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{{Table|2=asdf}}{{User sandbox}}
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== me messing around with dog gene article structure ==
{{short description|Alteration in the nucleotide sequence of a genome}}
<br />
Dog coat color is governed by how genes are passed from dogs to their puppies and how those genes are expressed in each dog. Dogs have about 19,000 genes in their genome but only a handful affect the physical variations in their coats. And the usual rules apply—most genes come in pairs, one from the dog’s mother and one from its father. Genes of interest have more than one version, or [[allele]]. Usually only one or a small number of alleles exist for each gene. So, at any one gene locus a dog will either be [[homozygous]], that is, the gene is made of two identical alleles (one from its mother and one its father) or [[heterozygous]], that is, the gene is made of two different alleles (again, one inherited from each parent).

To understand why a dog’s coat looks the way it does based on its genes requires an understanding of a handful of particular dog coat genes and their alleles. For example, if you wanted to find out how a black and white greyhound that seems to have wavy hair got its coat, you would want to look into the dominant black gene with its K and k alleles, the (white) spotting gene with its multiple alleles, and the R and r alleles of the curl gene.

== Terms to consider ==
follicular melanocytes

deposition of pigment granules/melanosomes

pigment switching

hair follicle: hair bulb

==Genes associated with coat color==
{{see also|biological inheritance|Introduction to genetics}}

=== Pigment production ===
{{CSS image crop
|Image = Localization of melanocyte stem cells in the hair follicle..jpg
|bSize = 500
|cWidth = 275
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|Description = Melanocytes localize to the bulb of a hair follicle. These cells produce pigment granules (melanosomes), which are transferred into the growing hair.
}}

Each [[hair follicle]] is surrounded by many [[Melanocyte|melanocytes]] (pigment cells), which make and transfer the pigment [[melanin]] into a developing hair. Dog fur is colored by two types of melanin: [[eumelanin]] (brownish-black) and[[phaeomelanin]] (reddish-yellow). A melanocyte can be signaled to produce either color of melanin.

The various dog coat colors are from patterns of:

*'''Eumelanin''' — black, chocolate brown, grey or taupe pigment;
*'''Phaeomelanin''' — tan pigment, including all shades of red, gold and cream pigment; and/or
*'''Lack of melanin''' — white (no pigment).

Melanin is synthesized and stored in specialized organelles inside the melanocyte called [[Melanosome|melanosomes]]. When mature, these melanosomes are transferred out of the cell and into the developing hair. Melanin synthesis is a multistep process; some enzymes are involved in both the eumelanin and phaeomelanin pathways, while others are used to produce only one of the pigments.<ref>{{Cite journal|last=D’Mello|first=Stacey|last2=Finlay|first2=Graeme|last3=Baguley|first3=Bruce|last4=Askarian-Amiri|first4=Marjan|date=2016-07-15|title=Signaling Pathways in Melanogenesis|url=http://www.mdpi.com/1422-0067/17/7/1144|journal=International Journal of Molecular Sciences|language=en|volume=17|issue=7|pages=1144|doi=10.3390/ijms17071144|issn=1422-0067|pmc=PMC4964517|pmid=27428965}}</ref>

The process of coloring a hair is complicated, and coat color can be altered at many steps along the way, including:

* pigment cell (melanocyte) development and survival.
*signaling a melanocyte to produce eumelanin vs phaeomelanin.
*melanin synthesis pathway.
*transport of melanosomes into the hair follicle. <ref name=":2" />

Currently eight [[gene]]s in the canine [[genome]] are verified to determine coat color. Each of these has at least two known [[allele]]s. Together these genes account for the variation in coat color seen in dogs. Each gene has a unique, fixed location, known as a [[locus (genetics)|locus]], within the dog genome.

=== Pigment color loci ===
Several loci can be grouped as determining a "baseline" melanin color: the Brown (B) and Dilution (D) loci.

==== B (brown) locus ====
{{Multiple image
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| image1 = Black Labrador in Snow.jpg
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| caption1 = Genotype B/B or B/b
| image2 = MG 3867 Joucas 20090418.jpg
| caption2 = Genotype b/b
}}
The gene at the B locus is known as '''[[TYRP1|tyrosinase related protein 1]]''' (TYRP1). This gene affects the color of the eumelanin pigment produced, making it either black or brown. TYRP1 is an enzyme involved in the synthesis of [[Melanin|eumelanin]]; alleles at the B locus affect TYRP1 production in the coat and skin (including the nose and paw pads).<ref name=":1">{{Cite journal|last=Schmutz|first=Sheila M.|last2=Berryere|first2=Tom G.|last3=Goldfinch|first3=Angela D.|date=2002-07-01|title=TYRP1 and MC1R genotypes and their effects on coat color in dogs|journal=Mammalian Genome|volume=13|issue=7|pages=380–387|doi=10.1007/s00335-001-2147-2|issn=0938-8990|pmid=12140685}}</ref> Each of the known mutations appears to eliminate or significantly reduce TYRP1 enzymatic activity.<ref name=":2">{{Cite journal|last=Kaelin|first=Christopher B.|last2=Barsh|first2=Gregory S.|date=January 2013|title=Genetics of Pigmentation in Dogs and Cats|journal=Annual Review of Animal Biosciences|volume=1|issue=1|pages=125–156|doi=10.1146/annurev-animal-031412-103659|issn=2165-8102|pmid=25387014}}</ref> This modifies the final shape of the eumelanin molecule produced,<ref>{{Cite web|title=Dog Coat Colour Genetics|url=http://www.doggenetics.co.uk/liver.html|website=www.doggenetics.co.uk|access-date=2020-05-20}}</ref> '''<u>''????? or dilution????''</u>'''meaning that the pigment is a different color (instead of, for example, changing pigment density).TYRP1 affects the eumelanin synthesis pathway very late, after the split from phaeomelanin has occurred; it is not unexpected that phaeomelanin color would appear unaffected.<ref name=":1" />

There are four known alleles that occur at the B locus:

*'''''B'' = Black eumelanin.''' An animal that has at least one copy of the ''B'' allele will have a black nose, paw pads and eye rims and (usually) dark brown eyes.
*'''''b'' = Brown eumelanin.''' Includes several alleles: '''''b<sup>s</sup>''''', '''''b<sup>d</sup>''''' and '''''b<sup>c</sup>'''''. An animal with any matched or unmatched pair of the ''b'' alleles will have brown, rather than black, hair, a liver nose, paw pads and eye rims, and hazel eyes. Phaeomelanin color is unaffected.<ref name=":2" /><ref name=":1" /> Only one of the alleles is present in the [[English Setter]] (b<sup>s</sup>), [[Doberman Pinscher]] (''b<sup>d</sup>'') and [[Italian Greyhound]] (''b<sup>c</sup>''), but in most breeds with any brown allele 2 or all 3 are present.<ref>https://homepage.usask.ca/~schmutz/dogbrown.html</ref> It is unknown whether the different brown alleles cause specific shades or hues of brown. No obvious differences in the shade of brown have been noted between the different alleles.<ref name=":1" /> <ref name=":2" />
**novel mutation/allele in australian shepherd (2017). <ref>{{Cite journal|last=Hrckova Turnova|first=Evelina|last2=Majchrakova|first2=Zuzana|last3=Bielikova|first3=Marcela|last4=Soltys|first4=Katarina|last5=Turna|first5=Jan|last6=Dudas|first6=Andrej|date=2017|title=A novel mutation in the TYRP1 gene associated with brown coat colour in the Australian Shepherd Dog Breed|url=http://doi.wiley.com/10.1111/age.12563|journal=Animal Genetics|language=en|volume=48|issue=5|pages=626–626|doi=10.1111/age.12563|via=}}</ref>

''B'' is dominant to ''b''.

====D (dilute) locus====
[[File:Adult Male Weimeraner on the Prowl.jpg|thumb|175x175px|[[Weimaraner]] (standard): KB for dominant black and solid fur colour, genotype bb for brown eumelanin lightened by a dilute genotype dd.]]
The '''[[melanophilin]] gene''' (MLPH) at the D locus causes a dilution of eumelanin and phaeomelanin and determines the intensity of pigmentation. MLPH codes for a protein involved in the distribution of melanin - it is part of the [[melanosome]] transport complex. <ref>{{Cite journal|last=Drögemüller|first=Cord|last2=Philipp|first2=Ute|last3=Haase|first3=Bianca|last4=Günzel-Apel|first4=Anne-Rose|last5=Leeb|first5=Tosso|date=2007-07-01|title=A Noncoding Melanophilin Gene (MLPH) SNP at the Splice Donor of Exon 1 Represents a Candidate Causal Mutation for Coat Color Dilution in Dogs|url=http://academic.oup.com/jhered/article/98/5/468/2187775/A-Noncoding-Melanophilin-Gene-MLPH-SNP-at-the|journal=Journal of Heredity|language=en|volume=98|issue=5|pages=468–473|doi=10.1093/jhered/esm021|issn=1465-7333}}</ref> Defective MLPH prevents normal pigment distribution, resulting in pigment clumping and a paler colored coat.<ref>{{Cite journal|last=Philipp|first=Ute|last2=Hamann|first2=Henning|last3=Mecklenburg|first3=Lars|last4=Nishino|first4=Seiji|last5=Mignot|first5=Emmanuel|last6=Günzel-Apel|first6=Anne-Rose|last7=Schmutz|first7=Sheila M|last8=Leeb|first8=Tosso|date=2005|title=Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs|url=http://bmcgenet.biomedcentral.com/articles/10.1186/1471-2156-6-34|journal=BMC Genetics|volume=6|issue=1|pages=34|doi=10.1186/1471-2156-6-34|pmc=PMC1183202|pmid=15960853|via=}}</ref>

There are two known alleles: D and d.

