The X chromosome frequently lags behind in female lymphocyte anaphase.
Pancentromeric FISH and X-chromosome painting were used to characterize anaphase aberrations in 2,048 cultured lymphocytes from a healthy 62-year-old woman. Of 163 aberrant anaphases, 66.9% contained either chromosomes or their fragments that lagged behind. Characterization of 200 laggards showed that 49% were autosomes, 33. 5% were autosomal fragments, and 17.5% were X chromosomes. The X chromosome represented one-fourth of all lagging chromosomes and was involved much more often than would be expected by chance (1/23). Labeling of the late-replicating inactive X chromosome with 5-bromo-2'-deoxyuridine revealed that both X homologues contributed equally to the laggards. Among 200 micronuclei examined from interphase cells, the proportion of the X chromosome (31%) and autosomal fragments (50%) was higher than among anaphase laggards, whereas autosomes were involved less often (19%). These findings may reflect either selection or the fact that lagging autosomes, which were more proximal to the poles than were lagging X chromosomes, were more frequently included within the main nucleus. Our results suggest that the well-known high micronucleation and loss of the X chromosome in women's lymphocytes is the result of frequent distal lagging behind in anaphase and effective micronucleation of this chromosome. This lagging appears to affect the inactive and active X chromosomes equally.
Catalán
J
J
Laboratory of Molecular and Cellular Toxicology, Department of Industrial Hygiene, Finnish Institute of Occupational Health, Helsinki, Finland.
Falck
G C
GC
Norppa
H
H
D000705:Anaphase / Q000235:genetics*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000235:genetics; D020223:Chromosome Painting; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D048629:Micronuclei, Chromosome-Defective / Q000235:genetics; D008875:Middle Aged; D013692:Telophase / Q000235:genetics; D013997:Time Factors; D014960:X Chromosome / Q000235:genetics*
D004247:DNA