I know that successful breeders advocate and practice inbreeding, but success in dog shows does not turn a bad practice in good practice. Health and success are two things of different nature: dog health can be objectively analyzed; the success in dog shows not. The dilemma isn’t inbreeding yes or no. The nature of the problem of endogamy and population structure in the Dobermann breed it is qualitative: the selection has been made by inbreeding on few dogs (strong popular sire effect), and quantitative: a practice sustained over time on a population with few founders and a big bottleneck in the World War II. That's the problem!
As the old Breed Warden of Dobermann Verein, Dr. Reinhard Haberzettl noted in his report “Increasing Hereditary Health Problems in the Breeding of Purebred Dogs: A Comparative Overview Using Dobermans in Germany, Europe and in the USA as Examples”
(2002): “Heterozygosity was a great health advantage. Up to approximately 1950, there were practically no hereditary health problems, worldwide. The Doberman was vigorous and long-lived. These qualities still remained in the populations of East Germany and Eastern Europe up to the nineties”…. “In less than 20 years the Doberman changed from a very healthy, vital and long-lived dog breed to a breed that is susceptible to disease with an average life-expectancy less than 7 years
Eventually a close breeding are used by breeders (test mating) to check whether a sire, dam or both are carriers of certain inherited disorders of unknown aetiology. Apart from ethical issues (an increased number of affected individuals must be expected), this is true for dominant disorders with full penetrance but not for autosomal dominance disorders with reduced penetrance as Dilated Cardiomyopathy (DCM) in Dobermann. Mating of two affected dogs may produce an unaffected carrier (silent carrier) which disseminates the disease in his progeny without us noticing.
Is inbreeding on popular sires correlate with genetic diseases?
Apart from the loss of heterosis (hybrid vigour), inbreeding is not bad “per se” but for the presence and concentration of deleterious alleles from few founders and a breed history with an important bottleneck. Inbreeding practices on popular sires increases the probabilities of homozygous of these genes. Even when they were healthy, popular sires are heterozygous carriers of deleterious genes. Inbreeding is what makes them homozygous.
Genetic drift is the change in frequency of particular alleles over time because of random sampling or chance of the genes during the formation of gametes. This genetic phenomenon is especially accentuated in small or isolated populations (as pure breed dogs) with few founders or historical bottlenecks, and those where only a small proportion of animals are used in breeding or there is a disproportion in the reproductive population between males and females (popular sires). Over time there is a tendency for this to lead to complete loss of some alleles, and concentration of others and fixed its frequencies:
The footprint of genetic drift in the genome is the linkage disequilibrium (LD) between alleles. When LD is evidenced some combinations of alleles at two or more loci occur more frequently in a population than would be expected from a random formation of haplotypes from alleles. Association of alleles is due to selection for particular phenotypes as many conformation and character traits. Both traits are polygenic but character traits have low heritability and assorted matings are most probable in the selection. Gray et al., (Genetics 181: 1493–1505, April 2009)
have measured the size of LD for different breeds, included Dobermann. The value for Dobe is 826 kb (kilobases), very similar to Portuguese water dog PWD (846 kb), a breed with a very strong bottleneck in the past (population reduced to very few dogs) and very little population (inscriptions AKC 2006 of 11546 for Dobe versus 1454 for PWD, eight times higher).
As Professor Frank Nicholas underlines (An Introduction to Veterinary Genetics. Blackwell's Science. 2009. Third Edition p. 156
): “A genetic contribution to the aetiology of a disorder is indicated if incidence is higher in some families than in others within a breed, and also incidence is higher in some breeds than in others
”. Nearly half of genetic diseases reported in dogs occur predominantly or exclusively in one or a few breeds. Susceptibility of some breeds to particular diseases coupled with a near absence in other breeds indicates that a subset of dog breeds is strongly enriched for particular disease alleles propitiated by origination from a small group of founders, population bottlenecks and popular sire effects (Sutter and Ostrander. Nat Rev Genet. 2004 Dec; 5(12):900-10
Dobermann breed is predisposed for about 70 diseases (Breed Predispositions to Disease in Dogs & Cats, Alex Gough & Alison Thomas, 2000, Blackwell Publising, ISBN 1-4051-0748-0
); many of them have a genetic or familial component. Most recent genetic disorder described in Dobermann is a canine compulsive disorder: pica and flank sucking /blanket sucking; it is associated with a risk allele located in chromosome 7 within the region of adhesion neuronal protein N-CDH mediator in the regulation of synaptic activity (Dodman et al. 2010. Molecular Psychiatry 15, 8–10
). Also recently is described the Dobermann’s predisposition to a unusual soft tissue tumour in dogs: canine synovial myxoma (Craig et al., July 2010, Veterinary Pathology, 47 (4)
Population structure of a breed is the amount and distribution of genetic variation among populations through her history. Studies of population structure demonstrate that popular sires are critical for genetic diversity much more that the absolute value of inbreeding coefficient (Calboli et al. 2008; Genetics 179(1): 593–601
). The method of selection on popular sires and not the total population is decisive to accumulate disorders, as probe the study of Summers et al. (Veterinary Journal, Volume 183, Issue 1, January 2010, Pages 39-45)
. The breeds accumulate a major number of diseases are the most popular: German shepherd and Golden Retriever.