*'''''D'' = Not diluted'''. Black or brown eumelanin (determined by Brown locus), reddish or orangish tan phaeomelanin.
*'''''d'' = Diluted.''' Fur color: black eumelanin (''B/-'') diluted to bluish grey (ranging from light blue-grey to dark steel); brown eumelanin (''b/b'') diluted to taupe or [[isabelline (colour)|"Isabella"]]. Phaeomelanin is diluted from red to yellowish tan.<ref>{{Cite journal|last=Welle|first=M.|last2=Philipp|first2=U.|last3=Rüfenacht|first3=S.|last4=Roosje|first4=P.|last5=Scharfenstein|first5=M.|last6=Schütz|first6=E.|last7=Brenig|first7=B.|last8=Linek|first8=M.|last9=Mecklenburg|first9=L.|last10=Grest|first10=P.|last11=Drögemüller|first11=M.|date=2009-07-01|title=MLPH Genotype—Melanin Phenotype Correlation in Dilute Dogs|url=https://academic.oup.com/jhered/article/100/suppl_1/S75/886518|journal=Journal of Heredity|language=en|volume=100|issue=suppl_1|pages=S75–S79|doi=10.1093/jhered/esp010|issn=0022-1503}}</ref> Slight to moderate dilution of the paw pads and eye rims towards bluish grey if ''B/-'' or taupe if ''b/b'', and slight to moderate reduction of eye color from brown towards amber in a ''B/-'' animal, or from hazel towards light amber in a ''b/b'' animal. [[Dog coat genetics#Theoretical genes for color and pattern|asd]]

''D'' is completely dominant to ''d''.

Homozygosity of ''d'' is sometimes accompanied by hair loss and recurrent skin inflammation, a condition referred to as either [[Canine follicular dysplasia#Color dilution alopecia|color dilution alopecia (CDA)]] or [[canine follicular dysplasia|black hair follicular dysplasia (BHFD)]] depending upon the breed of dog.<ref>{{cite journal|author1=Ute Philipp|author2=Henning Hamann|author3=Lars Mecklenburg|author4=Seiji Nishino|author5=Emmanuel Mignot|author6=Anne-Rose Günzel-Apel|author7=Sheila M Schmutz|author8=Tosso Leeb|date=June 2005|title=Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs|journal=BMC Genetics|volume=6|issue=34|page=34|doi=10.1186/1471-2156-6-34|issn=1471-2156|pmc=1183202|pmid=15960853}}</ref>
==== Color gene interactions ====
{{multiple image
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| image1 = 2014 Black Labrador head (mirror).jpg
| caption1 = B/_ D/_
| image2 = Weimaraner stick.jpg
| caption2 = B/_ d/d
| image3 = Chocolate Lab.jpg
| caption3 = b/b D/_
| image4 = Angus, braco de Weimar..JPG
| caption4 = b/b d/d
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}}

{| class="wikitable"
|-
| align="center" |'''COLOUR GENE <br> INTERACTIONS<ref name="europepmc.org">{{Cite journal|last1=Cadieu|first1=E.|last2=Neff|first2=M. W.|last3=Quignon|first3=P.|last4=Walsh|first4=K.|last5=Chase|first5=K.|last6=Parker|first6=H. G.|last7=Vonholdt|first7=B. M.|last8=Rhue|first8=A.|last9=Boyko|first9=A.|last10=Byers|first10=A.|last11=Wong|first11=A.|year=2009|title=Coat Variation in the Domestic Dog is Governed by Variants in Three Genes|journal=Science|volume=326|issue=5949|pages=150–153|bibcode=2009Sci...326..150C|doi=10.1126/science.1177808|pmc=2897713|pmid=19713490|first17=M.|first20=E. A.|last20=Ostrander|first19=R. K.|last19=Wayne|first18=C. D.|last18=Bustamante|last12=Mosher|first12=D. S.|first16=K. G.|last16=Lark|first15=C.|last15=André|first14=T. C.|last14=Spady|first13=A. G.|last13=Elkahloun|last17=Cargill}}</ref>'''
| align="center" |'''Not Dilute<br>(''D/D'' '''or''' ''D/d'')'''
| align="center" |'''Dilute<br>(''d/d'')'''
|-
| align="center" |'''Black<br>''B/B'' '''or''' ''B/b'''''
| align="center" | Black eumelanin<br>Red* phaeomelanin
| align="center" | Blue-grey eumelanin<br>Yellow phaeomelanin
|-
| align="center" |'''Brown<br>''b/b'''''
| align="center" | Chocolate-brown eumelanin<br>Red* phaeomelanin
| align="center" | Taupe or "Isabella" eumelanin<br>Yellow phaeomelanin
|-
| colspan="3" | *<small> Note that phaeomelanin is frequently diluted by intensity factor of theoretical I locus.</small>

|}<br />
=== Pigment-type switching loci ===
[[File:Poil agouti.svg|thumb|128x128px|Diagram of an agouti hair.|alt=|left]]Many genes are involved in controlling whether a melanocyte produces eumelanin or phaeomelanin. Time-dependent pigment switching leads to the production of a single hair with bands of eumelanin and phaeomelanin.<ref name=":2" /> Spatial-dependent signaling results in parts of the body with different levels of production of each pigment.

MC1R (the '''E locus''') is a receptor on the surface of melanocytes. When active, it causes the melanocyte to synthesize eumelanin; when inactive, the melanocyte produces phaeomelanin instead. ASIP (the '''A locus''') binds to and inactivates MC1R, thereby causing phaeomelanin synthesis. DEFB103 (the '''K locus''') in turn prevents ASIP from inhibiting MC1R, thereby increasing eumelanin synthesis. <ref name=":2" />

====A (agouti) locus====
{{Multiple image
| align =
| direction = vertical
| total_width = 200
| image1 = Eurasier_BailyWtatze.jpg
| alt1 =
| caption1 = Sable: allele A<sup>y</sup> {{refn|group=note| A "fawn" appearance with very limited eumelanin can be almost impossible to distinguish from "recessive red" (e/e) dogs. The presence of any eumelanin hairs or dark whiskers indicates the dog must be tan due to the Agouti locus. [1] }}
| image2 = Wolf_on_alert.jpg
| caption2 = Agouti: Allele a<sup>w</sup> <ref>''[https://alaskafurid.wordpress.com/2009/11/02/wolf/#jp-carousel-1362 Banded hairs on agouti wolf back]''</ref><ref>''[http://www.doggenetics.co.uk/tan.html#wolfgrey Agouti Wolf Grey]''</ref>
| image3 = 03 Snow Bunny Talitha Rottweiler.jpg
| caption3 = Tan points: allele a<sup>t</sup>
| image4 = Black-german-shepherd-29944091920.jpg
| caption4 = Recessive black: allele a {{refn|group=note|A recessive black appearance is identical to black caused by dominant K<sup>B</sup>. [[German Shepherd|German shepherds]] are known to carry the recessive black allele.}}
}}
{{See also|Agouti coloration genetics}}The alleles at the A locus are related to the production of [[Agouti-signaling protein|'''agouti signalling protein (ASIP)''']] and determine whether an animal expresses an [[Agouti (coloration)|agouti appearance]], and, by controlling the distribution of pigment in individual hairs, what type of agouti.

ASIP works with other genes to regulate which color of melanin is produced in a hair shaft; ASIP induces the production of phaeomelanin. In a wild-type agouti appearance (wolves and some dogs), each hair has several alternating bands of black and tan. Generally, a mutation that increases ASIP cause more tan (phaeomelanin) and mutations that decrease ASIP activity cause a darker coat (more eumelanin). <ref>{{Cite journal|last=Fontanesi|first=Luca|last2=Forestier|first2=Lionel|last3=Allain|first3=Daniel|last4=Scotti|first4=Emilio|last5=Beretti|first5=Francesca|last6=Deretz-Picoulet|first6=Séverine|last7=Pecchioli|first7=Elena|last8=Vernesi|first8=Cristiano|last9=Robinson|first9=Terence J.|last10=Malaney|first10=Jason L.|last11=Russo|first11=Vincenzo|date=2010-03-01|title=Characterization of the rabbit agouti signaling protein (ASIP) gene: Transcripts and phylogenetic analyses and identification of the causative mutation of the nonagouti black coat colour|url=http://www.sciencedirect.com/science/article/pii/S0888754309002559|journal=Genomics|language=en|volume=95|issue=3|pages=166–175|doi=10.1016/j.ygeno.2009.11.003|issn=0888-7543}}</ref> A non-functional ASIP mutation would result in a coat with no phaeomelanin.

There are four known alleles that occur at the A locus:

*'''''A<sup>y</sup>'' = Fawn or sable.''' Tan with black whiskers and varying amounts of black-tipped and/or all-black hairs dispersed throughout. Fawn typically refers to dogs with clearer tan and sable to those with more black shading. More ASIP activity -> broader tan (phaeomelanin) bands on each hair.

