Cat coat genetics

The browning gene B/b/b^l codes for TYRP1 (Q4VNX8), an enzyme involved in the metabolic pathway for eumelanin pigment production. Its dominant form, B, will produce black eumelanin. It has two recessive variants, b (chocolate) and b^l (cinnamon), with b^l being recessive to both B and b.[1] Chocolate is a rich dark brown color, and is referred to as chestnut in some breeds. Cinnamon is a light reddish brown, but is sometimes not reddish at all.

Basic colors

A male red tabby showing the OO-genotype

A female black tortoiseshell cat showing the Oo-genotype

Diluted colors

A cream (diluted red) tabby cat

A blue (diluted black) tortoiseshell cat

The sex-linked red "Orange" locus, O/o, determines whether a cat will produce eumelanin. In cats with orange fur, phaeomelanin (red pigment) completely replaces eumelanin (black or brown pigment).[2] This gene is located on the X chromosome. The orange allele is O, and is codominant with non-orange, o. Males can typically only be orange or non-orange due to only having one X chromosome. Since females have two X chromosomes, they have two alleles of this gene. OO results in orange fur, oo results in fur without any orange (black, brown, etc.), and Oo results in a tortoiseshell cat, in which some parts of the fur are orange and others areas non-orange.[3] One in three thousand tortoiseshell cats are male, making the combination possible but rare- however, due to the nature of their genetics, male tortoiseshells often exhibit chromosomal abnormalities.[4] In one study, less than a third of male calicos had a simple XXY Klinefelter's karyotype, slightly more than a third were complicated XXY mosaics, and about a third had no XXY component at all.[4]

The pelt color commonly referred to as "orange" is scientifically known as red. Other common names include yellow, ginger, and marmalade. Red show cats have a deep orange color, but it can also present as a yellow or light ginger color. Unidentified "rufousing polygenes" are theorized to be the reason for this variance. Orange is epistatic to nonagouti, so all red cats are tabbies. "Solid" red show cats are usually low contrast ticked tabbies.[5]

The precise identity of the gene at the Orange locus is unknown. It has been narrowed down to a 3.5 Mb stretch on the X chromosome in 2009.[5]

The Dense pigment gene, D/d, codes for melanophilin (MLPH; A0SJ36), a protein involved in the transportation and deposition of pigment into a growing hair.[5] When a cat has two of the recessive d alleles (Maltese dilution), black fur becomes "blue" (appearing gray), chocolate fur becomes "lilac" (appearing light, almost grayish brown-lavender), cinnamon fur becomes "fawn", and red fur becomes "cream".[6] Similar to red cats, all cream cats are tabbies. The d allele is a single-base deletion that truncates the protein. If the cat has d/d genes, the coat is diluted. If the genes are D/D or D/d, the coat will be unaffected.[5]

Two amber tabby Norwegian Forest cats, showing the colour difference with age. On the left a female kitten, on the right a male adult.

• Barrington Brown is a recessive browning gene that dilutes black to mahogany, brown to light brown and chocolate to pale coffee. It is different from the browning gene and has only been observed in laboratory cats.[7]
• The Dilution modifier gene, Dm, "caramelizes" the dilute colors as a dominant trait. The existence of this phenomenon as a discrete gene is a controversial subject among feline enthusiasts.
• Amber, a mutation at the extension locus E/e (the melanocortin 1 receptor, MC1R) changes black pigment to amber or light amber, similar in appearance to red and cream. Kittens are born dark but lighten up as they age. Paws and nose still exhibit the original undiluted color, this in contrast to other diluted colors, where paws and nose have the diluted color. This phenomenon was first identified in Norwegian Forest cats.[8]
• Another recessive mutation at extension was discovered which causes the russet color in Burmese cats. It is symbolized as e^r. Like amber cats, russet cats lighten as they age.[9]
• A modifying factor has also been hypothesized in shaded silver and chinchilla Persians whose fur turns pale golden in adulthood, due to low levels of phaeomelanin production. These cats resemble shaded or tipped goldens, but are genetically shaded or tipped silvers. This is probably related to the phenomenon known as "tarnishing" in silvers.

The Agouti gene, with its dominant A allele and recessive a allele, controls the coding for agouti signaling protein (ASIP; Q865F0). The wild-type A produces the agouti shift phenomenon, which causes hairs to be banded with black and an orangish/reddish brown, this revealing the underlying tabby pattern (which is determined by the T alleles at the separate tabby gene). The non-agouti or "hypermelanistic" allele, a, does not initiate this shift in the pigmentation pathway and so homozygotes aa have pigment production throughout the entire growth cycle of the hair—along its full length.[10] As a result, the non-agouti genotype (aa) is solid and has no obvious tabby pattern (sometimes a suggestion of the underlying pattern, called "ghost striping", can be seen, especially in bright slanted light on kittens and on the legs, tail and sometimes elsewhere on adults). Agouti is found on chromosome A3.

