Meiotic segregation analysis of a 14;21 Robertsonian translocation carrierby fluorescence in situ hybridization

Meiotic segregation of chromosomes 14 and 21 in sperm from a 14;21 Robertso nian translocation carrier was analyzed with dual-color FISH using two locu s-specific DNA probes (Tel 14q and LSI 21). The frequency of normal or chro mosomally balanced sperm, resulting from alternate segregation, was 88.42%. The frequency of unbalanced sperm, resulting from adjacent segregation, wa s 11.25%. These observed frequencies deviated significantly from the theore tical frequencies (33.33% and 66.67%, respectively) based on random chromos ome segregation, with sperm resulting from alternate segregation being pref erentially produced in the translocation carrier. With respect to the chrom osomally unbalanced sperm, the frequency of 21q disomic sperm was 2.45%, wh ich is in agreement with the frequencies of unbalanced fetuses or offspring at the time of amniocentesis or at term (0-4.3%) reported by others. Altho ugh the frequency of 14 or 21 nullisomic sperm should be theoretically equa l to that of 14q or 21q disomic sperm in both the carrier and controls, the frequency of nullisomic sperm was significantly higher than that of disomi c sperm in the carrier (P=0.0009 for chromosome 14, P<0.0001 for chromosome 21) but not in the controls (P=0.091 fur chromosome 14, P=0.74 for chromos ome 21). This evidence suggests the occurrence of maturation arrest during spermatogenesis of the carrier.