*'''''a<sup>w</sup>'' = Wild-type agouti.''' Each hair with 3-6 bands alternating black and tan. Also called wolf sable. Wild type banding.
*'''''a<sup>t</sup>'' = Tan point.''' Black with tan patches on the face and underside - including saddle tan (tan with a black saddle or blanket) <ref>{{cite journal | last1 = Dreger | first1 = Dayna L. | last2 = Schmutz | first2 = Sheila M. | year = 2011 | title = A SINE Insertion Causes the Black-and-Tan and Saddle Tan Phenotypes in Domestic Dogs | url = | journal = Journal of Heredity | volume = 102 | issue = Suppl 1| pages = S11–S18 | doi=10.1093/jhered/esr042 | pmid=21846741| doi-access = free }}</ref><ref>Dreger DL, Parker H, Ostrander E, Schmutz SM. The involvement of RALY in a complex gene interaction producing the saddle tan phenotype in dogs. A presentation at Advances in Canine and Feline Genomics and Inherited Diseases 2012 Conference, Visby, Sweden. June 1, 2012.</ref>
*'''''a'' = Recessive black.''' Black, inhibition of phaeomelanin (only eumelanin produced).
*'''''a<sup>yt</sup>'' = Recombinant fawn.''' Black with tan patches on the face and underside. Has been identified in numerous Tibetan Spaniels and individuals in other breeds, including the Dingo. Its hierarchical position is not yet understood.<ref name="Dreger1">{{cite journal |url= https://www.biorxiv.org/content/10.1101/654343v1.full#disqus_thread|title= True Colors: commercially-acquired morphological genotypes reveal hidden allele variation among dog breeds, informing both trait ancestry and breed potential |journal= PLOS One |volume= 14 |issue= 10 |pages= e0223995 |accessdate= September 23, 2019 |date= May 29, 2019 |author= Dayna L Dreger |display-authors=etal|doi= 10.1371/journal.pone.0223995|pmid= 31658272 |pmc= 6816562 }}</ref><ref>''[http://www.doggenetics.co.uk/tan.html#saddle Agouti Series]''</ref>

Most texts suggest that the dominance hierarchy for the A locus alleles appears to be as follows: ''A<sup>y</sup> > a<sup>w</sup> > a<sup>t</sup> > a''; however, research suggests the existence of pairwise dominance/recessiveness relationships in different families and not the existence of a single hierarchy in one family.<ref>{{cite journal |author1=Julie A. Kerns |author2=J. Newton |author3=Tom G. Berryere |author4=Edward M. Rubin |author5=Jan-Fang Cheng |author6=Sheila M. Schmutz |author7=Gregory S. Barsh |title=Characterization of the dog Agouti gene and a nonagouti mutation in German Shepherd Dogs |journal=Mammalian Genome |volume=15 |issue=10 |pages=798–808 |date=October 2004 |issn=0938-8990 |pmid=15520882 |doi=10.1007/s00335-004-2377-1 }}</ref>

*''A<sup>y</sup>'' is incompletely dominant to ''a<sup>t</sup>'', so that heterozygous individuals have more black sabling, especially as puppies and ''A<sup>y</sup>a<sup>t</sup>'' can resemble the ''a<sup>w</sup>a<sup>w</sup>'' phenotype. Other genes also affect how much black is in the coat.
*''a<sup>w</sup>'' is the only allele present in many Nordic spitzes, and is not present in most other breeds.
*''a<sup>t</sup>'' includes tan point and saddle tan, both of which look tan point at birth. Modifier genes in saddle tan puppies cause a gradual reduction of the black area until the saddle tan pattern is achieved.
*''a'' is only present in a handful of breeds. Most black dogs are black due to the K locus allele KB for dominant black.<ref>Sheila Schmutz: ''[https://homepage.usask.ca/~schmutz/agouti.html Agouti]''</ref>

{{Multiple image
| align = none
| direction =
| perrow = 2
| total_width =
| image1 = Eurasier_BailyWtatze.jpg
| alt1 =
| caption1 = Sable: allele A<sup>y</sup> {{refn|group=note| A "fawn" appearance with very limited eumelanin can be almost impossible to distinguish from "recessive red" (e/e) dogs. The presence of any eumelanin hairs or dark whiskers indicates the dog must be tan due to the Agouti locus. [1] }}
| image2 = Wolf_on_alert.jpg
| caption2 = Agouti: Allele a<sup>w</sup> <ref>''[https://alaskafurid.wordpress.com/2009/11/02/wolf/#jp-carousel-1362 Banded hairs on agouti wolf back]''</ref><ref>''[http://www.doggenetics.co.uk/tan.html#wolfgrey Agouti Wolf Grey]''</ref>
| image3 = 03 Snow Bunny Talitha Rottweiler.jpg
| caption3 = Tan points: allele a<sup>t</sup>
| image4 = Black-german-shepherd-29944091920.jpg
| caption4 = Recessive black: allele a {{refn|group=note|A recessive black appearance is identical to black caused by dominant K<sup>B</sup>. [[German Shepherd|German shepherds]] are known to carry the recessive black allele.}}
}}

====E (extension) locus====
{{Multiple image
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| align =
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| image1 = Pug in the snow.jpg
| caption1 = Fawn dog with melanistic mask: ''A<sup>y</sup>/- ; E<sup>m</sup>/-''
| image2 = Chart perski f444 (mirror).jpg
| caption2 = Grizzle modified tan point: ''a<sup>t</sup>/a<sup>t</sup>; E<sup>g</sup>/-''
| image3 = Persian Saluki.JPG
| caption3 = Saluki with normal tan points: ''a<sup>t</sup>/a<sup>t</sup>; E/-''
| image4 = Golden Retriever with tennis ball.jpg
| caption4 = Recessive red: ''e/e''
| alt1 =
}}

{{CSS image crop
|Image = Persian Saluki.JPG
|bSize = 200
|cWidth = 150
|cHeight = 150
|oTop = 0
|oLeft = 30
}}

{{Multiple image
| total_width =
| align =
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| image1 = Chart perski f444.jpg
| caption1 = Grizzle modified tan point: ''a<sup>t</sup>/a<sup>t</sup>; E<sup>g</sup>/-''
| image2= {{CSS image crop|Image = Persian Saluki.JPG |bSize = 500|oTop = 0 |oLeft = 100}}
| alt2 = dog
}}

The gene at the E locus is the '''[[melanocortin 1 receptor]] (MC1R)''' - it determine whether an animal expresses a [[melanistic mask]], as well as determining whether an animal can produce [[eumelanin]] in its coat. MC1R activity promotes eumelanin synthesis; MC1R inactivity results in phaeomelanin production. A non-functional MC1R would thus result in a red-yellow coat - no eumelanin (no black).

Any area that contains eumelanin pigment can be affected by genes affecting eumelanin color (i.e. Brown or Dilution).

There are three known, plus two more theorized, alleles that occur at the E locus:

*'''''E<sup>m</sup>'' = Mask.''' A eumelanin mask is added to the face. The distribution of the pigments on the rest of the face and on the body is determined by the agouti locus. Any tan (phaeomelanin) areas on the mask area are replaced with eumelanin (black/etc.) The mask can vary from the muzzle, to the face and ears, to a larger area with shading on the front and sides as in the [[Belgian Tervuren]].
**The mask ''E<sup>m</sup>'' is unaffected by the greying gene ''G'' and will remain dark in a ''G/-'' animal while the rest of the dog pales, such as in [[Kerry Blue Terrier]]s. Some puppies are born with a mask which fades away within a few weeks of birth: these puppies do not have the ''E<sup>m</sup>'' allele and their temporary mask is due to sabling (A<sup>y</sup>).

