DIRECT MICRODISSECTION AND MICROCLONING OF A TRANSLOCATION BREAKPOINTREGION, T(1-11) (Q42.2-Q21), ASSOCIATED WITH SCHIZOPHRENIA

We describe the generation of large-fragment microclone libraries from the chromosomal breakpoint of a reciprocal balanced translocation lin ked to schizophrenia. The abnormality was visible under the phase-cont rast microscope, allowing direct dissection from unstained, unbanded m etaphases. Two separate microdissection experiments yielded 443 and 67 2 recombinants, respectively. Following complete EcoRI digestion, inse rts with an average size of 0.3 kb (range, 0.2-3 kb) were obtained in the first experiment and 1.5 kb (range, 0.15-6.5 kb) in the second. FI SH analysis of pooled clones ''painted'' back onto the derivative chro mosome and assignment of microclones to somatic cell hybrids confirmed the fidelity of the method. Microdissection of chromosome regions ide ntified by karyotype rearrangements in unstained, unbanded metaphases is a potentially powerful tool for positional cloning.