DETECTION OF STRUCTURAL ABNORMALITIES IN SPERMATOZOA OF A TRANSLOCATION CARRIER T(3-11)(Q27.3-Q24.3) BY TRIPLE FISH

Structural chromosome abnormalities in spermatozoa represent an import ant category of paternally transmittable genetic damage. A couple was referred to our centre because of repetitive abortions and the man was found to be a carrier of a reciprocal translocation t(3;11)(q27.3;q24 .3). A tailored fluorescence in situ hybridisation (FISH) approach was developed to study the meiotic segregation patterns in spermatozoa fr om this translocation carrier. A combination of three DNA probes was u sed, a centromeric probe for chromosome 11, a cosmid probe for chromos ome 11q and a YAC probe for chromosome 3q. The frequency of spermatozo a carrying an abnormal chromosome constitution was compared with basel ine frequencies in control semen specimens and it was found that a sig nificantly higher percentage of spermatozoa carried an abnormal consti tution for the chromosomes involved in the translocation. A normal or balanced chromosome constitution was found in 44.3% of the analysed sp ermatozoa, while the remainder exhibited an abnormal chromosome consti tution reflecting different modes of segregation (15.9% adjacent I seg regation, 6.5% adjacent II segregation, 28.9% 3:1 segregation, 0.8% 4: 0 segregation, 3.6% aberrant segregation). The frequency of aneuploidy for chromosomes X, Y, 13 and 21 was assessed using specific probes bu t there was no evidence of interchromosomal effects or variations in t he sex ratio in spermatozoa from the translocation carrier. In conclus ion, structural aberrations can be reliably assessed in interphase spe rmatozoa using unique DNA probe cocktails, and this method provides in sight into the genetic constitution of germ cells and enables evaluati on of potential risks for the offspring.