*'''''E<sup>G</sup>'' = Grizzle.''' A dark overlay covering the top and sides of the body, head and tail, and the outside of the limbs; underparts are pale color. Appearance is that of a modified "tan point" - grizzle requires that the animal be homozygous ''a<sup>t</sup>''/''a<sup>t</sup>'' at the agouti locus and not possessing ''K<sup>B</sup>''.<ref name=":0">{{cite journal|author1=Dayna L. Dreger|author2=Sheila M. Schmutz|date=Jun 2010|title=A New Mutation in MC1R Explains a Coat Color Phenotype in 2 ''Old'' Breeds: Saluki and Afghan Hound|journal=Journal of Heredity|volume=101|issue=5|pages=644–649|doi=10.1093/jhered/esq061|pmid=20525767|doi-access=free}}</ref>
**The E<sup>G</sup> allele is confirmed only in the Saluki and Afghan Hound, the latter in which it is referred to as "Domino", but also occurs in the [[Borzoi]]. Its placement in the dominance hierarchy has not been solidified. Black with fawn-tan points (''a<sup>t</sup>/a<sup>t</sup>'' ''E/-'') is instead dark-sable with extended clear-tan points (''a<sup>t</sup>/a<sup>t</sup>'' ''E<sup>G</sup>/-''). Brindle affects fawn and sable areas, resulting in black with bridled-tan points (''a<sup>t</sup>/a<sup>t</sup>'' ''E/-'' ''K<sup>br</sup>/-'') or brindle with clear-tan points (''a<sup>t</sup>/a<sup>t</sup>'' ''E<sup>G</sup>/-'' ''K<sup>br</sup>/-'').<ref name=":0" /> ''E<sup>G</sup>'' is theorized to have no effect on the phenotype of non-''at/-'' nor ''K<sup>B</sup>'' dogs. This is a single amino acid substitution in the MC1R protein.<ref name=":0" />
*'''''E''''' = Normal extension. Expression of eumelanin and/or phaeomelanin according to the alleles present at the A and K loci
*'''''e<sup>h</sup>''''' = Cocker sable (if ''K<sup>B</sup>/-'' and may require ''a<sup>t</sup>a<sup>t</sup>'', tan with a dark overlay covering the top and sides of the body, head and tail, and the outside of the limbs)
**The ''e<sup>h</sup>'' sable extension allele has been studied only in English Cocker Spaniels and produces sable in the presence of dominant black ''K<sup>B</sup>'' and tan point ''a<sup>t</sup>/a<sup>t</sup>''. Its expression is dependent upon the animal not possessing ''E<sup>m</sup>'' nor ''E'' nor being homozygous for ''e''. ''e<sup>h</sup>'' is theorized to be on the E locus and to have no effect on ''k<sup>y</sup>/k<sup>y</sup>'' dogs. All cocker spaniels are homozygous for ''a<sup>t</sup>'', so it is unknown how the gene may function in the presence of other A-series alleles.
*'''''e''''' = Recessive red or clear fawn. Inhibition of eumelanin over entire coat; only pigment is pheomelanin.<ref>Sheila Schmutz: ''[https://homepage.usask.ca/~schmutz/dogE.html The E Locus in Dogs]''</ref> Eumelanin can be in nose, eye lids and paw pads but not in the fur. An animal that is homozygous for ''e'' will express a red to yellow coat regardless of most alleles at other loci. Eumelanin is inhibited, so there can be no black hairs anywhere, even the whiskers. Pigment on the nose leather can be lost at the middle ([[Dudley nose]]). In combination with ''a/a'' (phaeomelanin inhibitor), an ''e/e'' dog will be white to off-white; in combination with ''U/U'' or ''U/u'', an ''e/e'' dog will be off-white or cream.<ref>https://asas.org/docs/default-source/wcgalp-proceedings-oral/278_paper_10239_manuscript_1637_0.pdf?sfvrsn=2</ref>

The dominance hierarchy for the E locus alleles appears to be as follows: ''E<sup>m</sup>'' > ''E<sup>G</sup>'' > ''E'' > ''e<sup>h</sup>'' > ''e''.

====K (dominant black) locus====

The alleles at the K locus (the [[DEFB103A|β-Defensin 103]] gene or DEFB103) determine the coloring pattern of an animal's coat.<ref>{{cite journal |author1=Sophie I. Candille |author2=Christopher B. Kaelin |author3=Bruce M. Cattanach |author4=Bin Yu |author5=Darren A. Thompson |author6=Matthew A. Nix |author7=Julie A. Kerns |author8=Sheila M. Schmutz |author9=Glenn L. Millhauser |author10=Gregory S. Barsh |title=A β-Defensin Mutation Causes Black Coat Color in Domestic Dogs |journal=Science |volume=318 |issue=5855 |pages=1418–1423 |date=November 2007 |pmid=17947548 |pmc=2906624 |doi=10.1126/science.1147880 |bibcode=2007Sci...318.1418C }}</ref> There are three known alleles that occur at the K locus:

*''K<sup>B</sup>'' = Dominant black (black)
*''k<sup>br</sup>'' = [[Brindle]] (black stripes added to tan areas)
*''k<sup>y</sup>'' = Phaeomelanin permitted (pattern expressed as per alleles present at A and E loci)

The dominance hierarchy for the K locus alleles appears to be as follows: ''K<sup>B</sup>'' > ''k<sup>br</sup>'' > ''k<sup>y</sup>''.

*''K<sup>B</sup>'' causes a solid eumelanin coat (black, brown, grey or taupe) except when combined with ''e/e'' (tan or white), ''E<sup>h</sup>/-'' (Cocker sable) or ''E<sup>m</sup>/- G/-'' and appropriate coat type (light eumelanin with dark eumelanin mask)
*''k<sup>br</sup>'' causes the addition of eumelanin stripes to all tan areas of a dog except when combined with ''e/e'' (no effect) or ''E<sup>G</sup>/- a<sup>t</sup>a<sup>t</sup>'' non-''K<sup>B</sup>/-'' (eumelanin and sabled areas become striped, tan areas remain tan)
*''k<sup>y</sup>'' is wild-type allowing full expression of other genes.

==== Interactions of pattern genes ====
Alleles at the Agouti (A), Extension (E) and Black (K) loci determine colour pattern (eumelanin vs phaeomelanin):

{| class="wikitable"
|-
| colspan="2" align="center" |'''PATTERN GENE <br> INTERACTIONS<ref name="europepmc.org" />'''
| align="center" |'''Fawn or Sable<br>''A<sup>y</sup>/-'''''
| align="center" |'''Wolf Sable<br>''a<sup>w</sup>/a<sup>w</sup>''''',''' ''a<sup>w</sup>/a<sup>t</sup>'' '''or''' ''a<sup>w</sup>/a'''''
| align="center" |'''Tan Point<br>''a<sup>t</sup>/a<sup>t</sup>'' '''or''' ''a<sup>t</sup>/a'''''
| align="center" |'''Rec. Black<br>''a/a'''''
|-
| rowspan="3" align="center" |'''Dom. Black<br>''K<sup>B</sup>/-'''''
| align="center" |'''Mask<br>''E<sup>m</sup>/-'''''
| align="center" | black<br>(with mask)*
| align="center" | black<br>(with mask)*
| align="center" | black<br>(with mask)*
| align="center" | black<br>(with mask)*
|-
| align="center" |'''wildtype E<br>''E/E'' or ''E/e'''''
| align="center" | black
| align="center" | black
| align="center" | black
| align="center" | black
|-
| align="center" |'''Cocker Sable'''<sup>†</sup>'''<br>''e<sup>h</sup>/e<sup>h</sup>'' '''or''' ''e<sup>h</sup>/e'''''
| align="center" | ?
| align="center" | ?
| align="center" | cocker sable
| align="center" | ?
|-
| rowspan="3" align="center" |'''Brindle<br>''K<sup>br</sup>/K<sup>br</sup>'' '''or''' ''K<sup>br</sup>/k<sup>y</sup>'''''
| align="center" |'''Mask<br>''E<sup>m</sup>/-'''''
| align="center" | brindle<br>with mask
| align="center" | brindle<br>with mask
| align="center" | black & brindled tan<br>with mask
| align="center" | black<br>(with mask)*
|-
| align="center" |'''wildtype E<br>''E/E'' '''or''' ''E/e'''''
| align="center" | brindle
| align="center" | brindle
| align="center" | black & brindled tan
| align="center" | black
|-
| align="center" |'''Grizzle'''<sup>†</sup>'''<br>''E<sup>G</sup>/E<sup>G</sup>'', ''E<sup>G</sup>/E'' '''or''' ''E<sup>G</sup>/e'''''
| align="center" | ?
| align="center" | ?
| align="center" | brindle & tan
| align="center" | ?
|-
| rowspan="3" align="center" |'''wildtype K<br>''k<sup>y</sup>/k<sup>y</sup>'''''
| align="center" |'''Mask<br>''E<sup>m</sup>/-'''''
| align="center" | fawn or sable<br>with mask
| align="center" | wolf sable<br>with mask
| align="center" | black & tan<br>with mask
| align="center" | black<br>(with mask)*
|-
| align="center" |'''wildtype E<br>''E/E'' '''or''' ''E/e'''''
| align="center" | fawn or sable
| align="center" | wolf sable
| align="center" | black & tan
| align="center" | black
|-
| align="center" |'''Grizzle'''<sup>†</sup>'''<br>''E<sup>G</sup>/E<sup>G</sup>'', ''E<sup>G</sup>/E'' '''or''' ''E<sup>G</sup>/e'''''
| align="center" | ?
| align="center" | ?
| align="center" | grizzle
| align="center" | ?
|-
| align="center" |'''any K<br>''-/-'''''
| align="center" |'''Clear Fawn<br>''e/e'''''
| align="center" | tan
| align="center" | tan
| align="center" | tan
| align="center" | white
|-
| colspan="6" | *<small> Note that the black mask on a black dog is only phenotypically evident in presence of ''G/-'' and an appropriate coat type.</small><br>
<sup>†</sup><small> ''e<sup>h</sup>'' and ''E<sup>G</sup>'' are only included in the table where their interactions are known.</small>

|}

Alleles present at the Intensity (I), Urajiro (U), Greying (G) and Albino (C-like) loci determine melanin shade.

=== Patching, spotting and white markings ===
Alleles present at the Merle (M) and Harlequin (H) loci cause patchy reduction of melanin to half (merle), zero (harlequin) or both (double merle). Alleles present at the Spotting (S), Ticking (T) and Flecking (F) loci determine white markings.

