A trait is some aspect of an organism that can be described or measured

Basic Genetics as Revealed by Cats

Although there is not complete agreement on the origin of the domestic cat, Felis catus, it is generally believed that domestication occurred in Egypt some 3500 years ago. The most likely wild African candidate for the ancestral cat is the African wild cat (Felis libyca). However, the European wild cat (Felis silvestris) may also have contributed to the genetic composition of the domestic cat by hybridizing with the African wild cat.

Important Concepts and Facts about Cat Genetics

Phenotype vs. Genotype

A trait is some aspect of an organism that can be described or measured. The phenotype is the observed state of the trait. Phenotype is a product of the interaction between genotype and environment. First, we will consider the effects of genotype.

Cats have 19 pairs of chromosomes. One member of each pair comes from Mom and one from Dad. Along the chromosomes are genes. Genes provide the information necessary to produce a cat. All the genes in all the chromosomes comprise the genome, which is the complete cat blueprint. Each gene is also called a locus (plural: loci), indicating that it has a physical location on the chromosome. Thus, each cat has two alleles of each gene; one inherited from each parent. The genotype at a locus is a determined by the identities of those two alleles.

For example, the genotype of a longhaired cat at the longhaired locus, which controls fur length, is ll. This genotype is homozygous (both alleles are the same).

Dominance

Longhaired

It isn’t possible to determine the longhaired genotype of a shorthaired cat simply by observation. This is because the shorthaired allele, L, is dominant to the longhaired allele, l, which means that in a heterozygote (Ll, i.e., each allele is different) the effect of the shorthaired allele over-rides, or dominates the effect of the recessive longhaired allele. Dominant alleles are usually symbolized by capital letters and recessive alleles with lower case letters.

It is possible to infer the genotype of a shorthaired cat by observing the phenotypes of its offspring from a mating with a longhaired cat. Such a mating is called a test cross (Table 1).

Table 1. Test cross to determine the genotype of a shorthaired cat. The numbers in the boxes below indicate the proportion of progeny of each phenotype expected to result from a mating of the shorthaired of unknown genotype to a homozygous recessive longhaired.

Tester		Possible genotypes of shorthaired phenotype
phenotype	genotype	Ll	ll
longhaired	ll	50% longhaired: 50% shorthaired	100% longhaired

Question 1: What assumptions about the inheritance of alleles must you make to use a test-cross to determine the genotype of an individual expressing the dominant phenotype?

Other genes with dominant alleles are the agouti gene, which controls color expression along the length of each shaft of hair, and the eumelanin and dilute genes, which also influence coat color.

More than two alleles

The colors in hair, skin, and eyes are caused by melanin. Microscopic granules of melanin are deposited in the hair shafts. The shape, size, and arrangement of these granules affect coat color. There are two different kinds of melanin: eumelanin and phaeomelanin. Eumelanin granules are thought to be spherical in shape and absorb almost all light, giving black pigmentation. Phaeomelanin granules are thought to be elongated like footballs, and to reflect light in the red-orange-yellow range.

Black

The black gene has three alleles that control the density of eumelanin granules in the hair shaft. The black allele, B, is dominant and produces a black (actually super-dark brown) coat. This black color is evident in all-black cats, the black stripes of a tabby cat, and the dark ear-tips, feet and tails (the points) of seal point Siamese cats. The dark-brown allele, b, reduces black to a dark brown, chocolate color. This allele is less common and occurs almost exclusively in pedigreed cats such as Siamese and Burmese. It is believed that the b allele migrated into Europe from Asia via importation of Siamese cats during the 1800’s. The light-brown allele, b^l, further reduces melanin density to produce a medium brown coat, called cinnamon. It is not too likely that you will find cats homozygous for these recessive alleles in Berkeley’s general cat population. The dominance heirarchy of these alleles is B > b > b^l (Figure 2).

