Unique chromosomal translocations and specific deletions are highly associated with distinct human malignancies and congenital deletion syndromes. Inter-chromosomal translocations that occurred at the site of a known gene have enabled the molecular cloning of new genes and an assessment of their role in neoplasia. However, the majority of disease associated chromosomal breakpoint are located at a considerable distance from known genes or merely cytogenetically defined, lacking a neighboring known gene. The goal of this project is to develop approaches to characterize such chromosomal abnormalities molecularly. The initial project will be to clone and characterize a large candidate fragment containing a t(11;14) (p15;q11) chromosomal translocation found in T cell acute lymphoblastic leukemia. Pulse field gel electrophoresis of a t(11;14) leukemia defined a 180 Kb rearranged SalI fragment within the enormous # T cell receptor locus as an excellent candidate to contain the chromosomal juncture. A yeast artificial chromosome (YAC) vector will be used to clone this 180 Kb fragment. The insert will be mapped, chromosome segment 11p15 material identified, and the translocation breakpoint sequenced. The isolation of 11p15 sequences will enable a new gene to be looked for and its cDNA and genomic structure, expression and role in leukemia assessed. This model system should establish an approach to characterize a number of disease associated chromosomal abnormalities located considerable distances from known genes.
| Haimovich, Gal; Zabezhinsky, Dmitry; Haas, Brian et al. (2016) Use of the MS2 aptamer and coat protein for RNA localization in yeast: A response to ""MS2 coat proteins bound to yeast mRNAs block 5' to 3' degradation and trap mRNA decay products: implications for the localization of mRNAs by MS2-MCP system"". RNA 22:660-6 |
