The goals of this project are the identification, isolation and characterization of important genes that reside on human chromosome 5 and play important role on regulating the growth of the cells, exhibiting also the additi onal property of suppression of tumor formation. As a consequence of these properties, their loss from a particular region of chromosome 5 predisposes the cells for abnormal growth and eventually leads to leukemia. A unique mo del to study such a hypothesis and to isolate candidate genes with these pr operties is the so called 5q-syndrome, which will be used as a source for the isolation of such genes. We will use the genetic material (DNA)from pat ients with this syndrome, as well as DNA from normal controls and from cells that contain chromosome 5 as the only human chromosome. Isolation of the candidate gene(s) will be accomplished by a series of novel techniques of recombinant DNA technology and the role of these genes on cell growth and tumor suppression will be tested using several functional bioassays. These approaches will eventually lead to a better understanding of the leuk emia process and to more efficient treatment of the leukemic patients. Two additional ramifications of the benefits of this proposal are also anticipa ted: 1) Any novel important genomic or expressed DNA sequence (CDNA) charac terized within this 'critical region' can serve to other European colleague s as a probe to fish out (from other genomes of important species) homologo us genes, thus giving access to functions otherwise beyond grasp. These genes can be further manipulated (i.e. homologous recombination-knock out) so that they can lead to indispensable animal models of human diseases. 2) All the cloned genes and YAC clones generated by this project can serve as useful and essential tools to other groups in Europe that are currently inv olved or will be engaged with the Human Genome Analysis programme.
Funding SchemeCSC - Cost-sharing contracts
SE1 9RT London