ANALYSIS OF CENTROMERIC ACTIVITY IN ROBERTSONIAN TRANSLOCATIONS - IMPLICATIONS FOR A FUNCTIONAL ACROCENTRIC HIERARCHY

Approximately 90% of human Robertsonian tranlocations occur between no nhomologous acrocentric chromosomes, producing dicentric elements whic h are stable in meiosis and mitosis, implying that one centromere is f unctionally inactivated or suppressed. To determine if this suppressio n is random, centromeric activity in 48 human dicentric Robertsonian t ranslocations was assigned by assessment of the primary constrictions using dual color fluorescence in situ hybridzation (FISH). Preferentia l activity/constriction of one centromere was observed in all except t hree different rearrangements. The activity is meiotically stable sinc e intrafamilial consistency of a preferentially active centromere exis ted in members of six families. These results support evidence for non random centromeric activity in humans and, more importantly, suggest a functional hierarchy in Robertsonian translocations with the chromoso me 14 centromere most often active and the chromosome 15 centromere le ast often active.