A few clarifications needed By Mike Tempest

Created: 25/07/2012

Many thanks to readers of this column for their emailed comments and questions - your interest is much appreciated. I thought that as many of the comments were on currently topical matters that I would be best dealing with them before I move on to a new topic.
  Reader’s question – what is a merle? A merle is where there are blotches (sometimes referred to as splashes or marbling) of dark colour on a lighter background. Merle occurs in only a few breeds – it is common in Rough and Smooth Collies, Shetland Sheepdogs, Australian Shepherds, Great Danes (in which it is known as ‘harlequin’) and Dachshunds (in which it is referred to as ‘dapple’).
  It is caused by the merle gene M, or more correctly the dominant allele M of the merle gene, in effect reducing the pigment in certain areas (main body coat, eyes, nose). So if for example we started with a basic black, tan and white tricolour, with the M allele the black colour will be in patches on a silvery grey-blue background and will be known as a ‘blue merle’. If the basic colour was liver (chocolate), with the M allele the liver colour would be in patches on a beige background and this would be referred to as a ‘red merle’ (eg in Australian Shepherds). In deep red Dachshunds, the M allele would result in dapples of deep red on a lighter red background. If black or blue Great Danes have the M allele then they have ‘torn’ black or blue patches on a white background.
  In conventional representation the other alternative form of the merle gene is the recessive non-merle allele ‘m’. Most breeds are ‘mm’ and therefore do not have the M allele that causes merling, so dogs are the colour determined by their other colour genes. In all the above examples it only takes one copy of M to produce those effects ie ‘Mm’. If two copies are present ie ‘MM’, dogs are all-white. We thus have a situation where the dominant-recessive combination produces a different effect to the dominant-dominant combination when conventionally we would expect the same effect with the dominant allele masking the effect of the recessive allele. It is this fact that has caused the conventional representation of the alleles to be ‘modernised’.
  Reader’s comment and question – I was confused by the letters used in the KC announcement of its ban on registering merles in certain breeds, and banning certain merle matings. The announcement read "There are two alleles of the M gene: MM (merle) and M+ (non-merle), with merle (MM) being dominant to non-merle (M+).” It seemed that one allele was being represented by two letters instead of one. Is this representation correct?
  Answer – What the KC was trying to represent was the modern format, which is to use M with superscripts to represent the different alleles. MM should have been shown as M with a superscript M, and M+ as M with a superscript +. The diagram below shows the correct modern representation.
  Reader’s question – what are the other effects of the merle gene? There are some further aesthetic effects, some coat colour appearances that seem to confuse the genetics, and also more seriously some health problems. The aesthetic effects accompanying the coat colour change are that the M allele also causes wall eye (either a completely light blue eye or blotched with colour), and pink (flesh colour) and butterfly noses (partly pigmented). Furthermore the effect of M seems to be greater on black pigment than on tan pigment, these being the two basic subdivisions of melanin pigment (black/brown and tan/yellow/reddish).
  For example, in gold sable Collies, Mm may not show a very marked effect and simply give gold patches on a lighter gold background. With the long coat of the Collie these slight variations in gold colour just blend in with one another, and such a dog may not appear visibly to have the merle coat pattern. This coat colour appearance can confuse the genetics, as such a dog will not be physically identifiable as a merle, and not registered as a merle, but genetically it is.
Importantly the lack of visible merle coat pattern in this situation is not a reason for advancing the argument that the merle mutation is a dominant with incomplete penetrance, and not a normal dominant:recessive. As the KC have banned merle-merle matings perhaps it ought to require a DNA test for the merle mutation in gold sables before allowing them to be mated with merles.
  The reason for banning the introduction of merles into some breeds where merles do not occur ‘naturally’, and banning merle to merle breeding combinations in breeds where merle does occur ‘naturally’, is to avoid health problems associated with the merle gene. In this regard, as with colour, ‘MM’ and ‘Mm’ produce different effects. ‘Mm’ can give rise to deafness, but when the genotype is ‘MM’ the problems of deafness, blindness and structural defects are more serious.
  These differences in the degree of effect have been described by other scientists as potentially leading to impaired heterozygotes (Mm) but severely handicapped homozygotes (MM). It is therefore by no means certain that Mm animals are free from problems.
  The assertion in the DW Comment (May 25) and by Simon Parsons that the breeding of merles (Mm) with tricolours (in other words non-merle mm) carries no greater risk of inherited problems than any other mating does not stand up as heterozygotes (Mm) will continue to be produced. From a health point of view it would be best if the merle allele (M) was eliminated completely. The KC is correct in banning merle to merle matings, and it may have banned the introduction of the merle allele into Chihuahuas, but it should also ban the introduction of merles into other breeds such as Bearded Collies.
  While on the subject of merles I also need to say in passing that there is debate between geneticists on the genetic status of harlequin Great Danes. Some think that harlequin is a third allele of the merle gene (M with a superscript h, which is dominant to m). This is because ‘M(superscript h)m’ produces a whitish background whereas ‘Mm’ produces a greyish blue background. Others think that harlequin is a totally different gene (the H gene with a dominant allele H and a recessive allele h). It is easy to find ‘suggestions’ and ‘implications’ for these differing views, but difficult to find unequivocal scientific evidence for either. Suffice to say for now that colour inheritance is a topic for another day.
There have been several readers’ questions on whether there are different sorts of carriers depending on how the carrier had been identified. Is a carrier identified by a DNA test different to a carrier identified by pedigree analysis? The answer to this should be a definite ‘no’, a carrier is a carrier no matter how it is identified, but there is a bit of a subtle quirk to explain.
  Pedigree analysis has been used for many decades to identify carriers of recessive conditions – they are either the parents or offspring of an affected dog – and a carrier identified in this way is a definite and certain prognosis. Now we have DNA testing which should be able to identify carriers for various conditions. Unfortunately while a DNA test will positively identify genetically clear dogs and genetically affected dogs with absolute certainty, there is still some doubt about its accuracy in determining the carrier status for some conditions, and this is the quirk.
  The AHT maintains, at the very least for the condition of primary lens luxation, that between two and 20 per cent of carriers will actually be genetically affected, this proportion varying in different breeds. It does therefore mean that the DNA test is not 100 per cent accurate in determining carriers. On the other hand pedigree analysis is 100 per cent accurate in detecting carriers because they are automatically the consequence of an affected dog actually being diagnosed.
  So a DNA test is accurate for determining genetic clears but not 100 per cent accurate in determining carriers, and pedigree analysis is accurate for determining carriers but cannot determine genetic clears. I know breeders will be frustrated at this, but we still have to go along with DNA testing to identify genetically clear dogs for breeding, and it does explain my personal position of why I will not breed from carriers – some of them could be affecteds; I will only breed from genetic clears determined from DNA testing, and that includes hereditary clears.
  Reader’s question – how does an official DNA testing scheme remove a mutant gene from a breed’s gene pool? My answer is it doesn’t – testing schemes do nothing but test and tell you the result (and maybe publish the result in the Breed Records Supplement and on Mate Select, and mark the test result on registration certificates). Testing on its own will not remove the mutant gene – that will only be achieved by appropriate breeding action that is based on the test result. Breeding action that is insisted upon by a KC control scheme will remove the mutant gene and keep it removed, but there aren’t many of these.
  Reader’s comment – Andrew Smith in DW Letters of May 18 claimed that there was a stigma wrongly attached to carriers which encourages breeders to conceal DNA test results. It is incorrect that breeders can conceal test results in the UK, as submission for DNA testing means automatic publication of the results by the KC.