What genes (i.e. ASIP MC1R KIT) are modified by each loci?

[user 7388]

Hello again, been a while since I've popped by. I'm getting back into my research and needed some help.
I've searched the forum and found a few discussions about this, but nothing comprehensive.

Does anyone have a list of all the genes mutated at each locus?

From my research this is as far as I've got:

A - ASIP
B - TYRP1
C - TYR, I think
D - MLPH
E - MC1R
P - OCA2
En - KIT
V - MITF, maybe?

Looking for more info about Du and W, mainly. And Si. I'm pretty sure I had a tab open for a gene I suspected was related to Si but I've lost it now and my brain is fried. I know a few of you have dug deep enough to have an idea about the actual genes themselves so hopefully you either have a resource or just know off hand.

Is Du also KIT, or MITF? Is W also ASIP, somehow? Is Si IRF4, like premature greying in humans?

Thanks in advance!

Edit: wait, is Du MITF and is v OCA4/SLC45A2, maybe? Seems to have the same effect in dogs, according to Wikipedia... there’s also EDNRB as a culprit. Thanks again!

 

[Zass]

It's interesting. Do you have any sources?

 

[user 7388]

Edit: Actually you can ignore everything below this and just look at: https://www.mdpi.com/2076-3417/11/1/373/pdf This 2019-2020 study says everything all these links below say, that is tested and known. It would appear further colour mutation gene mechanisms are unknown, although this paper also shows rex, angora, and has a chart with each allele mutation as well. Quite comprehensive. Unfortunately this suggests that I won't find the answers I'm looking for and will have to make guesses for now. Thanks!

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I was asking for sources! Actually I was hoping you would know, Zass, I saw you talking about some of the genes like KIT in another thread.

But here are the studies I pulled what I have from:
ASIP https://pubmed.ncbi.nlm.nih.gov/20004240/
TYRP1 https://pubmed.ncbi.nlm.nih.gov/24814776/
TYR https://www.tandfonline.com/doi/pdf/10. ... 21.1877574
MLPH https://journals.plos.org/plosone/artic ... ne.0084525
MC1R (ej) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236303/
MC1R https://onlinelibrary.wiley.com/doi/10. ... 06.01494.x

A lot of that is already super well understood in rabbits, as well as cats, dogs, horses, mice, etc. The Wikipedia pages will also say as much. Given that this link talks about black and white rabbits and MITF, that's what's making me think Dutch might be the MITF gene: https://www.researchgate.net/publicatio ... oat_Colors

Black and white might have meant butterfly/broken/English spotting except there's this that suggests it's KIT for En: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988019/

We know lutino/P locus is OCA2. The P protein malfunction is well understood in pink-eyed albinism. "P protein, also known as melanocyte-specific transporter protein or pink-eyed dilution protein homolog, is a protein that in humans is encoded by the oculocutaneous albinism II (OCA2) gene." I don't have an article, but there's nothing groundbreaking here. Similarly, the TYR malfunction for cc albinism is well understood to be the cause of OCA1 albinism and is synonymous.

My inference, then, is that Vienna might be OCA4/SLC45A2. From Wikipedia: "SLC45A2 is the so-called cream gene responsible in horses for buckskin, palomino and cremello coloration, while a mutation in this gene underlies the white tiger variant. In dogs a mutation to this gene causes white fur, pink skin, and blue eyes." https://academic.oup.com/jhered/article ... 85/2961854 ...but I can't find a study for confirmation, so was asking with this post, hoping you might know.

Interestingly looking at the Wikipedia page for OCA in general, OCA3 seems to be another term for bb/TYRP1 dysfunction. Unless this is a more severe form, which suggests that there could one day be another B-locus mutation that's more recessive to chocolate which would be even more reduced pigment. https://en.wikipedia.org/wiki/Oculocutaneous_albinism It also talks about SLC24A5, but that doesn't seem to associate to any known rabbit mutation (these are, after all, human variants, although they correlate fairly 1:1 for a lot of dysfunctions.)

