Single cell CGH analysis reveals a high degree of mosaicism in human embryos from patients with balanced structural chromosome aberrations

Abstract

We have performed comparative genomic hybridization (CGH) analysis of single blastomeres from human preimplantation embryos of patients undergoing preimplantation genetic diagnosis (PGD) for inherited structural chromosome aberrations and from embryos of IVF couples without known chromosomal aberrations. The aim was to verify the PGD results for the specific translocation, reveal the overall genetic balance in each cell and visualize the degree of mosaicism regarding all the chromosomes within the embryo. We successfully analysed 94 blastomeres from 28 human embryos generated from 13 couples. The single cell CGH could verify most of the unbalanced translocations detected by PGD. Some of the embryos exhibited a mosaic pattern regarding the chromosomes involved in the translocation, and different segregation could be seen within an embryo. In addition to the translocations, we found a high degree of numerical aberrations including monosomies, trisomies and duplications or deletions of parts of chromosomes. All of the embryos (100%) were mosaic, containing more than one chromosomally uniform cell line, or even chaotic with a different chromosomal content in each blastomere.

The importance of aneuploidy screening in reciprocal translocation carriers

“…No statistically significant difference was found between female and male carriers when analysing mosaicism. A high degree of mosaicism has previously been detected in human embryos of patientswith balanced structural chromosome aberrations; the frequencies are as high as 73%, 98% and even 100% (Iwarsson et al 2000, Malmgren et al 2002, Emiliani et al 2003.…”

“…Chromosome alterations related to chromosomes different from those involved in the translocation (Malmgren et al 2002) could be the cause for the high incidence of arrest and poor embryo development in translocation carriers (Findikli, 2003).…”

Whole genome amplification in preimplantation genetic diagnosis

“…With image-processing software, duplication or deletion, and unbalanced structural differences between the normal reference and test specimens can be revealed. This technique has already been applied to PGD during the past few years, including chromosomal mosaicism, unbalanced structural chromosome aberrations, and chromosome breakage and aneuploidy (Malmgren et al, 2002;Shanske et al, 2004;Fragouli et al, 2006).…”

Preimplantation genetic diagnosis: present and future

“…The generated sticky ends reunite as a ring Isochromosome Loss of one chromosome arm and duplication of the other resulting embryos [22,28,29,33]. Several published reports have identified highly abnormal chromosome complements in 70-100% of embryos generated from some patients with poor reproductive histories attributed to a structural rearrangement (reviewed in [34]).…”