A major exception to the solid masking of the tabby pattern exists: the O allele of the O/o locus is epistatic over the aa genotype. That is, in red or cream colored cats, tabby striping is displayed despite the genotype at the agouti locus.

However, some red cats and most cream cats show a fainter tabby pattern when they have no agouti allele to allow full expression of their tabby alleles. That is, in genetically red cats (O males and OO and Oo females) the aa does still have an effect, especially in dilute coats (when having dd genotype at the D gene locus), where the tabby pattern is sometimes not expressed except on the extremities.

The Tabby gene on chromosome A1 accounts for most tabby patterns seen in domestic cats, including those patterns seen in most breeds. The dominant allele Ta^M produces mackerel tabbies, and the recessive Ta^b produce classic (sometimes referred to as blotched) tabbies.[11] The gene responsible for this differential patterning has been identified as transmembrane aminopeptidase Q (Taqpep, M3XFH7). A threonine to asparagine substitution at residue 139 (T139N) in this protein is responsible for producing the tabby phenotype in domestic cats. In cheetahs, a base pair insertion into exon 20 of the protein replaces the 16 C-terminal residues with 109 new ones (N977Kfs110), generating the king cheetah coat variant.[12]

The wild-type (in African wildcats) is the mackerel tabby (stripes look like thin fishbones and may break up into bars or spots), the most common variant is the classic tabby pattern (broad bands, whorls, and spirals of dark color on pale background usually with bulls-eye or oyster pattern on flank).[12] The classic tabby is most common in Iran, Great Britain and in lands that were once part of the British Empire and Persian Empire.

Spotted tabbies have their stripes broken up into spots, which may be arranged vertically or horizontally. A 2010 study suggests that spotted coats are caused by the modification of mackerel stripes, and may cause varying phenotypes such as "broken mackerel" tabbies via multiple loci. If the genes are Sp/Sp or Sp/sp the tabby coat will be spotted or broken. If it is an sp/sp gene, the tabby pattern will remain either mackerel or blotched. This gene has no effect on cats with a ticked coat.[11]

The Ticked (Ti) locus on chromosome B1 controls the generation of ticked coats, a non-patterned agouti coat having virtually no stripes or bars but still considered a tabby coat. Ticked tabbies are rare in the random-bred population, but fixed in certain breeds such as the Abyssinian and Singapura.[13] Ti^A is the dominant allele that produces ticked coats; Ti⁺ is the recessive one. The causative gene for ticked tabby markings is Dickkopf-related protein 4 (DKK4). Two different alleles are responsible for the Ti^A ticked tabby phenotype: a cysteine to tyrosine substitution at residue 63 (C63Y) and an alanine to valine substitution at residue 18 (A18V). Both variants are present in the Abyssinian breed, and the A18V variant is found in the Burmese breed.[13] Stripes often remain to some extent on the face, tail, legs, and sometimes the chest ("bleeding through"). Traditionally, this has been thought to happen in heterozygotes (Ti^ATi⁺) but be nearly or completely nonexistent in homozygotes (Ti^ATi^A). The ticked tabby allele is epistatic to and therefore completely (or mostly) masks all the other tabby alleles, “hiding” the patterns they would otherwise express.[11]

It was once thought that Ti^A was an allele of the Tabby gene, called T^a, dominant to all other alleles at the locus.[14]

Rosette pattern in a Bengal.

• Other genes (pattern modifier genes) are theorized to be responsible for creating various type of spotting patterns, many of which are variations on a basic mackerel or classic pattern. There are also hypothetical factors which affect the timing and frequency of the agouti shift, affecting agouti band width and the number and quality of alternating bands of eumelanin and phaeomelanin on individual hairs.
• There is a gene not yet identified, but believed to be related to the agouti gene in the Chausie breed that produces silver-tipped black fur similar to Abyssinian ticked fur, known as "grizzled." This phenomenon is purported to have been inherited from the hybridization of the domestic cat to the jungle cat (Felis chaus).
• The rosette tabby pattern is a pattern similar to that of a leopard, where rosette spots are spread over the body. The pattern is found in hybrid cat breeds, such as the Bengal and Safari.[15]
• The inhibited pigment gene, I/i. The dominant allele (I) produces tipped hairs that are fully colored only at the tip and have a white base. This allele appears to interact with other genes to produce various degrees of tipping, ranging from deeply tipped silver tabby to lightly tipped shaded silver and chinchilla silver. The inhibitor gene interacts with the non-agouti genotype (I-aa) to produce the color known as smoke. The homozygous recessive genotype when combined with the agouti gene (iiA-), produces tabby coloration, which can vary along a spectrum ranging from a deeply patterned brown tabby, to a lighter "golden tabby", to the very lightly colored shaded or chinchilla golden colors. Red and cream cats with the inhibitor gene (I-O-) are commonly called "cameo".

