Genetic diseases are disorders where the disease is passed from parents to offspring. They arise because a mutation changes one copy of the gene in one individual to a different form which is less effective or frequently totally ineffective.

Mutations are caused by environmental factors such as radiation and chemical mutagens; they are unavoidable and the body has mechanisms to seek out and eradicate them. They happen when parts of the DNA of the gene are cut out, when a new and inappropriate piece of DNA is inserted into the DNA of a gene or when just a tiny change in the composition of the DNA happens - we could be looking at a change as small as 1 in 2,500,000,000 of the total DNA of an individual. Occasionally, however, a mutation escapes these processes and persists in the population. The pattern of inheritance of genetic diseases can be simple, where only one gene is involved such as haemophilia, or more complex where several genes are involved such as hip dysplasia. Determining the mode of inheritance of a genetic disease is an important first step to identifying the gene responsible for the disorder.

For diseases caused by a single gene, patterns of inheritance are well defined. Many common conditions are inherited in a recessive fashion where two copies of the gene, one inherited from the sire and the other from the dam, have to be present for a dog to show clinical symptoms. Individuals with one copy of the disease form of the gene and one of the normal form of the gene (called carriers) generally show no symptoms but are able to pass the disease form of the gene onto their offspring. If two carriers are crossed, on average 25% of the litter will have two copies of the disease form of the gene, and be affected, and 50% will have one copy of the disease form of the gene and will be carriers. Carriers represent a hidden reservoir of the disease within the population. It is very difficult to accurately identify carriers in a population unless DNA Testing is available.

Genetic diseases are a major health problem in pedigree dogs. Over 400 diseases showing a simple mode of inheritance have already been identified - only humans suffer a greater number. Most breeds are affected with one or more genetic diseases. The incidence of the diseases within the population can fluctuate, and for recessive disorders can apparently appear from nowhere. If an important dog within a breed happens to be a carrier for such a disease, even if mated only to clear dogs, on average half of the offspring will be carriers. In the next generation these carriers will be bred together and a rash of dogs affected with that disease will appear.

Genes underlying canine hereditary diseases are being investigated at the Animal Health Trust and other veterinary centres across the world. For some, such as haemophilia, the very close similarities to the human disease give strong clues to where the problem lies in the canine equivalent. Where human medicine can provide no help, it is necessary to identify initially where the gene for that condition lies on the chromosomes - the microscopic structures within cells that contain an individual's DNA. The inheritance of the disease is compared with the inheritance of each of a set of DNA markers covering all the chromosomes. Once the disease has been tracked down to the vicinity of a DNA marker, we can look in the neighbourhood of that marker, on the chromosome, for genes which could be the site of the problem. From there, we can find the damaging change in the gene - the mutation - itself by reading the DNA of the gene in affected and clear dogs and then comparing the two.

The DNA of a gene provides the blueprint for that gene. DNA itself (deoxyribonucleic acid) is an enormously long molecule, which, with the exception of identical twins, is different for every individual animal on the planet. There are gross differences between the DNA of say, a horse and a dog, but there are also fine differences between individual dogs or individual horses. The genes are strung out along the DNA. Encoded within the DNA is the structure of every gene in the body, together with other stretches of DNA to regulate the expression of genes. You can think of the code being in the form of the alphabet, but an alphabet of only four letters A, C, G and T - the initial letters of the chemical building blocks of the DNA. Mammals such as dogs and horses have around 2,500,000,000 of these letters. Disease genes arise when there is a mistake in the message encoded in the DNA for that gene. It can be a large change, such a portion of the DNA being totally lost and therefore unreadable, or it can be much more subtle, just one letter having been replaced by another letter, A,C,G or T.

Since most cells in the body contain two sets of DNA, one inherited form the mother and the other from the father, there are also two copies of every gene in most cells. Why then do some cells form one organ, for example liver, and other cells another organ such as lungs? The answer lies in the way that the genes are expressed, in any particular tissue genes inappropriate to that organ will be switched off. The universal nature of DNA throughout the body has an important consequence - we can take DNA form anywhere in the body to look at any gene. Therefore, for a disorder that affects the eye, for example, we do not need to take cells for the eye to extract the DNA, we can analyse the DNA from samples which are easy and safe to take, like a blood sample or a sample of cheek cells swabbed form inside the mouth, and yet still test for a disorder within the eye.