Embryo Screening

This is taken from a discussion I took part in concerning preimplantation genetic diagnosis, a very touchy subject from an ethical point of view, and also from a technical point of view:

“…. There have been many issues with genetic testing of the embryos for hereditary diseases such as Huntington Disease for many reasons. First, of course, during pregnancy women can have a genetic test performed on the fetus in order to find out if their infants will be affected by a known disease or not. However, many centers refuse to perform this test as it divulges information about the parents as well and usually leads to pregnancy termination. The test in itself cannot predict the time of onset of course. However, more interestingly in my opinion, this opens the door to a whole new approach to birth, in vitro fertilization with pre-implantation genetic diagnosis (PGD). This procedure is also known as embryo screening and it allows couples at risk of transmitting a genetic disease to ensure their descendants to be unaffected by the genetic disorder through artificially combining many sperm cells from a man with many egg cells from a woman to create many embryos. Then, cell samples are taken from all of the embryos and the DNA analyzed for the defective genes. The non-disease carrier embryos are selected and artificially implanted into the mother’s uterus. This allows the parent to ensure a “disease free” child and avoid having to go through the painful termination process, in case the pre-natal test is positive (see below link to video for Comprehensive Chromosome Screening technic, a novel approach to embryo screening). This method, while very appealing, is an ethical nightmare, as it opens the door to the quest for a “perfect baby” …”

Y.S.H.

  

References:

  • Embryo Screening and the Ethics of Human Genetic Engineering, By: Leslie A. Pray, Ph.D. © 2008 Nature Education
  • [Ethics and medical genetics], Lacombe D., J Int Bioethique. 2012 Jun;23(2):95-102, 178-9. French.
  • Preimplantation genetic screening: “established” and ready for prime time?, Gleicher N, Weghofer A, Barad D.,Fertil Steril. 2008 Apr;89(4):780-8. Epub 2008 Mar 18. Review.

RNA interference

Cells have many ways of regulating gene expression, and one of the most efficient of them would be RNA interference (RNAi). This method allows the cell to effectively silence, or repress, expression of genes by using different types of short RNAs that binds to homologous sequences in order to inhibit translation, to degrade or/and, sometimes, to silence the promoter of the target gene mRNA. This method is so effective that it is now widely used in laboratories for in vivo experiments and, thus, I thought I should say a few words about it before introducing the video made by Nature about this technique:

Neurotrophins

Cells of multi-cellular organisms not only require oxygen and nutrients to survive, they also need survival signals called trophic factors. In the absence of such signals, signaling pathways that prevent the cell to undergo a “suicide” program are not activated and, thus, result in cell death.

Analysis of the development of the nervous system demonstrated the essentiality of trophic factors in cellular development. Indeed, it was shown that more cells grew than actually survived when neurons developed to connect to other neurons (or muscles), even over long distances. It was further demonstrated that only those cells that succeeded in making connections survived while the others died.

An example of such trophic factors was discovered through the study of innervation of developing limbs in chick embryos and was simply known as nerve growth factor (NGF). It was then identified to belong to the neurotrophins, which binds to and activate a family of receptor tyrosine kinases called Trk. NGF binds with high affinity to TrkA and, through this binding, provides the necessary surviving signal to avoid “suicide” for different classes of neurons that successfully made connections. Indeed, only Trk receptors produced on the growth cones of the extending axons of neurons trying to make connections bind neurotrophins produced by target tissues.

This process is key during developmental processes as it ensures that the right neurons survive and in the required amount for proper target innervation. Furthermore, neurotrophins allow for cell fate decision, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. Neurotrophins were also found to regulate many aspects of neural function, e.g. in the mature nervous system, they were demonstrated to control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.

Y.S.H.

 

References:

  • Lodish et al., Molecular Cell Biology, Sixth Edition, 2008, pp. 936-938
  • Neurotrophins: roles in neuronal development and function, Huang EJ, Reichardt LF., Annu Rev Neurosci. 2001;24:677-736. Review.