Copyright information: information content copyright owned by Cat World expires 70 years from  July 1976 at which time the information minus the research notes may be placed in the public domain.
Research note: Added illustrative pictures to aid in understanding.  Added link to web for more information about a specific character providing a 3D aspect to the document. Also the use of color -- how else could this be enhanced? Any ideas about infolinks? Links to glossaries -- are these the best way to do online pressentation of glossaries? 

College of Cat Genetics: Part XVIII
by Patricia Turner

Study Unit 18

Studies in organisms other than cats have shown that there are genes which are linked to each other in inheritance by virtue of the fact that they are situated at loci on the same chromosome.  It has been demonstrated that the number of linkage groups can be expected, in every species, to be the same as as the number of chromosome pairs.  In mice, for example, there are twenty chromosome pairs and twenty linkage groups have been detected.  In cats there are nineteen chromosome pairs but to date no linkage groups have been found.

Genes are described as linked when they are situated on the same chromosome but at different loci, and cat breeders could be forgiven for thinking that each chromosome would thus be inherited as a whole complete with the set of genes situated upon it.  In fact the situation is nothing like so simple because the crossing over process at meiosis in which segments of matching chromosomes are exchanged affords ample opportunity for exchange of alleles which would otherwise remain together.

In studies of linkage the process of crossing over has to be taken very much into account as it can result in two characteristics being inherited together in some kittens of a litter and then separated in others.  Also the closer on the chromosome are the genes concerned the less space there is for crossing over and the less often they will become separated.  At the other extreme, where the two genes are a considerable distance apart they may have so much space for crossing over that the rate will be increased until they can almost be said to be recombining freely.  In fact, when they are so far apart they may cross over at a rate of 50% or more they ARE said to be recombining freely and are then equivalent to genes situated on different chromosomes altogether.

As in all studies into genetics, the only way to appreciate the problem is to study actual pedigrees.  Tests for linkage can become extremely complicated but the methods set out by Race and Sanger for the detection of linkage involving blood groups in man are relatively simple if the cats of the correct genotypes for test matings can be produced and identified.  The classic test mating is the double back cross:  the mating of a cat heterozygous for the two characters concerned with one homozygous for both of them.  All the while there are two or more progeny from such a mating it is possible to make a score for or against linkage.

Confusion often arises over the definitions of linkage and association.  In linkage the two characteristics concerned are inherited together or separately, but in association they would appear together much more frequently than would be expected by chance.  It is often difficult to distinguish between them, especially if the number of individuals available for study are restricted.

A family with half its members showing a particular characteristic may show a propensity for the development of another in those affected by the first.  Yet no unaffected member may show the second characteristic.  In such a circumstance it would be concluded that the gene for the first characteristic had a secondary or pleitropic effect resulting in association.  On the other hand the cause could lie with two genes linked so closely that no crossing over could occur.  On one pairing alone neither association nor linkage could be proved, but if similar families were found where some members showed one characteristic while others showed the other, i.e. both characteristics present but in separate individuals, then the case for association would be destroyed and linkage would be strongly suspected.

The sort of linkage fo far described is autosomal linkage.  But certain genes are situated on the sex chromosome (X or Y chromosomes) and are thus described as sex-linked.  Sex-linkage is quite different to sex-limited or sex-controlled inheritance, the latter being the terms for genes which can express themselves only on one sex.  The gene complex of the opposite sex suppresses their effects.

Sex Linkage and Orange Coat Colour

The term sex-linkage describes the linkage of genes with one or other sex chromosomes and usually is used only in reference to linkage of genes to the X chromosome.  This chromosome is considerably larger than the Y chromosome and this may account for the fact that most known cases of sex linkage in animal genetics, including man, involve linkage with X.  There is a part of the Y chromosome which does not pair with X so that some genes on it could never have the opportunity to cross over from X to Y as do those on autosomal chromosomes, but there is no reason why they cannot cross over from X to X and this is most important.

In cats the classic example of sex linkage is that of orange coat colour--producing the Red and Cream breeds in the cat fancy and the gingers and pale gingers amongst non-pedigree populations.  In fact the colours are basically similar, it is the terminology that is different.  As with autosomal characteristics described earlier, sex-linked genes can also show imcomplete dominance or recessivity characteristics resulting in the heterozygote showing some characteristics of each homozygote.  This is the case with sex-linked orange where the heterozygous females carry the wild type alternative to O on one X chromosome and O itself on the other, thus showing one colour in some parts and the other colour in others.

