):4230-42. doi: 10.1002/ece3.819. Epub 2013 Sep 30.

    Estimating genome-wide heterozygosity: effects of demographic history and marker type.
    Miller JM, Malenfant RM, David P, Davis CS, Poissant J, Hogg JT, Festa-Bianchet M, Coltman DW.
    Heredity (Edinb). 2014 Mar;112(3):240-7. doi: 10.1038/hdy.2013.99. Epub 2013 Oct 23.
    Applications and implications of neutral versus non-neutral markers in molecular ecology.
    Kirk H1, Freeland JR.
    Int J Mol Sci. 2011;12(6):3966-88. doi: 10.3390/ijms12063966. Epub 2011 Jun 14.
  • My breeding recommendations for Standard Poodles

    These are my personal opinions, based on research, given the information we have now. 
    These may change as we get more information and depending on whether breeder culture changes. They aren't simplistic, but the dog genome has over 19,000 genes and over 2.5 billion base pairs so genetics aren't simplistic either.
    Choose your own path, of course. I won't judge.
    • Do not cull siblings or parents of affected dogs. Do not cull dogs with risky haplotypes but do not breed them early. Do not breed without testing. Do not breed affected dogs.

    • Select for health, temperament and structure as usual.

    • Use pedigree information for what you know of the dogs in the recent pedigree, their health temperament and structure. Assume many close relatives with similar traits raises the possibility of those traits being in the dog, whether good or bad. 

    • Breed gradually or more aggressively for more rare and fewer common alleles for now, based on your comfort level. The goal will be to have fewer and fewer rare and common alleles in the population as the alleles get better distributed. 
    • Breed for lower IR than parents, lower than 0 as a goal, and balance lowest IR value with best type when selecting puppies, depending on your priorities.

    • With SA risk but no AD risk, breed for lowest IR to a dog with low AD risk.

    • With AD risk but no SA risk, breed for higher IR to a dog with no SA risk. Breed for lower IR in subsequent generations as AD risk is lowered.

    • With both AD and SA risk, breed to a genetic outlier. Look for dogs with over 10 rare and under 18 common alleles and over 2007 in DLA Class II haplotypes.

    • If your dog has the DLA extended haplotype 1003/2001 (frequency of 15.7%), it carries slightly higher risks of AD and SA, so check carefully for autoimmune disease in pedigree and breed as above.  

    • If your dog has the DLA extended haplotype 1006/2004 (frequency of 2.7%) and probably 1006/2007 (frequency of 1.6%), it has 2.8 times the risk for SA. Breed for lowest IR to a dog with low AD risk, preferably with haplotypes over 2007, and/or to a dog with over 10 rare and under 18 common alleles. Test and select best offspring without it. 

    • If your dog has a DLA extended haplotype of 1007/2006 (frequency of 3.2%), it has 2.4 times the risk for Addison's. Breed for higher IR to a dog with low SA risk and preferably haplotypes over 2007 and/or over 10 rare and under 18 common alleles. Test and select best offspring without it. Breed for lower IR in subsequent generations. 
  • Primer on Genetics Data #2

    For those who want to understand more about the DNA analysis methodology, here are some more details. Some of your eyes may glaze over, which is fine because the gist is in the previous post, but for those who really want to understand the nitty gritty, here it is.

    The two best known ways to determine genes in an individual differ in several ways.

    STRs are “short tandem repeats” and that’s the older technology, the kind that has proved paternity and guilt in courts of law for decades. So it’s tried and true.

    DNA tends to do predictable things, and one of the things it does sometimes is “stutter” in specific areas when it’s replicating to make new cells, like eggs and sperm. Remember that DNA is coded using 4 elements, represented by G, A, C, and T. It's kind of like Morse cod, which uses dots and dashes in patterns, but using 4 materials.

    So if a part of the sequence of DNA is GCATCTCGCA, when making an egg or sperm, the replication process might stutter and make GCATCATCATCTCGCA in the egg or sperm, which is then passed down to the next generation. As you can see, the CAT in the sequence has been repeated three times in the second example.

    This stutter doesn’t change gene function, but it does act as a sort of marker that researches can find - like putting paint on trees in a large forest to mark a trail. Using places on the DNA that are known to have these stutters, or repeats, individuals can be compared. Each slightly different sequence is called an allele, and each place on the DNA is called a locus. To analyse each dog, they find the same place on the DNA and notate the sequence. Each sequence is given a label; UC Davis uses numbers. Doing this at a large number of loci makes it possible to identify each individual because individuals have unique combinations of these alleles. Relatives have some alleles in common. 

