Incidence and origin of symmetric and asymmetric dicentrics in Bloom's syndrome.

The incidence and origin of dicentric chromosomes has been analyzed in Bloom's syndrome (BS) lymphocytes. In diploid cells, the dicentrics are predominantly asymmetric, consisting of two nonhomologous chromosomes. In contrast, in tetraploid cells, the majority of dicentrics are formed by two homologs, which, judging from Q-banded metaphases, have broken at identical points. Our earlier assumption that most, possibly all, chromosome abnormalities in BS originate in S-G2 is further supported by the present observation that only 26/79 cells with dicentrics also had a fragment. In other words, the dicentrics have not arisen in the previous G1 but in S-G2 of a preceding cell cycle. The symmetric dicentrics would arise in diploid cells from an adjacent counterpart to a mitotic chiasma between two homologs, and in tetraploid cells, from an adjacent exchange between two sister chromosomes in a diplochromosome. The asymmetric dicentrics can be assumed to result primarily from segregation of an adjacent QR between two nonhomologous chromosomes. Based on the frequency of symmetric dicentrics in tetraploid cells (25/61 cells), and assuming that the ratio of adjacent exchanges to mitotic chiasmata is around 1/50, we predict that the chiasma frequency in diplochromosomes of BS lymphocytes will turn out to be as high as 20/cell.