Chromosome translocations: segregation modes and strategies for preimplantation genetic diagnosis

Abstract

Preimplantation genetic diagnosis (PGD) offers polymerase chain reaction tests for an increasing range of single gene defects, and fluorescence in situ hybridization tests for sex determination (for X-linked conditions) and for aneuploidy detection. Patients carrying chromosome translocations with a high reproductive risk are increasingly seeking to increase their chances of a normal pregnancy with the help of PGD, for which they present a special challenge. This paper describes the behaviour of reciprocal translocations at meiosis, discusses current methods of detecting meiotic outcomes at the preimplantation stage and outlines ways forward for preimplantation diagnosis of these common rearrangements. We also propose a more general strategy using recently developed chromosome-specific sub-telomeric probes, combined, if possible, with proximal probes, to form a strong diagnostic tool.

A healthy live birth after successful preimplantation genetic diagnosis for carriers of complex chromosome rearrangements

“…In cases of reciprocal translocation between two chromosomes, 32 types of gamete were produced, and the rate of transferable embryos was between 20% and 30% (18)(19)(20). Especially in carriers of CCRs with three breakpoints, if a crossover between centromere and breakpoint occurs, >100 types of imbalanced gametes may be produced.…”

Interchromosomal effects for chromosome 21 in carriers of structural chromosome reorganizations determined by fluorescence in situ hybridization on sperm nuclei

“…At present, the use of preimplantation genetic diagnosis techniques (PGD) in these cases allows the selection of normal embryos provided that a proper combination of DNA probes is used (Coonen et al 1998;Scriven et al 1998;Vidal et al 1998). Furthermore, when the carrier is the male partner, it has been suggested that an analysis of meiotic segregation prior to PGD should be carried out by FISH on decondensed sperm heads (Van Assche et al 1999;Vidal et al 1999) in order to evaluate the percentage of abnormal sperm.…”

Reciprocal translocation identified in Vigna angularis dominates the wild population in East Japan

“…LG6-16 fertility when a plant with translocation-type chromosomes is hybridized with a plant with normal chromosomes (Scriven et al 1998), we counted and calculated seed numbers in each pod ( Table 2). As a result, F 1 plants derived from 'Kyoto-Dainagon' did not necessarily show reduced fertility.…”

“…Indeed, reciprocal translocations disturb balanced transmission of genetic information during meiosis, leading to aneuploidy (reviewed by Scriven et al 1998). Aneuploidy often leads to reduced viability of gametes or embryos that in turn causes reduced fertility.…”