THE HUMAN GENOME PROJECT AND ITS IMPACT ON CHILD HEALTH

Andrea Ballabio

Telethon Institute of Genetics and Medicine (TIGEM) and Faculty of Medicine, Università "Vita-Salute San Raffaele", Milan, Italy

We are rapidly approaching the time when the sequence of the entire human genome will be available. There is no question that this unprecedented conquest of human knowledge will have a tremendous impact on human health. But how can we transform the structural knowledge of genes into medical utility? And how can we do it in a systematic way for thousands of genes and proteins? These are the major challenges of today's biomedical research.

Two main pathways will likely be followed. The first pathway includes the systematic functional analysis of human genes. This strategy, also known as functional genomics, utilizes a variety of approaches such as bioinformatic analysis of gene families, cross-species sequence comparisons, and systematic characterization of gene expression patterns and protein profiles. These methods provide important, albeit sometimes superficial, information on the function of human genes, which can be instrumental in the process of disease gene identification. Furthermore, the systematic generation and characterization of mutant animals provides an important tool to understand the function of a given gene and to predict the phenotypical consequences of gene dysfunction. Among the wide variety of species used by geneticists, C. elegans, Drosophila and mouse offer several advantages. While the first two species are ideally suited to dissecting complex biological pathways, the mouse remains the best available model organism to study human genetic diseases. There is great hope, but still limited evidence, that we will be able to use the fundamental knowledge on disease pathogenesis generated by functional analysis of human genes for the development of novel drugs. Furthermore, the direct and effective use of genes as therapeutic devices, namely gene therapy, is an ambitious goal and will require many years of experimentation before becoming a medical reality.

The second pathway to be followed involves the characterization of the human genome sequence with respect to its diversity among individuals. The first draft of the entire human genome sequence, due to be released in April this year, has been obtained from the DNA of several donor individuals and will represent only a "reference" genome. However, each of us has a genome which is, on the average, 0.1% different from that of another individual. Most importantly, hidden in these minutes differences are not only the phenotypic characters that make us each unique but also the genetic factors causing or predisposing us to diseases. Identifying these mutations and linking them to human diseases is of pivotal importance, as this will lead to the design of effective molecular tests allowing the prevention of genetic diseases.