Dilute

The dilute locus has two alleles that affect the distribution of pigment granules in the fur. The dominant dense allele, D, produces dense color, whereas the recessive dilute allele (d) causes clumpng of pigment granules in the hair shaft, leaving large areas between the clumps containing no granules. These open areas cause color dilution (Figure 2).

Figure 2. Effect of black (eumelanin), orange (phaeomelanin), and dilute genes on cat coat colors.

Codominance

Dominance is a continuous phenomenon, which runs the gamut from completely dominant (e.g. the shorthaired allele, which completely masks the recessive longhaired allele) to codominant, where the hetrozyogote resembles neither homozygote.

Albino

Two alleles at the albino locus, pointed, c^s, and sepia, c^b, provide an example of codominance. Both alleles are recessive to the full-color allele, C, but are codominant with each other. The homozygous genotype c^sc^s reduces pigment expression across most of the animal. Reducing pigment production in the eyes produces bright blue eyes, while reducing pigment density in the hair shaft reduces the basic coat color from black/brown to a light beige with dark brown “points” in the classic Siamese pattern. The homozygous c^bc^b genotype has a similar but smaller reduction in pigment production, reducing a black coat to very dark brown (similar to the color of the “points” on the Siamese) and yielding green or green-gold eyes. These cats are called “Burmese”. The heterozygote possesses one of each of the alleles, c^bc^s, and yields a combination phenotype called “Tonkinese”: a Siamese-patterned coat with darker base body color and turquoise (aquamarine) eyes. All three alleles (C, c^s, and c^b) are dominant to the very rare albino alleles, c and c^a, which when homozygous produce white cats with either lightly pigmented (c^ac^a) pale blue eyes or unpigmented (cc) pink eyes. The dominance hierarchy at the albino locus is: C > c^b = c^s > c^a > c.

Question 3: Why do population geneticists prefer to work with codominant genes?

Genotype by Environment Interaction

Most cat coat color traits show little influence from the environment. However, there is one fascinating exception to this rule. The Siamese allele, c^s, at the albino gene causes temperature-sensitive pigment expression. The allele produces a temperature-sensitive tyrosinase gene that is inactive at the cat’s core body temperature, leaving a light brown background. However, at the tips of the extremities, which are much cooler, the enzyme is active and produces normal amounts of pigment, creating the characteristic dark “points” of the Siamese. Indeed, “indoor” Siamese cats living in warm homes tend to be lighter than their “outdoor” compatriots, which can become quite dark during cold winters. The c^b allele is also temperature sensitive, but less so than the c^s allele, and therefore produces a darker coat.

Epistasis: Gene-Gene Interaction

Orange

The orange gene has two alleles: non- orange and orange. The non-orange allele, o, is recessive and allows full expression of the black locus. The dominant orange allele, O, however, influences expression of the black and agouti loci because it substitutes the production of phaeomelanin for eumelanin. It masks the effect of the black gene by converting a black or brown coat to orange. The ability of one gene to mask the effect of another gene is called epistasis. Further, all orange cats are tabbies because the orange allele is epistatic to the non-agouti (solid coat) phenotype normally produced by aa at the agouti locus. This masking occurs because the orange band of phaeomelanin granules in the hair shaft is not visible against the yellowish background of the hair without melanin granules.

Sex-linked Traits

The other interesting characteristic of the orange gene is that it is carried on the X chromosome, which makes it sex-linked. In male cats, this locus can normally produce only two phenotypes, black or orange, whereas in females it can produce three phenotypes: black, orange, and tortoiseshell. This is because males are normally XY (heterogametic), and therefore have only one X-chromosome. Thus, if a male carries the orange allele at all, he will be orange (OY). Females are XX, meaning they have two X-chromosomes (homogametic). If both chromosomes carry the orange allele, then the cat will be orange. However, if she is heterozygous (Oo), her coat will be a patchwork of orange and black patches, called tortoiseshell. This pattern reveals an interesting phenomenon. To ensure that the amount of gene product in female cells is equal to that found in male cells, early in female embryonic development, one X-chromosome is inactivated in each cell. Thus, in a female that is heterozygous at the orange locus, some cells produce phaeomelanin (the active X-chromosome contains the O allele) and others do not (the active X-chromosome contains the o allele). Which X-chromosome is inactivated is an entirely random decision. Further, this decision is passed on to all cells in any cell line, making the female a mosaic of cell patches with one or the other X-chromosomes actively producing its gene products.

