Errors in mitotic divisions were assayed using various satellite DNAs as probes, hybridized in situ, to show that they included nondisjunction, chromosome and chromatid lagging, chromatid malsegregation, and monopolar segregations. The total rates of error were 1.7, 1.1, and 0.6% for chromosomes X, 17, and 18, respectively. Lagging was the most common error for all chromosomes and chromatid malsegregation, a source of 3:1 segregations occurred at about the same frequency as nondisjunction. In some cells, lagging of both X chromatids occurred and there were several cells where both X chromosomes showed errors in segregation. The disjunction of chromosomes was shown to be independent of their segregation and is speculated to involve a different mechanism.

A probe from the 3’ noncoding region of a murine type I keratin intermediate filament (IF) gene (<i>Krt-1.14</i>) localizes to band D of murine Chromosome 11 using in situ hybridization. This localization provides a physical confirmation of the assignment of the type I keratin genes by linkage analysis in the mouse. It also demonstrates that the <i>Krt-1.14 </i>genes are at a single locality in the mouse in contrast to the two locations on the short and long arms of chromosome 17 in humans.

A probe from the 3' noncoding region of a murine type I keratin intermediate filament (IF) gene (Krt-1.14) localizes to band D of murine Chromosome 11 using in situ hybridization. This localization provides a physical confirmation of the assignment of the type I keratin genes by linkage analysis in the mouse. It also demonstrates that the Krt-1.14 genes are at a single locality in the mouse in contrast to the two locations on the short and long arms of chromosome 17 in humans.

An excess of hypoploid cells has repeatedly been reported in studies of aneuploidy and has often been attributed to technical artifact. We have examined at least 200 anaphase or early-telophase cells from each of 28 normal women and found that chromosome or chromatid lagging occurs in an average of 2.43% of cells. In a separate study, we have examined the frequency of micronuclei in cytochalasin B-arrested, binucleate cells and shown that a similar frequency of cells (1.6%) contain one or more micronuclei. Using in situ hybridization of an alpha centromeric probe (alpha R1), which hybridizes to 9 of the 22 human autosomes, we were able to infer that most, if not all, of the micronuclei contain whole chromosomes or chromatids. Since the loss of a chromosome by lagging will induce hypoploid daughter nuclei (two where a chromosome is lost and one where a chromatid is lost), we conclude that lagging is a major mechanism for chromosome loss in human lymphocyte cultures. This loss occurs in the cells of normal individuals under control conditions.

A novel measurement, that of chromosome flexion, has been used to assess the degree of spindle polymerization at metaphase in human lymphocytes. It was found that this measurement showed a highly repeatable quantitative response to nocodazole exposure. Thus this measurement could be used to assess the potential for chemicals to depolymerize spindles. Under controlled conditions, individual differences were observed between the subjects which might be related to their age. However, the response to nocodazole-induced spindle depolymerization, as measured by flexion, was uniform for all subjects. 4 chemicals reported to induce aneuploidy in mammalian cells were used in a flexion assay. Only substances known to depolymerize microtubules reduced chromosome flexion.

This paper considers whether the model proposing chromosome displacement as a primary step in the induction of mitotic aneuploidy (Ford and Roberts, 1983a) is consistent with experimental data relating to spindle structure, chromosomal attachment to spindles, the promotion of aneuploidy and the relative involvement of the different human chromosomes in aneuploidy. It is concluded that the model is consistent with all the parameters thus far tested for autosomal chromosomes.