Sometimes I write articles that for various club political reasons the publisher decides would be bad for business and kills the article. This is one of them:
The ABCs of DNA, the Z-List, and Albinos
Alan: "My uncle Roger says he saw an albino polar bear once."
Stu: "Really? Polar bears are white, how did he know it was albino?"
Alan: "This one was black."
Stu: "Uh, are you sure it wasn't a black bear?"
Alan: [after thinking] "Whatevs."
--From that movie classic, The Hangover 2.
The jury's still out on whether albino polar bears exist. But they probably do, since albino black bears and other bears exist. As well as albino humans, monkeys, bats, rats, mice, snakes, alligators, birds, lobsters and even bugs. And remember Moby Dick? The Great White Whale wasn't necessarily a figment of Melville's imagination. A 45 ft albino humpback whale was sighted off the coast of Australia in 1991.
So where are the Moby Dicks of dogdom? You'd think that as malleable as the canine species is, with all the various traits and oddities selectively bred to make new breeds, pink-eyed dogs would be as common as pink-eyed lab rats. Or polar bears.
In fact, until recently, a lot of people denied they even existed. Sort of like Moby Dick. Sure, white dogs are everywhere. But albino dogs aren't just white; they have a complete or almost complete lack of pigment in the fur, skin, eyes, and nose.
In 1976, a white female Doberman Pinscher named Padula's Queen Shebah was born to two black and rust parents. Shebah was bred to her son to produce more white Dobermans. Since then, several thousand Dobermans, many of them "white," have descended from Shebah.
Although they're called white, they're actually light cream, with blue eyes and pink nose, lips and eye rims. The Doberman Pinscher Club of America (DPCA), backed by several geneticists, contended early on they were albinos. Many white Dobe proponents argued they were not albinos, contending they had some pigmentation and that further, albinos were not seen in any dog breeds.
They were wrong.
Albinism comes in many forms, and isn't limited to the prototypical white fur and pink eyes. More than 60 different gene mutations in various species are known to cause albinism, often with slightly different effects. Light hair with blue eyes is typical of the most common type of albinism, oculocutaneous albinism type 2 (OCA2), in humans. Dogs with light cream fur and blue eyes are seen in several domestic dog breeds, most notably Pekingese, but they've also been seen in Shih Tzu, Poodles, Pit Bulls, Beagles, Pugs, Dachshunds and doubtless, many others. It is now acknowledged that white Dobermans are in fact albinos, and the causative gene has recently been discovered.
In 1982, the DPCA amended its standard to allow only four colors: black, red, blue and fawn (all with tan points). The inheritance of these colors is well established, and occurs through the interaction of alleles at two loci. Genes at the B locus determine whether the color will be black (BB or Bb) or red (bb). Genes at the D locus determine whether colors will be undiluted (DD or Dd) or diluted (dd). A diluted black is blue; a diluted red is fawn (also called Isabella). Initially, nobody knew how white (albino) was inherited.
(Note: from http://cal.vet.upenn.edu/projects/genetic/coatclr/example/page2.htm)
In 1983 the DPCA acquired two albino dogs for test matings. Bred to colored Dobes, the albinos produced only colored offspring, consistent with a recessive mode of inheritance. Further information came from a report of an albino to Isabella (bbdd) mating that produced only black offspring. Since the Isabella parent had to be genetically bbdd, the black offspring must have received the dominant black (B) and dominant undiluted (D) alleles from their albino parent. This meant the albino gene covered up the color that would otherwise have been produced. The results pointed to a recessive gene at a different locus than the B or D genes. A dog with two copies of the albino gene (aa) masks the color that would otherwise be expressed.
(Note: from http://www.discoveryandinnovation.com/BIOL202/notes/lecture4.html)
Health and Temperament Problems?
Albinism is associated with vision and skin problems in many species. Some Doberman breeders also believe it is associated with temperament problems.
Because they lack pigment in the iris (colored part) of the eye, light passes right through the iris and more light reaches the retina. Thus, albino Dobermans are bothered by bright light. They squint in sunlight and may avoid it. In many species, albinism is associated with abnormal visual pathways in the brain, and possibly diminished visual fields or acuity. This is the case with Siamese and albino cats, but it has not been studied in the dog.
Albino Dobermans are prone to sunburn, which may lead to skin tumors. A recent study (Winkler PA, Gornik KR, Ramsey DT, Dubielzig RR, Venta PJ, et al. (2014) A Partial Gene Deletion of SLC45A2 Causes Oculocutaneous Albinism in Doberman Pinscher Dogs. PLoS ONE 9(3): e92127. doi:10.1371/journal.pone.0092127) by doctoral student Paige Winkler and colleagues compared skin and eye tumors of albino Dobermans with normal colored Dobermans. Winkler, of the College of Veterinary Medicine at the University of Michigan in East Lansing, found albino Dobermans have a much higher incidence of eye and skin melanocytic tumors. More than half the 20 albino dogs had at least one of these tumors, compared with only one of the 20 regular-colored dogs. Every albino dog over age 5 had at least one tumor.
