MOSAICISM, TORTIE TOMCATS AND GENETICALLY IMPOSSIBLE KITTENS
1996 - 2012 Sarah Hartwell

When this article was originally written (1996), I had heard from a breeder who owned a fully fertile tortoiseshell and white stud cat. She wanted to know why he only passed on the gene for red and never for black. Her stud turned out to be a red-and-white bicolor mosaic (meaning a somatic mosaic). Since these mosaics breed as for bicolors, his black hairs were not inheritable - they were the equivalent of moles in humans. Due to the increasing amount of information on tortie tomcats and several case studies, gender anomalies (which can occur in mosaics and non-mosaics alike) are now discussed in Mosaicism 2: Gender Anomalies.

Originally, tortoiseshell tomcats were believed to be XXY individuals (this is explained in more detail later on) which accounted for them being infertile and having "female" colouration. Some also behaved more like females and this was also attributed to their XXY genetic make-up. With genetics testing still in its infancy, and too expensive for use with pets, the other conditions now known to cause tortoiseshell males were not recognised or understood.

In earlier feline genetics texts, mosaic was defined as a genetically red/red-and-white (or dilute of these) cat which has patches of black hairs so that it appears to be tortoiseshell/calico. The black patches (or hairs) are not genetically inherited; they are caused by localised mutation of skin cells in the embryo (somatic mutation). The mutant skin cells produce black pigment. This form of mosaicism was once thought to account for many of the fertile 'tortoiseshell' males since test matings showed them to be genetic reds/red-and-whites. It also occurs in females, but is mistaken for normal tortoiseshell.

As genetics knowledge has advanced, the terms "mosaic" and "mosaicism" have been (and often still are) used to mean different things. Some texts use "mosaic" to mean the outward appearance, regardless of the cause while other texts use mosaic to mean a genetic effect which may or may not be visible. To avoid confusion, I have tried to keep to a consistent set of definitions e.g. somatic mosaic, XY/XXY mosaic.

The discussion of cats with unusual chromosome complements (XXY, XYY etc) brings us on to gender anomalies which is a fascinating field in itself. I have expanded this article to include these. Many of the listed anomalies have not been documented in cats, but their existence in other mammals means there is a probability that they do occur in cats. Gender/fertility problems are only usually investigated in pedigree cats in breeding programs. In the random breeding feline population (60-90% of pet cats, depending on where you live) such anomalies are likely to go unnoticed.

Allele: there are different variants of most genes; these variants are properly known as alleles (for simplicity I use "gene" throughout this article).
Autosome: any chromosome other than the X or Y "sex" chromosomes.
Genotype: the genetic make-up of an organism.
Phenotype: the outward appearance of an organism (several different genotypes may result in the same phenotype).
Dominant: most genes are inherited in pairs; the dominant gene of a pair is the one which is physically expressed.
Recessive: the recessive gene is only physically expressed if both genes in a pair are the same recessive gene.

Hermaphrodite: having the sex organs of both male and female.
Intersex: Having undifferentiated sex organs, which are neither fully male nor fully female, but intermediate between the two.

Mosaic (1) having a coat with multiple colours e.g. brindle or tortoiseshell; (2) an individual whose cells have different genetic composition e.g. XY/XXY; (3) having somatic mosaicism.
Somatic mosaicism the presence of genetically distinct populations of somatic cells in a given organism due to DNA mutations/damage or chromosome abnormalities.
Germ-line mosaicism a particular mutation early in the development of an embryo means that, later in life, some of the egg or sperm cells will carry the mutated gene which can be passed on to offspring. This will only be detected in offspring which inherit the mutation.
Chimaera an individual which developed from two genetically distinct germ-lines e.g. where two embryos fused in the womb. Scientists have created a deliberate chimaera by mixing sheep and goat embryos; this "geep" had some goatlike body parts and some sheep-like body parts (in fact it looked like a goat's legs had been stitched onto a sheep body!).

A single individual can have more than one form of mosaicism. The fraction of cells having each genotype is quite variable, reflecting how early during embryo development the mosaicism originated. While mosaics and chimeras both have more than one genetically-distinct population of cells and the outward appearance may be identical, there is a clear distinction between mosaicism and chimaerism. In mosaics, the genetically different cell types all arise from a single embryo, whereas chimeras originate from fusing more than one embryo.