• The basic tortoiseshell pattern has several different colors depending on the color of the eumelanin (the B locus), and dilution (the D locus).
• Tortoiseshell tabbies, also known as torbies, display tabby patterning on both red- and black-based colors. Calico tabbies are also called calibys or tabicos.[19]

The silver series is caused by the Melanin inhibitor gene I/i. The dominant form causes melanin production to be suppressed, but it affects phaeomelanin (red pigment) much more than eumelanin (black or brown pigment). On tabbies, this turns the background a sparkling silver color while leaving the stripe color intact, making a cold-toned silver tabby. On solid cats, it turns the base of the hair pale, making them silver smoke.[31] The term cameo is commonly used for red silver and cream silver (inhibitor gene (I-O-)) colored coats in cats.

Silver agouti cats can have a range of phenotypes, from silver tabby, to silver shaded (under half the hair is pigmented, approx. 1/3 of hair length), to tipped silver also called chinchilla or shell (only the very tip of the hair is pigmented, approx. 1/8 of hair length). This seems to be affected by hypothetical wide band factors, which make the silver band at the base of the hair wider. Breeders often notate wide band as a single gene Wb/wb, but it is most likely a polygenic trait.

• 
  Smoke
• 
  Shaded
• 
  Tipped (chinchilla / shell)
• 
  Cameo shaded (red / cream silver)

If a cat has the wide band trait but no silver melanin inhibitor, the band will be golden instead of silver. These cats are known as golden tabbies, or in Siberian cats sunshine tabbies. The golden color is caused by the CORIN gene. Shaded golden and tipped golden are also possible, in the same hair length distribution as the silver-gene. However, there is no golden smoke, because the combination of wide band and nonagouti simply produces a solid cat.[32][33]

The genetics involved in producing the ideal tabby, tipped, shaded, or smoke cat is complex. Not only are there many interacting genes, but genes sometimes do not express themselves fully, or conflict with one another. For example, the silver melanin inhibitor gene in some instances does not block pigment, resulting in a grayer undercoat, or in tarnishing (yellowish or rusty fur). The grayer undercoat is considered less desirable to fanciers.

Likewise, poorly-expressed non-agouti or over-expression of melanin inhibitor will cause a pale, washed out black smoke. Various polygenes (sets of related genes), epigenetic factors, or modifier genes, as yet unidentified, are believed to result in different phenotypes of coloration, some deemed more desirable than others by fanciers.

The genetic influences on tipped or shaded cats are:

• Agouti gene.
• Tabby pattern genes (such as T^a masking the tabby pattern).
• Silver/melanin inhibitor gene I/i.
• Golden CORIN gene.
• Factors affecting the number and width of bands of color on each hair, such as the hypothetical wide band gene wb. Resulting in shaded or tipped (chinchilla/shell) pigmentation.
• Factors affecting the amount and quality of eumelanin and/or phaeomelanin pigment expression (such as theorized rufousing factors)
• Genes causing sparkling appearance (such as glitter in the Bengal, satin in the Tennessee Rex, grizzle in the Chausie).
• Factors to clear up residual striping (hypothetical Chaos, Confusion, Unconfused, Erase, and Roan factors).

• Silver series
• 
  Black silver spotted tabby Egyptian Mau.
• 
  Black smoke cat.
• 
  Cameo (red silver) shaded Maine Coon.
• 
  Black silver tipped (chinchilla) Persian cat.

• Golden series
• 
  Sunshine blotched tabby Siberian Cat.
• 
  Black golden ticked tabby British Shorthair.
• 
  Black golden ticked tabby British Shorthair.
• 
  Blue golden tipped (chinchilla) Persian cat.

Down, awn and guard hairs of a domestic tabby cat

Cat fur can be short, long, curly, or hairless. Most cats are short-haired, like their ancestor.[37] The fur can naturally come in three types of hairs; guard, awn, and down hair. The length, density and proportions of these three hairs varies greatly between breeds, and in some cats only one or two types are found.[37][38]

Most oriental breeds only express one single layer of silky coat.[37] However, cats can also have double-layered coats out of two hair types in which the down hairs form the soft, insulating undercoat, and the guard hairs form the protective outer coat.[37]

A typical cat coat exists of all three natural hair types, but due to the equal lengths of two of these hairs, the coat is still considered double-layered.[37] Typically, the down and awn hairs comprise the undercoat.[37][38] Double-coated cats with thick undercoats require daily grooming as these coats are more prone to matting.[37] Double coats are found in for example the Persian, British Shorthair, Maine Coon and Norwegian Forest cat.