Question 4: Develop a table describing the possible genotypes and their phenotypes that could result from a cross between a tortoiseshell and a black cat. Assume both cats are homozygous BB.

Complex Traits

Complex traits are controlled by more than one gene. Of course, cat color is controlled by multiple genes. However, even within this complex trait, categories can be distinguished which allow us to ascertain genotype at several loci. Some component traits are themselves complex, probably because they are determined in part by a locus with major effect, but also in part by loci with small effects. These loci with small effects are often called minor loci or modifier genes.

Tabby

The tabby gene causes banded (ticked) hairs to alternate with stripes, blotches, or spots of solidly colored hairs, creating the striping pattern in cat coats. There are two common striping patterns (Figure 3): mackerel (parallel stripes) or classic (characterized by thick stripes or whorls that create a blotched or bulls-eye pattern). The parallel stripe is produced by the dominant tabby allele, T. It is probably the ancestral striping pattern, which is seen in the African wild cat (Felis libyca) and the European wild cat (Felis silvestris). The recessive blotched allele, t^b, produces the classic pattern, and probably arose much later by mutation. A third allele in the series, Abyssinian (T^a) produces the Abyssinian phenotype that has faint striping only on the face or tail and has a dark stripe down the center of the back. The hierarchy of dominance for the three alleles is T^a > T > t^b. However, T^a allele shows some degree of incomplete dominance since either T^aT or T^at^b heterozygotes may show faint striping on the legs and tail.

Question 5: What effect might a striped (vs. solid) coat have on the fitness of a wild cat?

Figure 3. Striping patterns determined by the tabby gene.

T‑ t^bt^b T^a‑

All cats have one of the above tabby patterns - even solid black cats. However, because the agouti gene is epistatic to the tabby gene, striping cannot be seen in non-agouti cats. This is because the recessive aa agouti genotype blocks the production of banded hairs, thereby masking the expression of the tabby phenotype. It is nevertheless sometimes possible to see “ghost” striping on black cats, especially kittens, when viewed in the proper light. It is also important to note that because the O allele at the orange locus is epistatic to the agouti gene, tabby striping is not masked on solid orange cats, or on orange patches on tortoiseshell cats. That is, O is epistatic to the epistatis of aa on the tabby gene.

The genetic mechanism behind a fourth tabby phenotype, the spotted tabby, is not completely understood. There are probably two different mechanisms. The first appears to be a modification of the mackerel tabby, in which the narrow bars are broken up into small dark patches. This effect is though to be the result of several modifier genes acting on the major tabby gene. There is another rarer spotted phenotype called the Ocicat (because of its resemblance to the wild ocelot) which has larger, more distinct round spots. This phenotype may be due to a separate major gene. However, because it is so rare, for the purposes of this project we will consider any spotted tabby to have the mackerel tabby phenotype, with modifications.

Pleiotropy

When a gene affects more than one trait, it is termed pleiotropic. Most coat color genes have pleiotropic effects on eye color. However, two genes also have an interesting pleiotropic effect on hearing ability.

Dominant White

The dominant white allele, W, overrides all other genes for pigmentation, and produces a white coat and blue eyes. Thus, the dominant white allele is epistatic to all other coat color genes. Of course, the other genes for color and pattern are present, but their effects are completely hidden because the dominant white mutation blocks production of specialized melanin-producing cells called melanocytes.

Interestingly, the cochlea of the ear contains a band of melanocytes that regulate ion balance. Normally, hearing occurs via electrical signals stimulated by vibration of the hair cells in the cochlea. Transmission of these signals to the brain requires constant regulation of ion balance. When ion balance is not maintained, signal transmission to the brain degenerates within a few days after birth, producing irreversible deafness. Thus, the dominant white locus exhibits plieotropy, affecting both coat color and hearing.

