Analysis of genetic variations in formalin-fixed, long-term preserved pathological tissues

Museal wet preparations of malformed bodies or organs, such as those of the Pathological-Anatomical Collection in Vienna, could play an important role in revealing genetic variations causing rare diseases. A prerequisite for genetic analyses is that DNA can be isolated from these preparations in high purity, high integrity, and sufficient quantity. However, wet preparations have commonly been fixed with formalin to maintain morphology of the tissues and prevent their degradation. Formaldehyde not only forms methylene bridges between proteins but also cross-linkages between nucleic acids and proteins. Thus, the application of standard DNA extraction protocols to formalin-fixed, long-term preserved specimens generally results in low quantities of impure and highly fragmented DNA.

We attempt to improve DNA isolation from formalin-fixed, long-term preserved specimens by pursuing different strategies, focusing on pre-treatment steps prior to cell lysis and tissue digestion. Currently, we are dealing with samples from foetuses with craniofacial abnormalities, and foetuses without craniofacial abnormalities serving as controls. Samples from different organs of the foetuses were taken by using a minimal-invasive 3D-based technology. The long-term goal is to reveal single nucleotide polymorphisms (SNPs) that are associated with facial dysmorphia.   

Cooperation partners.

  • Pathological-Anatomical Collection, Vienna
  • Andreas Glowania, Klinikum Bielefeld
  • Rudolf Schmidt, Intramed