By this definition, tortoiseshell males would appear to be impossible but, in fact, a number of these have been reported.  In many cases misclassification is a decided possibility; if chocolate brown is present in the pedigree as well as agouti in one or other parent, the tortoiseshell male could well turn out to be a cinnamon tabby, similarly a blue-cream male could easily be a blue tabby.

One hypothesis explaining the tortoiseshell phenotype is that put forward by Mary Lyon, namely that only one X chromosome is genetically active in any cell of a female and that it may be derived from either the male or the female parent, male derived X chromosomes being active in some cells while female derived X chromosomes are active in others.  The hypothesis assumes that inactivation occurs quite early in embryonic development and that thus some cell lines are formed containing an active maternal majority while others will contain an active paternal majority.  The phenotypes of heterozygotes would thus consist of patches of O and patches of wild type colour with the areas of colour being dependent upon embryonic development.

Another hypothesis, proposed by H. Gruneberg in 1967, following work with mice, is that there is partial inhibition of gene action on both X chromosomes instead of complete inactivation of one or the other, thus causing a process of partial inhibition to spread along both chromosomes.  If either hypothesis is correct it would point to the fact that cat breeders have little hope of controlling the areas of inactivation on the X chromosomes or of the allocation of active X chromosomes.  In that event, the occurrence of relatively large areas of one or other colour in areas where it is not considered ideal by fashion or breed standards (which are more or less the same thing) must be accepted as an inevitable accessory to the tortoiseshell phenotype.  While selection for breeding or show stock may give the impression that any one line is free from solid feet or legs, etc., such selection would then appear to do nothing whatsoever to increase the incidence of well broken tortoiseshell pattern in subsequent progeny.

The only known way to increase  or decrease the size of the orange or wild type areas is to add or remove dominant white spotting to the genotype.  Its presence results in much larger patterns of colour although the reasons for this are not known.

Despite the errors of classification made with many reported tortoiseshell males there is no doubt that such cats have appeared from time to time.  The generally accepted view is that they are the equivalent to the Klinefelter's Syndrome in man, where those affected look and behave like males and often go through life without having any cause to ask for medical advice.  Other than the facts that the testes and prostate are small and that the voice is higher pitched than average they may well appear normal and have a normal sex life.  However, fluid is derived from the prostate and accessory glands and spermatoza are not present.  They are XXY instead of XY, having two doses of the female X chromosome instead of one.

If the tortoiseshell male is the equivalent of the Klinfelter Syndrome in man, then the presence of XO females (Turner's Syndrome), XXX females (super-females) and XO males would be inferred.  However, the fact that the X chromosome carries the blood clotting factors would appear to make the latter inviable.  Turner females are characteristically infantilistic and lacking in secondary characteristics, usually also showing a number of other congenital defects.  Great variation is seen, with some patients only affected to a minor degree and thus being capable of producing children.  Triple X super-females in the human species show little physical abnormality and are sometimes fertile.

Other proposed explanations for tortoiseshell male cats, and unexpected phenotypes in females, involve complicated mosaics of the individual's whole chromosomal picture (Karyotypic mosaics).

Such anomalies rarely concern breeders of pedigree cats and of more importance to them is an understanding that sex-linked orange may be inherited alongside black, brown, blue or chocolate/blue (lilac) in a genotype.  The black orange and the brown orange may appear identical but the blue orange and the brown/blue orange will be cream.  A table below gives expectations from crosses involving orange but the word type is used as a shortening of the term wild type to denote the alternative to orange and can be taken to mean black, brown, blue or lavender in full colour cats; seal, chocolate, blue or lilac in Siamese; brown, champagne, chocolate, blue or platinum in Burmese, etc.  Tortoiseshell describes pattern only and may be interpreted to mean any of the possible colour combinations.

Matings Involving Sex Linked Orange
Parents Kittens
Sire Dam Males Females
type
orange
orange
type
orange
type
tortoiseshell
type tortoiseshell type
orange
type
tortoiseshell
orange tortoiseshell type
orange
orange
tortoiseshell