Additionally, there even exist cats which express all three natural types of cat hair in different lengths and structures, which form three different layers. These cats are called triple-coated. Siberians and Neva Masquerades are known for their unique triple coats,[37] which provides double insulation to withstand their natural cold climate.

There have been many genes identified that result in unusual cat fur. These genes were discovered in random-bred cats and selected for. Some of the genes are in danger of going extinct because the cats are not sold beyond the region where the mutation originated or there is simply not enough demand for cats expressing the mutation.

In many breeds, coat gene mutations are unwelcome. An example is the rex allele which appeared in Maine Coons in the early 1990s. Rexes appeared in America, Germany and the UK, where one breeder caused consternation by calling them "Maine Waves". Two UK breeders did test mating which indicated that this was probably a new rex mutation and that it was recessive. The density of the hair was similar to normally coated Maine Coons, but consisted only of down type hairs with a normal down type helical curl, which varied as in normal down hairs. Whiskers were more curved, but not curly. Maine Coons do not have awn hairs, and after moulting, the rexes had a very thin coat.

Cat fur length is governed by the Length gene in which the dominant form, L, codes for short hair, and the recessive l codes for long hair. In the longhaired cat, the transition from anagen (hair growth) to catagen (cessation of hair growth) is delayed due to this mutation.[39] A rare recessive shorthair gene has been observed in some lines of Persian cat (silvers) where two longhaired parents have produced shorthaired offspring.

The Length gene has been identified as the fibroblast growth factor 5 (FGF5; M3X9S6) gene. The dominant allele codes for the short coat is seen in most cats. Long coats are coded for by at least four different recessively inherited mutations, the alleles of which have been identified.[40] The most ubiquitous is found in most or all long haired breeds while the remaining three are found only in Ragdolls, Norwegian Forest Cats, and Maine Coons.

Wavy fur of a Devon Rex cat

There are various genes producing curly-coated or "rex" cats. New types of rex arise spontaneously in random-bred cats now and then. Some of the rex genes that breeders have selected for are:

• Devon Rex
  • Mutation in KRT71 (E1AB55), the same gene causing hairlessness in Sphynx cats. re is an allele completely recessive to the wildtype and completely dominant to hr found in Sphynx.[41]
• Cornish Rex
  • Mutation in LPAR6 (A0A5F5XLZ8). A completely recessive allele termed r.[42]
• Ural Rex
  • Mutation in LIPH.[43]
• German Rex
  • Provisionally an allele termed gr. Same locus as Cornish, but proposed as a different allele. However, most breeders consider the German Rex to have r/r genotype.
• Oregon Rex (extinct)
  • A hypothetical recessive allele termed ro.
• Selkirk Rex
  • A dominant allele termed Se, although sometimes described as an incomplete dominant because the three possible allele pairings relate to three different phenotypes: heterozygous cats (Se/se) may have a fuller coat that is preferred in the show ring, while homozygous cats (Se/Se) may have a tighter curl and less coat volume. (se/se type cats have a normal coat.) This phenomenon may also colloquially be referred to as additive dominance.
• LaPerm
  • Provisional completely dominant Lp allele.

Hairless cats are often born even without whiskers

There are also genes for hairlessness:

• h=French hairless cat, recessive.
• hd=British hairless cat, recessive.
• Hp=Russian Donskoy and Peterbald, dominant.
• hr=Sphynx cat, recessive. Identified on KRT71.[41]

Some rex cats are prone to temporary hairlessness, known as baldness, during moulting.

Here are a few other genes resulting in unusual fur:

• The Wh gene (dominant, possibly incomplete) results in Wirehair cats. They have bent or crooked hair producing springy, crinkled fur.
• A hypothetical Yuc gene, or York Chocolate undercoat gene, results in cats with no undercoat. However, the proportional relationship between guard, awn, and down hair production varies greatly between all breeds.
• A recessive autosomal gene for Onion hair which causes roughness and swelling on the hairs. The swelling is due to enlargement of the inner core of medulla cells.
• A recessive autosomal gene spf for sparse fur. As well as sparse coat, the hairs are thin, straggly and contorted and there is brown exudate around the eyes and nose and on the chest and stomach. A similar condition is linked to Ornithine Transcarbamylase Deficiency in mice.