==== H (harlequin) locus ====
DNA studies have isolated a missense mutation in the 20S proteasome β2 subunit at the H locus.<ref>{{cite journal|last1=Clark|first1=LA|last2=Tsai|first2=KL|last3=Starr|first3=AN|last4=Nowend|first4=KL|last5=Murphy|first5=KE|year=2011|title=A missense mutation in the 20S proteasome β2 subunit of Great Danes having harlequin coat patterning|url=|journal=Genomics|volume=97|issue=4|pages=244–248|doi=10.1016/j.ygeno.2011.01.003}}</ref> The H locus is a modifier locus (of the M locus) and the alleles at the H locus will determine if an animal expresses a harlequin vs merle pattern. There are two alleles that occur at the H locus:

*''H'' = Harlequin (if ''M/-'', patches of full colour and white)
*''h'' = Non-harlequin (if ''M/-'', normal expression of merle)
''H/h'' heterozygotes are harlequin and ''h/h'' homozygotes are non-harlequin. Breeding data suggests that homozygous ''H/H'' is embryonic lethal and that therefore all harlequins are ''H/h''.<ref name="Murphy1">{{cite journal|author1=Leigh Anne Clark|author2=Alison N. Starr|author3=Kate L. Tsai|author4=Keith E. Murphy|date=July 2008|title=Genome-wide linkage scan localizes the harlequin locus in the Great Dane to chromosome 9|journal=Gene|volume=418|issue=1–2|pages=49–52|doi=10.1016/j.gene.2008.04.006|pmid=18513894}}</ref>
* The Harlequin allele is specific to [[Great Danes]]. Harlequin dogs (''H/h M/m'') have the same pattern of patches as merle (''h/h M/m'') dogs, but the patches are white and [[harlequin]] affects eumelanin and phaeomelanin equally. ''H'' has no effect on non-merle ''m/m'' dogs.

====M (merle) locus====
{{See also|Merle (dog coat)}}

The alleles at the M locus (the silver locus protein homolog gene or [[SILV]], aka premelanosome protein gene or PMEL) determine whether an animal expresses a [[merle (coat color in dogs)|merle]] pattern to its coat. There are two alleles that occur at the M locus:
*''M'' = Merle (patches of full colour and reduced colour)
*''m'' = Non-merle (normal expression)

''M'' and ''m'' show a relationship of both co-dominance and no dominance.
* On heterozygous ''M/m'' merles, black is reduced to silver on ~50% of the animal in semi-random patches with rough edges like torn paper. The fraction of the dog covered by merle patches is random such that some animals may be predominantly black and others predominantly silver. The merle gene is “faulty” with many merle animals having one odd patch of a third shade of grey, brown or tan.
* On homozygous ''M/M'' “double merles”, black is replaced with ~25% black, ~50% silver and ~25% white, again with random variation, such that some animals have more black or more white.
* Eumelanin (black/etc.) is significantly reduced by ''M/m'', but phaeomelanin is barely affected such that there will be little to no evidence of the merle gene on any tan areas or on an ''e/e'' dog. However, the white patches caused by ''M/M'' affect both pigments equally, such that a fawn double merle would be, on average, ~75% tan and ~25% white.
* The merle gene also affects the skin, eye colour, eyesight and development of the eye and inner ear. Merle ''M/m'' puppies develop their skin pigmentation (nose, paws, belly) with speckled-edged progression, equally evident in ''e/e'' merles except when extensive white markings cause pink skin to remain in these areas. Blue and part-blue eyes are common.
* Both heterozygosity and homozygosity of the merle gene (i.e., ''M/m'' and ''M/M'') are linked to a range of auditory and ophthalmologic abnormalities.<ref>{{cite journal |author1=Leigh Anne Clark |author2=Jacquelyn M. Wahl |author3=Christine A. Rees |author4=Keith E. Murphy |title=Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog |journal=PNAS |volume=103 |issue=5 |pages=1376–1381 |date=January 2006 |issn= 0273-1134 |pmid= 16407134 |pmc= 1360527 |doi=10.1073/pnas.0506940103 }}</ref> Most ''M/m'' merles have normal-sized eyes and acceptably functional eyesight and hearing; most ''M/M'' double merles suffer from microphthalmia and/or partial to complete deafness.<ref name="George Strain on Merle">{{cite web|title=George Strain on Merle|url=http://www.merlepoms.org/Articles/George%20Strain%20on%20Merle.pdf|publisher=Merle Poms|accessdate=27 October 2011}}</ref>

====S (spotting) locus====

The alleles at the S locus (the [[microphthalmia-associated transcription factor]] gene or ''MITF'') determine the degree and distribution of white spotting on an animal's coat.<ref name="Schmutz2">{{cite journal |author1=Sheila M. Schmutz |author2=Tom G. Berryere |author3=Dayna L. Dreger |title=MITF and White Spotting in Dogs: A Population Study |journal=Journal of Heredity |volume=100 |issue=Supplement 1 |pages=566–574 |date=June 2009 |doi=10.1093/jhered/esp029 |doi-access=free }}</ref> There is disagreement as to the number of alleles that occur at the S locus, with researchers sometimes postulating a conservative two<ref>{{Cite book |last = Winge |first = Ojvind |others = Catherine Roberts (translator) |year = 1950 |title = '''Inheritance in Dogs: With Special Reference to the Hunting Breeds''' |publisher = Comstock Publishing |location = Ithaca, N.Y. |page = 194 }}</ref> or, commonly, four<ref name="Little1">{{Cite book |last = Little |first = Clarence Cook |year = 1957 |title = '''The Inheritance of Coat Color in Dogs''' |publisher = Comstock Publishing |location = New York |page = 194 |isbn = 978-0-87605-621-9 }}</ref> alleles. The alleles postulated are:
*''S'' = Solid color/no white (very small areas of white may still appear; a diamond or medallion on the chest, a few toe tips/toes, or a tail tip)
*''s<sup>i</sup>'' = Irish-spotting (white on muzzle, forehead, feet, legs, chest, neck and tail)
*''s<sup>p</sup>'' = [[Piebald]] (varies from coloured with Irish spotting plus at least one white marking on the top or sides of the body or hips, to mostly white which generally retains patches of colour around the eyes, ears and tail base)
*''s<sup>w</sup>'' = Extreme piebald spotting (extremely large areas of white, almost completely white)

''S'' is incomplete dominant (towards co-dominant) to ''s<sup>p</sup>''. DNA studies have not yet confirmed the existence of all four alleles, with some research suggesting the existence of at least two alleles (''S'' and ''s<sup>p</sup>'')<ref name="Schmutz2" /> and other research suggesting the possible existence of a third allele (''s<sup>i</sup>'').<ref>{{cite journal |author1=Karlsson E. K. |author2=Baranowska I. |author3=Wade C. M. |author4=Salmon Hillbertz N. H. |author5=Zody M. C. |author6=Anderson N. |author7=Biagi T. M. |author8=Patterson N. |author9=Pielberg G. R. |author10=Kulbokas E. J. III |author11=Comstock K. E. |author12=Keller E. T. |author13=Mesirov J. P. |author14=von Euler H. |author15=Kämpe O. |author16=Hedhammar A. |author17=Lander E. S. |author18=Andersson G. |author19=Andersson L. |author20=Lindblad-Toh K. |title=Efficient mapping of mendelian traits in dogs through genome-wide association |journal=Nature Genetics |volume=39 |issue=11 |pages=1304–1306 |date=November 2007 |pmid=17906626 |doi=10.1038/ng.2007.10 }}</ref>
*''S/s<sup>p</sup>'' heterozygotes usually have some white at birth on the chest and toes, which may be covered by ticking as the puppy grows. Animals of this genotype also commonly display pseudo-Irish spotting; in fact most Irish-spotted dogs are so due to heterozygosity for solid and piebald.
* A few breeds (e.g., [[Boston Terrier]]) are fixed for Irish spotting and therefore theorized to possess a different allele on the S locus (''s<sup>i</sup>'') or an allele on a completely separate gene.
* It has been suggested that what appears to be the result of an ''s<sup>w</sup>'' allele is in fact the result of plus and minus modifiers acting on one of the other alleles.<ref name="Schmutz2" /> It is thought that the spotting that occurs in [[Dalmatian (dog)|Dalmatians]] is the result of the interaction of three loci (the S locus, the T locus and F locus) giving them a unique spotting pattern not found in any other breed.<ref name="Murphy2">{{cite book |author=Edward J. Cargill1, Thomas R. Famula, Robert D. Schnabel, George M. Strain & Keith E. Murphy |title=The color of a Dalmatian's spots: Linkage evidence to support the TYRP1 gene |journal=BMC Veterinary Research |volume=1 |issue=1 |page= 1|date=July 2005 |isbn=978-1-74661-481-2 |pmid=16045797 |pmc=1192828 |doi=10.1186/1746-6148-1-1 }}</ref>
* White spotting also affects skin, causing pink patches.
* White spotting can cause blue eyes, microphthalmia, blindness and deafness; however, because pigmentation is generally retained around the eye/ear area, this is rare except among ''s<sup>w</sup>/s<sup>w</sup>'' dogs (or extreme versions of ''s<sup>p</sup>/s<sup>p</sup>'' if ''s<sup>w</sup>'' does not exist).
In 2014, a study found that a simple repeat polymorphism in the MITF-M Promoter is a key regulator of white spotting and that white color had been selected for by humans.<ref>[http://www.uu.se/en/research/news/article/?id=3578&area=2,4,10,16&typ=artikel&lang=en Why white dogs are white] Uppsala University 2014</ref><ref>{{cite journal|doi=10.1371/journal.pone.0104363|pmid=25116146|title=A Simple Repeat Polymorphism in the MITF-M Promoter is a Key Regulator of White Spotting in Dogs|journal=PLOS One|volume=9|issue=8|pages=e104363|year=2014|last1=Baranowska Körberg|first1=Izabella|last2=Sundström|first2=Elisabeth|last3=Meadows|first3=Jennifer R. S.|last4=Rosengren Pielberg|first4=Gerli|last5=Gustafson|first5=Ulla|last6=Hedhammar|first6=Åke|last7=Karlsson|first7=Elinor K.|last8=Seddon|first8=Jennifer|last9=Söderberg|first9=Arne|last10=Vilà|first10=Carles|last11=Zhang|first11=Xiaolan|last12=Åkesson|first12=Mikael|last13=Lindblad-Toh|first13=Kerstin|last14=Andersson|first14=Göran|last15=Andersson|first15=Leif|pmc=4130573|bibcode=2014PLoSO...9j4363B}}</ref>

