Basic Clinical Genetics
Dr Jeff Sampson
The Kennel Club
The last decade has seen immense advances in our understanding of mammalian genome structure and organisation. The Human Genome Project is, of course, the most spectacular and best known, but many other species, including sheep, cattle, mouse, horse and dog, also have genome projects of their own. One of the very positive spin-offs of such projects is an increase in our understanding of the genetics of inherited diseases in these species, and the development of genetic tests for such diseases.
Genes, of course, are the genetic plans that underlay the characteristics of living things. In mammals, they are inherited at conception, one maternal set of genes being provided by the egg and one paternal set provided by the sperm. These gene sets are used to drive the development and differentiation of the subsequent zygote and determine everything about the organism at birth and beyond.
The information that is embodied in genes is ultimately expressed, via a complex, but well understood, intracellular pathway that leads to the synthesis of a heterogeneous collection of proteins. Roughly speaking, one gene contains the information for the expression of one protein, although there are clearly exceptions to this and single mammalian genes are known that actually carry information for more than one different protein. It is the biological activity of these proteins, working either individually or in highly organised groups, that determines the various characteristics of the organism.
Genes are made of a chemical known as Deoxyribonucleic Acid (DNA) and the genetic information is stored in the chemical structure of the DNA that comprises a gene. Occasionally, this chemical structure can be altered by a process known as 'mutation.' Since a mutation alters the structure of the gene, and the structure of the gene is what carries the genetic plan for its corresponding protein, mutations commonly alter the protein that is subsequently synthesised. Sometimes this alteration is sufficient to alter the activity of the protein, or even cause the protein to be inactive. If such a protein were to be involved in some important metabolic function, then mutation of its gene, and the subsequent affect on the proteins activity, may well lead to an inherited disease.
The last 25 or so years has seen a steady increase in the availability of genetic tests for some of these inherited diseases that result as a consequence of the mutation of specific genes in the genome. Early genetic tests relied on being able to measure the activity of a particular protein and thus being able to identify an altered activity that resulted from genetic mutation. Increasingly, however, as we have learned more about the genes that make up particular species, and their structure, genetic tests have been developed that actually detect the mutation directly by examining the DNA structure within a given gene. The coming years will see an explosion in the availability of such DNA tests for inherited diseases in many different species.