The Human Genome Project

  1: What is the public project for sequencing the human genome?
  2: Has the human genome been completely sequenced?
  3: How many genes do humans have?
  4: Why is it so difficult to find the genes in a human genome sequence?
  5: Where did the sequenced human DNA come from?
  6: Is the human genome “freely available”? If not, who owns it?
  7: Why was there a Human Genome Project What is its use?
  8: Who were the members of the international consortium What was the role of each of them?
  9: What was the French contribution to the Human Genome Project?
  10: How much did the Human Genome Project cost?
  11: With the end of the Human Genome Project, are the large sequencing centers still useful?

  Since we learned to read the sequence of DNA in the 1970s, we have dreamed of knowing our own genome. This dream is almost reality today, even though we are not yet capable of understanding all the instructions contained in the genome sequence.

The interpretation of the sequence of the human genome is on the right track today, and numerous applications are expected in the decades to come. The most important advances will be in the domains of medicine and in fundamental research in biology, but the scientific results themselves will be the source of the large majority of new applications. However, these advances will not happen immediately: several years of research will be necessary. On the other hand, this research could not be undertaken without the genome sequence.

The first application of the sequence of the human genome is in the identification of human genes. This was the only way to complete an exhaustive and precise inventory of human genes. During the 1990s, some scientists placed their hopes in the sequencing of messenger RNAs, which are the products of gene expression: they judged that it would be useless and costly to sequence the 3 billion nucleotides of the human genome., of which only 3% correspond to the “coding” part of the genes (See” Why is it so difficult to find the genes in the sequence?”). The results have confirmed that, without the sequence of the genome, the collections of messenger RNA sequences do not lead to a reliable inventory of human genes. Systematic sequencing of the genome has furthermore proved to be more economical in the long run than a study of human genes on a case-by-case basis, which implies redundant efforts. This is what motivated the launching of the Human Genome Project at the beginning of the 1990s.

The inventory of human genes will first help in the identification of the genes implicated in genetic diseases. Genetic studies often lead to the definition of an “interval” on a chromosome in which the causative gene for a disease is found in its mutated form. The inventory of the genes in this interval (obtained by analysis of the sequence) permits selection of those which are most likely to be implicated in the pathology, because of the supposed or known properties of their products, and to begin the research on the best candidates. Before the sequence of the human genome was available, geneticists had to blindly explore intervals of several million nucleotides, looking at hundreds of genes in the interval. Thanks to the finished and “annotated” sequence, these groups can gain up to several years of fastidious work. In the near future, this should lead to the discovery of several thousand genes responsible for genetic diseases.

Knowledge of a gene in which a mutation provokes a genetic disease can lead to the development of a diagnostic test based on the DNA. The identification of the causative gene also makes it possible to understand the physiologic mechanism leading to the appearance of the disease, and in certain cases, to explore novel therapeutic approaches. It was in this way that a promising treatment for Friedreich’s ataxia was developed by a French group at the Necker Hospital in 1999, directly from a knowledge of the gene and its function.

Finally, the human genome sequence, together with the inventory of positions which are variable from one person to another, will facilitate the identification of genetic factors in susceptibility to common diseases. These diseases, such as diabetes or arteriosclerosis, certainly have a genetic component, but a multitude of factors make small contributions to the pathology and interact with environmental factors in a complex way. Thanks to the degree of resolution attained today by genetic studies, we will begin to unravel this knot and comprehend the molecular mechanisms of these diseases and better understand the role of the environment. This could lead to new treatments on one hand, and to more effective preventive measures on the other.