"This finally gives us the solid information we never had to educate the public that these albino dogs can have health problems," says former DPCA Health Education coordinator Kathy Davieds, DVM.
More difficult is the question of temperament. Anecdotal evidence of shy, aggressive or difficult to train albinos was bolstered by the dearth of successful albino Dobes at higher levels of performance competitions. Then along came Sprite (Vixen's Apparition Sprite), a rescue albino owned by Karen Kissinger. Sprite not only achieved Utility Dog, Rally Excellent, Masters Agility, Masters Agility Jumpers, and Masters Jumpers Bronze level titles but was a DPCA Obedience Top Twenty Finalist.
Sprite's invitation caused a huge controversy because at the time Sprite was invited the DPCA already had in place a policy stating that albinos shall be ineligible for nomination for all conformation and performance awards, certificates, agility certificates, and competitions of the DPCA including, but not limited to, Longevity Program, Working Aptitude Evaluation, Top Twenty competition, obedience certificates, agility certificates, tracking certificates, and that Z factored Dobermans be allowed to participate in performance awards programs such as Top 20 Obedience and Agility, performance recognition awards, and the WAE only upon submitting proof that the dog was neutered. This policy was re-examined by the DPCA Board several times, with an appeal to the AKC for clarification on whether dogs could be excluded from such events. The AKC said that if qualification is based on AKC competitions, then, no, they couldn't be. The DPCA countered that they may add additional requirements for invitational purposes, but that Dobes of any color can qualify for Top 20 Obedience or Agility ranking. The DPCA felt the inclusion of Sprite's photo at the DPCA legitimized albino breeding and contended that albino breeders used it to further the breeding of these dogs.
Kissinger, an experienced obedience instructor who has trained many dogs, doesn't believe albinos have any more temperament issues than other colors. She believes the poor temperaments described by the DPCA from the test breedings in the 1980s were more likely due to the dogs being kenneled with little human contact. "I've fostered and placed four other albino dogs and they all had delightful personalities," she says.
As far as training: "The only limitation with Sprite is trying to avoid being out in the intense summer sun. With no pigment, these dogs can burn in a short period of time. We train indoors, in the shade, or after dark. The only time she's had a problem with her vision is when she happened to be directly facing the rising or setting sun. She seems to see fine outside when the sun is overhead."
Sprite is Kissinger's second albino rescue. Her first, Bella, now age 12, was a therapy dog. "Even when the Alzheimer's patients pulled, poked, squeezed, and even tried to bite her nose, she stayed totally collected."
Both Sprite and Bella have led healthy lives, and "both tested normal for all the known diseases found in the breed. Normal vWD, thyroid, cardiac, and so on," says Kissinger, who is also a veterinary technician. "I've had absolutely no health issues and the new owners of my albino fosters have said the same. The albinos usually expire for all the same reasons as the others. The average age is between 10 to 14 years." No data exist to compare longevity between albino and colored Dobermans.
Kissinger doesn't believe albinos should be purposefully bred. "However, with that said, once they're here, they still make wonderful pets. They're no different than their colored relatives... It takes a little extra effort but they're still Dobermans."
The Z List
Because the albino gene is a recessive, the DPCA feared breeders could unknowingly mate two carriers and produce albinos. To prevent this, the AKC agreed to track all descendents of Shebah's parents, labeling any descendents born after 1995 with AKC registration numbers beginning with "WZ." Every AKC registered descendant of these dogs is recorded in the "Z list," even those who were born before the WZ registration numbers were instituted.
Every known albino Doberman has come from dogs on the Z list. However, a dog on the Z list doesn't necessarily carry the albino gene. Although both Shebah's parents must have carried the gene, on average one quarter of their offspring would not have inherited any copies. Even those that were carriers would have passed on their recessive gene to only half of their offspring on average. In each generation the chance of being a carrier is halved. This means that many of the dogs on the Z list are not carriers.
In addition, it's possible carriers could exist that aren't on the Z list. A notation on Shebah's pedigree describes her as the "first white Doberman not put to sleep," implying others were born before her; in fact her breeders claimed her parents had previously produced a white male that died. Researchers believe the albino gene mutation must have occurred at least five generations before Shebah. Since both Shebah's parents had to be carriers, it's most likely they in turn inherited it from a common ancestor. The first common ancestors behind Shebah's parents occur five generations before Shebah. Kathie Davieds, DVM and Marge Brooks, who is on the DPCA BOD, traced Shebah's pedigree and found the following common ancestors:
- Singenwald's Prince Kuhio appears four generations behind Shebah's sire and five behind her dam.
- Dobe Acres Cinnamon appears four and five generations behind Shebah's sire and six behind her dam.
· Seven generations behind both sire and dam appear (often multiple times) Dictator v Glenhuegel, Emporer of Marienland, Alcor v Millsdod and Dow's Illena of Marienland. In the next generation common ancestors are Domossi of Marienland, Westphalia's Uranus, Favoriet V. Franzhof and Blank vd Domstadt.