==Theoretical genes for color and pattern==

There are at least six additional theoretical loci thought to be associated with coat color in dogs. DNA studies are yet to confirm the existence of these genes or alleles but their existence is theorised based on breeding data:<ref name="Schmutz1">{{cite web |url= http://homepage.usask.ca/~schmutz/alleles.html |title= Coat Color Alleles in Dogs |accessdate= September 12, 2010 |date= December 27, 2008 |author= Sheila M. Schmutz }}</ref>

====C (colored) locus====
The alleles at the theoretical C locus are thought to determine the degree to which an animal expresses phaeomelanin, a red-brown protein related to the production of [[melanin]], in its coat and skin. Five alleles are theorised to occur at the C locus:
*''C'' = Full color (animal expresses phaeomelanin)
*''c<sup>ch</sup>'' = Chinchilla (partial inhibition of phaeomelanin resulting in decreased red pigment)
*''c<sup>e</sup>'' = Extreme dilution (inhibition of phaeomelanin resulting in extremely reduced red pigment)
*''c<sup>b</sup>'', ''c<sup>p</sup>'' = Blue-eyed albino/Platinum (almost total inhibition of phaeomelanin resulting in near albino appearance)
*''c<sup>a</sup>'' = [[Albino]] (complete inhibition of phaeomelanin production, resulting in complete inhibition of melanin production)

The ''C'' locus in dogs is not well understood and the theorised alleles are based on those present in other species.<ref name="Little1" /> True albinism has not been conclusively shown to exist in dogs. It is thought that an animal that is [[heterozygous]] for the ''C'' allele with any of the ''c'' alleles will express a result somewhere between the two alleles.<ref>{{cite web |url= http://www.labbies.com/genetics2.htm |title= B/b, E/e, and Beyond: A Detailed Examination of Coat Color Genetics in the Labrador Retriever |accessdate= September 11, 2010 |date= January 29, 2001 |author= Pamela A. Davol }}</ref>

White in Doberman Pinschers and albino-like animals of Asian/Tibetan companion breeds have a phenotype resembling a C locus dilution, but all tested animals have been ''C/C''. The gene responsible is recessive and not at the C locus.<ref>{{Cite journal | doi=10.1371/journal.pone.0092127| pmid=24647637| pmc=3960214| bibcode=2014PLoSO...992127W|title = A Partial Gene Deletion of SLC45A2 Causes Oculocutaneous Albinism in Doberman Pinscher Dogs| journal=PLOS One| volume=9| issue=3| pages=e92127|year = 2014|last1 = Winkler|first1 = Paige A.| last2=Gornik| first2=Kara R.| last3=Ramsey| first3=David T.| last4=Dubielzig| first4=Richard R.| last5=Venta| first5=Patrick J.| last6=Petersen-Jones| first6=Simon M.| last7=Bartoe| first7=Joshua T.}}</ref>

====F ([[flecking]]) locus====

The alleles at the theoretical F locus are thought to determine whether an animal displays small, isolated regions of white in otherwise pigmented regions (not apparent on white animals). Two alleles are theorised to occur at the ''F'' locus:
*''F'' = Flecked
*''f'' = Not flecked

It is thought that ''F'' is dominant to ''f''.<ref name="Murphy2" />

====G (progressive greying) locus====

The alleles at the theoretical G locus are thought to determine if progressive greying of the animal's coat will occur. Two alleles are theorised to occur at the G locus:
*''G'' = Progressive greying (melanin lost from hairs over time)
*''g'' = No progressive greying

It is thought that ''G'' is dominant to ''g''.
* The greying gene affects both eumelanin, and to a lesser extent phaeomelanin. In the presence of ''E<sup>m</sup>/-'' the eumelanin mask will be unaffected and remain dark. Grey dogs are born fully coloured and develop the greying effect over several months. New hairs are grown fully coloured but their colour fades over time towards white. Greying is most evident in continuous-growing coats (long + wire + curly) as individual hairs remain on the dog long enough for the colour to be lost. In short-haired dogs, hairs are shed out and re-grown before the colour has a chance to change.
* Premature greying, in which the face/etc. greys at a young age is not caused by ''G'' and has not been proven to be genetic.

====I (intensity) locus====
[[File:Labrador Retrievers yellow and red.jpg|thumb|191x191px|The I locus is thought to affect the intensity of phaeomelanin, causing red or yellow fur.]]

The alleles at the theoretical I locus are thought to affect phaeomelanin expression. Two alleles are theorised to occur at the ''I'' locus:
*''I'' = Intense red, not diluted
*''i'' = Not intense red

It is thought that ''I'' and ''i'' interact with semi-dominance, so that there are three distinct phenotypes. ''I/i'' heterozygotes are paler than ''I/I'' animals but darker than ''i/i'' animals.
*''i'' results in light-coloured phaeomelanin such as gold, yellow, buff and apricot. This gene is the most common cause of lighter tans, and unlike ''d/d'', it allows the skin and eyes to remain dark.

====T (ticking) locus====

The alleles at the theoretical T locus are thought to determine whether an animal displays small, isolated regions of pigment in otherwise ''s''-spotted white regions. Two alleles are theorised to occur at the T locus:
*''T'' = Ticked
*''t'' = Not ticked

It is thought that ''T'' is dominant to ''t''. [[Ticking]] may be caused by several genes rather than just one. Patterns of medium-sized individual spots, smaller individual spots, and tiny spots that completely cover all white areas leaving a roan-like or merle-like appearance (reserving the term large spots for the variation exclusive to the Dalmatian) can each occur separately or in any combination.
* The effect of the ticking gene(s) is to add back little coloured spots to areas made white by piebald spotting (''-/s'') or the limited white markings of ''S/S'' animals. It does not affect white areas that were caused by ''a/a e/e'' or ''M/M'' or ''M/m H/h''. The colour of the tick marks will be as expected or one shade darker. Tick marks are semi-random, so that they vary from one dog to the next and can overlap, but are generally present on the lower legs and heavily present on the nose.

[[File:Taka_Shiba.jpg|thumb|upright=1.1|right|[[Shiba Inu]] displaying urajiro pattern.]]

====U (urajiro) locus====

The alleles at the theoretical U locus are thought to limit phaeomelanin production on the cheeks and underside.<ref>http://www.doggenetics.co.uk/albino.html</ref> Two alleles are theorised to occur at the U locus:
*''U'' = Urajiro
*''u'' = Not urajiro

It is thought that ''U'' is dominant to ''u'' but incomplete with homozygosity required for complete dilution to off-white and heterozygotes displaying a darker cream. The [[urajiro]] pattern is expressed in the tan (phaeomelanin) areas of any dog who is not ''e/e''. In ''e/e'' dogs, the urajiro gene causes dilution of the entire dog to off-white or cream.

==Miscolours in dog breeds==
Miscolours occur quite rarely in dog breeds, because [[genetic carrier]]s of the recessive alleles causing fur colours that don't correspond to the breed standard are very rare in the [[gene pool]] of a breed and there is an extremely low probability that one carrier will be mated with another. In case two carriers have offspring, according to the [[Mendelian Inheritance|law of segregation]] an average of 25% of the puppies are homozygous and express the off-colour in the phenotype, 50% become carriers and 25% are homozygous for the standard colour. Usually off-coloured individuals are excluded from breeding, but that doesn't stop the inheritance of the recessive allele from carriers mated with standard-coloured dogs to new carriers.

In the breed [[Boxer (dog)|Boxer]] large white markings in heterzygous carriers with genotype S s<sup>i</sup> or S s<sup>w</sup> belong to the standard colours, therefore extreme white Boxers are born regularly, some of them with health problems.<ref>''[http://homepage.usask.ca/~schmutz/dogspots.html Boxer markings]''</ref> The cream-white colour of the [[Shiba Inu]] is not caused by any spotting gene but by strong dilution of pheomelanin. [[Melanocyte]]s are present in the whole skin and in the [[Neural crest|embryonic tissue]] for the auditory organs and eyes, therefore this colour is not associated with any health issues.<ref>''[http://homepage.usask.ca/~schmutz/dilutions.html#intense I locus - dilution of pheomelanin only]''</ref> Recessive genes can be a remnant of the gene pool of the breeds from which the current breed was bred in the past.