Many parts of this text are deliberately simplified so they can be understood by those with no previous genetic knowledge. Readers may also be interested in the book "Cats are Not Peas" which is about George, a male calico.

Every so often I am asked if a tortoiseshell or calico tomcat is valuable. You will find advertisements on the web, or in newspapers, placed by people hoping to sell a tortoiseshell tomcat for a large sum of money. One website even said that if you found a tortoiseshell tomcat, you could sell it for a fortune and retire!

Despite their rarity, tortoiseshell tomcats are not valuable in the financial sense. They have scientific value. Those that are fertile cannot pass on the tortoiseshell colour - you cannot breed more tortoiseshell males from them. As pets they are just like any other cat. As pedigree cats, there may be no colour class for them to enter so however fine they look, so they may be unable to win prizes (some breeds/shows have an "Any Other Colour" class). The abnormalities which have created a tortoiseshell male may also make him more susceptible to auto-immune disease or testicular tumours.

In short, if you have a tortoiseshell male cat, he is not going to make you rich! Even the minority of fertile tortie tomcats are not valuable in money terms because they don't breed true. So next time you see someone advertising a "rare tortie male" on Ebay, usenet or a bulletin board, you can wonder who is more gullible - the person expecting to make a fortune or the person who pays over-the-odds because they think the cat is going to make them a fortune!

Another myth about tortoiseshell male cats is that if an owner takes a tortie or calico cat to be spayed (quite reasonably believing it to be female) and it turns out to be a male which the vet then castrates, the owner is entitled to get the money back from the vet for unnecessarily neutering a cat which is already sterile. Even though a male calico is likely to be sterile, he probably still has the male hormones which make him spray. Many owners of tortoiseshell males like to mate the cat once to see if he is fertile. With so many unwanted kittens in the world, please don't do this unless you are involved in a genuine research programme.

To understand what creates tortoiseshell and calico males, we first have to look at the genes for red and for tortoiseshell. The white areas of calico cats are caused by different genes and will be ignored. The tabby pattern is also caused by other gene. In this article, "ginger" also includes "ginger-and-white" (red bicolour) and "red tabby" (with or without white). "Tortoiseshell" also includes "tortoiseshell-and-white" (calico) and "tortoiseshell tabby" (torbie) (with or without white). Cream is a dilute version of red. Blue (grey) is a dilute version of black.

The ginger colour of cats (known as "orange" or "red" to cat breeders) is caused by the "O" gene. The O gene changes black pigment into a reddish pigment. The O gene is carried on the X chromosome. A normal male cat has XY genetic makeup; he only needs to inherit one O gene for him to be a ginger cat. A normal female is XX genetic makeup. She must inherit two O genes to be a ginger cat. If she inherits only one O gene, she will be tortoiseshell. If she inherits no O genes, she will be black.

Normal male cats only inherit one X chromosome so this is active in all skin cells as there is nothing equivalent on the Y chromosome which could "switch off" the O gene. More rarely there are male cats with XXY genetic make-up (equivalent to human Klinefelter's syndrome). These turn out male because they have a Y chromosome. However, just like XX females, they undergo X-inactivation and are genetically mosaics. If only one of those X chromosomes carries the O gene, this can result in a tortoiseshell tomcat.

Mating together a red male and a red female can never give a tortoiseshell because the cats can only pass on the "O" genes to their kittens. However a tortoiseshell female called Royal Mainly's Otylia turned up in such a mating. Otylia has a small black patch on her ear, probably the result of a somatic mutation. Although tortie is normal in females, Otylia was a "genetically impossible kitten" because neither parent had a gene for black. In the random-breeding population, similar genetically impossible females go unnoticed because the paternity of the kittens is unknown.

Sometimes the description of how the O gene works becomes garbled. A newsgroup poster wrote "Male calicos are quite rare, because the gene that produces calico colouring is usually lethal in utero to male foetuses (the technical explanation's a bit complicated, but you could look it up in any good book on cats). This doesn't mean a male calico is highly valuable. For one thing, a true calico male is usually sterile, so it can't be used to breed a line of 'pure' calico cats." An explanation from 1992 said "The calico male is probably triploid i.e. XXY which allowed the calico recessive to show." As I have already described, calico is an interaction of genes, it is not a single recessive gene.