    Over generations, these stutters, or STRs, happen. Different families have different STRs at the same places on the DNA, and the longer a population is separated from others, the more likely they are to have different STRs. Sometimes a breed will have only 4 different STRs at a certain locus, and some breeds will have 10. The more STRs, or alleles, the more diversity there is in a population. 

    Randomly bred dogs, like village dogs in primitive communities, tend to have a great deal of diversity. Highly inbred breeds with few founders and a small breeding population have very little diversity. 

    Researchers design “panels,” or the mechanism by which they check the places on the DNA, that use loci that are well spread throughout the genome, so the STRs they use are on as many different chromosomes as possible. That way they get a very good sampling of the DNA in each individual.  This method can positively identify any human on earth because the chances of each human having the exact same markers at precisely the same places (unless he or she has an identical twin) is extremely low. The advantages of these STRs are that they are economical to process and analyze, they use cheek swabs rather than blood samples, and they identify more recent changes to DNA better than ancient ones. This makes them ideal for assessing diversity of many different wild animals, and now dogs and telling populations apart. They have been used for this purpose for many years. 

    The other method of recording is SNPs. SNPs are “single nucleotide polymorphisms” or each individual base pair in a sequence of DNA. Rather than specific repeats, SNP technology records changes in the single letters from one of G, C, A, or T to another one of those four, or additions of single base pairs or subtractions. This is newer technology and like the STRs, it catalogs only a tiny section of the DNA on each chromosome. It can track minute differences in the DNA that STRs cannot track, and so is better for certain tasks like looking for tiny mutations, or telling identical twins apart. It is no better at recording genetic diversity, however. It is also more expensive to do and often requires higher quality DNA samples, like from blood, and is not as practical for the purposes of testing hundreds of dogs.

    As referenced on the VGL website, the 33 loci STR panel was compared specifically to a 170,000 SNP panel and the results were comparable. That is one way they established the validity of the method for this purpose.

    More to come!

  • Primer on Genetic Data #1

    There seems to be some confusion about STRs, SNPs, frequencies and the database, and since these are crucial concepts in understanding whether this test is valid, this has to be explained carefully.

    If you hear someone comparing 200,000 “markers” to the 33 loci available from the UC Davis Genetic Diversity test, as though the 200,000 markers offer more information, you can be sure they are completely confused and do not comprehend the science. This would be the difference between counting apples, and counting huge apple orchards, and then comparing 1,000 apples to 100 apple orchards and saying one obviously has more apples because 1,000 is bigger than 100.

    So I will explain in a few posts. First, most people are familiar with the image of DNA, a spiral ladder. Each rung on the ladder is made up of two purine bases - certain organic materials - each half of the rung being one kind. There are only 4 of these purine bases that code DNA: guanine, adenine, cytosine and thymine, which are represented by the letters G, A, C, and T. Each rung on the ladder is either guanine and cytosine, or adenine and thymine. Those two pairs in various orders make up all DNA.

    A single gene is tens of thousands of base pairs long. The dog genome was mapped in 2003, and is made up of about 2.5 billion base pairs, found in 39 chromosomes, which are separate, compacted pieces of DNA. These 2.5 billion base pairs make up about 19,000 genes in total.

    The first whole genome sequencing of the dog - meaning a recording of every base pair in order - cost $30 million. It can be done now for about $7,000 per dog. The process of comparing the 2.5 billion base pairs of one dog to the 2.5 billion base pairs is quite a job, as we can imagine.

    Because there is so much genetic material, nearly all practical DNA testing involves testing only very small sections of the DNA. When looking for a disease gene, first researchers search regions of the genome they suspect may control the function of the disease. They don't search all 2.5 billion base pairs.

    There are several practical ways of recording DNA, or genotyping it, but the two main ones are STRs (short tandem repeats) or SNPs (single nucleotide polymorphisms). SNPs identify single base pairs. STRs identify patterns that indicate genes. An SNP panel of, say, 189,000 SNPs sounds like a lot - but it’s 189,000 out of 2.5 billion base pairs, which is about 0.00756% of the DNA of a dog. The UC Davis Genetic Diversity Test tests 66 genes, in 33 gene pairs, and 66 out of 19,000 is about 0.347% of the genes in the genome. While in each case this is only a tiny amount of DNA, because DNA is so specific in each individual, testing this amount is enough to be able to tell a great deal about individuals, to compare them to other individuals, and when done on a group, to develop a picture of their population structure.

