Pericentromeric organization at the fusion point of mouse Robertsonian translocation chromosomes

In mammals, Robertsonian (Rb) translocation (the joining of two telo/acroce ntric chromosomes at their centromere to form a metacentric) is the most ef fective process in chromosomal evolution leading to speciation; its occurre nce also affects human health (through the induction of trisomies) and the fertility of farm animals. To understand the mechanism of Rb translocation, we used the house mouse as a model system and studied the organization of pericentromeric satellite DNAs (satDNA) of telocentrics and Rb chromosomes, both minor and major satDNA, The chromosome-orientation fluorescence in si tu hybridization (CO-FISH) technique was used to analyze the major satDNA, To detect the very small amount of minor satDNA, a procedure was developed that combines GO-FISH with primed in situ labeling and conventional FISH an d is five times more sensitive than the GO-FISH procedure alone. It was fou nd that both the major and the minor satDNA tandem repeats are oriented hea d-to-tail in telocentric and Rb chromosomes, and their polarity is always t he same relative to the centromere. We suggest that all tandemly repetitive satDNAs in a species probably are locked into such a symmetry constraint a s a universal consequence of chromosomal evolution. Rb translocation breakp oints were found localized within the minor satDNA of telocentrics, and the se sequences contributed symmetrically to the formation of the centromeric region of the Rb chromosomes. These results are important for an understand ing of the geometry of Rb translocations and suggest the study of DNA orien tation as a new tool for investigating these rearrangements.