This century has been dubbed the century of biology — and for very good reason. Since the discovery of the structure of DNA by Watson and Crick in 1953, scientists have continued their unrelenting assault on the information hidden in the DNA of humans, other animals, and plants. Numerous nucleic acid-based techniques have been developed to allow us to identify macro- and micro-organisms, diagnose infectious disease, trace sources of microbial agents of disease, identify susceptibility to disease, and improve our understanding of evolution. Much of this work is based on identification of a single gene or a small set of genes. That approach continues to be important, but there is now considerable activity in taking a genomic approach, which addresses all the genes or a large subset of the genes in an organism, whether it be a virus, a bacterium, an animal, or a person.
The genomic approach is feasible because of technological developments that make it possible to determine the nucleotide sequence of millions of base pairs of DNA at increasing speed and decreasing cost. The human genome project was a major driver in these developments. This project took 13 years to complete in 2003 and cost 2.7 billion dollars. By 2007, DNA discoverer James Watson had his genome sequenced in 2 months at a cost of $2 million. There is now an international plan involving sequencing centres in the United States, the United Kingdom and China, to sequence 1000 genomes in 3 years. This will facilitate identification of moderately common and rare genetic variants and association of specific genetic variations with disease. This project will add 60 times the sequence data that have accumulated in public data bases over the past 25 years. The Wellcome Trust is funding a collaboration of some 60 institutes around the world to sequence 100 000 genomes in studies to associate genetic changes with 25 diseases. This will require the handling of over 100 billion pieces of genetic data. It appears that the $1000 genome is not far away.
There is enormous interest in developing applications from genome sequence data. Although the genomes of any two individuals are about 99.9% identical, the 0.1% variation allows for changes in a massive number of nucleotides, given that the human genome is approximately 30 billion base pairs. Medicine and agriculture are prime areas for these applications, which include pharmacogenomics (custom drugs and new approaches to drug design), diagnostics, gene therapy, and improved selection of animals. One area that is garnering a great deal of attention is the identification of genes that are associated in complex ways with disease. A haplotype map (a HapMap) that is being developed will reduce the search from some 10 million nucleic acid changes to about 500 000 haplotypes. The haplo-type is a combination of alleles along the chromosome that is identified on the basis that a variation at one site is associated with certain alleles at nearby variant sites (because these sets of genes are inherited as a block). The map will facilitate recognition of genes associated with diseases that have a significant heritable component and will make it easier to investigate the influence of environment and of interventions on disease.
Sequencing of the genomes of animals is of immense importance to agriculture, veterinary medicine, and human life. Sequence data will allow better selection of genetic stock and will enhance investigation of environmental influences, as well as drug and vaccine effects. Following his return from a recent “Biology of the Genomes” meeting in New York, Ewan Birney, senior scientist at the European Molecular Biology Laboratory noted in his blog that the most exciting session was on “non-traditional models — dogs, horses and cows, where the ability to do cost effective genotyping has completely revolutionized this field.” Genome sequences are now available for several animal species including the dog, cat, cow, chicken, pig and horse. In pet animals “personalized genetics” will permit more precise treatments; in food animals and horses we can expect more rapid and effective selection for desired traits. These developments will have significant implications for the way we educate veterinarians, for what clients will expect of veterinarians, and for the services that our profession will be able to offer.