  • Reality Check #2

    More questions and answers regarding the latest research on Standard Poodles. 

    Question: If sebaceous adenitis and Addison's are genetic, why don’t they follow a pattern, and sometimes seem to appear out of nowhere?

    Answer: The diseases are based on complex genetics so their appearance seems more random. Breeders are more used to single gene disorders. A single gene disorder is either dominant or recessive, and for a dominant, if the parent has the gene, that parent is affected and it passes that down to, statistically, half its puppies who will then be affected. For a recessive, both parents have to have the gene, and every puppy who inherits both dam’s and sire’s disease gene will be affected, roughly 1 in 4 of their puppies. These kinds of diseases are easier to understand and easier to see. PRA is this kind of disease. NE and vWD are like this as well - simple diseases with obvious modes of inheritance.

    With complex diseases, especially those that can be triggered or made worse by some environmental influence, the pattern is not as clear. Some dogs may carry all the genes necessary and never have clinical symptoms. Sometimes the onset is late and sometimes early. Some dogs produce one in 40 puppies. Some produce one in every litter. These are all the things that make the genes hard to pinpoint as well, and the randomness that drives breeders crazy, wondering if they fed the wrong food or stressed the dog out or vaccinated dogs too much or too quickly.

    When a disease is controlled by genes at a single locus, like  a simple dominant or recessive gene, there’s still an element of chance as to whether a dog will inherit the bad one or two genes. Can you imagine how much more of a chance there is when a dog has to inherit more than two genes to have the disease? This is why complex diseases tend to be rare in populations with no inbreeding, and far more common where there is historical inbreeding, like a isolated population of humans or any other animal.

    When a population starts seeing more and more of a complex disease that should be rare, it means the genes responsible for the disease are common in the population. We do not, for instance, see necrotizing meningoencephalitis in poodles, which is a well known autoimmune disease that affects many pugs. Since these are both the same species, if these complex diseases were not genetic, we would see these kinds of specific autoimmune diseases at the same rate in different dogs. The clue as to genetic basis is not whether a disease appears in a population, but rather how frequently it appears in a population.

    Question: Will the data change over time? If so, does that mean the data isn’t valid?

    Answer: No, the data gathered right now is the data gathered right now. No dog’s alleles will change. What may happen is that the FREQUENCIES of the alleles - how common or uncommon they are in the population will change. These frequencies may change very slightly as the database grows, but they will not change enough to conclude anything different about the population structure or breeding recommendations. The sample set was extremely large for a study of this kind, and comprised hundreds of full Standard Poodles from different countries and pedigrees. The vast majority of Standard Poodles are genetically very similar, and a minority of dogs is different from them and each other. A genetically healthy population with well managed diversity will be more evenly dispersed.  

    The only way frequencies will change substantively is from generation to generation. If breeding practices that are currently used do not change, we can expect the common alleles to become more common and the rare alleles gradually to become extinct. Once gone, there is no way to get new ones without bringing them in from a different variety or breed, so we  have a vested interest in not letting that happen.

    If breeding practices change because breeders want to preserve the breed as it is, while reducing risk for disease, then the rare alleles will become less rare and the common alleles won’t be quite as common and the diversity will become more evenly distributed. The goal is not to favor any specific rare alleles, or disfavor any common alleles, but to breed so all the alleles are all in a medium range of frequency. This can and should be done while selecting for type, temperament and health. This will take a number of generations to achieve.


    Question: Are the rare alleles rare because they are worse for Standard Poodles?

    Answer: No. The rare alleles found in Standard Poodles by the Genetic Diversity Test are not disease genes so they were never specifically selected against. They are therefore rare because there was an enormous bottleneck which effectively drowned out many lines. Breeders do select for health, which would make some disease genes very rare as long as the diseases they create are obvious, and the mode of inheritance is easy to see.  However, most complex disease genes can't be detected, and are therefore difficult to select against. What has made a great many rare alleles rare has been stringent selection for aesthetic attributes. 