Almost all female mammals are mosaics i.e. a patchwork mixture of two genetically different types of cell although this may not have a visible effect. Females inherit 2 X chromosomes while men have an X and a Y chromosome (a gene on the Y chromosome makes an embryos develop as a male). While other chromosomes must be inherited in matched pairs, males get along just fine with only 1 X chromosome. This suggested that having 2 X chromosomes could cause some sort of genetic abnormalities (too many genes), but female mammals overcome that problem by inactivating one or other X chromosome.

It had long been known that the cells of female mammals contain something called the "Barr body" and that tortoiseshell cats were almost always female. In the 1960s, geneticist Mary Lyon suggested that females switch off one X chromosome in every body cell - the Barr body is the bundled up corpse of the switched off X chromosome. Very early in the development of female embryos, each cell inactivates one of its X chromosomes at random. Each of these cells eventually gives rise to a patch of cells in the adult female that has the same inactivated X.

Random inactivation means that a female mammal is a mixture of two different cell types. Some regions of her body use the X she inherited from her mother, the rest use the X inherited from her father. She is a mosaic of two cell populations. Since the X chromosome carries around 5% of her genetic material, those different patches can be genetically very different! In cats this is visible as tortoiseshell females - some X chromosomes give rise to red fur while others give rise to black fur. A similar effect is seen in human females with Anhidrotic Ectodermal Dysplasia (reduces the number of sweat glands in the skin). Where only one X chromosome carries the faulty gene, the skin becomes a mosaic of small areas of sweating and non-sweating skin which only becomes visible in certain conditions.

Although the effect of mosaicism may not be visible (or is only visible in tortoiseshell cats), the whole body is a mosaic of genetically different cells. This was demonstrated when CC the cloned kitten was born. Cloned from a tortoiseshell-tabby female, CC could have turned out either red-tabby or brown-tabby (the white patches are caused by a different gene), but not tortoiseshell tabby. Nature's equivalent of clones are identical (monozygotic - coming from a single egg) twins. X chromosome inactivtion means that female identical twins may turn out to be very different and at the genetic level, they are not truly identical.

It is possible (though statistically unusual) for an embryo to use one X chromosome almost to the exclusion of the other. In female cats this can lead to genetically tortoiseshell females appearing to be wholly black or wholly ginger, but having unexpected black, ginger or tortie kittens. In apparently solid ginger or solid black females there be other coloured fur present, but it may be one or two hairs only - the equivalent of a needle in a haystack. If the cat also inherits the white spotting gene, those other coloured hairs may be obscured by white patches.

In 2006, I was contacted by Lisa Lorea whose tortie female displayed erratic behaviour and died of a neurological problem aged 9 years. Lisa had been told that torties were more prone to such problems. My own tortie girl, Motley, was put to sleep due to a brain tumour in 2006 (she had previously had a mammary tumour removed). It is possible, though I have not found any data or research to confirm it, that the X-chromosome inactivation that causes the tortie pattern may also be linked to a higher frequency of such problems and that this might be linked to their reputation as "naughty torties".

A condition that can, in some cases, mimic tortoiseshell in Norwegian Forest Cats cats of both genders is the recently discovered "amber" gene. This causes previous black fur to change to a cinnamon colour when the cat is mature. The visual effect depends on the original colour - solid, black-and-white or tabby. In this photo a black-silver tabby is shown during the change to amber; starting with the back. The areas already affected appear as red tabby. "Light amber" has a similar affect on grey fur of affected cat.

This Norwegian Forest Cat was bred by Yve Hamilton Bruce from a silver mackerel tabby female (imported from Denmark) and a classic red tabby and white male. The result was 1 silver tabbies and 2 silver tabbies with white. At just over 3 months old, this silver and white tabby male developed a large patch of bright red hair on his back. Eventually the whole fur will become amber.

According to leading cat geneticist Roy Robinson there were three possibilities which can cause tortoiseshell tomcats: somatic mutation (sometimes termed mosaicism), Klinefelter syndrome and chimaerism.

