Complex chromosomal rearrangement-a lesson learned from PGS.

Purpose: The aim of the study is to report a case of non-diagnosed complex chromosomal rearrangement (CCR) identified by preimplantation genetic screening (PGS) followed by preimplantation genetic diagnosis (PGD) which resulted in a pregnancy and delivery of healthy offspring.

Methods: A 29-year-old woman and her spouse, both diagnosed previously with normal karyotypes, approached our IVF-PGD center following eight early spontaneous miscarriages. PGS using chromosomal microarray analysis (CMA) was performed on biopsied trophectoderm.

Improving preimplantation genetic diagnosis (PGD) reliability by selection of sperm donor with the most informative haplotype.

Background: The study is aimed to describe a novel strategy that increases the accuracy and reliability of PGD in patients using sperm donation by pre-selecting the donor whose haplotype does not overlap the carrier's one.

Methods: A panel of 4-9 informative polymorphic markers, flanking the mutation in carriers of autosomal dominant/X-linked disorders, was tested in DNA of sperm donors before PGD. Whenever the lengths of donors' repeats overlapped those of the women, additional donors' DNA samples were analyzed.

Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons.

A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus.

Effects of laser polar-body biopsy on embryo quality.

Objective: To evaluate the effect of laser polar-body biopsy (PBB) for preimplantation genetic diagnosis on embryo quality.

Study Design: Retrospective case-control analysis. The quality of 145 embryos after PBB was compared to 276 embryos of the same group of women without biopsy.

Human embryonic stem cells carrying mutations for severe genetic disorders.

Human embryonic stem cells (HESCs) carrying specific mutations potentially provide a valuable tool for studying genetic disorders in humans. One preferable approach for obtaining these cell lines is by deriving them from affected preimplantation genetically diagnosed embryos. These unique cells are especially important for modeling human genetic disorders for which there are no adequate research models.

Snail genes at the crossroads of symmetric and asymmetric processes in the developing mesoderm.

Retinoic acid (RA) signalling ensures that vertebrate mesoderm segmentation is bilaterally synchronized, and corrects transient interferences from asymmetric left-right (L-R) signals involved in organ lateralization. Snail genes participate in both these processes and, although they are expressed symmetrically in the presomitic mesoderm (PSM), Snail1 transcripts are asymmetrically distributed in the L-R lateral mesoderm. We show that the alteration of the symmetric Snail expression in the PSM induces asynchronous somite formation.

Neural tube closure depends on nitric oxide synthase activity.

Neural tube (NT) closure is a multifactorial process that involves yet unresolved molecular mechanisms. It had been shown previously that high levels of nitric oxide (NO) block the process of NT closure in the chick embryo by inhibiting methionine synthase (MS). The MS inhibition and its effect on NT closure could be alleviated by folic acid, suggesting the involvement of the folate-methionine pathway in the process.

Evidence that nitric oxide regulates cell-cycle progression in the developing chick neuroepithelium.

In all developing epithelia, the nuclei continually migrate between the apical and basal sides of the cell during the cell cycle, with S phase occurring basally and mitosis occurring apically. The purpose and mechanism of this nuclear migration are unknown. Here, we show that nitric oxide (NO) is endogenously produced in the developing chicken neural tube, where it apparently regulates cell-cycle progression.