3D Genome Studies

Speaker:      Wouter de Laat (Hubrecht Institute)

Subject:       From 3D genome studies that uncover genome functioning to advanced methods for prenatal diagnosis

Location:     Faculty of Applied Sciences, TU Delft

Date:            Thursday, February 11 2016, 16:00-17:00

Jasper Veerman

 

If we attach all the DNA from our chromosomes and extend it, it would span 2 meters. This comparison is often used to create an image of how wonderfully the DNA is compacted into the ‘tiny’ nucleus. A comparison that remains fascinating, regardless of how often you have heard it. In this way, Wouter de Laat introduces his talk on 3D genome studies.

Besides the amount being enormous, its function may be of even higher interest. It is estimated that about 3% of the genome is coding DNA, while the other 97% is popularly called ‘junk DNA’. However, soon after the term was coined, researchers realized that the junk DNA was immensely important. Wouter de Laan suggested that this junk may contain activating switches, up to 1 Mbp basepair (1 million basepairs)  in front of a gene. In order to find these enhancing regions, DNA sequencing may not be sufficient. It is desired to use a technique that takes into account the three dimensional structure of the DNA.

The technique used for this is 3C: chromosome conformation capture. This technique, developed by Job Dekker, consist of crosslinking nearby DNA via proteins, subsequent digestion and ligation that result in plasmid formation, connecting pieces of DNA that were spatially close. Afterwards, reverse crosslinking removes the linking proteins, making the plasmid ready for sequencing. Using thismethod, enhancer-promotor loops have been found in for example the -globin locus. Repetition over time allows tracking subsequent activation of different types of -globin throughout someone’s life.

Besides his research, Wouter de Laat set up a company called Cergentis, which focuses on application of these techniques in healthcare. For example, the plasma from a pregnant woman contains some fetal DNA, that could be used for prenatal, noninvasive screening for disease. Of course, the ethics of this are a whole different field than the scientific discovery as such.

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