Update on genetic diseases

Origin of a genetic disease

Mutations represent any change in the DNA sequence as well as removal of some bases or addition of extra bases. They can occur anywhere in the DNA and in any cell.
Mutations are a natural consequence of life. Every time that a cell divides it has to make a complete copy of its DNA so that the two progeny cells each have a full DNA complement. This copying involves the faithful reproduction of a sequence containing three thousand million bases. The machinery that cells have evolved is incredibly efficient, containing systems that attempt to identify and correct any mistakes that might occur, but it is not absolutely perfect and copying errors do occur.

Mutations are only heritable when they occur in the germ cells (eggs and sperm), but mutations in the DNA of other (somatic) cells may lead to cancer. In each germ cell there would be around 100 hundred mutations compared to the original DNA sequence of the individual.
The consequences will very much depend on the gene in which it has occurred. Some mutations are silent and have no consequences; others can affect the gene to such an extent that the plan can no longer be used to make a functional protein.

Classification of genetic diseases

Two types of mutation can occur in genes and their different effects are determined by the fact that dogs have two copies of every gene. The first type is a dominant mutation which means that if such a mutation occurs in a gene, the consequences will be felt despite the fact that there will also be a perfectly normal copy of the gene present. So, any animal that inherits a dominant mutation will be affected. The second type, a recessive mutation, its effect is not noticed because the second, normal copy of the gene masks the presence of the recessive mutant gene. A disease caused by a recessive mutation will only be seen if an animal has two copies of the recessive mutation. This means that certain dogs can be carriers of a recessive mutation whilst outwardly appearing normal; you cannot tell a carrier just by looking at it. If two carriers mate, some of their offspring will inherit the recessive mutation from both the dam and the sire and therefore will be affected by the disease.

There are more than 400 inherited diseases in dogs and many are breed specific. The precise mode of inheritance of approximately 175 of these diseases is known.

85% are monogenic disorders (caused by a single gene mutation) with 70% resulting from a recessive mutation and 15% from a dominant mutation.
10% have complex patterns of inheritance which cannot be explained on the basis of a single gene mutation. These diseases are known as polygenic diseases because the disease state results from the mutation of more than one gene. The best known polygenic disease is hip dysplasia. Often environmental factors may influence the degree of expression of the mutant genes.

Some mutant genes are present on the X chromosome giving sex-linked or X-linked inheritance with a characteristic pattern of inheritance. The disease gene is passed down the female line, but is only usually expressed in male offspring, the female being carriers. The reason is that males possess a single X chromosome which they always inherit from their mother. If a male, by chance, inherits the maternal X containing the mutant gene, it will be affected. Mothers, on the other hand, are usually protected from the effects of the mutation by the presence of a normal gene on their second X chromosome. Sex-linked inheritance accounts for the final 5% of the diseases where the precise mode of inheritance is known.