    Pedigrees do tell this tale. In the 1960s, there were many different lines which came from very different origins. These are often seen today only far back in maternal lines, because as we know, the basic instructions have long been to breed your best bitch to the best dog available. By the 1960s, the dogs winning most in the ring were descended from the 10 dogs of the bottleneck. Any serious breeder with a bitch from different lines bred her to one of the winning dogs, all of whom were cousins. In the next generation, they would take their pick puppy bitch, who was now half the old lines and half the winning bottleneck lines, and breed it to another dog who was mostly descended from the 10 bottleneck dogs. Their third generation would then be closer to 75% bottleneck lines, and the perfectly acceptable genes in the original bitch would slowly be bred out. In this way great old white, brown, and silver lines were essentially drowned out, and only because breeders were doing what they thought was right by improving the breed. They didn’t know that everyone else the world over was doing the same thing, breeding to the same lines and breeding out all the other poodle genes.

    Had those breeders known what we know now, they could have improved their lines more slowly and safely by selecting for desired traits from less inbred litters and gotten the type they liked without the loss of diversity.

    Question: But aren’t the alleles in Standard Poodles specific to Standard Poodles? Aren't some of these alleles rare because they are from miniature poodles? Are they evidence of other breeds?

    Answer: No. Scientifically, genetically, dogs are all the same species, canis familiaris. In essence, breeds developed from two things - isolation and selection, but they are all dogs. Thus any known alleles can be found in any dog, and many breeds have a few of the same alleles in their populations. That does not mean they are somehow mixed breeds, but rather that hundreds or thousands of years ago they had similar ancestors. Thus the alleles that are recorded in the Genetic Diversity Test are not ones that determine breed.

    Nevertheless, since each breed’s database shows the alleles found and how often they are found (that’s called frequency)  it’s not difficult to tell whether a profile is from a standard poodle or a miniature by comparing frequencies. All or nearly all the alleles that are found in the Miniature population so far are also found in full Standards, which simply reflects their shared ancestry from decades or centuries ago,  but they are found at much smaller frequencies. Many of the same alleles are also found in vastly different breeds as well, since all dogs have common ancestors, although breeds developed due to isolation and selection - first from natural forces, and later because humans got involved, bred for specific traits and eventually closed the gene pools.

    This kind of differentiation happens in nature too - both in animals and humans. Irish people look a bit different from Spanish people - both  having evolved over hundreds of generations in separate areas with different environments, and different influences coming from nearby populations - Vikings for the Irish and Moors, who were Arabs, for the Spanish. Yet we are all human and have common ancestors from tens of thousands of years ago, and we can interbreed just as dogs can because we are all the same species. Human races have very different appearances as well, but also have shared ancestries, just further back. We nevertheless have many of the exact same alleles.

    In humans there are a few significant examples of isolated populations that have the same problem dog breeds have - namely an accumulation of disease genes. The Amish, Menonite and Hutterite populations now have a database of identified genetic disorders all due to founder effects, meaning they had severe genetic bottlenecks in their populations due solely to closing their gene pool. In 2011, research showed that Hutterites comprised 40,000 people with only 89 founders, and there are 32 identified genetic disorders affecting the population. In the broad, open population of humans these conditions are either unheard of or extremely rare, but they are common in these closed populations. These so-called “plain people” aren’t alone - Cajuns and Quebecois are at far higher risk of certain diseases, as are Ashkenazi Jews and Afrikaners - who were of European origin - in South Africa. Even fundamentalist Mormon sects are starting to report rare genetic diseases. An estimated 75% of the FLDS population are descended from the two men who founded the sect in the 1930s.  These are all groups isolated by language, culture or geography. Natives of Iceland, a population of 320,000 and an estimated founding population of between 8,000 and 20,000 people from Scandinavia, Ireland and Scotland, has a dating app for their phones so they don’t inadvertently date a cousin. They too have certain common genetic diseases.

    What would help such human communities would, of course, be new genetic infusions - which should seem obvious to all of us. I imagine there could be people from within those communities who would say that humans from outside their community were not “pure” or were excluded from the “pure” population because they were somehow inferior, but if they are experiencing high rates of disease due to historical, not recent, inbreeding,  disallowing a genetic infusion would be against the best interests of their population. It would also not be very logical to be afraid to “bring in” genetic diseases from outside a population that is already riddled with genetic diseases, since the increased frequencies of the disease genes came about precisely because of the isolation of the population.