So that leaves us with W and Si. I can't find any concrete info on these which is what I'm really looking for. I found this article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566412/ which mentions a few genes and proteins: Slc7a11 and POU2F1 in the title, the body mentions CREB1 which I hadn't encountered before. This article mentions "Melanocyte apoptosis rate was determined after knockdown of Slc7a11" which could be sisi. I also mentioned IRF1 for sisi: https://en.wikipedia.org/wiki/IRF4 From here, "A variant has been implicated in greying of hair." While I wouldn't necessarily call silvering the same as greying in humans, I suppose it could be...

So while I'm fairly confident on the gene mechanisms behind loci A, B, C, D, E, En, P based on established research, and somewhat satisfied with Du and V making some inferences (but need confirmation if anyone has it), I still need information about Si and W, if anyone has it.

 

[reh]

Maybe you can read this book in a library, not rabbit, but a lot of information about genes:
Lamoreux, Delmas & Bennett 2010. The Colors of Mice: A Model Genetic Network. Wiley-Blackwell.https://www.wiley.com/en-us/The+Colors+of+Mice:+A+Model+Genetic+Network+-p-9781405179546.

 

[user 7388]

@reh I'll check that out, thanks! I've read a few textbooks on rabbit genes/colouration as well as other mammal coat patterns but it's always classical genetics, not modern genetics. It looks like this book does discuss modern/molecular genetics, but as it's mice and not rabbits it won't have some of the niche and specific phenotypes I'm trying to suss out the root cause, but perhaps it can guide me in some interesting directions.

 

[reh]

It definitely will. I read it very thoroughly years ago. It explains how genes work and which genes are at work and all this signaling pathways and it even has at least one rabbit image (and dogs and other mammals).
I consider it like the robinson - on of the very comprehensive, important ones and it helped me a lot for the article series i wrote around 2012 (nonenglish).
But it dont contains anything about temperature sensitivity in tortoise rabbits ;-)

 

[reh]

I found something interesting about wideband in other animals:

If Corin is defective the agouti band becomes wide

Enshell-Seijffers, David, Catherine Lindon, und Bruce A Morgan. „The serine protease Corin is a novel modifier of the Agouti pathway“. Development (Cambridge, England) 135, Nr. 2 (Januar 2008): 217–25. The serine protease Corin is a novel modifier of the agouti pathway | Development | The Company of Biologists.
mice with wide agouti band

Xu, Xiao, Gui-Xin Dong, Anne Schmidt-Küntzel, Xue-Li Zhang, Yan Zhuang, Run Fang, Xin Sun, u. a. „The Genetics of Tiger Pelage Color Variations“. Cell Research 27, Nr. 7 (Juli 2017): 954–57. https://doi.org/10.1038/cr.2017.32.
golden wideband tigers with corin mutation

Avigad Laron, Efrat, Emil Aamar, und David Enshell-Seijffers. „The Serine Protease Activity of Corin Is Required for Normal Pigment Type Switching“. Journal of Investigative Dermatology 139, Nr. 1 (Januar 2019): 257–59. Redirecting.
"Initially, a direct protein-protein interaction between the LDLR domains of Corin and Agouti recruits Agouti to the vicinity of the protease domain, and subsequently, the serine protease activity of Corin inactivates Agouti by proteolytic cleavage."

Beauvois, H., C. Dufaure de Citres, V. Gache, und M. Abitbol. „Siberian Cats Help in Solving Part of the Mystery Surrounding Golden Cats“. Animal Genetics, 10. Mai 2021. Error - Cookies Turned Off.
golden cats with corin mutation

 

[reh]

Shades of meaning: the pigment-type switching system as a tool for discovery
https://onlinelibrary.wiley.com/doi/10.1111/j.1755-148X.2010.00721.x

 

[reh]

ok, corin is on chromosome 2, but agouti and dwarf on chr. 4 - wideband should be chr. 4 too..