Analysis of chiasma frequency and first meiotic segregation in a human male reciprocal translocation heterozygote, t(1;11) (p36.3;q13.1), using fluorescence in situ hybridisation

Abstract

In this study we have used a testicular biopsy from a human male with a 46, XY, t(1;11)(p36.3;q13.1) karyotype. Fluorescence in situ hybridisation with whole chromosome libraries and paracentromeric probes were applied to identify normal and derived chromosomes 1 and 11 in both first metaphase (MI) and second metaphase (MII) cells. The chiasma frequency distribution was established in the quadrivalent. A large proportion of MI cells was found to have at least one interstitial chiasma, resulting at MII in dimorphic chromosomes bearing one normal and one translocated chromatid. Alternate, adjacent I, adjacent II, and 3:1 products were all identified at MII. More than half of the cells analysed could not be assigned to a single segregation category because of the presence of interstitial chiasmata. Such MII cells could have arisen from either alternate or adjacent I segregation. We also calculated the proportion of sperm expected to be normal, balanced, and unbalanced. The latter data are in agreement with the results reported by Spriggs et al. (1992), who karyotyped sperm from the same individual.

Meiotic segregation analysis by FISH investigations in sperm and spermatocytes of translocation heterozygotes

“…4,6,7 Analysis of metaphase I demonstrated that the reciprocal translocation chromosomes regularly form quadrivalents as is generally the case, even when the translocated segments are very small. Most importantly, there is a high frequency of a single chiasma within the interstitial segments.…”

“…This was found in no less than 48% for the t(1;11), 31% for the t(15;20), 95% for the t(11;22) and 100% for the t(9;21) translocation heterozygotes. 4,6,7 These frequencies are substantially increased in comparison to chiasma formation within these segments in the normal male. 8 Adequate information on the occurrence of chiasmata within the interstitial segments can only be obtained by meiotic studies of the respective translocation carriers.…”

“…This is exemplified by the recent paper 3 still not possible to tell whether the gametes were derived from adjacent I or alternate segregations, where this is complicated by an interstitial chiasma. It is a well known fact, and is clearly stated in many publications, including textbooks, 4,5 that whenever an interstitial chiasma is present, asymmetric dyads are produced at anaphase I. These could be derived from either alternate or adjacent I segregations.…”

Meiotic segregation in males heterozygote for reciprocal translocations: analysis of sperm nuclei by two and three colour fluorescence in situ hybridization

“…As the normal chromosome and its translocated derivative contain the same centromeric sequences, it was not possible to differentiate between alternate or adjacent 1 segregation. Data from meiotic studies combined with FISH Hultén, 1993a and1993b) indicate that recombination within the interstitial segment (between the centromere and translocation breakpoint), render alternate and adjacent I segregation products cytologically indistinguish able, even after sperm karyotyping. Indeed, they have observed high proportions of dismorphic chromosomes, bearing two dif ferent chromatids (one translocated and one normal) in meta phase II spermatocytes.…”

Karyotyping of human synaptonemal complexes by cenM-FISH

“…This can be very helpful for the recombination analysis in translocations carriers, as it has been shown that the chiasma frequency and distribution in translocation carriers may vary for the same chromosome when compared to the normal situation. 22 In conclusion, our results indicate that cenM-FISH is a good tool for the analysis of SCs and meiotic chromosomes. The combined use of this technique with immunocytogenetic methods on SCs and also the application of cenM-FISH on meiotic chromosomes, would help us to better understand some of the mechanisms involved in the meiotic process, including those which lead to the generation of chromosome aberrations.…”