Genomics

The Human Genome Project reached a major milestone in 2001, with two separate publications of working drafts of the human genome. Although much knowledge has been generated, the sequence is not complete. Neither the actual number of genes nor all their structures have been determined. However, several major lessons have been learned. First the number of genes is estimated to be between 30,000 and 70,000, fewer than previously thought. In addition, it is clear that a very large proportion of our genes are highly similar to those in other organisms, such as the fruit fly and the microscopic worm, C. elegans. The observation that we can build humans with between 30,000 and 70,000 genes and a fruit fly with 15,000 genes suggests that we owe much of the complexity of humans to the fine regulation of genes and not their absolute number.

Genomics has also forced biologists to begin to look at the function of genes in an industrialized mode. This new field of functional genomics takes advantage of a number of new technologies. Since many fly and worm genes are so similar to human genes (homologs), these animals can be used as model systems to study gene function. In these model systems it is possible to mutate (or alter) the structure of every single gene, enabling researchers to determine each gene's function and how several of the genes interact in complex metabolic pathways. Similar efforts using systematic gene mutations are also underway to create DNA "libraries" of two vertebrates, mice and zebrafish, whose genes are surprisingly similar to humans. Once these genomes are fully sequenced and characterized, it will be possible to create animals with disorders that are more precisely like those of humans, allowing for a better understanding of complex diseases and determination of novel and effective therapies.

Genomics allows for the comparison of sequences between individuals, too. These studies can be used as a basis for the understanding and diagnosis of disease, especially of the complex disorders not governed by single genes. Knowledge of the entire human sequence is also the basis of the fields of pharmacogenetics and pharmacogenomics. Pharmacogenomics seeks a broader understanding of how genes influence drug response and toxicity, and the discovery of new disease pathways that can be targeted with tailor-made drugs. Pharmacogenetics is the study of the genetic factors involved in the differential response between patients to the same medicine. Polymorphisms, nucleotide changes that occur in more than 1 percent of the population, are the basis for our individuality but also account for our differential susceptibility to disease and the variable outcome of treatments. Through a variety of research efforts, more than one million polymorphisms have been identified in the human genome. The study of these variants, that occur once every 500 to 1,000 nucleotides in the human genome, should enable pharmacogenetics to define the optimal treatment regimens for subsets of the population, allowing a wider range of patients to be treated and more effective outcomes to be produced with any given drug.