    Now I’m not saying Standard Poodles are in the same genetic situation as those closed populations, but some breeds are, and Standard Poodles could be one day too. They will be if the breed community doesn’t manage the lopsided genetic diversity still existent in the population well. If not,  we will have no option but to bring in genes from an outside population.  All those who are deeply opposed to loss of Standard Poodle traits by crossing to Miniatures should therefore be committed to preserving and balancing the existing diversity - something that cannot be done with pedigrees and COI alone. 

  • Reality Check #1

    In the last week or so I've heard a lot of anxiety about the new Genetic Diversity Test and the recently published research on Addison's and SA. Is the test "valid?" Is it a flash in the pan like some others have been? How can people be expected to use it when it's so complicated? Did we really learn anything new? 

    Sometimes when there are scientific advances there will be a few people who don't see the advances as positive, but rather as a kind of threat. It's true in many fields, about many ideas and inventions. All I can say about this for the Poodle Fancy is that there is nothing in this test that can hurt people, their poodles or their programs. No one has to use it. It is a tool designed to help.

    Ten years ago there was a great deal of hostility toward using COIs as a breeding tool. Now they are widely used. This test is a much more accurate method of determining inbreeding and outcrossing than COI is. Consider the automobile vs. horse and buggy: they both work as modes of transportation, and they both have their pitfalls, but one just gets you places faster and makes life much easier.

    People taking a wait-and-see position is perfectly legitimate. Standard Poodle breeders and fanciers have always been on the forefront of thinking about genetic diversity and can think for themselves. There's a reason we prefer such smart dogs. Skepticism is understandable and even welcome. Open discussion and reasoned debate are always positive.

    The Standard Poodle Fancy has been waiting for years for more information on the inheritance of SA and Addison’s and here it finally is: funded research by the Poodle Club of America Foundation, done by a leading researcher who is also relatively conservative, AND it’s published in a highly respected peer reviewed journal. It's hard to have better credentials for new research. 

    All the legitimate, responsible breeders I know do everything they can to prevent lifelong diseases in the dogs they produce. They go to great lengths and expense to make perfect pairings and prove their dogs with health tests, titles or other criteria. This new tool can help breeders lower their risks for Addison's and SA, much as hip X-rays help lower risks for hip dysplasia.

    I remember about 10 years ago, when I met an elderly breeder, close to age 90, who refused to test the hips of his line. "Why would I do that? My dogs have never had hip problems," he said. "Plus, doesn't everyone know that radiation is bad for you?!" There was no use arguing with him and he lived his whole life happily not testing the hips of the dogs he bred.

    There will, likewise, certainly be those who will refuse to get a Genetic Diversity Profile done for their dogs, and they are absolutely within their rights to do so. They may even be so afraid of the change that they will advise against it. But think of it like hip X-rays; what you decide to do once you see what's there, once you have that information, that is entirely up to you. Its private and no one can share it without your permission. But you might really want to know.

    So let me address some of the anxieties I’ve heard recently directly so you have correct information.  I will do a few of these till all of the questions I get privately are addressed.

    Question: Has the recent research actually found anything new?

    Answer: Absolutely. The recent research proved, among other things:

    • that both Addison's and SA are in fact, categorically, indubitably genetic.

    • that both are so frequent in Standard Poodles due to significant historical inbreeding caused by a huge bottleneck.

    • that the major bottleneck predated Wycliffe and is based on ten dogs born from 1948 - 1953.

    • that while there is ample diversity in the breed, 70% of it is found in 30% of the dogs, while the majority, 70% of Standard Poodles, share only 30% of the diversity

    • that the minority 30% tends to be free of autoimmune disease

    • that SA affected Standard Poodles were significantly more inbred than healthy ones, indicating it likely has a recessive component to its mode of inheritance

    • that Addisonian dogs were as outbred as healthy dogs, indicating it is likely fixed in the main population of Standard Poodles

    Question: Can Genetic Diversity Tests determine the quality of a dog?

    Answer: No. Genetic Diversity Test results simply show which alleles a dog has at 33 different places on the DNA and which DLA haplotypes (a group of connected genes) a dog has at two different places. This information can tell certain things about a dog, but not quality.


    Question: Don't Genetic Diversity Tests track genes that we know nothing about? Doesn't that mean we will be selecting for or against mystery traits? What if we are selecting against or for the wrong things?