Somatic mutation causes ginger cats to have small black spots, much like moles or birthmarks in humans. Occasionally, these black blemishes may be large enough to give the appearance of a tortoiseshell cat, albeit one with a low amount of black. The size of the black patches may also depend on how early in embryo development the mutation happened. Very late and it gives a spot or speckle. Where it happens earlier, the black patches are larger as the cells multiply during embryo growth. Somatic mutation is rarely noticed in female cats because tortoiseshell is an unremarkable colour of females - it may be noticed if a black or tortoiseshell female kitten appears in a litter where black or tortoiseshell is a genetically impossible outcome of the mating. In ginger-and-white cats where there is a lot of white, the addition of even small black patches can give the appearance of a calico cat.

Fernando of Canpaza is a cream-coloured German Maine Coon (born 2002) with two small blue spots on the top of his head which may be due to a localised mutation of skin tissue. Several breeders told Fernando's breeder, Elvi Weidemann, to neuter this unusual tomcat and sell him as a pet. However, a veterinary hospital in Hannover (Germany) is running a study project on tortoiseshell tomcats and Fernando has been included in this project. A blood test proves he is a normal XY male. Breeder and researchers were keen to see if Fernando could father kittens - and what colour he passes on to his kittens. In December 2003, I heard the results of Fernando's matings. He was mated with Roxanna a black-silver tortie resulting in 8 kittens weighing between 70 and 95 grams (smallish, not unusual for a large litter): 1 cream-smoke male (Bucky), 1 black-silver tortie female, 1 red tabby female, 3 red males, 1 black tortie female, 1 cream male and a black-silver tortie male. Sadly the latter 5 kittens died of a bacterial infection; the black-silver tortie being an especial loss. Fernando will have one further test mating before being neutered.

Are there a disproportionate number of tortie males in the Maine Coon breed? Pretty Boy Floid is a famous fertile red, grey and white Maine Coon tortie male (he is an XY/XY chimera). Another Maine Coon tortie male, Koonikki Feirfiz Geezabird (Geezer), had intersex traits - testicular tissue in the position of an ovary plus one normally descended testicle. Geezer reportedly had both male and female behaviour and the vet believed him to be XXY. Like Skipper (Tortie Tomcats: Chimeras), he solicited other males to mate him, but he also attempted to mate females. His father has since sired another tortie male (tortie tabby from a brown tabby female) so possible the father is producing aberrant XY sperm. A third tortie Maine Coon, Stormwatch Maxwell, was reported in 1997. Sired by a black smoke, Maxwell was mostly bright red, but had a black patch on one side of the face. Perhaps all the brouhaha over Pretty Boy Floid has simply made people more likely to report these unusual males.

Very occasionally, the tortoiseshell "male" is not male at all. It is genetically a female cat which, due to hormonal problems during embryo development, has developed the external characteristics of a male cat. This is the normal condition in female hyenas where the clitoris is elongated to form a pseudo-phallus and there is also a false scrotum. It is occasionally been reported in other animals which appear to be hermaphrodite, intersex or are masculinised females (genetic females which look like males). Depending on the cause, the false scrotum may contain fatty tissue or ovarian tissue. This may explain those cases of tortoiseshell "males" which act like females - they are genetically female with an external male appearance. These gender anomalies are discussed in more detail in a later section.

All female mammals are mosaics due to X chromosome inactivation. There are other forms of mosaicism where the different genotypes are due to a mutation or abnormality occurring in a cell of the embryo. As the cells multiply, some parts of the embryo are built from the normal cell and other parts are built from the mutant cells. Although all parts of the embryo come from a single fertilized egg, that egg has given rise to 2 slightly different populations of cells.

Mosaicism (somatic mosaicism) is more common and better understood than chimaerism. Mosaics occur when a mistake during cell division in the early embryo stops the correct number of chromosomes segregating to each cell, or creates a mutation in a single gene. Where this happens in one of the first few cell divisions after fertilisation, a large proportion of cells will inherit the mutation or chromosomal anomaly.

