BREAKPOINT DIVERSITY ILLUSTRATES DISTINCT MECHANISMS FOR ROBERTSONIANTRANSLOCATION FORMATION

Robertsonian translocations are the most common chromosomal rearrangem ents in humans. The vast majority of the ten possible nonhomologous ty pes of Robertsonian translocations ascertained are rob(13q14q) and rob (14q21q). Recombination between homologous sequences on nonhomologous chromosomes has been proposed as a mechanism leading to the preferenti al formation of rob(13q14q) and rob(14q21q). However, little evidence exists to indicate whether the remaining less common Robertsonian tran slocations form through a similar mechanism. To better elucidate the m echanisms involved in Robertsonian translocation formation, we have us ed fluorescence in situ hybridization to localize the breakpoints in 5 6 nonhomologous Robertsonian translocations. This study revealed highl y variable locations of breakpoints in seven types of the less common Robertsonians, while nearly all rob(13q14q) and rob(14q21q) analyzed d isplayed breakpoints in the same locations, Therefore, this study prov ides direct evidence that rob(13q14q) and rob(14q21q) form through a s pecific mechanism, possibly involving homologous recombination, which is distinct from the mechanism(s) that contributes to the formation of the remaining types of Robertsonian translocations.