Strategy for molecular cloning of the fragile X site DNA

Fragile X syndrome is a common form of mental retardation associated with a fragile site on the human X chromosome. We have recently demonstrated that the fragile X chromosome, when isolated within a somatic cell hybrid, often participates in translocations involving rodent chromosome arms. Cytogenetic and molecular evidence strongly suggests that the human breakpoint of these translocations is within the fragile X sequence. Hence, the joining of heterologous DNA (i.e. from two species) may permit the molecular cloning of the fragile X site. We describe here the cloning approach employed to enhance the isolation of interspecific chromosome translocation junctions. The human portion of the translocation junction should be derived from the fragile X site sequence.