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post #1 of 5 (permalink) Old 08-21-2016, 07:21 AM Thread Starter
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CDA genetics

I've been wondering about the genetics behind CDA and how it can (could) affect non-dilute dobermans. I have seen it mentioned several places that it is believed that CDA is linked to a "faulty" d-locus gene, d(l), and that it has incomplete dominance to the healthy/normal dilution gene, d. This would account for the severity of CDA seen in dilutes: both healthy genes dd would be unaffected, heterozygous dd(l) would be moderately affected, and both unhealthy d(l)d(l) would be severely affected.

Forgetting the alopecia for a moment and discussing color: we know dilution d is recessive to non-dilution D. So, if you had a non-dilute doberman that carried an unhealthy dilution gene, Dd(l), could you not get a non-dilute dog affected by "CDA"? Or would the non-dilute D suppress any expression of the faulty d(l)?

I ask because Shiner's got some thinning hair on her rump (yes we're running a full thyroid panel) and the vet said that under the microscope her hair shafts display moderately-clumped melanin. Clumped melanin is the defining trait of CDA (though usually more/worse/larger clumps) and yet Shiner is red, not fawn or blue. And I've found a few other mentions of CDA affecting "reds sometimes" but no mention as to whether they were dilute-carrying or not.

By extension, if carrying a faulty dilution gene can produce mild symptoms of CDA in a red dog, could it not do the same for a black dog? Are there black dobermans who suffer from follicular dysplasia that resembles mild CDA?

I'm curious about this and no combination of google key words has led me to a definitive answer yet.
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post #2 of 5 (permalink) Old 08-21-2016, 10:44 AM
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I'd like to know where you have found information linking CDA to a gene mutation on the D locus. From fairly superficial evidence it is believed that CDA in the dilute Doberman is genetic--but to the best of my knowlege there is no specific evidence (yet) exactly what gene or genes might be involved.

So the short answer to the question of follicular dysplasia affecting both black and red dogs is yes--any text on dermatology discusses this. One of the things you can find quite a lot of information on is a problem called "black dog alopecia". Take a look at that. But since this is a disease that is found in many dogs but is more common in black dogs (hence it's name) it has never been linked to CDA as it appears in Dobes. Follicular dysplasia itself is found in many dogs of many breeds and many colors--it's definitely not confined to dilute Dobermans.

Here's some information that may be of interest. There are similar coat problems that occur in black and in red Dobermans--and they may or may not carry dilution so it is generally believed that the dilution gene does affect coats (other than the color). But these are not thought to be related to CDA.

There are a multitude of genetic issues that don't exhibit incomplete penetration. The black/red coat color in dobes. The recessive red if present doesn't modify the dominant color black. vWD is another--affected (two defective genes) may or may not be clinical (symptomatic) but carriers (one normal and one defective gene) aren't going to be sort of affected.

The geneticist whose brain I pick about stuff like this told me that the difference in how greatly affected by CDA a dilute dog may be is more likely to be an entirely separate gene which is a modifier--modifying genes are very common and often not at all easy to trace.

I don't think, at this time, there are any definitive answers--which probably explains why you haven't found any. But it wasn't all that long ago that there was no genetic test for dilution and even more recently there is now a test for albinism so there is still hope for the future.
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post #3 of 5 (permalink) Old 08-21-2016, 03:00 PM Thread Starter
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Quote:
Originally Posted by dobebug View Post
I'd like to know where you have found information linking CDA to a gene mutation on the D locus. From fairly superficial evidence it is believed that CDA in the dilute Doberman is genetic--but to the best of my knowlege there is no specific evidence (yet) exactly what gene or genes might be involved.
I first heard mention of it here: Dog Coat Colour Genetics
CDA does not occur on all dilutes and its frequency varies between breeds. It is particularly common in Dobermanns, occuring in up to 80% of dilute dogs. Dilutes in other species such as mice are caused by the same gene, and yet CDA is not known in these, implying it is not an unavoidable consequence of dilution. It is thought that CDA may be caused by a specific dilution gene - labelled dl. Just as there are various different b alleles that all cause the liver colour (phenotypically the same, so only distinguishable through genetic testing), it is probable that there are a number of different d alleles as well, and only one of these causes CDA. Technically this makes CDA a recessive allele, as it is recessive to D (non-dilute, non-CDA) however dl is most likely dominant over the standard d allele.

Which was corroborated by this article hosted on the DPCA site: https://www.dpca.org/BreedEd/article...ution-alopecia
A third allele (dl) which is associated with CDA has been proposed.6 While this is a long way from being proven, it could help explain why some dilute animals are unaffected. Dogs with a genotype dd would be normal coated dilutes, ddl would be intermediates (mildly affected?) and dldl would be CDA affected. A genotype of Ddl should represent deeply pigmented dogs which were carriers of CDA.