    Answer: The genes tracked by the test are not attached to any particular known trait. Many of them are the same ones used to establish parentage by the European FCI. These specific loci are chosen not for what the genes control, but rather as identifiers only. By selecting for certain ratios of rare alleles or common alleles, breeders are not selecting for any specific set of genes, but rather selecting for how unusual a dog is overall compared to the population or how common a dog is. This is the same general principle behind the IR calculation. There has been no recommendation to select for or against any specific alleles.

    Questions? Comments? Please email them. More to come!!

  • Nature's breeding program

    Here's an important thing to keep in mind. SELECTION is the main power behind evolution. The reason certain animals are well suited to their environments is because of natural selection. INDIVIDUALS who are not well suited to their environments, or any environment, are far less likely to procreate. But selection works best when there is ample DIVERSITY to select from. The constant random recombination of genes is one of Nature's most brilliant and elegant mechanisms. DIVERSITY and SELECTION work hand in hand to create the miraculous variety of living organisms on Earth.

    Breeders play God, or Nature. We decide who procreates or not and with whom, according to criteria of our own making. Shouldn't we have enough respect for the intricacies of biology to follow, to the best of our abilities, the principles of Nature that are already established? For decades breeders have been eliminating whole families and pedigrees because there are siblings with disease somewhere. This has served only to eliminate both the bad and the good genes in those families. The equivalent in Nature would be to kill off an entire wolfpack or a litter if one wolf or cub was less than fit. And that would of course be ridiculous, but it's what many breeders have done for decades.

    This might be useful if all siblings were the same, as COI and breeder culture suggests, and as inbreeding strives to produce, but obviously they are not. There is, however, only very limited inbreeding in Nature and there are multiple procreative mechanisms that favor the broadest diversity possible. Nature emphasizes diversity precisely so there are always some offspring that have a chance of survival in many different environments.

    It's important to consider pedigrees when breeding, but if every purebred dog with a relative who was sick for one reason or another was removed, no gene pool would be viable. It's a backward way of thinking to look at pedigrees and automatically eliminate healthy dogs based on a few sick relatives. If a pedigree shows risk, that's what health testing is for, and why it's important to wait for healthy dogs who come from risky pedigrees to mature. Some diseases are late onset - or appear AFTER a dog reaches breeding age. In such a case, one strategy is to have one litter while young, and then wait till those offspring mature before having another.

    It's also very important to be open about what's found in pedigrees. Often newer breeders and pet owners have no way of knowing what is in a pedigree and think everything will be fine, especially if there's health testing, usually for some unrelated condition. Breeders don't talk about problems often because perfectly healthy relatives will be tarred with the same brush by meanspirited gossip. And sometimes there aren't any problems, but meanspirited gossips will allude to one thing or another without proof or specifics.

    In our breed, the Poodle Heath Registry is meant to provide both proof - since they only accept vet documents - and openness, since they are public. So unless I hear about sickness directly from a breeder or owner, or something is listed on PHR, I can only consider it gossip. Too many times I have tried to run down rumors only to find they were half truths or fiction. Such cases only served to ruin the reputation for reliability of the person who gossiped.

    So while pedigree analysis is important, analysis of FACTS, not rumors, is most important when looking at pedigrees, and analyzing individuals should weigh at least as heavily as their pedigrees. All pedigrees have risk - and those risks should help determine when and to whom an otherwise sound dog should be bred. One of the great benefits of the new Genetic Diversity Test is that we have been able to see precisely how different siblings can be - which shows that just because one relative has a problem, it does NOT mean another will.

    Hopefully an added benefit of the test will be that more people can be more open about health issues in individuals because it ensures that no intelligent person will assume family members will automatically have the same disease. There's no accounting for those who cannot understand or who are unwilling to learn. But this way we will be able to preserve the healthiest from each family, just as nature would do. 

    Ironically we have seen large movements in various breeds where a deadly disease is found and whole lines are eliminated by the most caring and stringent breeders. The remaining dogs tend to be those of breeders who refused to eliminate dogs, often amidst much clucking and consternation, and their lines survived precisely because of these breeders' unwillingness to respond to peer pressure. Imagine how much more diversity there would be in these breeds if individuals but not lines were removed. 

    Happily we have the tools now both to preserve diversity and to select from it. There will never be a guaranteed method to produce perfect dogs, but we can help them stay healthier by mirroring Nature.