<gallery>
File:Dog coat genetics 1.png|[[Punnett square]]: Inheritance with one carrier of a recessive gene
File:Hündin mit Welpen.png|Litter of a [[Boxer (dog)|Boxer]] Genotype S s<sup>i</sup> mated with another s<sup>i</sup> carrier.
File:Dog coat genetics 2.png|Punnett square: Inheritance with two genetic carriers
File:Shiba Inu cream.jpg|[[Shiba Inu]]: According to the [[American Kennel Club|AKC]] cream-white is a non-standard colour<ref>''[http://www.fci.be/Nomenclature/Standards/257g05-en.pdf FCI standard No 257]''</ref> but is accepted by the [[The Kennel Club|British Kennel Club]].<ref>''[https://www.thekennelclub.org.uk/services/public/breed/standard.aspx?id=4110 Japanese Shiba Inu]''</ref>
File:Biewer Yorkie.jpg|For normal [[Yorkshire Terrier]]s [[Piebald|Piebald spotting]] s<sup>p</sup> s<sup>p</sup> is not allowed. Tricolor Yorkies became a separate breed.
File:Beagle 600.jpg|For the [[Beagle]] tricolor Genotype s<sup>p</sup> s<sup>p</sup> is the first colour in the breed standard.<ref>''[http://www.fci.be/Nomenclature/Standards/161g06-en.pdf FCI Standard No 161 Beagle]''</ref>
</gallery>
[[File:Doberman Pinschers black and blue.jpg|thumb|Blue Dobermann]]
The occurrence of a dominant coat colour gene not belonging to the standard colours is a suspicion for crossbreeding with another breed. For example the dilute gen D in the suddenly appeared variety "silver coloured" [[Labrador Retriever]] might probably come from a [[Weimaraner]].<ref>''[https://www.labradortraininghq.com/labrador-breed-information/silver-labrador-retriever/ Silver Labrador Retrievers Facts And Controversy]''</ref> The same applies for [[Dobermann Pinscher]]s suffering from Blue dog syndrome.<ref>''[http://www.fci.be/Nomenclature/Standards/143g02-en.pdf FCI Standard No 143 Dobermann]''</ref><ref>''[http://www.doggenetics.co.uk/problems.html#dilute Health problems linked to colour]''</ref><ref>''[http://www.bmel.de/cae/servlet/contentblob/631716/publicationFile/35840/Qualzucht.pdf Gutachten zur Auslegung von § 11b des Tierschutzgesetzes (Verbot von Qualzüchtungen)]'' page 15</ref>

== Genetic testing and phenotype prediction ==
In recent years genetic testing for the alleles of some genes has become available.<ref>{{cite web |title=Vet Gen |publisher=Veterinary Genetic Services |year=2010 |url=http://www.vetgen.com/index.html |accessdate=September 12, 2010}}</ref> Software is also available to assist breeders in determining the likely outcome of matings.<ref>{{cite web |title=Breeders Assistant |publisher=Premier Pedigree Software |year=2009 |url=http://www.tenset.co.uk/ba/index.html |accessdate=September 12, 2010}}</ref>

===Characteristics linked to coat colour===

The genes responsible for the determination of coat colour also affect other melanin-dependent development, including skin colour, eye colour, eyesight, eye formation and hearing. In most cases, eye colour is directly related to coat colour, but blue eyes in the [[Siberian Husky]] and related breeds, and copper eyes in some herding dogs are not known to be related to coat colour.

The development of coat colour, skin colour, iris colour, pigmentation in back of eye and melanin-containing cellular elements of the auditory system occur independently, as does development of each element on the left vs right side of the animal. This means that in semi-random genes (''M'' merle, ''s'' spotting and ''T'' ticking), the expression of each element is independent. For example, skin spots on a piebald-spotted dog will not match up with the spots in the dog's coat; and a merle dog with one blue eye can just as likely have better eyesight in its blue eye than in its brown eye.

===Loci for coat colour, type and length===

All known genes are on separate chromosomes, and therefore no [[gene linkage]] has yet been described among coat genes. However, they do share chromosomes with other major conformational genes, and in at least one case, breeding records have shown an indication of genes passed on together.

{| class="wikitable sortable"
|-
!'''Gene'''
!'''Chromosome<br>(in Dogs)'''<br><ref>https://homepage.usask.ca/~schmutz/mapping.html#loci</ref><ref name="europepmc.org" />
!'''Symbol'''
!'''Locus<br>Name'''
!'''Description'''
!'''Share<br>Chr'''<ref>{{cite journal | last1 = Hayward | first1 = J. J. | display-authors = etal | year = 2016| title = Complex disease and phenotype mapping in the domestic dog | url = | journal = Nat. Commun | volume = 7 | issue = 1| page = 10460 | doi = 10.1038/ncomms10460 }}</ref><ref>{{cite journal | last1 = Hytönen | first1 = | display-authors = etal | year = 2008 | title = Ancestral T-Box mutation is present in many, but not all, short-tailed dog breeds | url = | journal = Journal of Heredity | volume = 100| issue = 2| pages = 236–240| doi = 10.1093/jhered/esn085 }}</ref>
|-
| align="center" |'''ASIP'''
| align="center" | 24
|'''A<sup>y</sup>, a<sup>w</sup>, a<sup>t</sup>, a'''
| Agouti
| Sable, wolf-sable, tan point, recessive black; ''a<sup>s</sup>'' disproven
|
|-
| align="center" |'''TYRP1'''
| align="center" | 11
|'''B, b<sup>s</sup>, b<sup>d</sup>, b<sup>c</sup>'''
| Brown
| Black, 3 x chocolate / liver
|
|-
| align="center" |'''SLC45A2'''
| align="center" | 4
|'''C'''
| Colour
| No alleles known; possible tyrosinase gene<ref>https://homepage.usask.ca/~schmutz/dilutions.html</ref>
| STC2, GHR(1)<br>& GHR(2) size
|-
| align="center" |'''MLPH'''
| align="center" | 25
|'''D, d'''
| Dilution
| Black/chocolate, blue/isabella
|
|-
| align="center" |'''MC1R'''
| align="center" | 5
|'''E<sup>m</sup>, E<sup>g</sup>, E, e<sup>h</sup>, e'''
| Extension
| Black mask, grizzle, normal extension, cocker-sable, recessive fawn
|
|-
| align="center" |'''PSMB7'''
| align="center" | 9
|'''H, h'''
| Harlequin
| Harlequin, non-harlequin
|
|-
| align="center" |'''DEFB103'''
| align="center" | 16
|'''K<sup>B</sup>, K<sup>br</sup>, k<sup>y</sup>'''
| blacK
| Dominant black, brindle, agouti-enabler
|
|-
| align="center" |'''FgF5'''
| align="center" | 32
|'''L, l'''
| Longcoat
| Short coat, long coat
|
|-
| align="center" |'''PMEL'''
| align="center" | 10
|'''M, m'''
| Merle
| Double merle, merle, non-merle
| HMGA2 size
|-
| align="center" |'''KRT71'''
| align="center" | 27
|'''R, r'''
| cuRlycoat
| Straight coat, curly coat
|
|-
| align="center" |'''MITF'''
| align="center" | 20
|'''S, s<sup>i</sup>, s<sup>p</sup>'''
| Spotting
| Solid, Irish spotting, piebald spotting; ''s<sup>w</sup>'' not proven to exist
|
|-
| align="center" |'''RSPO2'''
| align="center" | 13
|'''W, w'''
| Wirecoat
| Wire coat, non-wire coat
|
|-
| align="center" |'''MC5R'''
| align="center" | 1
|'''n/a'''
| Shedding
| Single coat/minimal shedding, double coat/regular shedding
| C189G [[Natural bobtail|bobtail]]
|-
| align="center" |'''FOXI3'''
| align="center" | 17
|'''n/a'''
| Hairless
| Hairless, coated
|
|-
| align="center" |'''SGK3'''
| align="center" | 29
|'''n/a'''
| AHT
| Coated, AHT-hairless
|
|-
| align="center" |'''n/a'''
| align="center" | 18
|'''n/a'''
| Ridgeback
| Ridgeback, non-ridgeback
|
|-
| align="center" | --
| align="center" | 3
| -
| -
| No coat genes yet identified here.
| IGF1R size
|-
| align="center" | --
| align="center" | 7
| -
| -
| No coat genes yet identified here.
| SMAD2 size
|-
| align="center" | --
| align="center" | 15
| -
| -
| No coat genes yet identified here.
| IGF1 size
|}
There are size genes on all 39 chromosomes, 17 classified as "major" genes.<ref>https://www.nature.com/article-assets/npg/ncomms/2016/160122/ncomms10460/extref/ncomms10460-s1.pdf</ref> 7 of those are identified as being of key importance and each results in ~2x difference in body weight.<ref>http://genome.cshlp.org/content/suppl/2013/10/22/gr.157339.113.DC1/Supplemental_FigureS4.pdf</ref> IGF1 (Insulin-like growth factor 1), SMAD2 (Mothers against decapentaplegic homolog 2), STC2 (Stanniocalcin-2) and GHR(1) (Growth hormone receptor one) are dose-dependent with compact dwarfs vs leaner large dogs and heterozygotes of intermediate size and shape. IGF1R (Insulin-like growth factor 1 receptor) and HMGA2 (High-mobility group AT-hook 2) are incomplete dominant with delicate dwarfs vs compact large dogs and heterozygotes closer to the homozygous dwarfed phenotypes. GHR(2) (Growth hormone receptor two) is completely dominant, homozygous and heterozygous dwarfs equally small, larger dogs with a broader flatter skull and larger muzzle.<ref>{{cite journal | last1 = Rimbault | first1 = M | last2 = Beale | first2 = HC | last3 = Schoenebeck | first3 = JJ | last4 = Hoopes | first4 = BC | last5 = Allen | first5 = JJ | last6 = Kilroy-Glynn | first6 = P | display-authors = etal | year = 2013 | title = Derived variants at six genes explain nearly half of size reduction in dog breeds | url = | journal = Genome Res | volume = 23 | issue = 12| pages = 1985–1995 | doi = 10.1101/gr.157339.113 }}</ref> It is believed that the PMEL/SILV merle gene is linked to the HMGA2 size gene, meaning that alleles are most often inherited together, accounting for size differences in merle vs non-merle litter mates, such as in the Chihuahua (merles usually larger) and [[Shetland Sheepdog]] (merles frequently smaller).