The popular sire practice leads to a dissemination of genetic disorders. Simulations shown that under a realistic scenario regarding the imbalance in the use of sires, the dissemination of the risk was indeed 4.4 times higher than under random mating conditions. In contrast, line breeding and close breeding practices tend to decrease the risk of the dissemination of genetic disorders (Leroy and Baumung, Anim Genet. 2010, Journal compilation. Stichting International Foundation for Animal Genetics
). So? The problem is that with the population structure of Dobermann is impossible to make an inbreeding mating without a strong top sire effect.
The history is always the same and anyone can be to do it. It is not necessary be a genius. A typical breeding plan: "My approach would be to identify an outstanding, dominant stud dog: call him Superdobe. I'd buy two bitches whose grandsire on the dam's side was the same as Superdobe. I would breed bitches of the Superdobe’s grandsire to Superdobe. Assume, in this first generation, that I get two nice bitches. For the second generation, I'd breed them to a half-brother of these two bitches (Superdobe’s son, also a dominant sire)." Then problems arise. What can we do about genetic diversity of the population in the next generation if most dogs (males and females) are sired by Gino, Fedor, F’Hiram and relatives? Even these three dogs are related by kinship. What is the limit?
Everyone can do what he wants but the link between inbreeding on popular sires and the increase of genetic disease risk is a scientific conclusion not an interested view. A purebred dog with the genetic history of Dobermann it is a very delicate genetic entity to be handled carefully.
Genetic diversity and gene pool
However, as I have described in my last note, when we speak about genes of major histocompatibility complex MHC it is not required the existence of deleterious genes. The loss of heterozygosis and especially the allele loss increase “per se” the risk for immune or autoimmune diseases. It is a simple but critical problem of combinatory between MHC genes and alleles.
Different continental bloodlines share founder effect and bottleneck in the World War II, but not popular sires after fifties between America & Europe. There is a way of diversity to exploit with healthy dogs. Based on the paper of Quignon et al. (2007, Plos One, Issue 12, e1324)
I estimate an approximate 10% of genetic intercontinental variation in this way.
For the genes of Major Histocompatibility Complex (MHC) there isn’t solution because the problem is an irreversible loss of alleles although there are some differences in the MHC haplotypes between the American and European lines. The advantage of these matings is that the effect of MHC genes is codominant and additive.
My opinion above intercontinental matings for improves genetic diversity is just technical and I can fully understand that Americans dogs don’t like in Europe and on the contrary. In this case only remain the cross with another breed(s) and posterior backcrossing way or the resignation with the actual situation.
I think that mating with other breed or with a hybrid of two other breeds, and subsequent backcrossing is a reasonable way to overcome the problems of genetic diseases and diversity. Anyway I am somewhat sceptical because it does not much believe in the reaction of the breeder’s majority. People have always been fascinated with the idea of purity and elite hierarchy. Until European royalty has understood the need for marriages between not related individuals but dog breeders continue to consider “the sanctity of the breed purity”.
I tell you an instructive example:
Dalmatian is a breed with many genetic diseases, particularly hyperuricemia. This genetic disease is associated with a mutation of the SLC2A9 transporter gene and all Dalmatians are homozygous for the mutant recessive allele (Bannasch et al. 2008. PLoS Genetics; V4; Issue 11, e1000246, p.8
). The professor of Genetics Robert Schaible (Indiana University) starting in 1973 a backcross breeding program mating a Dalmatian to a English Pointer with normal levels of uric acid. Breed generation after generation of offspring back to purebred Dalmatians. In each generation he tests the offspring and used only those with normal levels of uric to produce the next generation. After four generations of backcrossing to Dalmatians, the dogs had all the characteristics of Dalmatians except for the uric acid defect.
At that point, Dr. Schaible contacted the AKC to request registration for two of his dogs. In 1981, after a careful review of all the data from Dr. Schaible's backcross breeding program, the AKC registered two of his dogs. The President of the AKC issued the following statement: "If there is a logical, scientific way to correct genetic health problems associated with certain breed traits and still preserve the integrity of the breed standard, it is incumbent upon the American Kennel Club to lead the way
Unfortunately, Dr. Schaible's remarkable achievement causes considerable controversy in Dalmatian breeding circles about “purity” although the stud book was open until the late 40's. In 1984, under pressure from members of the Dalmatian Club of America (DCA), the AKC informed Dr. Schaible they would not register any more Dalmatians from his line as long as DCA objected to them. So, Dr. Schaible turned to the United Kennel Club (UKC) to register his dogs. DCA refused newly in 2006 to reconsider the backcrossing project.
AKC Dalmatians can boast of being very pure but all Dalmatians are affected by this disorder and 34% of males show clinical manifestation of urate calculi. Although breed purity is important in purebred dogs, the small amount of Pointer DNA remaining in the backcrossing Dalmatians (minor of 0.05%) seems a small price to pay for disease elimination.