Piebald Spotting

White spotted, or piebald, cats are very common. Spotting may occur with any coat color, and is mainly due to the effect of one gene with two co-dominant alleles. The spotted allele, S, creates responsible for white spots, while the s allele is not. Hence, the homozygote, ss, has no white spots. The heterozygote, Ss, has restricted areas of white spotting; usually the feet, nose, chest, and belly. Finally, the SS homozygote has white regions covering more than half the body. In the latter case, people usually consider the dark patches to be spots. However, in reality, it is the larger white area that is the spot, and in fact, a “spotted” (SS) cat may even be completely white!

The degree of spotting varies tremendously, but spotting patterns usually follow a regular progression. Cats with the least spotting have small spots on the breast and belly. Increased spotting seems to progress to cover the entire belly, the neck, chin and front feet. Finally, cats with the most spotting have spots up the sides, over the back and onto the head. The tail seems to be the last area to have white spots. Since cats vary continuously in the extent of spotting, and the pattern of spotting is not completely random, it is unlikely that only one gene determines the degree of spotting. There is evidence of at least one other gene that has a weak spotting effect. It can cause a very small white spot on the throat, breast, or on the belly near the hind legs. In fact, several genes probably modify the action of the major spotting gene to produce the continuum of spotting patterns seen in cat populations. Since the action of these weak modifier genes is not well understood, we will score only the major spotting gene in our cat survey.

The spotted allele, S, hampers the migration of melanocytes during embryonic development. White spots are areas lacking melanocytes. Thus, within these patches a spotted cat will exhibit the same pleiotropy as caused by the dominant-white gene. For example, if an eye is within a spot, it will be blue. Thus, spotted cats may be blue-eyed or odd-eyed. Further, if the spot encompasses an ear, the cat will be deaf in that ear. Since a spot often covers the eye when it covers the ear, an odd-eyed cat will frequently be deaf on the blue-eyed side.

The spotting gene has in interesting effect on the patterning in tortoiseshell (Oo) cats. With the ss genotype, there is no white spotting and the orange and black are intermingled, usually without large patches of either orange or black. With either Ss or SS genotypes, there are white spots and the orange and black occur as distinct patches. These cats are called calico cats (or, sometimes, tortoiseshell and white). This pattern seems to be due to the effect of the spotting allele on embryonic melanocyte migration.

Special note about white cats

White cats can be produced in three distinct ways. It can be dominant white (W‑), albino (cc), or spotted (S‑) with one big white spot all over its body. It is therefore important to observe white cats carefully and take notes about their eye-color.

The dominant white allele, W, and the homozygous spotted genotype, SS, can both produce a translucent all-white coat with either orange or medium blue eyes. However, the spotted white cat often has a tuft of color somewhere on its body. If the cat has even one colored hair on its body, it is spotted rather than dominant white

The albino gene controls the amount of pigment produced in the melanocytes. A cat homozygous for albino, cc, at the albino locus is a true albino, in that its melanocytes cannot produce any pigment. It has a translucent white coat and pink eyes. A c^ac^a genotype at the albino locus produces a white cat with pale blue (almost grey) eyes. Both these alleles are very rare. Deafness in white cats is associated with white spotting (S), and with dominant white (W), but not with albino white (cc or c^ac^a).

Question 6: If you mated two white cats, would you be confident of always obtaining white progeny? Explain.

Question 7: What factors determine allele frequency? Is a dominant allele always the most frequent allele at a locus?

Question 8: Manx cats have no tail and relatively long rear legs. What is the genotype of a Manx cat? Do you expect the frequency of Manx cats to increase over time? Why or why not?

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Table 2. Effects of agouti and tabby on the black, dilute and orange gene effects. Note that here, an orange cat is described as “red”, and an Abysinnian is called a “ticked tabby”. The agouti and tabby genes also influence expression of the albino gene, but their effects have not been tabulated here.