Nobody knows which of Shebah's common ancestors might have been "the" common carrier. But any of these dogs could have been the one. Whichever one it was would have had a 50% chance of passing the albino gene to each of its offspring, which happened generation after generation on down to Shebah's parents. Only when two carriers were bred together did an albino occur. The problem is we don't know which one of these ancestors it was. To be fair, it could even be another common ancestor even farther back; however, if Shebah was in fact the first albino Dobe it seems more likely the original mutation occurred in a closer generation. But was she the first? Remember, printed (not handwritten) on her pedigree appears this statement: "Shebah was the first white Doberman that was not put to sleep."
If white Dobermans were born before Shebah, then Davieds and Brooks conlcude that "without knowledge of how many such puppies and more importantly, for how many generations this may have occurred prior to the appearance of Shebah, it is completely possible that the original spontaneous mutation occurred eight or more generations behind Shebah."
Every earlier carrier would be as much a carrier as would each of Shebah's offspring. Every carrier would warrant being on the Z list. But without knowing which lines brought the mutation to Shebah, all of these carriers escaped Z listing. And some of Shebah's common ancestors are behind many of today's popular lines. It's not just a possibility that some non-Z-list carriers are out there, but a probability. The only way the Z-list would have caught every carrier would be if the mutation occurred spontaneously in both Shebah's sire and dam, or if none of the common ancestors behind them produced any other existing descendants.
Note, however, there's never been a documented case of an albino Doberman born to a dog not on the Z list. Although there are accusations that show breeders euthanize albinos before anyone can know about them, it seems odd that none have been reported from all the Dobes bred in pet homes.
Without a DNA test, the Z list was the best tool available. That's now changed. Paige and colleagues screened DNA samples from albino Dobermans to determine if genes known to cause oculocutaneous albinism in humans were responsible. A mutation in SLC45A2 was found to be linked to albinism. Every albino dog tested had the mutation, whereas none of the non-Z-list dogs had it. The mutation is not a part of any of the known dog color loci. This includes the C series, where mutations causing albinism in many others species have been identified. However, mutations in SLC45A2 cause the OCA4 type of albinism responsible for cream-colored Bengal tigers, horses, and gorillas, as well as some albino humans.
"This comes as a welcome vindication that we were correct when we identified Shebah as an albino Doberman and not merely 'white' as others have claimed," says DPCA President Michelle Santana.
VetGen (www.vetgen.com) is now offering the DNA test for albinism in Doberman Pinschers commercially. Most of the 100 dogs they've tested so far were tested as part of research prior to offering the test. "We tested 80 phenotypically normal Z list dogs and 17 (21.25%) of them were carriers and the rest were clear," says Robert Loechel, chief scientific officer for VetGen Veterinary Genetic Services based in Ann Arbor, Mich. "Some of these dogs were known carriers and some came from kennels that regularly produced white dogs, so the true frequency of carriers in phenotypically normal dogs for the total Z list population is probably much lower."
Loechel believes the test should be of particular interest to owners of phenotypically normal Z list dogs who may want to know if their dogs are free of the mutation. "It may also be of interest to those with dogs that do not carry the WZ designation. Due to the recessive nature of the mutation, it seems likely it existed for at least a few generations prior to the dogs that mark the genesis of the Z list." Loechel says they haven't looked at enough non-Z-list dogs to know if any are carriers yet.
But the test is controversial. Advocates see it as a welcome means to allow cleared Z-list dogs back into the gene pool. Opponents contend Z-list dogs are so poorly bred that even if they don't carry albinism they still won't be good for the breed. They object to the DNA test because they see it as a tool for unscrupulous breeders aiming to produce albinos to screen their stock for the mutation and then purposefully breed two carriers together. Advocates counter that breeding carriers would be economically foolish if the aim were to produce albinos, since on average only a quarter of the puppies would be albino. Breeding albino to albino is the most economical way to produce more albinos.
Advocates also believe there may be Dobes not on the Z-list that carry the mutation, and feel they would breed with more confidence if all dogs---or at least those descending from Shebah's common ancestors---were screened beforehand. Once both parents are tested clear, there's no need for further testing of their offspring. And if a carrier is identified, it's no cause for Z-listing or shunning. Just make sure not to breed a carrier to another carrier, which is easily accomplished with DNA testing of prospective mates. Opponents of the test contend there is no need for testing as there is no record of non-Z-list Dobes producing albinos. "To our knowledge, Sheba was the first and only spontaneously born albino and we do not consider albinism to be a problem in our breed," says Santana. "That said, however, Sheba was exploited by breeders for the sole purpose of producing more albino Dobermans and that exploitation continues."
At present, the DPCA does not plan to change its policy regarding the Z list. "The DPCA vigorously opposes the deliberate breeding of a genetic defect without regard to the serious health problems inherent to albinism," says Santana. "For this reason, we will continue to enforce the use of Z-tracking in partnership with the AKC and any descendant of Shebah will be registered with the Z designation even if they test clear of the albino gene. It is our only way of tracking Shebah's descendants and it has been highly effective."