For example, some mosaics have patches of cells that have an extra chromosome (called trisomy). The individual develops trisomic patches of tissue - an XY male may have some XXY tissues (another potential cause of tortoiseshell male cats).

Mosaicism and X chromosome inactivation means that female identical twins never carry exactly the same genes. At a genetic level they are not identical! When an XX embryo splits in two, the two embryos follow their own developmental paths. The random nature of X inactivation in the two embryos can create startlingly different individuals. One female twin is colour blind or haemophiliac and the other isn't (these traits are carried on the X chromosome).

It is statistically unusual for the differences to be so extreme or for embryos to use one X chromosome almost to the exclusion of the other. In female cats this can lead to genetically tortoiseshell females appearing to be wholly black or wholly ginger, but having unexpected black, ginger or tortie kittens. The occurence of such genetically different twins leads researchers to suggest that it is X chromosome inactivation which triggers some cases of twins. X chromosome inactivation occurs early on and researchers suggest that an early split ensures that one embryo inherits the lion's share of good cells (having activated the more healthy X chromosome) while the other may not survive at all (comprising cells which activated the damaged X chromosome). Possibly an area of genetically less healthy cells is ejected (but continues to develop) to ensure that the other cells develop into a viable individual.

The usually invisible mosaic nature of females is suggested as the cause of auto-immune diseases; diseases where the body turns upon itself. Autoimmune disease occurs when the immune system treats part of the body as foreign tissue and attacks it. Since some auto-immune diseases are more common in females, it could be that immune cells commanded by one particular activated X chromosome are attacking body cells where the other X chromosome is activated. XXY (Klinefelter) males also seem prone to autoimmune disease.

Chimerism is less readily apparent in females. However this female tortie-and-white is a black-cream-white tricolour - an impossible colour combination. Black is a non-dilute colour, cream is a dilute colour. A normal tricolour would have been black-red-white or blue-cream-white because the dilution gene acts on both colours in the coat. To have a mosaic pattern of both black and cream, she would have to be a chimera of a black (non-dilute) embryo and a cream (dilute) embryo. Since she seemed structurally normal when spayed, both embryos were probably female. This is one of two black-cream-white females (both blue-eyed, but not colourpoints) I have seen.

Nicole S's cat Sybil also appears to have both dilute (cream) and non-dilute (black) colouring. The markings on her face, tail, and paws are black while markings on her back and face are cream (with ghost tabby markings). The black occurs beside her nose, behind one ear, around one eye and on the back of one leg . On her body she has dark grey markings with a black tabby pattern overlaid. Her eyes are blue. She is neither a red/black tortie nor a blue/cream, but has a mix of cream, black and grey. The difference in colours at the points and on the body is not consistent with colourpointing (despite the blue eyes) which suggests Sybil may be a chimera.

To properly identify a cat as a chimera, genetic tests are needed, so any cat with an impossible mix of colours (once everything else has been ruled out) can only be a "possible chimera". Grace. below, has a coat that is a mix of black, grey and white patches; the black and grey are not arranged in a tabby pattern. One front paw has a black spot on one side and a grey spot on the other. her owner, Roshelle Conner describes it as "when she is sitting, from the side, it almost looks like she has a long gown with a hoop skirt under it, and layers of lace (brindling), on the dress!"

Mosaic Albinos

Another different type of mosaicism was reported in a shaded cameo Devon Rex kitten. The cat had golden eyes but was photosensitive, he remained scrawny and suffered chronic eye and respiratory infections. Investigation showed that his immune system was very poor. After months of tests to find out what was wrong, the diagnosis of mosaic albino was made when it was noted that the cat's fur was growing progressively lighter in colour and he was becoming more light sensitive. He ended up almost pure white with a tiny amount of red on the edges of his ears. The eventual diagnostic symptom of his condition was that his scrotum was pure white. Any whole male with colour should have darker fur on the scrotum. The poor immune response was linked to albinism. The mosaic albino condition is found in horses but is uncommon in cats.

The distribution of orange and black in a normal tortoiseshell cat depends on the migration rate of the cells and on the randomness of X chromosome inactivation. The photos below show a selection of different tortoiseshell cats. Other variations of tortoiseshell and calico cats can be seen in Tortoiseshell and Tricolour Cats.