<br />

== pictures here ==
[[File:0312 Black Labrador IMG 8845.JPG|alt=labrador retriever with a black coat|thumb|Genotype BB or Bb]]
[[File:BoraDK20050331.JPG|alt=chocolate lab|thumb|Genotype bb]]{{multiple image
| perrow = 2
| total_width = 300
| image1 = 0312 Black Labrador IMG 3409.jpg
| caption1 = B/_ D/_
| image2 = Weimaraner stick.jpg
| caption2 = B/_ d/d
| image3 = Chocolate labrador in straw (2878965966).jpg
| caption3 = b/b D/_
| image4 = Weimaraner barking.jpg
| caption4 = b/b d/d
| footer = bodyshot
}}
[[File:Melanocyte signaling pathway.jpg|thumb|Overview of the steps of the eumelanin and phaeomelanin synthesis pathways.<ref name=":2" />]]
Lorem ipsum dolor sit amet, sed ne illud apeirian, ex sea alienum accumsan. Eam ut malorum feugiat. Ut elitr atomorum maiestatis ius. Mel eu tritani discere adversarium.

An vide nemore pro, sit suscipit invenire ei. Vis cu possim intellegat liberavisse, nam eu delenit corpora vituperata, et unum offendit duo. An delenit scaevola has, qui et esse ullamcorper. Id facer consequuntur est, eu stet natum iusto qui. Etiam accusata his ne, no aperiri molestie duo. Est quot nulla ut, iudico legendos efficiendi has et, quis persius virtute vis ut. Nam no dicam molestie concludaturque.

Ut vidisse aliquam detraxit est. Eam omnis atqui at, duo ad summo quaeque corpora, fastidii quaerendum sit an. Sea ea solum ignota. Has ex discere accusata nominati. Offendit consetetur accommodare his id, corpora invenire at vim. Eu vim aperiri gubergren.

Putant principes per no. Mundi scripta nominavi id sea, lorem tollit reformidans eu nam. Ut vivendo perpetua per. Possim torquatos assueverit in qui, id fabellas facilisis ullamcorper his. Ad quis facilisi contentiones pri. Ei nam eius habeo apeirian, fabulas periculis sententiae ex vix, ne sit repudiandae neglegentur.

Mea eu timeam conclusionemque, vim cu case sensibus maiestatis, utinam mucius fabellas et sit. Ne quo wisi habemus. Regione habemus necessitatibus ei mea, ubique perpetua constituto sit ut, sed graeci facilisis et. Meis ignota vix ei. Eum ei intellegat repudiandae, clita impetus appareat est ne.

Lorem ipsum dolor sit amet, sed ne illud apeirian, ex sea alienum accumsan. Eam ut malorum feugiat. Ut elitr atomorum maiestatis ius. Mel eu tritani discere adversarium.

An vide nemore pro, sit suscipit invenire ei. Vis cu possim intellegat liberavisse, nam eu delenit corpora vituperata, et unum offendit duo. An delenit scaevola has, qui et esse ullamcorper. Id facer consequuntur est, eu stet natum iusto qui. Etiam accusata his ne, no aperiri molestie duo. Est quot nulla ut, iudico legendos efficiendi has et, quis persius virtute vis ut. Nam no dicam molestie concludaturque.
{{multiple image
| perrow = 2
| total_width = 300
| image1 = Female Black Labrador Retriever.jpg
| caption1 = B/_ D/_
| image2 = Weimaraner stick.jpg
| caption2 = B/_ d/d
| image3 = BoraDK20050331.JPG
| caption3 = b/b D/_
| image4 = Weimaraner wb.jpg
| caption4 = b/b d/d
}}[[File:Silver Labrador Retriever Cooper.jpg|thumb|150x150px|[[Labrador Retriever|Labrador]] (non-standard): KB for dominant black and solid fur colour, genotype B_ for black eumelanin lightened by dilute genotype dd.<ref>''[https://www.labradortraininghq.com/labrador-breed-information/silver-labrador-retriever/ Silver Labrador Retriever Facts And Controversy]''</ref>]]Ut vidisse aliquam detraxit est. Eam omnis atqui at, duo ad summo quaeque corpora, fastidii quaerendum sit an. Sea ea solum ignota. Has ex discere accusata nominati. Offendit consetetur accommodare his id, corpora invenire at vim. Eu vim aperiri gubergren.

Putant principes per no. Mundi scripta nominavi id sea, lorem tollit reformidans eu nam. Ut vivendo perpetua per. Possim torquatos assueverit in qui, id fabellas facilisis ullamcorper his. Ad quis facilisi contentiones pri. Ei nam eius habeo apeirian, fabulas periculis sententiae ex vix, ne sit repudiandae neglegentur.

Mea eu timeam conclusionemque, vim cu case sensibus maiestatis, utinam mucius fabellas et sit. Ne quo wisi habemus. Regione habemus necessitatibus ei mea, ubique perpetua constituto sit ut, sed graeci facilisis et. Meis ignota vix ei. Eum ei intellegat repudiandae, clita impetus appareat est ne.

Lorem ipsum dolor sit amet, sed ne illud apeirian, ex sea alienum accumsan. Eam ut malorum feugiat. Ut elitr atomorum maiestatis ius. Mel eu tritani discere adversarium.

An vide nemore pro, sit suscipit invenire ei. Vis cu possim intellegat liberavisse, nam eu delenit corpora vituperata, et unum offendit duo. An delenit scaevola has, qui et esse ullamcorper. Id facer consequuntur est, eu stet natum iusto qui. Etiam accusata his ne, no aperiri molestie duo. Est quot nulla ut, iudico legendos efficiendi has et, quis persius virtute vis ut. Nam no dicam molestie concludaturque.

Ut vidisse aliquam detraxit est. Eam omnis atqui at, duo ad summo quaeque corpora, fastidii quaerendum sit an. Sea ea solum ignota. Has ex discere accusata nominati. Offendit consetetur accommodare his id, corpora invenire at vim. Eu vim aperiri gubergren.

Putant principes per no. Mundi scripta nominavi id sea, lorem tollit reformidans eu nam. Ut vivendo perpetua per. Possim torquatos assueverit in qui, id fabellas facilisis ullamcorper his. Ad quis facilisi contentiones pri. Ei nam eius habeo apeirian, fabulas periculis sententiae ex vix, ne sit repudiandae neglegentur.

Mea eu timeam conclusionemque, vim cu case sensibus maiestatis, utinam mucius fabellas et sit. Ne quo wisi habemus. Regione habemus necessitatibus ei mea, ubique perpetua constituto sit ut, sed graeci facilisis et. Meis ignota vix ei. Eum ei intellegat repudiandae, clita impetus appareat est ne.


{| class="wikitable"
|+
!Allele
!Name
!Appearance
!mutation
|-
|'''A<sup>y</sup>'''
|Fawn or Sable
|
|
|-
|'''''a<sup>w</sup>'''''
|Wild-type agouti, wolf sable
|
|
|-
|'''''a<sup>t</sup>'''''
|Tan point, saddle tan
|
|
|}
*

[[File:Pug portrait.jpg|thumb|[[Pug]] with melanistic mask '''''E<sup>m</sup>''/'''_ .]]

<gallery>
File:Eurasier liegend.jpg|E<sup>m</sup> allows the production of black and chocolate brown eumelanin in the fur and causes the melanistic mask.
File:Black and Tan Goldspalter.png|Dogs with Genotype EE or Ee can produce black or chocolate brown eumelanin for the fur.
File:Yorkshire Welpe ee.png|Dogs with Genotype ee can only store pheomelanin in the fur. BB or Bb on the B locus still allows a black nose.
File:Labrador Retrievers yellow and red.jpg|Homozygous ee causes red or yellow fur. Eumelanin can be in nose, eye lids and paw pads but not in the fur.
File:Vizsla dog in grass.JPG|Genotyp ee and bb for brown eumelanin causes red fur and liver-nose.
File:CatahoulaLitter wb.jpg|In dogs with recessive red the [[Merle (dog coat)|Merle factor]] can be hidden, as they don't have eumelanin in the fur.
</gallery>

==See also==
* [[Labrador Retriever coat colour genetics]]
* [[Cat coat genetics]]
* [[Equine coat color genetics]]
* [[Farm-Fox Experiment]]

==Notes==
{{reflist|group=note}}

==References==
{{Reflist}}

==External links==
*{{cite web | last = Schmutz | first = Sheila M. | title = Dog Coat Color Genetics | publisher = University of Saskatchewan | date = March 4, 2010 | url = http://homepage.usask.ca/~schmutz/dogcolors.html | accessdate = September 12, 2010}}
*http://www.doggenetics.co.uk/

Latest revision as of 17:12, 30 April 2022

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