Meiotic segregation and interchromosomal effects in a rare (1:2:10) complex chromosomal rearrangement

Abstract

Purpose Complex chromosomal rearrangements (CCR) are rare rearrangements involving more than two chromosomes and more than two breakpoints. CCR are associated with male infertility as a result of the disruption of spermatogenesis due to complex meiotic configurations and the production of chromosomally abnormal sperm. We examined a carrier of a t(1:2:10) CCR in order to determine the patterns of segregation and any presence of an interchromosomal effect (ICE). Methods Centromeric, locus specific and telomeric probes (Vysis, USA) were used for the study. On~1,000 sperm nuclei from the reciprocal translocation carrier, dual color Fluorescence in situ hybridization (FISH) was performed on each of the involved chromosomes to determine the patterns of segregation. FISH was also performed on chromosome 13, 18, 21, X and Y to determine any ICE. Results We observed abnormal chromosome complements in 24.3%, 19.5% and 15.8% of sperm for chromosomes 2, 10 and 1, respectively. There was a significantly increased rate of ICEs for chromosomes 13 and 21 when compared with controls. Conclusions CCR may present a lower risk for producing unbalanced chromosomes than other studies have indicated.CCRs may be at an increased risk for ICE especially among acrocentric chromosomes.

Sequential FISH allows the determination of the segregation outcome and the presence of numerical anomalies in spermatozoa from a t(1;8;2)(q42;p21;p15) carrier

“…Regarding the ICE evaluation, the significant increases of aneuploidies for chromosomes X, Y and 18 are consistent with the only two reported studies that evaluated ICE in CCR carriers [9,16]. This circumstance might be related again with the characteristics of the hexavalent configuration.…”

“…This fact clearly increases the complexity of the analysis, first due to the lack of commercial probes labelled with five different fluorochromes, second because of the difficulty of analysing five probes in the small area of a sperm nucleus. As a consequence, other strategies have been used including sperm karyotyping [3], multi-colour banding [16], primed in situ labelling [12], or aneuploidy screening of the chromosomes involved in the three-way rearrangement [9,13].…”

High-magnification sperm selection does not decrease the aneuploidy rate in patients who are heterozygous for reciprocal translocations

“…Although it was initially postulated that the parents of children with Down's syndrome had a greater incidence of translocation [21], the significance of ICEs is still subject to debate [19,26]. Given that reciprocal translocations could cause meiotic segregation disturbance of chromosomes not involved in this rearrangement, we also studied the sperm euploid rates for chromosomes 18, X and Y.…”

Sperm FISH and chromatin integrity in spermatozoa from a t(6;10;11) carrier

“…To date, only seven studies have examined meiotic segregants by FISH in the ejaculated spermatozoa of CCR carriers. Only three were classical three-way CCRs: t(1;19;13) (Loup et al 2010), t(5;13;14) (Pellestor et al 2011b) and t(1;8;2) (Godo et al 2013); two were exceptional CCRs: (1;2;10),inv(10) (Kirkpatrick & Ma 2012) and t(3;6),inv(8) (Ferfouri et al 2012); and two had double two-way translocations t(8;9),t(1;16) (Ferfouri et al 2013) and t(Y;15),rob(13;14) (Ferfouri et al 2014). In all the three-way studies, the percentage of unbalanced segregants ranged from 69.4 to 88.3%.…”

“…In cases of CCRs, a multivalent meiotic configuration generates a minimum of 64 different types of meiotic segregants: three-way CCR, hexavalent structure and reduced recombination (Saadallah & Hulten 1985, Johannisson et al 1988, Loup et al 2010, Pellestor et al 2011b. To date, only seven reports examining meiotic segregation in ejaculated spermatozoa in CCR cases have been published (Loup et al 2010, Pellestor et al 2011b, Ferfouri et al 2012, 2014, Kirkpatrick & Ma 2012, Godo et al 2013, two of which have evaluated the genetic content of sperm complements in the human-hamster oocyte penetration assay (Burns et al 1986, Cifuentes et al 1998. The percentage of unbalanced chromosome complements has been found to range from 69.4 to 88.3%.…”