I can't get beyond the paywall for this article: Colour Dilution Alopecia in Doberman Pinschers with Blue or Fawn Coat Colours: A Study on the Incidence and Histopathology of this Disorder - MILLER - 1990 - Veterinary Dermatology - Wiley Online Library
But another I have access to quotes it:
. Miller (1990) suggested that there were possibly multiple recessive alleles of the dilution gene

Quote:
Originally Posted by dobebug View Post
The geneticist whose brain I pick about stuff like this told me that the difference in how greatly affected by CDA a dilute dog may be is more likely to be an entirely separate gene which is a modifier--modifying genes are very common and often not at all easy to trace.
Fair enough! Conjecture about d(l) could very well be some sort of association between d and this other gene, like with (pre-LUA) dalmatians and HUA: it's not that the gene for spots caused HUA but that all genes for spots were associated with HUA. I guess I'll have to wait and see what the science ends up being in another ten or twenty years!
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post #4 of 5 (permalink) Old 08-21-2016, 07:16 PM
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it's called follicular dysplasia, and can occur in red or black dogs. in blues and fawns, the CDA is a type of follicular dysplasia.


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post #5 of 5 (permalink) Old 08-22-2016, 05:46 PM
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Quote:
Originally Posted by golai View Post
I first heard mention of it here: Dog Coat Colour Genetics
CDA does not occur on all dilutes and its frequency varies between breeds. It is particularly common in Dobermanns, occuring in up to 80% of dilute dogs. Dilutes in other species such as mice are caused by the same gene, and yet CDA is not known in these, implying it is not an unavoidable consequence of dilution. It is thought that CDA may be caused by a specific dilution gene - labelled dl. Just as there are various different b alleles that all cause the liver colour (phenotypically the same, so only distinguishable through genetic testing), it is probable that there are a number of different d alleles as well, and only one of these causes CDA. Technically this makes CDA a recessive allele, as it is recessive to D (non-dilute, non-CDA) however dl is most likely dominant over the standard d allele.
I finally had an chance to go read these sites--thanks so much for including them--I think from what I read that the existence of a dl gene remains pretty speculative.

Quote:
Which was corroborated by this article hosted on the DPCA site: https://www.dpca.org/BreedEd/article...ution-alopecia
A third allele (dl) which is associated with CDA has been proposed.6 While this is a long way from being proven, it could help explain why some dilute animals are unaffected. Dogs with a genotype dd would be normal coated dilutes, ddl would be intermediates (mildly affected?) and dldl would be CDA affected. A genotype of Ddl should represent deeply pigmented dogs which were carriers of CDA.
The DPCA Breeders Education article also uses the word "proposed" and goes on to note that "this is a long way from being proven,"

I lost a bunch of reference sites when an old computer basically gagged and died--eating the contents of its hard drive in the process. As far as I remember all of them who had information about possible genetic causes for CDA in the Doberman pretty much echo'd the fact that the possibility of a multiple d allel's incuding a defective dl were speculative.

Quote:
I can't get beyond the paywall for this article: Colour Dilution Alopecia in Doberman Pinschers with Blue or Fawn Coat Colours: A Study on the Incidence and Histopathology of this Disorder - MILLER - 1990 - Veterinary Dermatology - Wiley Online Library
But another I have access to quotes it:
. Miller (1990) suggested that there were possibly multiple recessive alleles of the dilution gene
I couldn't either, but genetics has come such a long way since the original 1990 study, although I'd like to have been able to read it I'm not sure that much of its information may have been superceded by now.

There was a vet dermatologist who some years ago was sure that he had the answer to red Dobermans who had follicular dysplasia--or rather the cause of it in red Dobermans. He was certain that it occured because they carried dilution. At that time there was no way to prove or disprove his theory because there was no gene test for dilution and most of us who had been in Dobes for any length of time knew of cases where, being the recessive that it was dilutions could lie hidden for generations. But ultimately that vet had to give up his theory (of course it was a study of only one case--and you could argue that the n was too small to prove anything) when a red Doberman he had dxd with follicular dysplasia secondary to carrying a dilution gene got tested for dilution when the gene test was released and the dog turned out to NOT carry dilution.

Quote:
Fair enough! Conjecture about d(l) could very well be some sort of association between d and this other gene, like with (pre-LUA) dalmatians and HUA: it's not that the gene for spots caused HUA but that all genes for spots were associated with HUA. I guess I'll have to wait and see what the science ends up being in another ten or twenty years!
Yeah, me too--but I've waited this long, so maybe I'll actually live long enough for the folks who do this stuff to figure it out.

<vbg> I'll leave you with another one to contemplate though--I've seen a very few old dilute dogs who had perfect coats right up the time they died--really very few--one blue and two fawns. And I've heard about a few more that I never saw--very few. And I know a vet, who, when she was still in vet school did a very elaborate study and produced a paper on CDA in dilute Dobermans. We talked about her paper and what she found several times and the thing I remember best was the fact that while she found some dilute dogs with good coats she said you'd never want to try to produce dilute Dobes with good coats from them. She said that they so little resembled a Doberman that if she hadn't seen the AKC registrations and pedigrees (some that went back 8 and 10 generations) she'd hardly have believed they were Dobe--but they did have great coats--the old dogs and the young dogs.
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