Human genome project: Italian contribution. Future directions
✍ Scribed by Renato Dulbecco
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 74 KB
- Volume
- 173
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
The Genome Project began in Italy in 1987, and I approaches: identification of CpG islands, homology to cDNAs, homology to genes known in other species, and was asked to act as its coordinator. It started with a recognition by analysis of sequences. This latter effort modest budget, about $1,125,000, not including rewas greatly helped by the development of efficient searchers salaries, and has continued until the end of methods for sequence analysis carried out by some 1995, with several reorganizations of bureaucratic naunits within the Project. Especially interesting was the ture. Bureaucracy is an Italian specialty. Another Italapproach based on the identification of CpG islands. ian specialty is that there was no budget for 1996, and
The Toniolo group in Pavia used, for this purpose, fragonly hope for one in 1997, but, more realistically, in ments generated by rare cutters restriction endonucle-1998.
ases, such as Eag1 (in combination with EcoR1) (Tribi-I will briefly go into the organization of the Project, oli et al., 1992); in this way, several genes were identibecause it offers interesting lessons; although they fied, most of them previously unknown, in a restricted apply especially to Italy, owing to the way research is region of the Xq28 band; eight of them had specific done there, they have general significance (Dulbecco, muscular or neurological expression and were used for 1990). From the beginning it was agreed that the work the discovery of genes responsible for diseases of these would be on the human genome. The organization was tissues, which were already mapped to that area. The based on two principles: cooperation among different study of cDNAs from patients affected by Emery Dreiresearch groups, and freedom of research, so that each fuss muscular distrophy (Bione et al., 1994) or by Barth group would continue to pursue the objectives in which syndrome (Bione et al., 1996) lead to the identification it was already engaged. This organization was agreed of the genes responsible for these diseases. upon at an initial meeting of the various units that had A further development of this approach was made by decided to take part in the Project. Collaboration was the Vezzoni's group in Milan, which has generalized required because no unit could carry out the project by the use of the restriction fragments already described itself, but together they had all the necessary compefor the discovery of genes; they call these fragments tences and tools. Collaboration was very intense for the ''Eag1-based STS'' (Frattini et al., In Press). A comduration of the project, not only among Italian groups puter based comparison of such Eag1 -STS obtained but also with foreign groups, and was the key to the from the Xq24 -qter region, with ESTs available in success of the Project. The other principle, freedom, data bases showed that 90% of previously known genes emerged from the initial discussions, when it was could be detected by this approach; in contrast, if ranagreed that investigators could continue to pursue the dom STS are used, the number of genes recognized is type of work in which they were interested; an optional much smaller. The genes detected are, probably, ubiqcommon goal was, however, adopted in the long arm of uitously expressed genes, which represent about 60% of the X chromosome, specifically the region Xq24all genes; thus, about half of all genes could be detected Xqter, which was known to be rich in genes, many of using this approach. them responsible for hereditary diseases, including a Much work was concentrated on the search for spefragile site. The adopted region was contained in a hycific genes. The Milano group, in collaboration with a brid culture (Nussbaum et al., 1986), which facilitated group from Brescia, concentrated on those responsible the work. Most units concentrated in this area, several for immunodeficiencies, inspired by the good results others continued work already initiated in other areas obtained with gene therapy by Bordignon's groups in of the human genome. Important results were obtained Milan in the treatment of the immunodeficiency due to in both places. deficiency of ADA (Bordignon et al., 1995). The two The results, at the end of 1995, could be summarized groups together studied three types of immunodefias follows. Most of the effort was concentrated in the ciencies: they cloned the gene responsible for the audiscovery of genes. In addition, extensive mapping was tosomal recessive Severe Combined Immunodeficiency, carried out of the bands Xq26 and Xq27, and part of showing that it codes for the JAK3 kinase (Macchi et Xq28; this work was greatly helped by the development al., 1995); they showed that the WASP gene, of which of a new panel of somatic cell hybrids and cytological I will say something later, is responsible for the Xtechnique for localizing genes on chromosomes. A fair amount of sequencing was also carried out in areas of interest for gene discovery.