Satellite III sequences on 14p and their relevance to Robertsonian translocation formation

Robertsonian translocations (ROBs) are the most common rearrangements in hu mans, contributing significantly to genetic imbalance, fetal wastage, menta l retardation and birth defects. Rob(14q21q) and rob(13q14q), which are for med predominantly during female meiosis, comprise the majority (similar to 85%) of all ROBs. Previous studies have shown that the breakpoints are cons istently located within specific regions of the proximal short arms of chro mosomes 13, 14, and 21. The high prevalence of these translocations, the co nsistent breakpoints found, and the fact that roughly 50% of cases occur sp oradically suggest that the sequences at or near the breakpoints confer sus ceptibility to chromosome rearrangement and that the rearrangements occur t hrough a specific mechanism. To investigate this hypothesis, we developed h amster-human somatic cell hybrids derived from de novo rob(14q21q) patients that contained the translocated chromosome segregated from the other acroc entric chromosomes. We determined the physical order of five satellite III subfamilies on 14p, and investigated their involvement in formation of thes e de novo translocations.