Analysis of non-crossover bivalents in pachytene cells from 10 normal men

Background: Bivalents with no recombination foci (possible achiasmates) are unable to orient properly on the metaphase plate or to segregate chromosomes to daughter cells. Non-crossover bivalents are known to cause meiotic arrest in various organisms. Methods: Individual non-cros sover bivalents were identified in 886 pachytene cells (19 492 bivalents) from testicular biopsies of 10 normal men. Fluorescence staining combined with centromere-specific multicolour fluorescence in situ hybridization (cenM-FISH) was used to identify mismatch repair gene mutation of human mutL homologue 1 (MLH1) recombination foci along each bivalent synaptonemal complex (SC). Results: A total of 60 autosomal non-crossovers (SCs without an MLH1 focus) were found, and of these, chromosomes 21 (2.1%) and 22 (1.7%) had a significantly higher proportion than chromosomes 11, 12, 19 (each 0.1%), 13 (0.2%), 14 (0.6%), 16 (0.5%) and 15, 17, 18, 20 (each 0.3%) (P < 0.05). Sex chromosome univalents had a frequency of 27%, higher than that observed in any autosomal bivalent (P < 0.0001). Conclusions: These results suggest that G-group chromosomes and sex chromosomes are most susceptible to having no recombination foci and thus would be more susceptible to non-disjunction during spermatogenesis. This is consistent with previous observations from sperm karyotyping and FISH analysis, which demonstrate that chromosomes 21 and 22 and the sex chromosomes have a significantly increased frequency of aneuploidy compared with other autosomes.