MOSAICISM 2: GENDER ANOMALIES
1996 - 2005 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. Tortie tomcats are discussed in Mosaicism 1: Tortie Tomcats and Genetically Impossible Kittens. This section looks at gender anomalies.

The discussion of cats with unusual chromosome complements (XXY, XYY etc) brings us on to gender anomalies which is a fascinating field in itself. With more and more being discovered about mosaics and chimeras, I have divided the original article into 2 parts. 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.

Normal sexual development of mammals is a 3 stage process: establishment of chromosomal (genetic) sex; development of gonadal sex and development of phenotypic sex.

Genetic sex means whether or not the individual has inherited a Y chromosome. In cats (and most mammals), XX = female and XY = male. Other combinations occur and are considered abnormal.

Gonadal sex means whether the embryonic gonad develops as testis or an ovary. Embryo gonads are programmed to become ovaries unless the genes instruct them to become testes. Some of the genes with instructions for making testes are actually on the autosomes not on the X or Y chromosome. In some cases, genetic changes in the embryo's gonadal cells or developmental abnormalities will cause the embryo to develop inappropriate or abnormal gonads for its genetic gender. "Ovotestes" are undifferentiated gonads which have not (or not yet) become ovaries or testes.

Phenotypic sex means making the outward appearance of the embryo male. Unless instructed otherwise, the embryo will be female in appearance. If a Y chromosome is present, this causes production of hormones which cause the embryo to build male internal and external structures. Hormonal abnormalities at this stage can mean a male embryo fails to respond to these hormones and appears to be female or that a female embryo can turn out appearing male (and various intermediate stages).

Chimeras are individuals composed of cells which come from different embryos. Mosaics are also composed of two or more cell populations, but the cells all originate within the same individual. In both cases, the different cells can contain different mixes of X and Y chromosomes. The gonadal sex of chimeras and mosaics depends upon the proportion of XX cells and XY cells present in the indifferent gonad at the time when gonadal sex determination happens. It also depends on whether those cells are able to form a functional testis or ovary. The type of gonad formed then determines the phenotypic sex i.e. whether the individual looks male, female, neither or both.

"Brain-Sex": In a mosaic or chimaera, the brain might be masculine or feminine depending on which cells it arose from (there is evidence that male and female brains are wired differently). If the brain and the gonads developed from different cell populations, the brain-sex of an individual might not match its apparent gender. For example, an individual which looks male might have female behaviour because its brain is mostly female. If there have been developmental abnormalities a genetic female might outwardly appear to be male or vice versa. Some tortoiseshell male cats might behave like females because genetically they are females or because the cells which formed the majority of their brain are XX while the cells which formed their gonads are XXY or XY.

A normal sperm cell carries either an X chromosome or a Y chromosome. A normal egg cell only has one X chromosome. These meet up to form either an XX (female) or XY (male) embryo.

Sometimes an egg is abnormal and contains either XX or no X chromosome. When fertilized by a normal sperm it becomes XXY, XXX or XO (YO will not develop). It might also be fertilized by an abnormal sperm (see below).

Abnormal sperm can be XX, XY, YY or O (O means no X or Y at all). If one of these sperm fertilizes a normal egg it can produce XXY, XYY, XXX or XO. If it fertilizes an abnormal egg it will produce XXXX. XXXY, XXYY etc. In humans, mental retardation is often found when there are 4, 5 or 6 X chromosomes present.

The frequency of these abnormal conditions in cats is not known.

in 2005, Carol Gravley emailed about her marmalade hermaphrodite cat. Early on, the cat appeared physically male with developing testicles and was neutered in a timely fashion. A few weeks later, s/he started displaying signs of being in heat and was taken back to the vet where s/he was spayed. The cat seems to have been functionally female and now has the appearance of an abnormal female. There are various possible causes of a female cat also having testicles, but without tissue testing it isn't possible to know whether it is chimerism or a chromosome abnormality.